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Quarta-feira, 17.06.15

Understanding Immunotherapy

Understanding Immunotherapy

Approved by the Cancer.Net Editorial Board, 05/2015

Immunotherapy, also called biologic therapy, is a type of cancer treatment designed to boost the body's natural defenses to fight the cancer. It uses materials either made by the body or in a laboratory to improve, target, or restore immune system function. It is not entirely clear how immunotherapy treats cancer. However, it may work in the following ways:

  • Stopping or slowing the growth of cancer cells
  • Stopping cancer from spreading to other parts of the body
  • Helping the immune system work better at destroying cancer cells.

There are several types of immunotherapy, including monoclonal antibodies, non-specific immunotherapies, and cancer vaccines.

Monoclonal antibodies

When the body’s immune system detects antigens, it produces antibodies. Antigens are harmful substances, such as bacteria, viruses, fungi, or parasites. Antibodies are proteins that fight infection. Monoclonal antibodies are made in a laboratory. When they are given to patients, they act like the antibodies the body produces naturally. A monoclonal antibody is directed against a specific protein in the cancer cells, and it does not affect the cells that do not have that protein. When a monoclonal antibody attaches to a cancer cell, they may accomplish the following goals:

  • Allow the immune system to destroy the cancer cell. The immune system doesn't always recognize cancer cells as being harmful. A monoclonal antibody can mark cancer cells by attaching to specific parts of cancer cells not found on healthy cells. This makes it easier for the immune system to find and destroy these cells. The monoclonal antibodies that target the PD-1 protein are a good example. PD-1 keeps the immune system from recognizing that a cell is cancerous, so drugs that block PD-1 allow the immune system to identify and eliminate the cancer.

  • Prevent cancer cells from growing rapidly. Chemicals in the body tell cells to grow by attaching to receptors on the surface of cells. These chemicals are called growth factors. The receptor they attach to is called a growth factor receptor. Some cancer cells make extra copies of the growth factor receptor. This makes the cancer cells grow faster than normal cells. Monoclonal antibodies can block these receptors and prevent the growth signal from getting through.

  • Deliver radiation directly to cancer cells. This treatment, called radioimmunotherapy, uses monoclonal antibodies to deliver radiation directly to cancer cells. By attaching radioactive molecules to monoclonal antibodies in a laboratory, they can deliver low doses of radiation specifically to the tumor while leaving healthy cells alone. Examples of these radioactive molecules include ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar). 

  • Diagnose cancer. Monoclonal antibodies carrying radioactive particles may also help diagnose certain cancers, such as colorectal, ovarian, and prostate cancers. Special cameras identify the cancer by showing where the radioactive particles build up in the body. In addition, a pathologist may use monoclonal antibodies to determine the type of cancer a person may have by analyzing the sample of tissue removed during abiopsy. A pathologist is a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease.

  • Carry drugs directly to cancer cells. Some monoclonal antibodies carry other cancer drugs directly to cancer cells. Once the monoclonal antibody attaches to the cancer cell, the treatment it is carrying enters the cell. This causes the cancer cell to die without damaging other healthy cells. One example is Brentuximab vedotin (Adcetris), a treatment for certain types of Hodgkin and non-Hodgkin lymphoma. Another example is trastuzumab emtansine or TDM-1 (Kadcyla), which is a treatment for HER2-positive breast cancer.

Other monoclonal antibodies approved by the U.S. Food and Drug Administration (FDA) to treat cancer include:

  • Alemtuzumab (Campath)
  • Bevacizumab (Avastin)
  • Cetuximab (Erbitux)
  • Ipilimumab (Yervoy)
  • Nivolumab (Opdivo)
  • Ofatumumab (Arzerra)
  • Panitumumab (Vectibix)
  • Pembrolizumab (Keytruda)
  • Rituximab (Rituxan)
  • Trastuzumab (Herceptin)

Clinical trials of monoclonal antibodies are ongoing for several types of cancers. Learn more about clinical trials.  

Side effects of monoclonal antibody treatment are usually mild and are often similar to an allergic reaction. Possible side effects include rashes, low blood pressure, and flu-like symptoms, such as fever, chills, headache, weakness, extreme tiredness, loss of appetite, upset stomach, or vomiting.

Although monoclonal antibodies are considered a type of immunotherapy, they are also classified as a type of targeted therapy. Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. Learn more about targeted treatments.

Non-specific immunotherapies

Like monoclonal antibodies, non-specific immunotherapies also help the immune system destroy cancer cells. Most non-specific immunotherapies are given after or at the same time as another cancer treatment, such as chemotherapy or radiation therapy. However, some non-specific immunotherapies are given as the main cancer treatment.

Two common non-specific immunotherapies are:

  • Interferons. Interferons help the immune system fight cancer and may slow the growth of cancer cells. An interferon made in a laboratory, called interferon alpha (Roferon-A [2a], Intron A [2b], Alferon [2a]), is the most common type of interferon used in cancer treatment. Side effects of interferon treatment may include flu-like symptoms, an increased risk of infection, rashes, and thinning hair.

  • Interleukins. Interleukins help the immune system produce cells that destroy cancer. An interleukin made in a laboratory, called interleukin-2, IL-2, or aldesleukin (Proleukin), is used to treat kidney cancer and skin cancer, including melanoma. Common side effects of IL-2 treatment include weight gain and low blood pressure, which can be treated with other medications. Some people may also experience flu-like symptoms.

Cancer vaccines

A vaccine is another method used to help the body fight disease. A vaccine exposes the immune system to an antigen. This triggers the immune system to recognize and destroy that protein or related materials. There are two types of cancer vaccines: prevention vaccines and treatment vaccines.

  • Prevention vaccine. A prevention vaccine is given to a person with no symptoms of cancer. It is used to keep a person from developing a specific type of cancer or another cancer-related disease. For example, Gardasil and Cervarix are vaccines that prevent a person from being infected with the human papillomavirus (HPV). HPV is a virus known to cause cervical cancer and some other types of cancer. Learn more aboutHPV and cancer. In addition, the U.S. Centers for Disease Control and Prevention recommends that all children should receive a vaccine that prevents infection with the hepatitis B virus. A hepatitis B infection may cause liver cancer. Learn more about hepatitis B screening.

  • Treatment vaccine. A treatment vaccine helps the body's immune system fight cancer by training it to recognize and destroy cancer cells. It may prevent cancer from coming back, eliminate any remaining cancer cells after other types of treatment, or stop cancer cell growth. A treatment vaccine is designed to be specific, which means it should target the cancerous cells without affecting healthy cells. At this time, sipuleucel-T (Provenge) is the only treatment vaccine approved in the United States. It is designed for treating metastatic prostate cancer. Additional cancer treatment vaccines are still in development and only available through clinical trials.

Learn more about cancer vaccines.

Questions to ask the doctor

Talk with your doctor about whether immunotherapy may be part of your treatment plan. If so, consider asking the following questions: 

  • What type of immunotherapy do you recommend? Why?
  • What are the goals of this treatment?  
  • Will immunotherapy be my only treatment? If not, what other treatments will be a part of my treatment plan?
  • How will I receive immunotherapy treatment and how often?
  • What are the possible side effects of immunotherapy, both in the short term and the long term?
  • How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
  • What clinical trials of immunotherapies are open to me?
  • Whom should I call for questions or problems?

More Information

How Cancer is Treated

Research Summaries

Side Effects

Additional Resources

American Cancer Society: Cancer Immunotherapy

National Cancer Institute: Cancer Vaccines

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por cyto às 18:20

Quarta-feira, 17.06.15

Giving cells star treatment

Giving cells star treatment

A three-dimensional star-shaped polymer network enhances cell adhesion and growth for tissue regeneration

Published online 10 June 2015

Schematic representation of the star-shaped polymer network showing the polyhedral oligomeric silsesquioxane (POSS) cores and crosslinked polycaprolactone (PCL)–polyurethane (PU) arms.

Adapted by permission from Macmillan Publishers Ltd: NPG Asia Materials (Ref. 1), copyright (2014)

Tissues and organs in the body are sometimes damaged to such an extent that they require artificial support to heal. Now, A*STAR researchers have used star-shaped polymers to produce a three-dimensional network that is both compatible with human tissue and facilitates cells to adhere and proliferate under controlled biological conditions¹.

To build this network, Ming-Yong Han, Khin Yin Win and co-workers from the A*STAR Institute of Materials Research and Engineering in Singapore incorporated an inorganic component ― polyhedral oligomeric silsesquioxane (POSS) ― into a common tissue engineering material, polycaprolactone–polyurethane. This addition was designed to enhance the material’s porosity and interaction with cells as well as improve its thermal and mechanical stability. POSS consisted of a silicacube bearing eight organic arms capable of covalent bonding with other polymers (see image). The silica cube provided a rigid core from which emerged polycaprolactone–polyurethane arms.

To generate this material, the researchers synthesized POSS cores terminated by reactive functional groups from an organic alcohol, in the presence of a silicon-based catalyst. They then attached polycaprolactone units to the cores to extend their arms. Finally, they added the polyurethane precursor as a crosslinker to complete the network.

Unlike its linear counterpart, the POSS-based material had a rough surface consisting of microscopic spheres from which fibrous structures spread. The unique surface morphology, which consisted of water-repelling POSS and polymer arms, helped the cells to adhere and proliferate. This biomaterial was biocompatible and had a high porosity; these properties allowed the material to promote cell growth while simultaneously permitting the exchange of nutrients and metabolites.

The researchers evaluated the degradation of the polymer network under physiological conditions for 52 weeks. The network decomposed little during the first 24 weeks, but subsequently lost weight rapidly.

Han explains that the water-repelling nature and protective effect of the POSS moieties limited the initial hydrolytic degradation. “The degradation accelerated only after these POSS moieties had broken down,” he adds.

This degradation behavior enables cell adhesion and proliferation on the network during the initial stage and elimination of the scaffold after tissue has formed, making the POSS-based network highly attractive as a scaffold. Moreover, most cells remained viable when exposed to the degradation products of these POSS-based and linear polymers, confirming their biocompatibility.

The team is currently exploring ways to apply the star-shaped polymer as a scaffold for tissue regeneration. “We are planning to use it for three-dimensional tissue reconstruction and modeling,” says Han.

 

The A*STAR-affiliated researchers contributing to this research are from the Institute of Materials Research and Engineering

 

Related Links

Nanoparticles: Polymer knots with silicon hearts

Regenerative medicine: Finding the sweet spot for cartilage formation

Biomaterials: Close to the bone

 

 

Reference

  1. Teng, C. P., Mya, K. Y., Win, K. Y., Yeo, C. C., Low, M., He, C. & Han, M.-Y. Star-shaped polyhedral oligomeric silsesquioxane-polycaprolactone-polyurethane as biomaterials for tissue engineering application. NPG Asia Materials 6, e142 (2014). | article

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por cyto às 18:08

Quarta-feira, 17.06.15

Tracking signals on the cell surface

Tracking signals on the cell surface

A cell-surface protein overexpressed in liver cancer offers a promising target for therapy

Published online 10 June 2015

Blocking the activity of an abundant protein found on the surface of liver cancer cells could lead to new therapies for one of the most common and deadly cancers in the world.

© Purestock/Thinkstock

Patients with cancer of the liver express elevated levels of Agrin, a specific protein which aids the growth and spread of the cancer, according to new research from A*STAR scientists1. The protein could be an attractive target for treating the liver cancer known as hepatocellular carcinoma, one of the most common and deadly cancers in the world.

“Current therapies such as sorafenibs andsunitinibs have been restricted to targeting kinase receptors, with modest effects on patient survival,” says Sayan Chakraborty, who led the investigation with Wanjin Hong and colleagues from the A*STAR Institute of Molecular and Cell Biology. “Our study shows that there is immense potential to combine anti-Agrin agents with the already available enzyme inhibitors for effective and improved treatment.”

Agrin is best known for its role as a signaling protein in junctions where muscle tissue connects with neural tissue. Using biochemical approaches and large-scale quantitative studies, the researchers identified high numbers of the molecule on the surfaces of liver cancer cells, suggesting a role in promoting tumor growth. Further clinical analysis of liver tissue samples from patients with hepatocellular carcinoma showed three to four times higher Agrin levels than samples from healthy patients.

When the researchers blocked Agrin expression in liver cancer cells, they observed a 42 per cent reduction in the rate of cellular proliferation and a more than 50 per cent increase in programmed cell death. The Agrin-depleted cells were also less likely to form free-floating colonies, migrate and invade noncancerous tissue. The shape of the cells changed from looking like prickly splinters to rounded cobblestones forming successive layers of cells. Mice injected with Agrin-depleted cancer cells developed tumors that were nearly 20 times smaller than those injected with the regular cancer cells.

The researchers were able to reverse these in vitro and in vivo effects, however, by reintroducing Agrin to the mutant cells.

To narrow in on the molecular mechanism of Agrin’s cancer-provoking activity, the researchers conducted a series of experiments that ruled out all but one target protein. “Agrin is well reported to induce acetylcholine receptors in neuromuscular junctions,” says Chakraborty. “To our surprise, we observed that Agrin hijacks the same receptor and downstream signaling repertoire in the liver to induce cell proliferation, invasion and tumorigenesis.”

The study provides solid support for the development of antibody therapies that inhibit Agrin activity, says Chakraborty. Furthermore, “the presence of Agrin in the plasma of hepatocellular carcinoma patients can also serve as an important diagnostic strategy,” he adds.

The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology. More information about the group’s research can be found at theProtein Trafficking and Cancer Cell Biology Group webpage.

 

Related Links

Cancer biology: Tightening the belt on tumor growth

Shoddy sorting disrupts memory-making signals

Cancer biology: Awakening the body’s anticancer defenses

 

 

Reference

  1. Chakraborty, S., Lakshmanan, M., Swa, H. L. F., Chen, J., Zhang, X. et al. An oncogenic role of Agrin in regulating focal adhesion integrity in hepatocellular carcinoma. Nature Communications 6, 6184 (2015). | article

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por cyto às 18:05

Quarta-feira, 17.06.15

Results of Nivolumab CheckMate 057 Study May Change Treatment of Lung Cancer

Results of Nivolumab CheckMate 057 Study May Change Treatment of Lung Cancer

 

The PD-1 immune checkpoint inhibitor nivolumab improves survival compared with docetaxel for subsequent treatment ofadvanced nonsquamous non-small cell lung cancer (NSCLC), as shown in results of the phase 3 CheckMate 057 study presented in at the 2015 Americal Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL.1

Options for treatment of patients with nonsquamous NSCLC who progress after initial therapy are limited—principally docetaxel is used if that agent was not part of prior therapy.2

Outcomes with subsequent therapies after platinum-based CT in general provide only minimal improvements in overall survival. In a previous phase 3 trial, nivolumab demonstrated improved survival compared with docetaxel for the treatment of previously treated squamous NSCLC.

This led to its approval in March 2015 as subsequent therapy of squamous NSCLC and its incorporation into the most recent National Comprehensive Cancer Network guidelines as a treatment option in this setting.2

Patients in the CheckMate 057 study had progressed after treatment with platinum-based doublet chemotherapy (CT) (and, if eligible, a tyrosine kinase inhibitor), a guideline-recommended first-line therapy for nonsquamous NSCLC. They were randomly assigned to subsequent treatment with nivolumab (3 mg/kg every 2 weeks; 292 patients) or docetaxel (75 mg/m2 every 3 weeks; 290 patients); both drugs were continued until progression or discontinuation due to toxicity.

The primary efficacy endpoint of the study was overall survival (OS). Treatment with nivolumab significantly improved median OS, with a hazard ratio for death of 0.73 (95% CI: 0.59, 0.89;P=0.00155) compared with docetaxel. One-year OS was 50.5% with nivolumab versus 39.0% with docetaxel.1

Other study endpoints included progression-free survival (PFS), objective response rate (ORR), and nivolumab efficacy by PD-L1 expression.

Significantly more patients had an objective response (19.2% vs. 12.4%; P=0.0235). At the time of the analysis, the median duration of response to nivolumab was 17.1 months, compared with 5.6 months for docetaxel.

