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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.

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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

Navigating Pancreatic Cancer—The Basics

A Q&A with Lola Rahib, PhD, Lead Scientist, Pancreas Cancer, at Cancer Commons, Los Altos, CA

Q: Navigating a pancreatic cancer diagnosis can be overwhelming and confusing for patients and their loved ones. How can patients and their caregivers ensure having the knowledge, support, and plan they need to be able to navigate treatment options and other aspects of the disease?

A: Patients and caregivers can regain control of a chaotic and anxiety-inducing process by making sure they maintain and organize detailed medical records and information about diagnosis, treatments, and options. As a patient it is critical to advocate for yourself and your needs. If this is not possible, ensure a designated family member or caretaker can advocate on your behalf.

Q: What are the specific aspects of the disease that are most important to navigate?

A: A little over ten years ago, Dr. Brown began a series of preclinical studies to test the possibility that an important contributor to the recurrence of malignant brain tumors after radiation therapy was reconstitution of the tumor vasculature. Specifically, he hypothesized that this reconstitution stemmed at least in part from circulating pro-angiogenic cells not in the tumor at the time of radiation—a phenomenon known as “vasculogenesis.” In agreement with this concept, a finding common to all of the tumor models he tested was a major influx into the irradiated tumors of bone marrow-derived cells, most of which were macrophages, that correlated with when tumors began to grow two to three weeks after completion of radiation. Further, he demonstrated that the mechanism for this influx was a radiation-induced hypoxia that triggered a cascade that led to the secretion of stromal cell-derived factor-1 (SDF-1), which was instrumental in attracting these cells. The apparent importance of excluding these cells’ entry into tumors post-irradiation suggests a new treatment strategy, which we call macrophage exclusion radiation therapy (MERT).

In August of 2014, based on these strong preclinical data, we launched a phase I/II clinical trial of MERT. This study examined the effects of administering a four-week continuous infusion of plerixafor (Mozibil)—the only commercially available agent that blocked the SDF-1 binding receptor CXCR4—at the end of irradiation to newly diagnosed GBM patients (NCT01977677). We enrolled 29 patients and established in phase 1 that the treatment was well tolerated at a dose that resulted in plerixafor serum values being maintained above the threshold level for CXCR4 blockade.

Two findings in phase II of this trial were particularly noteworthy: (i) a persistently lower relative cerebral blood volume within the irradiated field, and (ii) a much-improved control of the cancer in the treated field.

The noted overall median survival of nearly 22 months compared favorably with the best results obtained in other studies of GBM. However, it fell short of the dramatic improvements in survival noted in our preclinical studies, which utilized whole-brain irradiation (WBRT). WBRT was abandoned by clinicians in the early 1990s as a treatment for GBM because the high rate of local recurrence did not seem to justify the associated potential treatment-related issues of irradiating the entire brain (i.e., cognitive decline). However, we have shown that MERT is actually radioprotective for cognitive decline in rats given WBRT, consistent with the fact that tissue inflammation after radiation is related in large part to macrophage entry. Therefore, we have opened a new trial (currently open to accrual)using the same basic strategy in which a modest dose of WBRT has been added. Our expectation is that the widened radiation fields will further patient survival without excessive toxicity.

It is also important to note that the MERT strategy can be applied to any solid tumor in which local control using radiation is challenging. Further study of this strategy can therefore be of benefit to a wide spectrum of cancer patients.

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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.