Posts

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

When is the Best Time to Seek a Clinical Trial for Glioblastoma?

Curious Dr. George
Cancer Commons Contributing Editor George Lundberg, MD, is the face and curator of this invitation-only column.

Eric T. Wong, MD
Cancer Commons Expert Physician Advisor, Associate Professor of Neurology at Harvard Medical School, and Co-Director of the Brain Tumor Center at Beth Israel Deaconess Medical Center

For some people with glioblastoma brain tumors, enrolling in a clinical trial enables access to cutting-edge treatment. Here, our Curious Dr. George talks clinical trials with Cancer Commons Expert Physician Advisor, Eric T. Wong, MD. Dr. Wong is also Associate Professor of Neurology at Harvard Medical School and Co-Director of the Brain Tumor Center at Beth Israel Deaconess Medical Center.

Curious Dr. George: Malignant brain tumors are often treated initially by surgery and follow-up radiation. However, many recur and progress. Glioblastoma patients have many treatment options from which to choose, including clinical trials. But when is the best time to look for a clinical trial? Prior to initial therapy, immediately after initial treatment, or upon recognized tumor progression? How should a patient and their physician seek the most appropriate clinical trials?

Dr. Wong: This is a very important question for adult patients with glioblastoma and for a clinical neuro-oncologist like me who cares for them. At the time of diagnosis, the tumor is unstable and it is often difficult to determine the extent of microscopic spread to the adjacent brain. This is because glioblastoma is an infiltrative disease. Although MRI scans allow us to visualize the tumor, there are still microscopic tumors that we cannot see on head MRI scans. I always have to watch out for microscopic tumors causing motor or language dysfunctions.

Radiation is the mainstay of glioblastoma treatment, and it takes 6 weeks to administer. The reason is that we can only give a small fraction of radiation daily because normal brain and nerve cells cannot handle large fractions of radiation. The total dose needed to control the tumor is also at the maximum of brain tolerance. It takes at least 4 to 5 weeks to accumulate enough radiation dosage to exert an effect on the glioblastoma to halt tumor growth. Therefore, it is often a misconception that once radiation is started, tumor growth is controlled. In fact, the tumor can still grow during the initial 4 to 5 weeks of radiation, and it is not until the last week of 1.5 weeks that the radiation exerts its full effect on halting tumor progression.

For these reasons, it is often difficult to find a trial that fits a newly diagnosed patient with glioblastoma without delaying radiation. This is a logistics problem—a patient needs to be at the right time and right place where a clinical trial is available for them, and radiation can still be initiated within 4 to 6 weeks after surgery. It is my opinion that if a clinical trial cannot be found in a timely fashion, the patient should take conventional treatment. The time to look for clinical trials is when the tumor is stabilized with radiation and temozolomide.

After radiation and temozolomide, the patient goes into the adjuvant phase of treatment with monthly adjuvant temozolomide and monitoring with periodic head MRI scans. It is during this period that the patient has more time to look for a clinical trial in the event of recurrence or disease progression.

If you are at this point and looking for a trial, ask a family member to help you navigate the clinicaltrials.gov website or contact Cancer Commons and work with our Scientists to find a promising trial. At this point, you will also have more time to think about traveling and lodging in a faraway city, while talking to your neuro-oncologist about options. You and your care team should look at the inclusion and exclusion criteria to see if you fit into a particular trial. If none fits, your treating neuro-oncologist can still develop a personalized treatment for you.

Dr. Wong can be reached at ewong@bidmc.harvard.edu.

***

Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Behind the Scenes at Cancer Commons: Working with Patients

Curious Dr. George
Cancer Commons Contributing Editor George Lundberg, MD, is the face and curator of this invitation-only column.

Emma Shtivelman, PhD
Cancer Commons Chief Scientist

Cancer Commons helps advanced cancer patients identify and access their best-possible treatments. Here, our Curious Dr. George asks Chief Scientist Emma Shtivelman, PhD, for an inside look at how she helps the people who turn to us for guidance.

Curious Dr. George: As Chief Scientist at Cancer Commons for many years, you have helped thousands of patients with advanced cancer to better understand their options in difficult circumstances. What is the process you typically follow to provide useful information in a compassionate manner without instilling false hope?

Emma Shtivelman, PhD: The “simple” goal of Cancer Commons is to help cancer patients to find better treatments. Most of the patients who register with Cancer Commons have advanced or metastatic cancers, and the range of questions they ask is very wide. To name a few: requests to find clinical trials, advice for dealing with adverse effects of treatments, questions about drugs’ efficacy and side effects, suggestions for the “best” oncologist near them, and more.