No difference between nivolumab and docetaxel was observed in median PFS (2.3 months vs. 4.2 months; P=0.393). PD-L1 expression was associated with improved efficacy for patients treated with nivolumab, an effect most dramatically seen in patients with PD-L1 expression 5% or higher and 10% or higher, but evident at PD-L1 expression levels as low as 1% or higher.

Also of note, subgroup analysis favored nivolumab over docetaxel in all categories, except patients 75 years of age or older, never smokers, and those positive for EGFR mutations.

 

RELATED: Stereotactic Ablative Radiotherapy May Be Feasible for Non-Small Cell Lung Cancer

Treatment-related adverse reactions of grade 3 to 5 severity occurred at a higher rate with docetaxel (53.7%) than with nivolumab (10.5%).1

Luis Paz-Ares, MD, PhD, from the Hospital Universitario Virgen Del Rocio, Spain, presented the results at ASCO. 

He noted that “CheckMate 057 is the second phase 3 trial to demonstrate superior survival with nivolumab over docetaxel” in advanced NSCLC. Roy S. Herbst, MD, PhD, from the Yale Comprehensive Cancer Center in New Haven, CT, commented that this study showed “a particularly long benefit” in these patients and that nivolumab is less toxic than docetaxel.

Although PD-L1 expression was associated with improved survival and ORR, he noted that even patients without PD-L1 expression did at least as well as those treated with docetaxel.

Dr. Herbst added that the survival benefit across multiple patient subgroups combined with lower toxicity recommends nivolumab as a new standard of care for patients with previously treated nonsquamous NSCLC.

References

  1. Paz-Ares L, Horn L, Borghaei H, et al. Phase III, randomized trial (CheckMate 057) of nivolumab versus docetaxel in advanced non-squamous cell non-small cell lung cancer. J Clin Oncol.2015;33(Suppl):Abst LBA109. http://meetinglibrary.asco.org/content/154634-156. Accessed June 1, 2015.
  2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. Version 6.2015. www.nccn.org. Accessed June 1, 2015.

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por cyto às 18:03

Quarta-feira, 17.06.15

Lymphatic Vessels Connecting Brain, Immune System Discovered

Lymphatic Vessels Connecting Brain, Immune System Discovered

 

Researchers have discovered that the central nervous system and immune system are directly connected via lymphatic vessels in the lining of the dural sinuses, according to new research published in Nature.

Until now, scientists have had little understanding about how immune cells entered and exited the central nervous system. This new discovery challenges long-held assumptions about neuroimmunology. The discovery has critical implications for the way scientists study neuro-immune interaction. 

“We always perceived it before as something esoteric that can't be studied,” said Jonathan Kipnis, PhD, of the University of Virginia. “But now we can ask mechanistic questions."

The researchers believe their discovery will have major effects on the study and treatment of all neurological diseases that have immune components, from Alzheimer's disease to multiple sclerosis.

Although the lymphatic system has been mapped thoroughly throughout the body, these vessels had remained undetected. The researchers say it is due to their location; the vessels follow a major blood vessel down to the sinuses and are easy to overlook.

Antoine Louveau, a postdoctoral fellow at the University of Virginia, found the vessels while studying mice. He developed a method of mounting mice's meninges on a single slide. By fixing the meninges with a skullcap, the tissue is held in its physiological condition and then dissected.

The researchers detected patterns that resembled vessels when they looked at the immune cells of mice. Testing for lymphatic vessels confirmed their presence. The structures have all of the hallmarks of lymphatic endothelial cells. They can carry fluid and immune cells from the cerebrospinal fluid and are connected to deep cervical lymph nodes.

In terms of neurological disorders, the discovery of these vessels creates a myriad of new questions that now need to be explored or revisited. The researchers have already begun to hypothesize the roles the vessels could play. “In Alzheimer's, there are accumulations of big protein chunks in the brain,” Kipnis said. “We think they may be accumulating in the brain because they're not being efficiently removed by these vessels.” 

Further research will seek to precisely determine how these vessels play into various neuro-immunological disorders.

Reference

  1. Louveau, A et al. Nature. 2015; doi:10.1038/nature14432.
 

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por cyto às 17:53

Quarta-feira, 17.06.15

Molecular Classification May Improve Method Physicians Use to Diagnose, Treat Gliomas

Molecular Classification May Improve Method Physicians Use to Diagnose, Treat Gliomas

Junho 10, 2015

ROCHESTER, Minn -- June 10, 2015 -- The molecular makeup of brain tumours can be used to sort patients with gliomas into 5 categories, each with different clinical features and outcomes, according to research published online today in the New England Journal of Medicine.

The finding could change the methods that physicians rely on to determine prognosis and treatment options.

“Our findings are going to weigh heavily on the future classification of brain tumours,” said Daniel H. Lachance, MD, Mayo Clinic, Rochester, Minnesota. “The time of classifying these tumours solely according to histology as astrocytoma, oligodendroglioma or mixed oligoastrocytoma could be a thing of the past. This molecular data helps us better classify glioma patients, so we can begin to understand who needs to be treated more aggressively and who might be able to avoid unnecessary therapies.”

The new approach categorises gliomas according to the presence of 3 genetic alterations -- 1p/19q co-deletion, IDH mutation, and TERT mutation. The first 2 are already checked routinely in clinical practice, so a test that incorporates all 3 tumour markers could be available as early as this summer.

Gliomas are typically managed with a combination of surgery, radiation therapy, and chemotherapy, but even with aggressive treatment the majority of patients succumb to the disease.

For a significant number of cases, the standard methods -- which use histology to classify gliomas according to their visible characteristics -- are not effective enough to accurately predict the tumour’s subsequent behaviour, potential for response to therapy, and long-term prognosis.

Over the last 25 years, scientists have found hundreds of genetic defects that could form the basis of a more improved classification system. Three of these alterations stand out because they occur early during glioma formation, are more prevalent in gliomas, and are sometimes associated with desirable clinical outcomes.

The first one -- 1p/19q co-deletion -- has been associated with increased tumour sensitivity to chemotherapy. The second is a mutation in IDH1 or IDH2, which is generally associated with improved prognosis. The third is a mutation in TERT, which enhances the activity of the enzyme telomerase to lengthen the telomeres that protect the ends of chromosomes. These mutations can be seen in the most aggressive and least aggressive forms of human glioma.

The researchers explored whether these 3 tumour markers could be used to define molecular groups that better inform glioma treatment. First, they scored tumours as negative or positive for 1p/19q co-deletion, IDH mutation, and TERT mutation in 317 gliomas from the Mayo Clinic Case-Control Study. The researchers then compared patient characteristics among the top 5 molecular groups (triple-positive, TERT- and IDH-mutated, IDH-mutated-only, TERT-mutated-only, and triple-negative) and found that the patients within each group had similar age of onset and overall survival. They replicated and validated their results in 351 gliomas from the UCSF Adult Glioma Study, and 419 gliomas from the Cancer Genome Atlas (TCGA) Study.

The results will enable clinicians to make better predictions about which specific treatment course is necessary for each individual patient. For example, the researchers found that the molecular classification can identify patients with histologically defined lower-grade tumours who have less favourable outcomes and deserve more aggressive therapy.

Though the researchers focused on three main mutations to define their molecular groups, they recognised that gliomas likely contain other genetic alterations, such as variants that might predispose to cancer and mutations that might be acquired as tumours grow and progress. They looked for associations between the 5 molecular groups and variants they had previously shown were linked to glioma risk, as well as other mutations known to accumulate in cancer. The researchers found that these other genetic changes recurred in specific patterns within the molecular groups, further validating their biologic significance.

“These molecular groups could represent distinct types of gliomas, with different origins and paths to progression,” said Robert B. Jenkins, MD, Mayo Clinic. “Now that we know more about the germline alterations that predispose to these tumours and the ensemble of mutations that are associated with each type of glioma, we can start thinking about building models of the disease that can help us find new therapies to precisely target specific types of glioma.”

SOURCE: Mayo Clinic

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por cyto às 17:50

Quarta-feira, 17.06.15

ASCO Cancer Treatment and Survivorship Care Plans

ASCO Cancer Treatment and Survivorship Care Plans

ASCO developed two types of forms to help people diagnosed with cancer keep track of the treatment they received and medical care they may need in the future: a Cancer Treatment Plan and a Survivorship Care Plan.

First, an ASCO Cancer Treatment Plan is a form that provides a convenient way to store information about your cancer, cancer treatment, and follow-up care. It is meant to give basic information about your medical history to any doctors who will care for you during your lifetime.

Using the treatment plan, your current oncologist can enter the chemotherapy dose you received, the specific drugs that were used, the number of treatment cycles that were completed, surgeries done, and any additional treatment that was given, such as radiation therapy or hormonal therapy.

Second, ASCO offers a form called a Survivorship Care Plan. It contains important information about the given treatment, the need for future check-ups and cancer tests, the potential long-term late effects of the treatment you received, and ideas for improving your health.

None of these forms is intended to provide a complete medical record. And, no single treatment or survivorship care plan is appropriate for all patients due to the complexity of cancer care. Talk with your doctor for more information about your individual treatment and follow-up care. The ASCO Cancer Treatment Plan and Survivorship Care Plan should be used with the guidance of your doctor.

Any Cancer

ASCO Treatment Plan

ASCO Survivorship Care Plan

ASCO Answers Guide to Cancer Survivorship (PDF; 44 pages)

Breast

Breast Cancer Survivorship Care Plan

Follow-up Care for Breast Cancer

Colorectal

Colorectal Cancer Survivorship Care Plan

Follow-Up Care for Colorectal Cancer

Lung

Lung Cancer (Non-Small Cell) Survivorship Care Plan 

Adjuvant Treatment for Lung Cancer

Chemotherapy for Stage IV Non-Small Cell Lung Cancer

Lung Cancer (Small Cell) Survivorship Care Plan

Lymphoma

Diffuse Large B-Cell Lymphoma Survivorship Care Plan

Prostate

Prostate Cancer Survivorship Care Plan

Follow-Up Care for Prostate Cancer

More Information

Keeping a Personal Medical Record

Organizing Your Cancer Care

Survivorship

Additional Resources

Journey Forward: Survivorship Care Plan Builder 5.0

LIVESTRONG Care Plan

Permission to Use ASCO Treatment and Survivorship Care Plan Templates

Patients and other consumers may use ASCO’s Treatment and Survivorship Care Plan Templates without seeking permission from ASCO.

Practitioners may incorporate the Templates into their workflow and/or into their electronic medical records system without seeking permission from ASCO. If the templates will be altered in any way, including the addition of institutional branding, ASCO requires that all ASCO identifiers be removed.

For permission to use the Templates in a commercial manner or in any manner not described above, please contact permissions@asco.org.

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por cyto às 17:44

Quarta-feira, 17.06.15

Brain Stem Glioma - ASCO 2015 - 2

Brain Stem Glioma - Childhood - About Clinical Trials

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will learn more about clinical trials, which are the main way that new medical approaches are tested to see how well they work. To see other pages, use the menu on the side of your screen.

What are clinical trials?

Doctors and scientists are always looking for better ways to care for children with brain stem glioma. To make scientific advances, doctors create research studies involving volunteers, called clinical trials. In fact, every drug that is now approved by the U.S. Food and Drug Administration (FDA) was previously tested in clinical trials.

Many clinical trials are focused on new treatments, evaluating whether a new treatment is safe, effective, and possibly better than the current (standard) treatment. These types of studies evaluate new drugs, different combinations of existing treatments, new approaches to radiation therapy or surgery, and new methods of treatment. Children who participate in clinical trials are often among the first to receive new treatments before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

There are also clinical trials that study new ways to ease symptoms and side effects during treatment and manage the late effects that may occur after treatment. Talk with your child’s doctor about clinical trials regarding side effects. In addition, there are ongoing studies about ways to prevent the disease.

Deciding to join a clinical trial

People decide to participate in clinical trials for many reasons. For some children, a clinical trial is the best treatment option available. Because standard treatments are not perfect, people are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other people volunteer for clinical trials because they know that these studies are the only way to make progress in treating brain stem glioma. Even if they do not benefit directly from the clinical trial, their participation may benefit future children with brain stem glioma.

Sometimes people have concerns that, in a clinical trial, their child may receive no treatment by being given a placebo or a “sugar pill.” The use of placebos in cancer clinical trials in this way is rare overall and not done at all in childhood cancer research. Find out more about placebos in cancer clinical trials.

Patient safety and informed consent

To join a clinical trial, parents and children must participate in a process known as informed consent. During informed consent, the doctor should list all of the patient’s options, so that the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different from the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment.

People who participate in a clinical trial may stop participating at any time for any personal or medical reason. This may include that the new treatment is not working or there are serious side effects. Clinical trials are also closely monitored by experts who watch for any problems with each study. It is important that parents talk with the doctor and researchers about who will be providing their child’s treatment and care during the clinical trial, after the clinical trial ends, and/or if the patient chooses to leave the clinical trial before it ends.

Finding a clinical trial

Research through clinical trials is ongoing for all types of tumors. For specific topics being studied for brain stem glioma, learn more in the Latest Researchsection.

Cancer.Net offers a lot of information about clinical trials in other areas of the website, including a complete section on clinical trials and places to search for clinical trials for a specific type of tumor.

In addition, this website offers free access to a video-based educational program about cancer clinical trials, located outside of this guide.

The next section in this guide is Latest Research and it explains areas of scientific research currently going on for this type of cancer. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Latest Research

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will read about the scientific research being done now to learn more about brain stem glioma and how to treat it. To see other pages, use the menu on the side of your screen.

Doctors are working to learn more about brain stem glioma, ways to prevent it, how to best treat it, and how to provide the best care to children diagnosed with this disease. The following areas of research may include new options for patients through clinical trials. Always talk with your child’s doctor about the diagnostic and treatment options best for your child.

  • Improved imaging and surgery. Imaging techniques are being developed that help the surgical oncologist pinpoint the tumor’s exact location to reduce or prevent damage to the healthy parts of the brain. For example, image-guided stereotaxis allows surgeons to visualize and operate on the brain using three-dimensional computerized outlines of the brain and the tumor. Along with specialized software, these images help guide the surgeon to the tumor. Tumors that were once considered inoperable can now be removed using this technique. In certain instances, these imaging techniques are also being used to better understand the benefits and risks of using a biopsy to diagnose children with diffuse brain stem glioma.
  • Improved radiation therapy. Conformal radiation therapy is a way to give high doses of radiation directly to a tumor and not healthy tissue. This technique creates detailed, three-dimensional maps of the brain and tumor so doctors know exactly where to deliver the radiation therapy. In addition, drugs designed to enhance the effectiveness of radiation therapy or to slow or stop tumor growth are also being studied.
  • Molecular features. Other research is focused on evaluating the abnormal molecular features of brain stem glioma cells to better diagnosis and categorize these tumors. These features are found by examining the tumor after a biopsy and may eventually help doctors find treatments that target the tumor based on the specific molecular features.
  • Immunotherapy. Immunotherapy, also called biologic therapy, is designed to boost the body's natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function. For brain stem glioma, doctors are researching vaccines that may treat the tumor. Learn more about the basics of immunotherapy and cancer vaccines.
  • New ways to give chemotherapy. The blood-brain barrier, which protects the brain and spinal cord from damaging chemicals, also keeps out many types of chemotherapy. New methods of giving chemotherapy called convection enhanced delivery are also being studied. This method uses a narrow tube called a catheter that is placed into the brain so chemotherapy can be directed at the tumor.
  • Palliative care. Clinical trials are underway to find better ways of reducing symptoms and side effects of current brain stem glioma treatments in order to improve patients’ comfort and quality of life.
  • Tissue donation. Some families find that donating tissue feels appropriate as part of the grieving process after their child’s death. Similar to organ donation, tissue donations can help researchers learn more about how tumors change and spread to help develop new treatments for children with brain stem glioma. Talk with your doctor for more information about tissue donation. 

Looking for More About the Latest Research?

If you would like additional information about the latest areas of research regarding brain stem glioma, explore these related items that take you outside of this guide:

  • To find clinical trials specific to your child’s diagnosis, talk with your child’s doctor or search online clinical trial databases now.
  • Visit ASCO’s CancerProgress.Net website to learn more about the historical pace of research for childhood cancers. Please note this link takes you to a separate ASCO website.
  • Visit the website of the Conquer Cancer Foundation to find out how to help support research for every cancer type. Please note this link takes you to a separate ASCO website. 

The next section in this guide is Coping with Side Effects and it offers some guidance in how to cope with the physical, emotional, and social changes that cancer and its treatment can bring. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Coping with Side Effects

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will find out more about steps to take to help cope with physical, social, and emotional side effects. This page includes several links outside of this guide to other sections of this website. To see other pages, use the menu on the side of your screen.

Fear of treatment side effects is common after a diagnosis of a tumor, but it may help to know that preventing and controlling side effects is a major focus of your child’s health care team. This is called palliative care, and it is an important part of the overall treatment plan, regardless of the stage or grade of disease.

There are possible side effects for every treatment, but patients don’t experience the same side effects when given the same treatments for many reasons. That can make it hard to predict exactly how your child will feel during treatment. Common side effects from each treatment option for brain stem glioma are described in detail within the Treatment Options section. Learn more about the most common side effects of a tumor and different treatments, along with ways to prevent or control them. Side effects depend on a variety of factors, including the disease’s grade, the length and dosage of treatment(s), and your child’s overall health. Also, side effects of newer treatments or treatments in clinical trials may be different and not as well studied as older treatments.

Talking with your child’s health care team about side effects

Before treatment begins, talk with your child’s doctor about possible side effects of each type of treatment your child will be receiving. Ask which side effects are most likely to happen, when they are likely to occur, and what can be done to prevent or relieve them.

And, ask about the level of caregiving your child may need during treatment and recovery, as family members and friends often play an important role in the care of a child with brain stem glioma. Learn more about caregiving.

In addition to physical side effects, there may be emotional and social effects as well. Patients and their families are encouraged to share their feelings with a member of their health care team who can help with coping strategies, including concerns about managing the cost of medical care

During and after treatment, be sure to tell the health care team about the side effects your child experiences, even if you feel they are not serious. Sometimes, side effects can last beyond the treatment period, called a long-term side effect. A side effect that occurs months or years after treatment is called a late effect. Treatment of both types of effects is an important part of survivorship care. Learn more by reading the Follow-up Care section of this guide or talking with your child’s doctor.

The next section in this guide is Follow-up Care and it explains the importance of check-ups after treatment is finished. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Follow-Up Care

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will read about your child’s medical care after treatment is finished and why this follow-up care is important. To see other pages, use the menu on the side of your screen.

Care for children diagnosed with brain stem glioma doesn’t end when active treatment has finished. Your child’s health care team will continue to check to make sure the tumor has not returned, manage any side effects, and monitor your child’s overall health. This is called follow-up care. All children treated for brain stem glioma should have life-long, follow-up care.

This plan may include regular physical examinations and/or medical tests to monitor your child’s recovery for the coming months and years. Learn more about the importance of follow-up care.

Watching for recurrence

One goal of follow-up care is to check for a recurrence. A tumor recurs because small areas of tumor cells may remain undetected in the body. Over time, these cells may increase in number until they show up on test results or cause signs or symptoms.

During follow-up care, a doctor familiar with your child’s medical history can give you personalized information about the risk of recurrence. Your doctor will also ask specific questions about your child’s health. Some children may have blood tests or imaging tests as part of regular follow-up care, but testing recommendations depend on several factors, including the type and stage of tumor originally diagnosed and the types of treatment given.

Managing long-term and late side effects of childhood cancer

Sometimes, side effects may linger beyond the active treatment period. These are called long-term side effects. In addition, other side effects called late effects may develop months or even years afterwards. Late effects can occur almost anywhere in the body and include physical problems, such as heart and lung problems and second cancers, and emotional and cognitive (memory, thinking, and attention) problems, such as anxiety, depression, and learning difficulties.

Based on the type of treatment your child received, the doctor will recommend what examinations and tests are needed to check for late effects. The possible late effects from specific treatments are discussed below:

  • Radiation therapy to the brain and spine can cause cognitive (thought-process) and endocrine (hormonal) symptoms over time, although the severity can vary depending on the dose given and your child’s age.
  • The risks and possible side effects of surgery vary widely, depending on the location and features of the tumor.
  • The risks of chemotherapy and the chance of a secondary tumor strongly depend on the specific drugs used and the dosage.

For each of these issues, it is important to discuss the specific aspects of the tumor and the options for treatment with the doctors that are involved in your child's care before, during, and after treatment. Follow-up care should also address your child’s quality of life, including any developmental or emotional concerns.

The Children's Oncology Group (COG) has studied the physical and psychological effects that childhood cancer survivors face. Based on these studies, COG has created recommendations for long-term follow-up care for childhood, adolescent, and young adult cancer survivors that can be found on a separate website: www.survivorshipguidelines.org.

Keeping a child’s personal health record

You are encouraged to organize and keep a personal record of the child’s medical information. The doctor will help you create this. That way, as the child enters adulthood, he or she has a clear, written history of the diagnosis, the treatment given, and the doctor’s recommendations about the schedule for follow-up care. ASCO offers forms to help create a treatment summary to keep track of the treatment your child received and develop a survivorship care plan once treatment is completed.

Some children continue to see their oncologist, while others transition back to the general care of their family doctor or another health care professional. This decision depends on several factors, including the type and stage of tumor, side effects, health insurance rules, and your family’s personal preferences. Talk with your health care team about your child’s ongoing medical care and any concerns you have about his or her future health.

If a doctor who was not directly involved in your child’s care will lead the follow-up care, be sure to share the treatment summary and survivorship care plan forms with him or her, as well as all future health care providers. Details about the specific treatment given are very valuable to the health care professionals who will care for your child throughout his or her lifetime.

The next section in this guide is Survivorship and it describes how to cope with challenges in everyday life after a diagnosis of brain stem glioma. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Survivorship

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will read about how to cope with challenges in everyday life after your child’s diagnosis. To see other pages, use the menu on the side of your screen.

What is survivorship?

The word survivorship means different things to different people, but it often describes the process of living with, through, and beyond cancer. In some ways, survivorship is one of the most complex aspects of the cancer experience because it is different for every patient and his or her family.

After active treatment ends, children and their families may experience a mixture of strong feelings, including joy, concern, relief, guilt, and fear. Some people say they appreciate life more after a diagnosis of brain stem glioma. Other families stay very anxious about their child’s health and become uncertain of how to cope with everyday life.

One source of stress may occur when frequent visits to the health care team end following treatment. Often, relationships built with the health care team provide a sense of security during treatment, and children and their families miss this source of support. This may be especially true as new worries and challenges surface over time, such as any late effects of treatment, educational issues, emotional challenges, sexual development and fertility concerns, and/or financial issues.

Every family faces different concerns and challenges. With any challenge, a good first step is being able to recognize each fear and talk about it. Effective coping requires:

  • Understanding the challenge your family is facing,
  • Thinking through solutions,
  • Asking for and allowing the support of others, and
  • Feeling comfortable with the course of action your family chooses.

It may be helpful to join an in-person support group or online community of childhood cancer survivors. Support groups also exist for parents of children diagnosed with cancer. This allows you to talk with people who have had similar first-hand experiences. Other options for finding support include talking with a friend or member of your health care team, individual counseling, or asking for assistance at the learning resource center of the center where you received treatment.

Changing role of caregivers

Parents, other family members, and friends may also go through periods of transition. A caregiver plays a very important role in supporting a child diagnosed with brain stem glioma, providing physical, emotional, and practical care on a daily or as-needed basis. Many caregivers become focused on providing this support, especially if the treatment period lasts for many months or longer.

However, as treatment is completed, the caregiver's role often changes. Eventually, the need for caregiving related to a child’s diagnosis will become much less or come to an end as your child gets older. Family counselors at pediatric cancer centers can help with this transition. You can also learn more aboutadjusting to life after caregiving in this article.

Healthy living after treatment

Survivorship often serves as a strong motivator to make positive lifestyle changes, often for the family as a whole. 

Children who have had brain stem glioma can enhance the quality of their future by following established guidelines for good health into and through adulthood, including not smoking, maintaining a healthy weight, eating well, managing stress, and participating in regular physical activity. Talk with the doctor about developing a plan that is best for your child’s needs. Learn more about making healthy lifestyle choices.

In addition, it is important that your child has recommended medical check-ups and tests (see Follow-up Care) to take care of his or her health. Rehabilitation may be recommended, and this could mean any of a wide range of services such as physical therapy, family or individual counseling, nutritional planning, and/or educational assistance. The goal of rehabilitation is to help survivors and their families regain control over many aspects of their lives and remain as independent and productive as possible.

Talk with your doctor to develop a survivorship care plan that is best for your child’s needs.

Looking for More Survivorship Resources?

For more information about cancer survivorship, explore these related items. Please note these links will take you to other sections of Cancer.Net:

  • Survivorship Resources: Cancer.Net offers a lot of information and resources to help survivors cope, including specific sections for children, teens, and young adults. There is also a main section on survivorship for people of all ages.
  • ASCO Answers Cancer Survivorship Guide: This 44-page booklet (available as a PDF) can help with the transition into life after treatment. It includes blank treatment summary and survivorship care plan forms.
  • Cancer.Net Patient Education Video: View a short video led by an ASCO expert that provides information about childhood cancer survivorship.

The next section offers Questions to Ask the Doctor to help start conversations with your child’s health care team. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Questions to Ask the Doctor

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will find some questions to ask your child’s doctor or other members of the health care team, to help you better understand your child’s diagnosis, treatment plan, and overall care. To see other pages, use the menu on the side of your screen.

Talking often with the doctor is important to make informed decisions about your child’s health care. These suggested questions are a starting point to help you learn more about your child’s care and treatment. You are also encouraged to ask additional questions that are important to you. You may want to print this list and bring it to your child’s next appointment, or download Cancer.Net’s free mobile app for an e-list and other interactive tools to manage your child’s care.

Questions to ask after getting a diagnosis

  • What type of tumor has been diagnosed?
  • Where exactly is the tumor located?
  • Is the tumor diffuse or focal? What does this mean?
  • Can you explain my child’s pathology report (laboratory test results) to me?
  • Are other tests needed to confirm this diagnosis?
  • What is your familiarity with my child’s tumor type and its treatment?

Questions to ask about choosing a treatment and managing side effects

  • What are the treatment options?
  • What clinical trials are open to my child at this center? How do I find out more about them?
  • What new research is being done at other treatment centers? Where are they located, and are these clinical trials open to my child?
  • What treatment plan do you recommend? Why?
  • What is the goal of each treatment? Is it to eliminate the tumor, help my child feel better, or both?
  • What are the chances for success with the planned treatments?
  • Who will be part of my child’s health care team, and what does each member do?
  • Who will be coordinating my child’s overall treatment?
  • What are the possible side effects of this treatment, both in the short term and long term?
  • How will this treatment affect my child’s daily life? Will he or she be able to go to school and perform his or her usual activities?
  • Could this treatment affect my child’s ability to become pregnant or have children in the future? If so, should I talk with a fertility specialist before treatment begins?
  • If I’m worried about managing the costs related to my child’s medical care, who can help me with these concerns?
  • What support services are available to my child? To my family?
  • Whom should I call for questions or problems?

Questions to ask about having radiation therapy or chemotherapy

  • What type of treatment is recommended?
  • What is the goal of this treatment?
  • How long will it take to give this treatment?
  • What side effects can I expect during treatment?
  • What are the possible long-term effects of having this treatment?
  • What can be done to relieve the side effects?

Questions to ask about having surgery

  • What type of surgery will my child have?
  • How long will the operation take?
  • How long will my child be in the hospital?
  • Can you describe what recovery from surgery will be like?
  • What are the possible long-term effects of having this surgery?

Questions to ask about planning follow-up care

  • What is the risk of the tumor returning? Are there signs and symptoms I should watch for?
  • What long-term side effects or late effects are possible based on the treatment my child received?
  • What follow-up tests will my child need, and how often will he or she need them?
  • How do I get a treatment summary and survivorship care plan to keep in my child’s records?
  • Who will be coordinating my child’s follow-up care?
  • What survivorship support services are available to my child? To my family?

The next section in this guide is Additional Resources, and it offers some more resources on this website beyond this guide that may be helpful to you. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Patient Information Resources

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will find some helpful links to other areas of Cancer.Net that provide information about care and treatment for a child with brain stem glioma. This is the final page of Cancer.Net’s Guide to Childhood Brain Stem Glioma. To go back and review other pages, use the menu on the side of your screen.

Cancer.Net includes many other sections about the medical and emotional aspects of being diagnosed with a CNS tumor, both for the patient and their family members and friends. This website is meant to be a resource for you and your loved ones from the time of diagnosis, through treatment, and beyond.

Beyond this guide, here are a few links to help you explore other parts of Cancer.Net:

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Brain Stem Glioma - Childhood - Overview ASCO 2015 - 1

Brain Stem Glioma - Childhood - Overview

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will find some basic information about this disease and the parts of the body it may affect. This is the first page of Cancer.Net’s Guide to Childhood Brain Stem Glioma. To see other pages, use the menu on the side of your screen. Think of that menu as a roadmap to this full guide.

About the brain stem

The brain stem connects the brain to the spinal cord. It is the lowest portion of the brain, located above the back of the neck. The brain stem controls many of the body’s basic functions, such as motor skills, sensory activity, coordination and walking, the beating of the heart, and breathing. It has three parts:

  • The midbrain, which develops from the middle of the brain
  • The medulla oblongata, which connects to the spinal cord
  • The pons, which is located between the medulla oblongata and the midbrain

About brain stem glioma

Brain stem glioma is a type of central nervous system (CNS; brain and spinal cord) tumor that begins when healthy cells in the brain stem change and grow uncontrollably, forming a mass called a tumor. A tumor can be cancerous or benign. A cancerous tumor is malignant, meaning it can grow and spread to other parts of the body. A benign tumor means the tumor can grow but will not spread. A glioma is a tumor that grows from a glial cell, which is a supportive cell in the brain.

Usually, by the time brain stem glioma is diagnosed, it is most often diffuse, which means it has spread freely through the brain stem. This type of tumor is typically very aggressive, meaning that it grows and spreads quickly. A small percentage of brain stem tumors are very localized, called focal tumors. A focal tumor is often less likely to grow and spread quickly.

Brain stem glioma occurs most commonly in children between five and 10 years old. Most brain stem tumors develop in the pons and grow in a part of the brain stem where it can be difficult to perform surgery, making brain stem glioma challenging to treat (see the Treatment Options section).

This section covers brain stem glioma diagnosed in children. Read more about brain tumors in adults.

Looking for More of an Overview?

If you would like additional introductory information, explore these related items. Please note these links will take you to other sections on Cancer.Net:

The next section in this guide is Statistics and it helps explain how many children are diagnosed with this disease and general survival rates. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Statistics

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will find information about how many children are diagnosed with brain stem glioma each year and some general survival information. Remember, survival rates depend on several factors. To see other pages, use the menu on the side of your screen.

Approximately 4,000 CNS tumors are diagnosed each year in children younger than 20. Brain stem tumors account for 10% of all childhood brain tumors. After leukemia, CNS tumors are the second most common childhood cancer, accounting for about 26% of cancer in children younger than 15.

The survival rate is the percentage of people who survive after the tumor is found. The survival rate for children with brain stem glioma varies depending on the location of the tumor. Long-term survival rates for children with a tumor in the midbrain or the medulla oblongata range from 65% to 90%. However, a pontine glioma, which is a tumor located in the pons, is more difficult to treat and often worsens quickly. It is uncommon for a child with a tumor in this location to live longer than 12 to 14 months after diagnosis.

Survival statistics should be interpreted with caution. Estimates are based on data from thousands of children with this type of tumor, so the actual risk for a particular individual may be different. It is not possible to tell a person how long he or she will live with a brain stem glioma. Because the survival statistics are measured in multi-year intervals, they may not represent advances made in the treatment or diagnosis of this cancer. Learn more about understanding statistics.

Statistics adapted from the American Cancer Society's publication, Cancer Facts and Figures 2015 and St. Jude Children’s Research Hospital.