To answer these questions, here is the process I follow:

  • Collect and review all relevant medical records after securing the patient’s consent to share them.
  • Decide whether the patient needs a new treatment (most often they do, because patients typically contact us when they experience progression) or a new oncologist.
  • If indicated, suggest seeking a second opinion at a nearby comprehensive cancer center.
  • Mutational profiling often opens new treatment options for cancer patients. Thanks to our collaboration with the company Tempus, we offer mutational testing to Cancer Common patients who have no other means to have this done—even though it should be an integral part of modern cancer care. The results, which we can access immediately and directly, often generate suggestions for new treatment options.
  • If the patient’s performance status does not warrant further active treatment, we may suggest considering palliative care only, or hospice, usually in support of the opinion of the treating oncologist. These are difficult emails and calls. Some patients (and often their caregivers) do not understand the gravity of their situation.
  • Search for clinical trials: I have always considered finding relevant clinical trials as the most important contribution Cancer Commons can make to patients’ treatment. I try to suggest trials with investigational drugs that have, preferably, preliminary evidence of clinical activity, or at least very strong evidence of relevant preclinical activity. The search for clinical trials can be both the most rewarding and most frustrating part of my work. If I see a highly relevant trial, I rejoice, but later I may hear from patients that they are unable to enroll for a variety of reasons. For instance, travel for trial treatment may be not feasible, the treating oncologist might prefer to start another line of chemotherapy (which may make patient ineligible for most trials in the future), or the particular cohort may no longer be enrolling at a trial site nearby.

My work with patients can pose significant challenges. Here are the major problems that can arise:

  • Patients often do not provide relevant information about their conditions and treatments, because they may not have a clear understanding of what information is most important, or because they do not have access to their medical records.
  • Patients sometimes seek only “alternative” treatments not supported by clinical evidence.
  • Because I communicate with patients and not with their doctors, the information I provide—in particular about relevant clinical trials—may not be conveyed to or discussed with the treating oncologist. Some patients are hesitant to do so because they are afraid to offend their doctors. Others may have difficulty understanding the information they receive and dismiss it.
  • The most daunting obstacles I face have to do with obscure and often inconsequential medical history that excludes patients from participating in clinical trials. For a given patient, I can easily screen out trials based on listed eligibility criteria (such as preexisting health conditions, organ dysfunction, brain metastases, HIV infection, number of previous lines of treatment, or previous malignancies). However, on occasion, we encounter what I consider to be unjustified pre-existing conditions that preclude enrollment. Two examples of this are a left bundled branch block in a patient without a history of heart disease and asymptomatic pulmonary mycobacterium avium complex diagnosed incidentally 15 years earlier. When trial exclusion happens because of rigid and hard-to-justify trial protocols, it is very frustrating for me and the patients I work with.

Despite the challenges of our work, I always hope, and sometimes know, that patients and their oncologists can arrive at new, more promising treatments based on Cancer Commons’ personalized research. This is what drives me to continue working with cancer patients.

Dr. Shtivelman can be reached at emma@cancercommons.org.

***

Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

What Is a Cancer Commons Options Report?

Curious Dr. George
Cancer Commons Contributing Editor George Lundberg, MD, is the face and curator of this invitation-only column.

Lola Rahib, PhD Lead Scientist in Pancreatic Cancer at Cancer Commons

As a Cancer Commons Scientist, Lola Rahib, PhD, helps cancer patients and caregivers navigate treatment. Some of these patients receive a Cancer Commons Options Report. Here, our Curious Dr. George asks Dr. Rahib to share what goes into each Options Report.

Curious Dr. George: Cancer Commons provides advanced cancer patients who seek information with additional options for them to consider, all free of charge. What does a typical Cancer Commons Options Report consist of and look like?

The first page of the report contains information about the patient, including patient goals, molecular alterations, and a short case summary. Patient goals may include treatment and quality of life goals, ability to travel for treatment, and any other life goals or preferences the patient or their caregiver shares with us. The molecular alterations section is extracted from the patient’s molecular profiling report(s). Molecular profiling is an important consideration, as it can guide treatment. The short case summary gives a brief overview of the patient’s diagnosis and treatment history.

The report also contains a comprehensive, personalized case summary detailing the patient’s cancer history. The personalized case summary is created by reviewing the patient’s medical records, and includes information about the patient’s diagnosis, pathology, treatment history, treatment response, genomic sequencing, and other testing as available. This detailed summary is found at the end of the report and may be helpful for patients to take with them to appointments, especially if they are visiting with a new physician.

A sample Cancer Commons Options Report; click to see full report.

The detailed summary is used to generate personalized therapeutic options, including investigational therapies, clinical trials, off-label combinations, and testing modalities such as next generation sequencing, liquid biopsies, and other diagnostics. These options are presented in a table format with therapy descriptions and scientific rationale. Molecular targets for specific treatment options are indicated when appropriate.

Feedback and consensus from a Virtual Tumor Board is also provided when applicable. Currently, Cancer Commons has a Virtual Tumor Board program for brain and pancreatic cancer patients. The Virtual Tumor Board program allows Cancer Commons to present a patient’s case to nationally recognized experts. The panel performs a comprehensive review of the patient’s diagnosis, treatment history, molecular profiling, genetics, and other relevant information. Based on this information they discuss and provide feedback on treatment options including clinical trials, and any further diagnostics and evaluations. This feedback is provided in a summary along with the detailed treatment options.

The final decision regarding tests and treatments is always up to the patient and their care team. We encourage patients to discuss these options with their treating oncologist.

We capture decisions and rationales, and patients’ progress is monitored over time. This supports learnings and insights from every patient. Our artificial intelligence platform uses the Virtual Tumor Board’s recommendations, treatment decisions, and clinical results to get smarter. Our goal is to continuously learn from every patient’s experience and use that knowledge in real-time to help the next patient.

Dr. Rahib can be reached at lola.rahib@cancercommons.org.

***

Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.