The next section in this guide is Medical Illustrations and it offers drawings of body parts often affected by this disease. Or, use the menu on the left side of your screen to choose another section to continue reading this guide.  

 

Brain Stem Glioma - Childhood - Medical Illustrations

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will find a basic drawing about the main body parts affected by this disease. To see other pages, use the menu on the side of your screen.

Brain Stem Glioma Anatomy

Larger image

To continue reading this guide, use the menu on the side of your screen to select another section.  

The next section in this guide is Risk Factors and it explains what factors may increase the chance of developing this disease. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Risk Factors

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will find out more about the factors that increase the chance of developing brain stem glioma. To see other pages in this guide, use the menu on the side of your screen.

A risk factor is anything that increases a person’s chance of developing a tumor. Although risk factors often influence the development of a tumor, most do not directly cause a tumor. Some people with several risk factors never develop a tumor, while others with no known risk factors do.

Doctors and researchers don’t know what causes most childhood tumors, including brain stem glioma. There is some evidence that genetic factors may play a role in a small percentage of brain stem gliomas.

The following genetic conditions are associated with a higher risk of developing a CNS tumor:

The next section in this guide is Symptoms and Signs and it explains what body changes or medical problems this disease can cause. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Symptoms and signs

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will find out more about body changes and other things that can signal a problem that may need medical care. To see other pages, use the menu on the side of your screen.

Children with a brain stem glioma may experience the following symptoms or signs. Sometimes, children with a brain stem glioma do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not a brain stem glioma.          

  • Double vision or not being able to close the eyelids
  • Drooping of the face
  • Difficulty chewing and swallowing food
  • Weakness in the arms and legs, clumsiness or wobbliness, and difficulty walking
  • Difficulty talking
  • Headache
  • Vomiting

If you are concerned about one or more of the symptoms or signs on this list, please talk with your child’s doctor. The doctor will ask how long and how often your child has been experiencing the symptom(s), in addition to other questions. This is to help find out the cause of the problem, called a diagnosis.

If brain stem glioma is diagnosed, relieving symptoms remains an important part of care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with the health care team about the symptoms your child experiences, including any new symptoms or a change in symptoms.

The next section in this guide is Diagnosis and it explains what tests may be needed to learn more about the cause of the symptoms. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Diagnosis

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will find a list of the common tests, procedures, and scans that doctors can use to find out what’s wrong and identify the cause of the problem. To see other pages, use the menu on the side of your screen.

Doctors use many tests to diagnose a brain stem glioma and find out if it has spread to another part of the body, called metastasis. Some tests may also determine which treatments may be the most effective. For most other types of tumors, a biopsy is the only way to make a definitive diagnosis. In general, a biopsy is avoided in children with diffuse brain stem glioma because the results of the biopsy do not change treatment options. In addition, the procedure can have serious risks. However, a biopsy may be used when a brain stem glioma has unusual features. As new treatments based on molecular information from the tumor increase and the risk of a biopsy decreases, these procedures may be done more often.

For most patients, diagnosing a brain stem glioma is done with magnetic resonance imaging (MRI) only (see below). Because of this, diffuse brain stem glioma is unlike most other tumors. For a focal tumor, a biopsy and removing the tumor with surgery may be considered. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Other imaging tests may be used to find out whether the tumor has spread.

This list describes options for diagnosing brain stem glioma, and not all tests listed will be used for every person. Your child’s doctor may consider these factors when choosing a diagnostic test:

  • Age and medical condition
  • Type of tumor suspected
  • Signs and symptoms
  • Previous test results

In addition to a physical examination, the following tests may be used to diagnose a brain stem glioma:

  • MRI. An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. A special dye called a contrast medium is given before the scan to create a clearer picture. This dye can be injected into a patient’s vein or given as a pill to swallow.
  • Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. A CT scan can also be used to measure the tumor’s size. Sometimes, a contrast medium is given before the scan to provide better detail on the image. This dye can be injected into a patient’s vein or given as a pill to swallow. For a brain stem glioma, this test generally does not provide enough information to make a definite diagnosis, and an MRI is still needed.
  • Biopsy. A biopsy is the removal of a small amount of tissue for examination under a microscope. A biopsy is generally not done for the more common, diffuse type of brain stem tumor. However, for a focal tumor, it is often used to find out the type of tumor. If possible, a doctor called a neurosurgeon will remove a small piece of tissue from the brain. A neurosurgeon specializes in treating a CNS tumor using surgery. A pathologist then analyzes the sample(s). A pathologist is a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease.

After diagnostic tests are done, your child’s doctor will review all of the results with you. If the diagnosis is brain stem glioma, these results also help the doctor describe the tumor; this is called staging and grading.

The next section in this guide is Stages and Grades, and it explains the system doctors use to describe the extent of the disease. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Stages and Grades

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will learn about how doctors describe the growth or spread of brain stem glioma. This is called the stage or grade. To see other pages, use the menu on the side of your screen.

Staging is a way of describing where the tumor is located, if or where it has spread, and whether it is affecting other parts of the body. Doctors use diagnostic tests to find out the tumor's stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's prognosis, which is the chance of recovery. There are different stage descriptions for different types of tumors.

There is no formal staging system for childhood brain stem glioma. A tumor may be classified as either diffuse or focal. In addition, the tumor may be classified by its grade.

Grade

Grade describes how much tumor cells look like healthy cells when viewed under a microscope. The doctor compares the tumor’s tissue with healthy tissue. Healthy tissue usually contains many different types of cells grouped together. If the tumor cells looks similar to healthy tissue and contains different cell groupings, it is called differentiated or a low-grade tumor. If the tumor tissue looks very different from healthy tissue, it is called poorly differentiated or a high-grade tumor. The tumor’s grade may help the doctor predict how quickly it will spread. In general, the lower the tumor’s grade, the better the prognosis.

Below are the general classifications for brain stem glioma:

  • Diffuse brain stem glioma. This type of tumor spreads freely throughout the pons and often spreads to the midbrain, the medulla, or nearby parts of the brain. These tend to be high-grade tumors; they are very aggressive and contain abnormal-looking cells.
  • Focal brain stem glioma. About 20% of brain stem tumors are focal, meaning they occur in one area or are contained within a small portion of the brain stem. They usually occur in the midbrain or medulla, rather than the pons. These are usually benign or low-grade tumors; they are less aggressive and the tumor cells look fairly healthy.
  • Recurrent brain stem glioma: Recurrent brain stem glioma is a tumor that has come back after treatment. If the tumor does return, there will be another round of tests to learn about the extent of the recurrence. These tests and scans are often similar to those done at the time of the originaldiagnosis.

Information about the tumor’s grade will help the doctor recommend a specific treatment plan. The next section in this guide is Treatment Options. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

Brain Stem Glioma - Childhood - Treatment Options

This section has been reviewed and approved by the Cancer.Net Editorial Board, 04/2015

ON THIS PAGE: You will learn about the different ways doctors use to treat children with brain stem glioma. To see other pages, use the menu on the side of your screen.

In general, tumors in children are uncommon, so it can be hard for doctors to plan treatments unless they know what has been most effective in other children. That’s why more than 60% of children are treated as part of a clinical trial. Clinical trials are research studies that compare standard treatments (the best known treatments available) with newer approaches to treatments that may be more effective. Clinical trials may test such approaches as a new drug, a new combination of standard treatments, or new doses of current therapies. Studying new treatments involves careful monitoring using scientific methods, and all participants are followed closely to track their health and progress.

To take advantage of these newer treatments, children should be treated at a specialized cancer center. Doctors at these centers have extensive experience in treating children and have access to the latest research. A doctor who specializes in treating children with cancer is called a pediatric oncologist. For brain stem glioma, a neuro-oncologist may also be involved with treatment. A neuro-oncologist is a doctor who specializes in CNS tumors. If a pediatric cancer center is not nearby, general cancer centers sometimes have pediatric specialists who are able to be part of your child’s care.

In many cases, a team of doctors works with a child and the family to provide care; this is called a multidisciplinary team. Pediatric cancer centers often have extra support services for children and their families, such as child life specialists, dietitians, physical and occupational therapists, social workers, and counselors. Special activities and programs to help your child and family cope may also be available.

Descriptions of the most common treatment options for brain stem glioma are listed below. Treatment options and recommendations depend on several factors, including the type and grade of the tumor, possible side effects, the family’s preferences, and the child’s overall health. Your child’s care plan may also include treatment for symptoms and side effects, an important part of care. Three types of treatments are used to treat brain stem glioma in children: radiation therapy, chemotherapy, and surgery. Sometimes, these treatments are used together.

The treatment of brain stem glioma for children with the genetic condition neurofibromatosis type 1 may differ. A tumor in a child with NF1 may be low-grade even though it looks diffuse. Therefore, active surveillance or watchful waiting may be recommended to watch the tumor for signs that it is worsening. Treatment would begin if the tumor started to grow and spread.

Take time to learn about all of your child’s treatment options and be sure to ask questions about things that are unclear. Also, talk about the goals of each treatment with the doctor and what you can expect during the treatment. Learn more about making treatment decisions

Radiation therapy

Radiation therapy is the most common treatment for children with brain stem glioma. Radiation therapy is the use of high-energy x-rays or other particles to destroy tumor cells. A doctor who specializes in giving radiation therapy to treat a tumor is called a radiation oncologist. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. When radiation therapy is given using implants, it is called internal radiation therapy or brachytherapy. A radiation therapy regimen (schedule) usually consists of a specific number of treatments given over a set period of time.

Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished. Because radiation therapy can sometimes cause problems with the growth and development of a child’s brain, the doctor may choose to treat the tumor in another way. To avoid or reduce the need for radiation therapy in young children, the doctor may first use chemotherapy to shrink the tumor. Learn more about the basics of radiation therapy.

Chemotherapy

Chemotherapy is the use of drugs to destroy tumor cells, usually by stopping the tumor cells’ ability to grow and divide. Chemotherapy is given by a medical oncologist, a doctor who specializes in treating a tumor with medication, or a pediatric oncologist.

Systemic chemotherapy gets into the bloodstream to reach tumor cells throughout the body. Common ways to give chemotherapy include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally).

A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive one drug at a time or combinations of different drugs at the same time.

Chemotherapy by itself is not an effective treatment for brain stem glioma. Sometimes, a doctor may use chemotherapy at the same time as or after radiation therapy. The side effects of chemotherapy depend on the individual and the dose used, but they can include fatigue, risk of infection, nausea and vomiting, hair loss, loss of appetite, and diarrhea. These side effects usually go away once treatment is finished.

Learn more about the basics of chemotherapy and preparing for treatment. The medications used to treat brain stem glioma are continually being evaluated. Talking with your child’s doctor is often the best way to learn about the medications prescribed for your child, their purpose, and their potential side effects or interactions with other medications. Learn more about your child’s prescriptions by using searchable drug databases.

Surgery

Surgery is the removal of the tumor and some surrounding healthy tissue during an operation. A neurosurgeon is a doctor who specializes in treating a CNS tumor using surgery. Surgery is used to treat brain stem glioma only when the tumor looks focal on an MRI scan (see Diagnosis). This means that it may be possible to remove the tumor without damaging the brain, such as when a tumor grows out from the brain stem instead of into the brain stem. For most children with diffuse types of brain stem glioma, surgery is not recommended or possible because of the location of the tumor and the risk involved. Learn more about the basics of surgery.

Getting care for symptoms and side effects

Brain stem glioma and its treatment often cause side effects. In addition to treatment to slow, stop, or eliminate the tumor, an important part of care is relieving a person’s symptoms and side effects. This approach is called palliative or supportive care, and it includes supporting the patient with his or her physical, emotional, and social needs.

Palliative care is any treatment that focuses on reducing symptoms, improving quality of life, and supporting patients and their families. Any person, regardless of age or type and stage of cancer, may receive palliative care. It works best when palliative care is started as early as needed in the treatment process. People often receive treatment for the tumor and treatment to ease side effects at the same time. In fact, patients who receive both often have less severe symptoms, better quality of life, and families report they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional support, and other therapies. Your child may also receive palliative treatments similar to those meant to eliminate the tumor, such as chemotherapy, surgery, or radiation therapy. Talk with your child’s doctor about the goals of each treatment in the treatment plan.

Before treatment begins, talk with your child’s health care team about the possible side effects of your specific treatment plan and palliative care options. And during and after treatment, be sure to tell your child’s doctor or another health care team member if your child is experiencing a problem so it can be addressed as quickly as possible. Learn more about palliative care.

Remission and chance of recurrence

A remission is when the tumor cannot be detected in the body and there are no symptoms. This may also be called having “no evidence of disease” or NED. 

A remission may be temporary or permanent. This uncertainty causes many people to worry that the tumor will come back. While many remissions are permanent, it’s important to talk with your child’s doctor about the possibility of the tumor returning. Understanding your child’s risk of recurrence and the treatment options may help you feel more prepared if the disease does return. Learn more about coping with the fear of recurrence.

If the tumor does return after the original treatment, it is called a recurrent tumor. It may come back in the same place (called a local recurrence), nearby (regional recurrence), or in another place (distant recurrence).

When this occurs, a cycle of testing will begin again to learn as much as possible about the recurrence. After testing is done, you and your child’s doctor will talk about the treatment options. Often the treatment plan will include the treatments described above such as radiation therapy, chemotherapy, and surgery, but they may be used in a different combination or given at a different pace. Your child’s doctor may also suggest clinical trials that are studying new ways to treat this type of recurrent tumor. Whichever treatment plan you choose, palliative care will be important for relieving symptoms and side effects.

Treatment for recurrent brain stem glioma depends on the type of tumor, such as whether it is diffuse or focal, and the type of treatment that was given for the original tumor. Depending on the situation, the doctor may recommend either surgery or chemotherapy.

A recurrent tumor may bring up emotions such as disbelief or fear. You and your family are encouraged to talk with the health care team about these feelings and ask about support services to help you cope. Learn more about dealing with a recurrence.

If treatment fails

Although treatment is successful for the majority of children with a tumor, sometimes it is not. If a child’s tumor cannot be cured or controlled, this is called an advanced or terminal tumor. This diagnosis is stressful, and advanced brain stem glioma may be difficult to discuss. However, it is important to have open and honest conversations with your child’s doctor and health care team to express your family’s feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families.

Parents or guardians are encouraged to think about where the child would be most comfortable: at home, in a home-like setting elsewhere, in the hospital, or in a hospice environment. Hospice care is a type of palliative care for people who are expected to live less than six months. It is designed to provide the best possible quality of life for people who are near the end of life. Nursing care and special equipment can make staying at home a workable alternative for many families. Some children may be happier if they can arrange to attend school part-time or keep up other activities and social connections. The child’s health care team can help parents or guardians decide on an appropriate level of activity. Making sure a child is physically comfortable and free from pain is extremely important as part of end-of-life care. Learn more about caring for a terminally ill child and advanced care planning.

The death of a child is an enormous tragedy, and families may need support to help them cope with the loss. Pediatric cancer centers often have professional staff and support groups to help with the process of grieving. Learn more on grieving the loss of a child. Some families find comfort in getting involved in research efforts to advance knowledge about brain stem glioma. Learn more about tissue donation.

The next section in this guide is About Clinical Trials and it offers more information about research studies that are focused on finding better ways to care for people with cancer. Or, use the menu on the side of your screen to choose another section to continue reading this guide.

 

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por cyto às 17:39

Quarta-feira, 17.06.15

ASCO TREATMENT PLAN

 

ASCO TREATMENT PLAN

 

                                                                                       General Information

Patient Name:

Patient DOB:

Patient phone:

Email:

Health Care Providers (Including Names, Institution, Phone numbers)

Primary Care Provider:

Surgeon:       

Radiation Oncologist:

Medical Oncologist:

Other Providers (Navigator):

Diagnosis

Cancer Type/Location/Histologic type:

Diagnosis Date:

 

Tumor size:                               Lymph Nodes:                          Metastasis:

 

Stage:   ☐I    ☐II    ☐III   ☐IV    ☐Not available/applicable

 

Other information about the cancer:

 

Treatment Plan

Treatment Goal: ☐ To cure the cancer and relieve symptoms and side effects of treatment

              ☐ To slow the growth of the cancer and relieve symptoms and side effects of treatment

Treatment Plan

Surgery ☐ Yes   ☐No

Surgery Date(s) (year):

Procedure/location:

 

Radiation ☐ Yes   ☐No

Body area to be treated:

How many treatments over how many weeks:

 

Systemic Therapy (chemotherapy, hormonal therapy, other) ☐ Yes   ☐No

To be given before surgery or radiation (neoadjuvant) ☐ Yes   ☐No

Name of regimen and agents used:

 

 

 

Number of cycles planned and frequency:

To be given after surgery or radiation (adjuvant) ☐ Yes   ☐No

Name of regimen and agents used:

 

 

 

Number of cycles planned and frequency:

Additional information:

 

 

             

 

 

Symptoms or Side Effects

Symptoms or side effects common during your treatments:

☐Allergic reactions                                       ☐ Muscle/bone pain or soreness

☐Diarrhea/constipation                             ☐Nausea/vomiting      

☐Fatigue or being tired                              ☐Numbness and tingling in hands/feet                         

☐Hair loss                                                        ☐Skin changes                              

☐Heart damage                                            ☐Trouble thinking        

☐Infection/fever                                          ☐Trouble breathing                                       

☐Low blood counts                                     ☐Urinary symptoms

☐Mouth sores                                                               o Other:   

 

Please let us know if you have:

1.       A fever over 100.5F

2.       A brand new symptom;

3.       A symptom that doesn’t go away;

4.       Anything you are worried about that might be related to the cancer or treatment.

Other Concerns

People with cancer may have issues with the areas listed below. If you have any concerns, please speak with your doctors or nurses to find out how you can get help with them.

☐Emotional and mental health                              ☐Insurance                                                     ☐School/work                ☐Other

☐Fatigue                                                          ☐Memory or concentration loss            ☐Sexual Functioning

☐Fertility                                                          ☐Parenting                                                     ☐Stopping Smoking                    

☐Financial advice or assistance               ☐Physical functioning                                 ☐Weight changes 

 

A number of lifestyle/behaviors can affect your ongoing health, including the risk for the cancer coming back or developing another cancer. Discuss these recommendations with your doctor or nurse:

☐Alcohol use                  ☐Physical activity          ☐Tobacco use/cessation                           ☐Other

☐Diet                                 ☐Sun screen use           ☐Weight management (loss/gain)   

 

Please note that it is important that you continue to see your primary care provider for your other health care needs throughout your treatment. When your treatment is done, we will give you a survivorship care plan that outlines what happens after treatment is over.

Resources you may be interested in:

·         www.cancer.net

·         Other:

Other comments:

 

 

 

Prepared by:                                                                                      Delivered on:

 

 

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por cyto às 17:27

Quarta-feira, 17.06.15

Pembrolizumab and Ipilimumab Combo Safe for Melanoma and Renal Cell Carcinoma

Pembrolizumab and Ipilimumab Combo Safe for Melanoma and Renal Cell Carcinoma

Pembrolizumab plus low-dose ipilimumab combination considered to have an acceptable safety profile in melanoma or renal cell carcinoma.
Pembrolizumab plus low-dose ipilimumab combination considered to have an acceptable safety profile in melanoma or renal cell carcinoma.

CHICAGO–Pembrolizumab plus low-dose ipilimumab combination therapy was considered to have an acceptable safety profile in patients with advanced melanomaor renal cell carcinoma during an initial safety run-in period, a study presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, has shown.

Researchers conducted an assessment of the safety and tolerability of pembrolizumab 2 mg/kg plus low-dose ipilimumab 1 mg/kg every 3 weeks for four doses, followed by pembrolizumab 2 mg/kg every 3 weeks for up to 2 years, among participants of the ongoing phase I/II KEYNOTE-029.

Twenty-two patients were enrolled, of which 12 had melanoma and 10 had renal cell carcinoma.

Results showed that dose-limiting toxicities occurred in six of 19 evaluable patients.

“All dose-limiting toxicities were of grade 3 severity except for one episode of grade 4 lipase elevation,” said Michael B. Atkins, MD, lead author and Deputy Director of the Georgetown Comprehensive Cancer Center in Washington, DC.

Specifically, dose-limiting toxicities included ALT/AST elevation, colitis, uveitis, elevation of pancreatic enzymes, hyperthyroidism, lipase elevation, and pneumonitis. Two patients experienced two dose-limiting toxicities each.

“All dose-limiting toxicities had resolved except for elevated lipase, which was ongoing at the time of data cutoff,” Dr. Atkins said.

 

RELATED: Pembrolizumab May Be More Effective, Safer Than Ipilimumab for Advanced Melanoma

Assessment of antitumor activity is ongoing with 14 patients remaining on pembrolizumab at the time of data cutoff.

Due to the positive findings, researchers have initiated a protocol-specified, single-arm expansion cohort to further assess the safety, tolerability, and efficacy of pembrolizumab plus low-dose ipilimumab in patients with advanced melanoma.

Reference

  1. Atkins MB, Choueiri TK, Hodi FS, et al. Pembrolizumab (MK-3475) plus low-dose ipilimumab (IPI) in patients (pts) with advanced melanoma (MEL) or renal cell carcinoma (RCC): Data from the KEYNOTE-029 phase 1 study. J Clin Oncol. 2015:33(suppl; abstr 3009).

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por cyto às 12:01

Quarta-feira, 17.06.15

Organoid Biobanks in Colon Cancer Show Promise in Personalized Treatment Options

Organoid Biobanks in Colon Cancer Show Promise in Personalized Treatment Options

 
Tumor organoids (Photo courtesy of Marc van de Wetering, Hubrecht Institute)
Tumor organoids (Photo courtesy of Marc van de Wetering, Hubrecht Institute)

Biobanks of three-dimensional organoid cultures from colorectal cancer patients provided a substrate for genetic analysis and multidrug testing, showing promise for personalized treatment options in colorectal cancer.

Researchers at the Hubrecht Institute and the Cancer Genomics and University Medical Center, in the Netherlands, recently published their findings in Cell.  

"This is the first time that a collection of cancer organoids, or a living biobank, has been derived from patient tumors. We believe that these organoids are an important new tool in the arsenal of cancer biologists and may ultimately improve our ability to develop more effective cancer treatments," said geneticist Mathew Garnett at the Wellcome Trust Sanger Institute in a press release.

Previous studies using genetic sequencing have revealed numerous mutations in the pathogenesis of colorectal cancer, such as P53, WNT, RAS-MAPK, DNA mismatch repair, and TGF-Beta. However, incorporating the identified genetic mutations of an individual patient's tumor into predictable outcomes and treatment response has been limited.

Combining a previously established culture medium, including basement membrane extract, with nicotinamide, prostaglandin E2, p38 inhibitor, and Alk inhibitor, researchers were able to create a colon tissue organoid resembling the original epithelium of normal and cancerous colon in structure, ability to grow, and cell variety.

Tumor samples and adjacent normal tissue biopsies from 20 untreated colorectal cancer patients were obtained, which successfully produced 19 normal organoid cultures and 22 cancerous organoid cultures.

Genetic analysis of DNA extracted from tumor organoids revealed mutations commonly seen in colorectal cancer. “But now we've shown that when we look at the mutation pattern that they are faithful representations of the original tumor. Meaning that the genetic landscape is basically maintained, so that you can use them as a sort of reflection of the tumor itself,” said Marc van de Wetering of the Hubrecht Institute in the Netherlands.

Likewise, the researchers compared RNA expression of the normal and tumor organoids. The data was used to classify the results into subtypes based on the gene signatures and for analysis of individual gene expression in the organdies.

RELATED: Colon Cancer Biomarkers Appear Within Weeks of Diet Change

Finally, the researchers tested the organoids against 83 drugs in clinical trials and in clinical use, including first-line treatments such as oxaliplatin and 5-FU and cetuximab. The investigators detected several gene-drug associations, including nutlin-3a resistance and mutations in TP53. Cetuximab and afatinib resistance was also observed with organoids demonstrating KRAS mutations. Furthermore, one organoid with a mutation of RNF43 was noted to be responsive to porcupine inhibitor.

The researchers concluded they were able to establish a colorectal organoid biobank as a realistic technology for testing drug response for individual patients and noted a possibility of using it as a bridge between genetic research and clinical trials.

The researchers noted, “We perceive patient-derived organoids to be used to directly test drug sensitivity of the tumor in a personalized treatment approach. For this, we envision organoids to be tested against a limited number of clinically approved drugs within weeks after derivation.”

Thoughts for the future include clinical trials “where we look at the sensitivity of the organoids for a certain drug and then compare it to the sensitivity of the patient's tumor,” Wetering told Cancer Therapy Advisor.

Garnet noted further that "Cancer is a diverse and complex disease and having a large collection of organoids is necessary to encompass this diversity to enable scientists and clinicians to develop new treatments."

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por cyto às 11:59

Quarta-feira, 17.06.15

Study Classifies Gliomas Based on Tumor Markers

Study Classifies Gliomas Based on Tumor Markers

 
Gliomas classified by tumor markers were characterized by distinct mechanisms of pathogenesis, ages at onset and overall survival.
Gliomas classified by tumor markers were characterized by distinct mechanisms of pathogenesis, ages at onset and overall survival.

Gliomas classified by tumor markers were characterized by distinct mechanisms of pathogenesis, ages at onset, overall survival, and associations with germline variants, a new study published online ahead of print in The New England Journal of Medicine has shown.

For the study, researchers analyzed 1,087 gliomas as positive or negative for mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q, and classified them into five primary molecular groups. Researchers then compared associations between those groups and known glioma germline variants.

Gliomas were classified as being triple-positive, having TERT and IDH mutations, having only IDH mutations, having only TERT mutations, and being triple-negative.

Results showed that the average age at the time of diagnosis was lowest among those who had only IDH mutations. Age at onset was highest among patients who had gliomas with only TERT mutations.

 

RELATED: Efficacy of Chemotherapy Similar to Radiotherapy for Anaplastic Glioma

Researchers found that the molecular groups were independently associated with overall survival among those with grade II or III gliomas, but not grade IV gliomas. The study also demonstrated that the molecular groups were associated with specific germline variants.

The findings may ultimately better inform patient management and treatment decisions of patients with gliomas.

Reference

  1. Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015. [Epub ahead of print]. doi: 10.1056/NEJMoa1407279.

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por cyto às 11:54

Quarta-feira, 17.06.15

Nivolumab Plus Ipilimumab Demonstrates Activity in Recurrent Glioblastoma

Nivolumab Plus Ipilimumab Demonstrates Activity in Recurrent Glioblastoma

 
The adverse event profile of nivolumab with or without ipilimumab in patients with glioblastoma was encouraging.
The adverse event profile of nivolumab with or without ipilimumab in patients with glioblastoma was encouraging.

CHICAGO–The adverse event profile of nivolumab with or without ipilimumab in patients with glioblastoma was consistent with studies in other tumors and 6 month overall survival data is encouraging, a study presented at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL, has shown.

For the study, researchers enrolled 20 patients with first recurrence of primary glioblastoma multiforme and no prior bevacizumab treatment. Patients were randomly assigned 1:1 to receive nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks followed by nivolumab 3 mg/kg every 2 weeks.

Results showed that drug-related adverse events experienced by three or more patients included fatigue and nausea with nivolumab and fatigue, diarrhea, AST/ALT elevation, lipase elevation, vomiting, amylase elevation, headache, hyperthyroidism, nausea, and macropapular rash with the combination.

Researchers found that all adverse events associated with nivolumab treatment alone were grade 1 or 2, while 80% of those treated with nivolumab plus ipilimumab experienced grade 3 or 4 adverse events. Four patients discontinued combination treatment due to treatment-related adverse events prior to completing four doses of treatment. No patients died as a result of treatment.

In regard to efficacy, the overall survival rate at 6 months was 75% (70% in the nivolumab arm and 80% in the nivolumab plus ipilimumab arm). At 9 months, the overall survival rate was 60% in both arms.

In an interview with Cancer Therapy Advisor, John H. Sampson, MD, PhD, lead author and chief of the Division of Neurosurgery at Duke University in Durham, NC, said, “It's early on. We certainly see evidence of response in some patients, which is rare for patients with glioblastoma…We saw less toxicity with nivolumab alone that with the combination, and we have encouraging preliminary overall survival statistics at 6 and 9 months.”

 

RELATED: First-Line Bevacizumab for Glioblastoma Not Likely To Be Cost-Effective

More cohorts in this trial are planned to evaluate nivolumab plus radiotherapy with or without temozolomide in patients with newly diagnosed glioblastoma.

Due to the encouraging findings, the phase III portion of CHECKMATE-143 has been initiated to assess the efficacy of nivolumab 3 mg/kg monotherapy with bevacizumab in patients with recurrent glioblastoma multiforme.

Reference

  1. Sampson JH, Vlahovic G, Sahebjam S, et al. Preliminary safety and activity of nivolumab and its combination with ipilimumab in recurrent glioblastoma (GBM): CHECKMATE-143. J Clin Oncol. 2015:33;(suppl; abstr 3010).

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por cyto às 11:49

Quarta-feira, 17.06.15

BRAF mutations in non-small cell lung cancer

BRAF mutations in non-small cell lung cancer

 

BRAF mutations occurs in a small proportion of patients with non-small cell lung cancer (NSCLC) that lack other driver mutations, such as KRAS and EGFR, a study published in the journal Translational Lung Cancer Research has shown.

For the study, researchers conducted a mutation analysis for EGFR, KRAS, and BRAF in 273 cases of NSCLC. All patients had been treated at Royal Prince Alfred Hospital in Sydney, Australia, between March 2012 and March 2014.

Results showed that 2.6% of cases had BRAF mutations. Of those, all were former smokers, three were male, and three were female. Patients with BRAF mutations had a median age of 70 years. Six cases were adenocarcinomas and one was not otherwise specified NSCLC. None had EGFR and KRAS mutations in addition to BRAF mutations.

Researchers identified V600E, K601N, L597Q, and G469V as the BRAF mutations.

The findings suggest that studies investigating the treatment of BRAF-positive NSCLC with BRAF inhibitors are warranted.

BRAF mutations are typically seen in patients with melanoma and patients with papillary thyroid carcinoma. The BRAF V600E mutations accounts for more than 90% of BRAF melanomas.

Treatments for BRAF V600-positive unresectable or metastatic melanomas include vemurafenib and dabrafenib. 


This research investigates the prevalence and clinicopathological features of BRAF mutations in NSCLC cases submitted for routine mutation testing.

Background: BRAF is a proto-oncogene encoding a serine/threonine protein kinase which promotes cell proliferation and survival. BRAF mutations are commonly seen in melanoma and papillary thyroid carcinoma. We aimed to investigate the prevalence and clinicopathological features of BRAF mutations in non-small cell lung cancer (NSCLC) cases submitted for routine mutation testing at our institution.

Methods: Mutation analysis for BRAF,EGFR and KRAS was performed using Sequenom MassARRAY platform with OncoCarta panel v1.0. Pathological features were reviewed and immunohistochemistry for BRAF V600Ewas also performed.

Results: Seven out of 273 cases (2.6%) had BRAF mutations (three males and four females, median age 70 years, all smokers), with six adenocarcinomas and one NSCLC, not otherwise specified (NOS). All had wild-typeEGFR and KRAS.

The identified BRAF mutations were V600E (4/7, 58%), K601N, L597Q and G469V. BRAFV600E immunohistochemistry was positive in two cases with V600E and negative in one case with K601N (tissue available in three cases only). No significant difference in age or gender was found (BRAFmutant vs. wild-type).

Conclusions: BRAF mutations occur in a small proportion of NSCLC that lack other driver mutations. The clinicopathological profile differs from that of EGFR mutant tumours. The potential benefits of BRAF-inhibitors should be investigated.

 

 

INTRODUCTION

The discovery of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) has allowed effective targeted therapy with EGFR tyrosine kinase inhibitors in patients that harbour these mutations1.

However, the majority of NSCLC cases have wild-type EGFR and it is now known that many other mutations can drive oncogenic pathways, including KRAS and less commonly, BRAF2. BRAF is a proto-oncogene encoding a serine/threonine protein kinase which is a downstream effector protein of RAS and transduces signalling through the mitogen-activated protein kinase pathway to promote cell proliferation and survival. This pathway functions downstream of various receptor tyrosine kinases such as EGFR and is a key mediator of oncogenesis3.

BRAF mutations are commonly seen in a range of malignancies, including hairy-cell leukemia (100%)4, melanoma (~40%)5, papillary thyroid carcinoma (30-50%) and colorectal carcinoma (~10%)6. The V600E mutation has been shown to constitutively activate BRAF which phosphorylates the downstream effectors MEK and subsequently ERK7.

ERK, in turn, activates transcription factors such as c-fos and Elk-1, driving cell cycle progression and survival8. The importance of the BRAF pathway is well established in melanoma, asBRAF inhibitors have been shown to significantly increase progression free survival of patients with advanced stage melanoma harbouring the BRAF V600E mutation9.

This raises the possibility that BRAF mutations may also be a feasible target in NSCLC. BRAFmutations in NSCLC are not well characterised in the literature due to their low prevalence.

In this study we aimed to investigate the prevalence and clinicopathological features ofBRAFmutations in NSCLC.

METHODS

Patients

We retrospectively reviewed 273 NSCLC cases that underwent mutation testing upon request of the treating oncologist at Royal Prince Alfred Hospital between March 2012 and March 2014. The patients underwent either a resection or a diagnostic procedure (biopsy or cytological specimen) and the tissue was formalin fixed, embedded in paraffin, sectioned and stained with hematoxylin and eosin (H&E).

The H&E sections were reviewed by a pathologist (SOT or WC) to ensure adequate tumour cells were present and to mark representative areas for deoxyribonucleic acid (DNA) extraction. Histological subtypes were classified according to the IASLC/ATS/ERS classification10. This study was approved by the Human Research Ethics Committee of Royal Prince Alfred Hospital.

Mutation detection

DNA was extracted from the formalin fixed paraffin embedded tissue using NucleoSpin FFPE DNA Kit (Macherey Nagel, Düren, Germany) according to the manufacturer's instruction with 2 hr proteinase digestion.

The quantity of the extracted DNA was assessed using Qubit® Fluorometer (Life Technologies, Mulgrave, Australia). A minimum of 300 ng of DNA was required for optimal mutational analysis.

Samples were amplified for 238 variant targets in a 24-multiplex PCR using the OncoCarta Panel v1.0 Kit (ABL1, AKT1, AKT2, BRAF,CDK, EGFR, ERBB2, FGFR1, FGFR3, FLT3, JAK2, KIT, MET,HRAS, KRAS, NRAS, PDGFR, PIK3CA, and RET) and analyzed based on the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) technology on the Sequenom MassArray platform11,12.

The targeted mutations in the 19 oncogenes comprising the OncoCarta v1.0 Panel are reported to be biologically significant in carcinogenesis or progression in a range of malignancies.

These mutational analyses and immunohistochemistry described below were performed at an Australian National Association of Testing Authorities (NATA) accredited medical laboratory.

Immunohistochemistry

BRAF V600E immunohistochemistry was performed on sections cut at four microns. Tissue was pre-treated on a Ventana Benchmark Ultra (Roche) with CC1 (Roche) for 64 minutes.

The anti-BRAF (VE1) mouse monoclonal antibody (Spring Bioscience) was used at 1:100 dilution with 16 minutes incubation.

Staining was performed using the OptiView DAB Immunohistochemistry Detection kit (Roche) for 8 minutes. Cases with 1+, 2+ and 3+ staining were regarded as positive and cases with no staining were regarded as negative.

Statistical analysis

Fisher's exact test was used to evaluate the difference in gender distribution between BRAF wild-type and mutant patients while Welch's t-test was used to evaluate the age difference. Data were analysed using the R environment for statistical computing13.  

RESULTS

Patient characteristics

The patient characteristics are summarised in Table 1. A total of 273 cases of NSCLC were tested and 7 (2.6%) were found to have BRAF mutations.

Of patients with BRAF mutations, there were three males and four females, median age 70 years, range from 51 to 76 years. All seven patients were former smokers with smoking history ranged from 3 to 90 pack years. BRAF wild-type was found in 266 cases with 141 males and 125 females, median age 66.5 years.

There was no significant difference in gender distribution (P=0.71) or age (P=0.65) between BRAFwild-type and mutant patients. Due to incomplete data on smoking history and tumour type in theBRAF wild-type group, statistical analysis could not be performed.

Table 1. Patient clinical characteristics and BRAF genotype

Patient no. Age (years) Gender Smoking status Procedure Predominant histological subtype other components BRAF mutation
1 51 F Ex-smoker 15 pk yrs Lung FNA non-small cell carcinoma, NOS   V600E
2 57 F Ex-smoker pk yrs not known Resection Adenocarcinoma–lepidic Papillary G469V
3 70 F Ex-smoker 10 pk yrs Resection Adenocarcinoma–micropapillary Lepidic V600E
4 70 M Ex-smoker 90 pk yrs Lung core biopsy Adenocarcinoma–acinar Papillary and lepidic K601N
5 73 F Ex-smoker 40 pk yrs Bronchial washing Adenocarcinoma   V600E
6 74 M Ex-smoker 40 pk yrs Bronchial biopsy Adenocarcinoma   L597Q
7 76 M Ex-smoker 3 pk yrs Resection Adenocarcinoma–micropapillary Acinar V600E
Note: F, female; M, male; NOS, not otherwise specified.

 

Six cases were adenocarcinomas and one case was a non-small cell carcinoma, not otherwise specified (NOS). The tumour diagnosed as non-small cell carcinoma, NOS, was from a fine needle aspiration specimen. Two cases of adenocarcinoma were diagnosed on bronchial biopsy or washing.

One case was diagnosed on core biopsy showing a mixture of acinar, papillary and lepidic patterns. In patients who underwent a resection, the histological subtypes were lepidic predominant with papillary component, micropapillary predominant with lepidic component and micropapillary predominant with acinar component. Representative H&E sections are shown in Figure 1.

BRAF mutation genotypes

Four BRAF mutation genotypes were identified. Three mutations were located in exon 15 which included V600E (c.1799T>A, 58%, n=4), K601N (c.1803A>T, 14%, n=1) and L597Q (c.1790T>A, 14%, n=1). One mutation was found in exon 11 which was G469V (c.1406G>T, 14%, n=1).

Representative spectra are shown in Figure 2. A female predominance of V600E mutations was noted (3 out of 4 V600E mutations). Furthermore, both patients with a micropapillary component harboured V600E mutation. No patient with a BRAF mutation had a concomitant EGFR or KRASmutation.

Immunohistochemistry

Due to limited availability of tissue, BRAF V600E immunohistochemistry was only performed in three cases.BRAF V600E immunohistochemistry was positive in two cases with V600E mutation and negative in one case with K601N mutation (Figure 3).

Thus the immunohistochemistry results were consistent with the Sequenom MassArray platform results.

DISCUSSION

In our population of Australian patients with NSCLC that underwent mutation testing, we found BRAF mutations occurred in 2.6% of patients who were all former smokers.

This is consistent with other studies reporting BRAFmutation prevalence between 2-5% in NSCL14-16.

While this is much less common than EGFRmutations that occur in approximately 15% of lung adenocarcinomas in Western populations17, there were approximately 6,000 new cases of NSCLC diagnosed in Australia in 200718, giving a predicted number of 156 patients with BRAF mutant lung cancer.

These patients could potentially benefit from targeted therapy as BRAFV600E NSCLC has shown some response to dabrafenib19. The prevalence rate is only slightly lower than that of ALK gene rearrangements that are found in ~3-5% of lung adenocarcinomas20.

We found all patients with BRAF mutation had a smoking history, in contrast withEGFR mutations which commonly occur in non-smokers21.

Although others have also reported an association between BRAFmutation and smoking16, one study reported V600E mutation to be associated with non-smokers while non-V600E mutations were associated smokers14.

Discrepancies between studies may be due to low numbers ofBRAF mutant cases in each study, relating to the low prevalence ofBRAF mutations in NSCLC.

A potential limitation of the targeted approach to mutation detection employed in the current study is that very rare mutations not on the OncoCarta panel may not be detected, such as BRAF mutations involving amino acids 421, 436, 439 and 471. 

However, these mutations represent less than 2% of all reported BRAF mutations in NSCLC22, making it highly unlikely for the overall BRAF mutation prevalence to be under-represented in the current study.

Furthermore our testing is more comprehensive than that performed by many centres who currently focus only of the BRAF V600 codon. 

Although the current study did not find a significant difference in gender distribution or age between BRAF wild-type and mutant patients, the small number of patients in the BRAF mutant group makes it difficult to draw definitive conclusions.

Interestingly, a predominance of BRAFV600E mutation in females has been reported by others14 while we found a non-statistically significant trend towards female predominance. BRAF mutation is also more commonly found in females in colorectal cancer23,24.

This finding is akin to the female predominance of EGFR mutations and may represent a similar underlying mechanism.

An association betweenEGFR mutation and oestrogen receptor has been found, possibly indicating a hormonally driven phenomenon25. However, a clear mechanism has yet to be substantiated.

The BRAF V600E mutation has been previously reported to be associated with the aggressive micropapillary subtype of lung adenocarcinoma14,26.

This finding is supported by the current study as both patients with a micropapillary component showed BRAF V600E mutation. However, it is difficult to be conclusive due to the small number of patients in the current study precluding statistical analysis.

The most common BRAF mutation in melanoma is the V600E mutation, which accounts for more than 90% of mutations6. However, the current study shows that BRAF V600E mutation only accounts for 58% of mutations in NSCLC.

This finding is supported by others who found the non-V600E mutation rate to be between 50-89%16,27. Although the biological significance of this is unknown, this raises the possibility thatBRAF-related oncogenesis in NSCLC arises from a different mechanism compared to melanomas with V600E mutations.

It has been shown that the V600E mutation confers a much higher kinase activity compared to other mutations within the kinase domain7. The G469V mutation found in the current study occurs in the P-loop which is the ATP binding site.

Mutations within the P-loop have been shown to have a lower activity compared to wild-type BRAF7, therefore whether these mutations drive oncogenesis is uncertain. Similarly, rare mutations at codons 439 and 440 (AKT phosphorylation motif) have been reported in NSCLC and they do not increase the oncogenic properties of BRAF28.

This indicates that the genotype of the BRAF mutation may be an important therapeutic consideration. Unfortunately, there is currently only limited phase I clinical trial data for RAF inhibitors in NSCLC19 and the significance of the different mutation spectrum remains uncertain.

In conclusion, the current study confirmed that a small proportion of NSCLC patients harbour BRAFmutations. Their clinicopathological characteristics appear to differ from patients with EGFRmutations and their genotype differs from that found in melanoma.

Further work needs to be done to determine whether this small subset of patients will benefit fromBRAF inhibitors.

Acknowledgements

The authors would like to thank Thang Tran for performing the statistical analysis. WC and SOT have received funding from National Foundation for Medical Research and Innovation.

Disclosure: The authors declare no conflict of interest.

Peter P. Luk1, Bing Yu2,3, Chiu Chin Ng2, Belinda Mercorella2, Christina Selinger1, Trina Lum1, Steven Kao4, Sandra A. O'Toole1,3,5, Wendy A. Cooper1,3,6

1Department of Tissue Pathology and Diagnostic Oncology, 2Department of Medical Genomics, Royal Prince Alfred Hospital, Sydney, Australia; 3Sydney Medical School, University of Sydney, Sydney, Australia; 4Lifehouse Cancer Centre, The Chris O'Brien Lifehouse, Sydney, Australia;5Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, Australia; 6School of Medicine, University of Western Sydney, Sydney, NSW,Australia

Correspondence to: A/Prof. Wendy Cooper. Department of Tissue Pathology and Diagnostic Oncology, The Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia. Email: wendy.cooper@sswahs.nsw.gov.au.

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Source: Translational Lung Cancer Research.

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por cyto às 11:41

Quarta-feira, 17.06.15

Study on how maternal proteins help regulate initial cell divisions during early development

Study on how maternal proteins help regulate initial cell divisions during early development

Published on June 10, 2015 at 10:19 AM ·

Researchers in the University of Georgia's Regenerative Bioscience Center are visually capturing the first process of chromosome alignment and separation at the beginning of mouse development. The findings could lead to answers to questions concerning the mechanisms leading to birth defects and chromosome instability in cancer cells.

"We've generated a model that is unique in the world," said Rabindranath De La Fuente, an associate professor in the UGA College of Veterinary Medicine. "Because we removed ATRX protein expression only in the oocyte, the female egg cell, we can now study its function at both the cellular and molecular level."

ATRX is a protein that binds to the centromere of all chromosomes in every single cell of the body, but when it malfunctions, chromosomes cannot segregate properly and lose their structural integrity. Using the ATRX protein, the researchers developed a mouse model to learn how an embryo responds to abnormal chromosome segregation.

In the study, published recently in the journal Development, De La Fuente and assistant professor Maria Viveiros, both in the college's department of physiology and pharmacology, have established that stability of a specialized chromosomal domain in an early embryo is absolutely vital for subsequent development and health.

The future goal of this study is to learn about the mechanisms of chromosomal defects, helping to someday reduce the risk of chromosome instability and increase prevention through improving early prenatal care.

There is an urgent need to develop additional non-invasive strategies concerning maternal health, Viveiros said, pointing out the classic example of how folic acid significantly reduced the risk of spina bifida "by the simple recommendation of taking a daily dose of the vitamin folic acid before and during pregnancy.

"With our unique model, by deleting the protein strictly in the female egg, we can begin to understand how maternal proteins help regulate these initial cell divisions during early development."

The first image captured by the team shows a mouse oocyte fertilized by sperm, when the maternal and paternal chromosomes come together for the first time to start a new embryo. Through the use of fluorescent markers, the process of how the maternal genome is being regulated can now be studied.

"What's amazing is we can actually visualize that very first division when this cell is going to get half of its chromosomes from mom and the other half from dad," Viveiros said.

They found that ATRX is inherited only from mom's chromosomes.

"That was totally unexpected for us--and the main reason for describing the process as 'epigenetic asymmetry' in the title of our publication," she said.

In the second image shown by a computer program that recognizes DNA sequences, in chromosome 16 a piece has gone missing and is now fused with chromosome 17, forming a translocation.

The team has been studying the role of chromatin remodeling proteins in the epigenetic control of chromosome instability for many years, and it's no small task to capture these images and analyze the data. The entire mouse genome is massive and contains billions of base pairs of DNA.

"We've been learning how these proteins work and publishing our results," De La Fuente said, "and at the same time independently in other laboratories around the world oncologists are discovering that ATRX is important to prevent chromosome breaks in tumors. Tumor cells have high rates of genomic instability and are often aneuploid, meaning they inherit the wrong number of chromosomes. This instability is often considered a 'hallmark' for cancer cells. But the mechanisms are not known--we have the model ready to start studying the mechanisms of chromosome instability at the cellular and molecular level."

As to the images presented in the paper, De La Fuente said, "What really keeps us going is a finding like this one, that no one in the world has ever seen before."

The study, "ATRX contributes to epigenetic asymmetry and silencing of major satellite transcripts in the maternal genome of the mouse embryo," is available at http://www.ncbi.nlm.nih.gov/pubmed/25926359.

Source:

University of Georgia

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por cyto às 11:37

Quarta-feira, 17.06.15

new way to treat T-cell acute lymphoblastic leukemia

Researchers report new way to treat T-cell acute lymphoblastic leukemia

Published on June 8, 2015 at 2:41 PM 

Researchers at NYU Langone Medical Center and its Laura and Isaac Perlmutter Cancer Center are reporting a potentially important discovery in the battle against one of the most devastating forms of leukemia that accounts for as many as one in five children with a particularly aggressive form of the disease relapsing within a decade.

In a cover story set to appear in the journal Cancer Cell online June 8, researchers at NYU Langone and elsewhere report that they have successfully halted and reversed the growth of certain cancerous white blood cells at the center of T-cell acute lymphoblastic leukemia, or T-ALL, by stalling the action of a specific protein receptor found in abundance on the surface of T cells at the core of T-ALL.

In experiments in mice and human cells, researchers found that blocking CXCR4 -- a so-called homing receptor protein molecule that helps T cells mature and attracts blood cells to the bone marrow -- halted disease progression in bone marrow and spleen tissue within two weeks. The experiments also left white blood cells cancer free for more than 30 weeks in live mice. Further, the research team found that in mice bred to develop T-ALL, depleting levels of the protein to which CXCR4 binds (CXCL12) also stalled T-ALL progression.

Researchers say their study results for the first time "clearly establish CXCR4 signaling as essential for T-cell acute lymphoblastic leukemia cell growth and disease progression."

"Our experiments showed that blocking CXCR4 decimated leukemia cells," says co-senior study investigator and NYU Langone cell biologist Susan Schwab, PhD.

Schwab, an assistant professor at NYU Langone and its Skirball Institute of Biomolecular Medicine, says similar laboratory test plans are underway for more potent CXCR4 antagonists, most likely in combination with established chemotherapy regimens. She notes that anti-CXCR4 drugs are already in preliminary testing for treating certain forms of myeloid leukemia, and have so far proven to be well-tolerated, but such treatments have not yet been tried for T-ALL.

Schwab says T-ALL is "a particularly devastating cancer" because there are not many treatment options.

One American survey, she points out, showed that only 23 percent of patients lived longer than five years after failing to sustain remission with standard chemotherapy drugs.

Co-senior study investigator and cancer biologist Iannis Aifantis, PhD, says the study offers the first evidence that "drugs targeting and disrupting leukemia cells' microenvironment -- or what goes on around them -- could prove effective against the disease."

Aifantis, the chair of the Department of Pathology at NYU Langone and a member of its Perlmutter Cancer Center, and an early career scientist at the Howard Hughes Medical Institute, says experiments in his laboratory had shown that leukemia-initiating cells concentrate in the bone marrow near CXCL12-producing blood vessels. This finding prompted a collaborative effort to investigate expression and function of CXCR4 because it binds to CXCL12, which in turn led to the researchers determining the vital role played by CXCR4-CXCL12 molecular signaling in disease growth.

Aifantis says more research needs to be done to decipher how CXCR4 is able to promote and sustain T-ALL.

As part of the new study, researchers deleted CXCL12 production specifically from bone marrow vasculature in leukemic mice. Disease progression in the bone marrow stalled within three weeks and tumors were smaller than in similar mice that retained CXCL12 production. Deletion of the CXCR4 gene led to sustained T-ALL remission within a month in similar mice, as well as movement of the cancerous blood cells away from the bone marrow. Subsequent transplant of millions of human T-ALL cells into normal mice that were then treated with an anti-CXCR4 drug induced remission within two weeks, with diseased spleen and bone marrow tissue nearly returning to normal.

Source:

NYU Langone Medical Center

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por cyto às 11:34

Quarta-feira, 17.06.15

fibromyalgia benefit from hyperbaric oxygen therapy

Women who suffer from fibromyalgia benefit from hyperbaric oxygen therapy

Published on June 3, 2015 at 4:41 AM ·

Women who suffer from fibromyalgia benefit from a treatment regimen in a hyperbaric oxygen chamber, according to researchers at Rice University and institutes in Israel.

A clinical trial involving women diagnosed with fibromyalgia showed the painful condition improved in every one of the 48 who completed two months of hyperbaric oxygen therapy. Brain scans of the women before and after treatment gave credence to the theory that abnormal conditions in pain-related areas of the brain may be responsible for the syndrome.

Results of the study appear in the open-access journal PLOS ONE.

Fibromyalgia is a chronic pain syndrome that can be accompanied by - and perhaps related to - other physical and mental conditions that include fatigue, cognitive impairment, irritable bowel syndrome and sleep disturbance.

More than 90 percent of those diagnosed with the syndrome are women, said Eshel Ben-Jacob, a lead author of the proof-of-concept study who developed the analytical method used to show the association between patients' improvement and changes in their brains. He is an adjunct professor of biosciences at Rice University, a senior investigator at Rice's Center for Theoretical Biological Physics and a professor of physics and member of the Sagol School of Neuroscience at Tel Aviv University.

"Symptoms in about 70 percent of the women who took part have to do with the interpretation of pain in their brains," Ben-Jacob said. "They're the ones who showed the most improvement with hyperbaric oxygen treatment. We found significant changes in their brain activity."

Scientists have not pinned down the syndrome's cause, although another recent PLOS One study identified a possible RNA-based biomarker for its diagnosis. A variety of treatments from drugs to lifestyle changes have been tried to relieve patients' suffering, with limited success, Ben-Jacob said.

"Most people have never heard of fibromyalgia," he said. "And many who have, including some medical doctors, don't admit that this is a real disorder. I learned from my M.D. friends that this is not the only case in which disorders that target mainly women raise skepticism in the medical community as to whether they're real or not. However, these days there are increasing efforts to understand the effect of gender on body disorders."

Researchers at the Sagol Center for Hyperbaric Medicine and Research at the Assaf Harofeh Medical Center and Tel Aviv University were studying post-traumatic brain injury patients when they realized hyperbaric oxygen treatment (HBOT) could help patients with fibromyalgia.

"Patients who had fibromyalgia in addition to their post-concussion symptoms had complete resolution of the symptoms," said Dr. Shai Efrati, who noted his own mother suffers from the syndrome. Efrati is lead author of the study, head of the research and development unit at the Assaf Harofeh Medical Center and a member of the Sagol School of Neuroscience at Tel Aviv University.

Hyperbaric oxygen chambers that expose patients to pure oxygen at higher-than-atmospheric pressures are commonly used to treat patients with embolisms, burns, carbon monoxide poisoning and decompression sickness (known to divers as "the bends"), among many other conditions.

One effect of exposure is to push more oxygen into a patient's bloodstream, which delivers it to the brain. Efrati's earlier trials found HBOT induces neuroplasticity that leads to repair of chronically impaired brain functions and improved quality of life for post-stroke and mild traumatic brain injury patients, even years after the initial injury.

Ben-Jacob said two patients spearheaded the push for the study. One was an Oxford graduate student who developed fibromyalgia after suffering a traumatic brain injury in a train crash. "By chance, the secretary of the department where she worked is the mother of the nurse in charge of the HBOT. She said you have to go and try to do it," he recalled.

The other, he said, is a professor of sociology who specializes in post-traumatic stress disorders due to child abuse. The professor had suffered from fibromyalgia for many years. Her symptoms got worse through the initial treatments - a common experience for other patients in the study who she said had suppressed memories due to child abuse - before they got better. But by the end of treatment both women showed remarkable improvement, Ben-Jacob said.

Efrati said some patients will likely require follow-up sessions. "The abnormalities in brain regions responsible for the chronic pain sensation in fibromyalgia patients can be triggered by different events," he said. "Accordingly, the long-term response may be different.

"We have learned, for example, that when fibromyalgia is triggered by traumatic brain injury, we can expect complete resolution without any need for further treatment. However, when the trigger is attributed to other causes, such as fever-related diseases, patients will probably need periodic maintenance therapy."

The clinical trial involved 60 women who had been diagnosed with fibromyalgia at least two years earlier. A dozen left the trial for various reasons, but half of the 48 patients who completed it received 40 HBOT treatments five days a week over two months. Half of the 48 patients who completed the trial received 40 HBOT treatments five days a week over two months. The 90-minute treatments exposed patients to pure oxygen at two times the atmospheric pressure.

The other half were part of what Ben-Jacob called a crossover-control group. They were evaluated before the trial and after a control period that saw no improvement in their conditions. After the two-month control, they were given the same HBOT treatment as the first group and experienced the same relief, according to the researchers.

The researchers noted the successful treatment enabled patients to drastically reduce or even eliminate their use of pain medications. "The intake of the drugs eased the pain but did not reverse the condition, while HBOT did reverse the condition," the researchers wrote.

Efrati said the findings warrant further study. "The results are of significant importance since, unlike the current treatments offered for fibromyalgia patients, HBOT is not aiming for just symptomatic improvement," he said. "HBOT is aiming for the actual cause -- the brain pathology responsible for the syndrome. It means that brain repair, including even neuronal regeneration, is possible even for chronic, long-lasting pain syndromes, and we can and should aim for that in any future treatment development."

Source:

Rice University

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por cyto às 11:31

Quarta-feira, 17.06.15

gene mutation linked to anaplastic oligodendroglioma

Scientists identify gene mutation linked to anaplastic oligodendroglioma

Published on June 12, 2015 at 9:23 AM · 

Scientists have identified a gene mutation linked to the development of an aggressive form of brain cancer.

Researchers found that errors in a gene known as TCF12 - which plays a key role in the formation of the embryonic brain are associated with more aggressive forms of a disease called anaplastic oligodendroglioma.

The new research is the largest ever genetic study of oligodendrogliomas, and provides important insights into their causes - and how they might be treated.

Oligodendrogliomas are fast-growing cancers that account for around 5-10 per cent of all tumours of the brain and central nervous system, and typically have a very poor prognosis.

Researchers at The Institute of Cancer Research, London, in collaboration with laboratories in France and Canada, compared the genetic sequence of 134 of these brain tumours with the DNA of healthy cells.

The study was largely funded by Investissements d'avenir and Génome Québec, with support from Cancer Research UK, and was published in the journal Nature Communications.

Researchers identified mutations in the TCF12 gene in 7.5 per cent of anaplastic oligodendrogliomas. They found that this subset of cancers grew more rapidly, and in other ways seemed more aggressive, than those where the gene was intact.

TCF12 is the genetic code for a protein that binds to DNA and controls the activity of other genes. The researchers found that mutations in TCF12 rendered the protein less able to bind to DNA, and this in turn led to a reduction in activity of other key genes - including one already associated with cancer spread, known as CHD1.

The researchers initially read the DNA sequence of 51 tumours and went on to look for TCF12 mutations in an additional group of 83.

The researchers also discovered errors in the gene IDH1 in 78 per cent of the tumours, confirming the findings of an initial scan of the data.

Finding out more about what genetic faults cause anaplastic oligodendrogliomas will allow scientists and clinicians to develop new personalised therapies that target a range of the mutations driving the disease.

Professor Richard Houlston, Professor of Molecular and Population Genetics at The Institute of Cancer Research, London, said:

"Our in-depth study has set out many of the genetic defects that cause this rare but highly aggressive form of brain cancer - including identifying a gene mutation that appears in particularly fast-growing forms.

"Anaplastic oligodendrogliomas are difficult to remove by surgery and don't respond well to other forms of treatment. We hope this new information might be used to discover new targeted therapies, offering patients a better chance at survival from this aggressive cancer."

Source:

Institute of Cancer Research

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por cyto às 11:30

Quarta-feira, 17.06.15

first clinical trial of Tumor Paint BLZ-100 for children with brain tumors

Seattle Children's opens enrollment for first clinical trial of Tumor Paint BLZ-100 for children with brain tumors

Published on June 5, 2015 at 3:00 AM ·

Seattle Children's today announced the opening of patient enrollment for the first clinical research trial of the drug Tumor Paint BLZ-100, which is designed to improve surgical outcomes in children with brain tumors – the most common solid tumor cancer in kids. The phase 1 trial, which is being conducted under an open U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) application, is open to infants through young adults under age 30 who have been diagnosed with a brain tumor.

Complete removal of a brain tumor in surgery is the greatest predictor of survival for patients with brain cancer. However, tumor cells are difficult to distinguish from healthy cells in surgery, and the removal of healthy tissue can lead to serious long-term side effects. Tumor Paint BLZ-100, which was developed by Blaze Bioscience based on technology licensed from Seattle Children's, Fred Hutch and the University of Washington, aims to enable better detection and surgical resection of solid tumors without injuring surrounding healthy tissue. The drug acts as a molecular flashlight that binds to tumors cells and makes them glow, providing surgeons with real-time, high-resolution visualization of cancer cells.

"Cure is not just about successful treatment of a tumor, but successful treatment of a child," said Dr. Sarah Leary, principal investigator for the new trial and an oncologist at Seattle Children's. "Much of cancer treatment for children is a trade-off where curative therapy comes with serious long-term side effects. Tumor Paint BLZ-100 is different. In addition to potentially improving surgical outcomes, Tumor Paint BLZ-100 has the added potential to greatly increase the quality of life for children by reducing treatment-related damage to the healthy brain."

In the pediatric trial, which is funded by a generous $800,000 grant from Gateway for Cancer ResearchSM, Tumor Paint BLZ-100 will be administered by intravenous injection prior to surgery. Researchers expect it to make tumor tissue glow in the operating room when exposed to laser light and imaged with a near-infrared camera system. Tumor tissue will be imaged during surgery in the operating room and after surgery in Seattle Children's Department of Laboratory Medicine and Pathology to determine how well the drug targets brain tumors in children.

"Tumor Paint has the potential to completely revolutionize surgical oncology," said Dr. Jim Olson, inventor of Tumor Paint technology, co-founder of Blaze Bioscience, a pediatric neuro-oncologist at Seattle Children's and Fred Hutch, a researcher in the Center for Clinical and Translational Research at Seattle Children's Research Institute, and a professor of pediatrics at the University of Washington. "My patients inspired me to invent this technology, because for many, a complete surgical resection means the difference between life and death. It also means that some patients need only half as much radiation to their brain. We began this work in my lab a decade ago and nothing is more rewarding than seeing this technology reach pediatric patients for the first time through the launch of this clinical trial."

Leary said she hopes this phase 1 trial at Seattle Children's, which has the largest pediatric Brain Tumor Program and the most pediatric neurosurgeons in the Northwest, will be followed by other studies that lead Tumor Paint BLZ-100 to become the standard of care for brain tumor surgery.

"In the future, I think we'll look back and wonder how these surgeries were ever done without the lights on," said Leary, who is also a researcher in the Center for Clinical and Translational Research at Seattle Children's Research Institute and an associate professor of pediatrics at the University of Washington.

Source:

Seattle Children’s

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por cyto às 11:28

Quarta-feira, 17.06.15

potential treatment option for childhood leukemia

Researchers identify potential treatment option for childhood leukemia

Published on June 10, 2015 at 3:15 AM

Researchers at NYU Langone Medical Center and its Laura and Isaac Perlmutter Cancer Center are reporting a potentially important discovery in the battle against one of the most devastating forms of leukemia that accounts for as many as one in five children with a particularly aggressive form of the disease relapsing within a decade.

In a cover story set to appear in the journal Cancer Cell online June 8, researchers at NYU Langone and elsewhere report that they have successfully halted and reversed the growth of certain cancerous white blood cells at the center of T-cell acute lymphoblastic leukemia, or T-ALL, by stalling the action of a specific protein receptor found in abundance on the surface of T cells at the core of T-ALL.

In experiments in mice and human cells, researchers found that blocking CXCR4 — a so-called homing receptor protein molecule that helps T cells mature and attracts blood cells to the bone marrow — halted disease progression in bone marrow and spleen tissue within two weeks. The experiments also left white blood cells cancer free for more than 30 weeks in live mice. Further, the research team found that in mice bred to develop T-ALL, depleting levels of the protein to which CXCR4 binds (CXCL12) also stalled T-ALL progression.

Researchers say their study results for the first time "clearly establish CXCR4 signaling as essential for T-cell acute lymphoblastic leukemia cell growth and disease progression."

"Our experiments showed that blocking CXCR4 decimated leukemia cells," says co-senior study investigator and NYU Langone cell biologist Susan Schwab, PhD.

Schwab, an assistant professor at NYU Langone and its Skirball Institute of Biomolecular Medicine, says similar laboratory test plans are underway for more potent CXCR4 antagonists, most likely in combination with established chemotherapy regimens. She notes that anti-CXCR4 drugs are already in preliminary testing for treating certain forms of myeloid leukemia, and have so far proven to be well-tolerated, but such treatments have not yet been tried for T-ALL.

Schwab says T-ALL is "a particularly devastating cancer" because there are not many treatment options. One American survey, she points out, showed that only 23 percent of patients lived longer than five years after failing to sustain remission with standard chemotherapy drugs.

Co-senior study investigator and cancer biologist Iannis Aifantis, PhD, says the study offers the first evidence that "drugs targeting and disrupting leukemia cells' microenvironment — or what goes on around them — could prove effective against the disease."

Aifantis, the chair of the Department of Pathology at NYU Langone and a member of its Perlmutter Cancer Center, and an early career scientist at the Howard Hughes Medical Institute, says experiments in his laboratory had shown that leukemia-initiating cells concentrate in the bone marrow near CXCL12-producing blood vessels. This finding prompted a collaborative effort to investigate expression and function of CXCR4 because it binds to CXCL12, which in turn led to the researchers determining the vital role played by CXCR4-CXCL12 molecular signaling in disease growth.

Aifantis says more research needs to be done to decipher how CXCR4 is able to promote and sustain T-ALL.

As part of the new study, researchers deleted CXCL12 production specifically from bone marrow vasculature in leukemic mice. Disease progression in the bone marrow stalled within three weeks and tumors were smaller than in similar mice that retained CXCL12 production. Deletion of the CXCR4 gene led to sustained T-ALL remission within a month in similar mice, as well as movement of the cancerous blood cells away from the bone marrow. Subsequent transplant of millions of human T-ALL cells into normal mice that were then treated with an anti-CXCR4 drug induced remission within two weeks, with diseased spleen and bone marrow tissue nearly returning to normal.

Source:

NYU Langone Medical Center

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por cyto às 11:25

Quarta-feira, 17.06.15

Detect Lung Cancer Early With One Drop of Blood

MD Anderson and Exact Sciences Announce Partnership To Detect Lung Cancer Early With One Drop of Blood

Researchers at The University of Texas MD Anderson Cancer Center and Exact Sciences recently announced that they have created a partnership with the goal of developing a blood test that targets biomarkers associated with lung cancer (LC).  This test would be utilized to screen nearly 11 million Americans considered high risk smokers and former smokers, in an effort to detect LC early, which is the key to saving lives.

 Background Terminology:

  • Biomarker: short for biological markers, are the measures used to perform a clinical assessment. Examples include blood pressure or cholesterol level, that are used to monitor and predict patient’s health status.

According to the World Health Organization, LC is a leading cause of death worldwide.  In the US alone, it accounts for close to 160,000 deaths annually. Unfortunately, LC is silent in the early stages, making it hard to detect. This leads to the majority of LC cases being diagnosed at an advanced stage when it is harder if not impossible to treat.

In a company press release about the importance of this partnership, Dr. Sam Hanash, MD, PhD, director of MD Anderson’s Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, stated “Lung cancer is, and will continue to be, America’s leading cancer killer unless we identify new approaches to diagnose it early, at its most treatable stages. Our collaboration with Exact Sciences provides a great opportunity to create tests that could shift the lung cancer detection paradigm for the benefit of patients.”

Dr. Hanash and his research team plan to test a variety of biomarkers including DNA, proteins, metabolites, and autoantibodies, with the goal of choosing the best performing biomarkers to successfully detect LC early.

In an explanation of what this partnership means to Exact Sciences, Kevin Conroy, Exact Sciences’ Chairman and CEO, said “Our common vision is to help win the war on cancer through early detection.  Taking on lung cancer offers an opportunity to build on the success of Cologuard. A simple blood test to complement a CT scan could significantly improve early-stage lung cancer detection. Our experience working with regulators and insurers coupled with MD Anderson’s world-class research and development capabilities are an ideal match to make a meaningful difference in the war on cancer.”

This partnership is a product of work done through MD Anderson’s Moon Shots Program. The program utilizes the expertise of over 175 faculty members including clinicians, surgeons, medical and radiation oncologists, pathologists and basic and translational researchers, all working to change the clinical landscape of cancer.

“Wouldn’t it be great to have a blood test as our first line of defense? If the blood test signals possible cancer, then, and only then, would patients be sent for further testing,” explains Dr. Hanash.  For all stakeholders involved in LC treatment from patients to healthcare providers Dr. Hanash’s vision gives hope that decreasing LC’s mortality rate may be a possibility just  over the horizon.

About the Moon Shot Program:

Inspired by America’s drive a generation ago to put a man on the moon, The University of Texas MD Anderson Cancer Center has launched an ambitious and comprehensive action plan called the Moon Shots Program to make a giant leap for patients — to rapidly and dramatically reduce mortality and suffering in several major cancers.

The nation’s top-ranked hospital for cancer care, with its unparalleled resources and capabilities, is uniquely positioned to accelerate the end of cancer

About Exact Sciences

Exact Sciences Corporation is a molecular diagnostics company focused on the early detection and prevention of the deadliest forms of cancer. The company has exclusive intellectual property protecting its noninvasive, molecular screening technology for the detection of colorectal cancer. Cologuard is included in the colorectal cancer screening guidelines of the American Cancer Society and stool DNA is included in the U.S. Multi-Society Task Force on Colorectal Cancer.

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por cyto às 11:23

Quarta-feira, 17.06.15

New Cancer Immunotherapy Drug Developed by UTEP Funded by Premier Biomedical

New Cancer Immunotherapy Drug Developed by UTEP Funded by Premier Biomedical

Researchers from the University of Texas El Paso (UTEP), funded by Premier Biomedical, Inc., recently developed a single antibody that has the ability to bind three immune inhibitors, CTLA-4, PD1, and BTLA. Last May, a Provisional Patent Application was completed for this antibody family by Premier Biomedical.
 
Premier Biomedical, Inc. (OTCQB: “BIEI”) is a company focused on discovery and development of medical therapies for several human diseases, such as cancer, sepsis and multiple sclerosis. Premier features several prominent research collaborators, such as the Department of Defense’s Center of Expertise at the William Beaumont Army Medical Center and the University of Texas at El Paso (UTEP). Premier Biomedical is preparing an application for approval by the Food and Drug Administration (FDA) for this new antibody to be used as a key cancer immunotherapy drug, an approach designed to potentiate immune responses in order to fight cancer.
 
Dr. David Vigerust, Vice President of Scientific Development of Premier Biomedical, said in the news release that they are very enthusiastic about this new advancement discovered together with the UTEP team.  He added that their first results showed higher adhesion to CTLA-4, a protein receptor that downregulates the immune system and improves blocking, than previous studies have ever demonstrated. This antibody has the potential to perform better than the already available anti-cancer compounds. These promising results accelerated the launch of the test and development program.
 
William A. Hartman, President and CEO of Premier Biomedical, stated that this new development positions the company as an authority on cancer research in an industry that has been valued at over 40 billion dollars. He added that they will do everything in their means to finish laboratory experiments and move into human clinical studies as quickly as possible in order to accelerate drug development toward FDA approval.
 
Dr. Georgialina Rodriguez of UTEP, a principal investigator on the project said the research team together with Premier are heavily involved in understanding more about the way these immune therapies or cancer checkpoint inhibitors function to fight and eliminate cancer, including antibodies that target molecules like CTLA4 on T-cells, a protein receptor that downregulates the immune system. Recent findings showed that targeting more than one of these proteins may have superior ability to fight cancer making this research very stimulating.

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por cyto às 11:21

Quarta-feira, 17.06.15

Simple Alzheimer’s Blood Test

UNTHSC Part of International Working Group Developing Simple Alzheimer’s Blood Test

These specific guidelines will be utilized in research for Alzheimer’s blood-based biomarkers and will ensure that every lab is properly following the same standardized procedures to collect blood, explained Dr. O’Bryant, who is a member of the international research group and lead author of the paper.

“You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice. You’ll have one lab doing it one way and another lab doing something different,” he added.

O’Bryant has been working for many years with representatives from the United States, Germany, Australia, England and other countries so that standards for the test can eventually be created. With the new criteria, all aspects of the test have been specified for the guidelines, from the type of needle used to draw the blood to blood storage time.

Just in the same way that blood tests are conducted for many other diseases, such as diabetes, protocols are established to ensure that every lab performs the test in the very same way. Guidelines are required before FDA approval can be requested to use such a test in a clinical context. “For UNTHSC, our next step is take these blood guidelines and implement them into a clinical trial. That’s never been done before,” concluded Dr. O’Bryant.

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por cyto às 11:15

Quarta-feira, 17.06.15

Injected immune cells found safe for patients with multiple myeloma

Injected immune cells found safe for patients with multiple myeloma

 
Injected immune cells found safe for patients with multiple myeloma
Injected immune cells found safe for patients with multiple myeloma

In a report on what is believed to be the first small clinical trial of its kind, researchers reported safely using immune cells grown from patients' own bone marrow to treat multiple myeloma, a cancer of white blood cells. Results of the trial involving marrow-infiltrating lymphocytes(MILs), a type of tumor-targeting T cell, were described in Science Translational Medicine (2015; doi:10.1126/scitranslmed.aaa7014).

"What we learned in this small trial is that large numbers of activated MILs can selectively target and kill myeloma cells," said study leader Johns Hopkins immunologist Ivan Borrello, MD, an immunologist at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland.

MILs, he explained, are the foot soldiers of the immune system and attack foreign cells, such as bacteria or viruses. But in their normal state, they are inactive and too few in number to have a measurable effect on cancer.

For the clinical trial, 25 patients with newly diagnosed or relapsed multiple myeloma were enrolled, although three of the patients relapsed before they could receive the MIL therapy.

The scientists retrieved MILs from each patient's bone marrow, grew them in the laboratory to expand their numbers, activated them with microscopic beads coated with immune-activating antibodies, then intravenously injected each of the 22 patients own cells into their bloodstream. Three days before the injections of expanded MILs, patients received high doses of chemotherapy and a stem cell transplant, standard treatments for multiple myeloma.

One year after receiving the MIL therapy, 13 of the 22 patients had at least a partial response to the therapy, meaning that their cancers had shrunk by at least 50%.

Seven patients experienced at least a 90% reduction in tumor cell volume and lived, on average, 25.1 months without cancer progression. The remaining 15 patients had an average of 11.8 progression-free months following MIL therapy. None of the participants had serious side effects from the MIL therapy.

The overall survival was 31.5 months for those with less than 90% disease reduction, but this number has not yet been reached in those with better responses. The average follow-up time is currently more than 6 years.

Borrello noted that several US cancer centers have conducted similar experimental treatments, known as adoptive T cell therapy, but says the Johns Hopkins team is believed to be the only one to use MILs. Other types of tumor-infiltrating cells can be used, but they are usually less plentiful in patients' tumors and may not grow as well outside the body, said Borrello.

The small trial helped researchers learn more about which patients may benefit from MIL therapy. For example, they were able to determine how many of the MILs grown in the lab were specifically targeted to the patient's tumor and whether they continued to target the tumor after being infused.

In addition, the scientists found that patients whose bone marrow contained a high number of immune cells known as central memory cells before treatment, also had better response to MIL therapy. Patients who began treatment with signs of an overactive immune response did not respond as well.

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por cyto às 11:13

Quarta-feira, 17.06.15

FDA approves brain implant to help reduce Parkinson’s disease and essential tremor symptoms

FDA News Release

FDA approves brain implant to help reduce Parkinson’s disease and essential tremor symptoms

For Immediate Release

June 12, 2015

Release

The U.S. Food and Drug Administration today approved the Brio Neurostimulation System, an implantable deep brain stimulation device to help reduce the symptoms of Parkinson’s disease and essential tremor, a movement disorder that is one of the most common causes of tremors. The Brio Neurostimulation System can help some patients when medication alone may not provide adequate relief from symptoms such as walking difficulties, balance problems, and tremors. 

An estimated 50,000 Americans are diagnosed with Parkinson’s disease each year, according to the National Institutes of Health, and about one million Americans have the condition. The neurological disorder typically occurs in people over age 60, when cells in the brain that produce a chemical called dopamine become impaired or die. Dopamine helps transmit signals between the areas of the brain that produce smooth, purposeful movement -- like eating, writing and shaving.

Essential tremor affects several million people and usually occurs in those over age 40.  “There are no cures for Parkinson’s disease or essential tremor, but finding better ways to manage symptoms is essential for patients,” said William Maisel, M.D., M.P.H., acting director of the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “This new device adds to the array of treatment options to help people living with Parkinson’s and essential tremor enjoy better, more productive lives.”

The Brio Neurostimulation System consists of a small (1.9in x 2.1in x 0.4in) battery-powered, rechargeable electrical pulse generator implanted under the skin of the upper chest and wire leads that attach to electrodes placed within the brain at specific locations depending on whether the device is being used to treat Parkinson’s disease or essential tremor. The electrical pulse generator continuously delivers low intensity electrical pulses to target areas in the brain. Health care providers make adjustments to the pulse generator to optimize the effects of the Brio Neurostimulation System.

Data supporting the safety and effectiveness of the device system included two clinical studies. One study included 136 patients with Parkinson’s disease and the other included 127 patients with essential tremor. In both studies, patients had symptoms, including tremors, that were not adequately controlled with drug therapy. 

The Brio Neurostimulation System was used in addition to medication for patients with Parkinson’s disease and the majority of patients with essential tremor who used the device were able to control their symptoms without the need for medications. Researchers implanted the Brio Neurostimulation System in all patients and assessed effectiveness for Parkinson’s disease patients at three months and essential tremor patients at six months. Both groups showed statistically significant improvement on their primary effectiveness endpoint when the device was turned on compared to when it was turned off. 

Serious adverse events included intracranial bleeding, which can lead to stroke, paralysis or death. Other device-related adverse events included infection and dislocation of the device lead under the skin. The Brio Neurostimulation System is manufactured by St. Jude Medical in St. Paul, Minnesota.

Brio Neurostimulation System is the second device approved by the FDA for Parkinson’s and essential tremor. The first device, Medtronic’s Activa Deep Brain Stimulation Therapy System, was approved in 1997 for tremor associated with essential tremor and Parkinson’s disease. In 2002, the indications were expanded to include the symptoms of Parkinson’s disease.

In its early stages, Parkinson’s disease typically affects one side of the body and starts as problems with movement, stiffness, and mild tremors. Gradually, the symptoms can affect both sides of the body and medications may become less effective. People with late stage Parkinson’s disease have many symptoms including: trouble walking, impaired posture and balance, muscle stiffness and tremors in the arms and hands that make it difficult to perform everyday tasks.  

Essential tremor most often affects the hands and arms and can be slowly progressive, starting on one side of the body but eventually affecting both sides. Hand tremor is the most common symptom, but tremors can also affect movement in the head, arms, voice, tongue, legs, and trunk. About half of essential tremor cases result from a genetic mutation. For the remainder of cases, the cause is unknown.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency is also responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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por cyto às 11:10

Quarta-feira, 17.06.15

Cognitive, Physical Activity Does Not Prevent Development of Alzheimer's

Cognitive, Physical Activity Does Not Prevent Development of Alzheimer's

 

HealthDay News — Physical and cognitive activity don't prevent the development of biomarkers of Alzheimer's disease, a new study published in Neurology suggests.

Keith Johnson, MD, co-director of the Neuroimaging Core at the Massachusetts Alzheimer's Disease Research Center and a professor of radiology at Harvard Medical School in Boston, and colleagues collected data on the current and lifetime physical and mental activity of 186 people without cognitive deficits. Their average age was 74. People in the study had positron-emission tomography and magnetic resonance imaging so researchers could gauge the amount of β-amyloid deposits in their brains. The scans also measured the brain's metabolism and hippocampus volume. In addition, participants took tests to evaluate their cognitive skills.

The researchers found that those who kept their brains busy with stimulating mental activities had higher IQs and better cognitive performance compared with those who did not often take part in such activities, but found no relationship between mental or physical activity and signs of Alzheimer's disease in the brain. Johnson told HealthDay that studies following people's activities over a long period are needed to confirm these findings.

Despite the current results, Johnson said that a lifetime of physical and mental activity may help keep the brain sharper with age. He also stressed that these findings should not be taken as a reason to not keep mentally and physically active, since other studies have shown these can benefit the brain.

Reference

  1. Gidicsin CM et al. Neurology. 2015; doi:10.1212/WNL.0000000000001704.

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por cyto às 11:09


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