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

Just Diagnosed with Advanced Lung Cancer: What Now?

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

Howard (Jack) West, MD
Associate Clinical Professor in Medical Oncology and Executive Director of Employer Services at City of Hope Comprehensive Cancer Center

A new cancer diagnosis is overwhelming. Patients often ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks lung cancer expert Howard (Jack) West, MD, how he would handle his own diagnosis of advanced lung cancer. Dr. West is a Princeton- and Harvard-educated oncologist with additional training and experience in Boston and Seattle focusing on lung cancer. He is now an Associate Clinical Professor in Medical Oncology and Executive Director of Employer Services at City of Hope Comprehensive Cancer Center in Duarte, California.

Curious Dr. George: What would you do if you personally were discovered on a routine chest X-ray to have a unilateral pleural effusion which was found by cytopathology to contain mixed squamous and adenocarcinoma cells? How would you proceed?

Dr. West: Though I’m a never-smoker, we know that is no guarantee of immunity from lung cancer, the cancer type I’ve focused on for the past two decades. Perhaps I develop a persistent cough and worsening shortness of breath over a few months. I get a chest X-ray that shows a large right pleural effusion, and a same-day chest CT confirms this and bilateral lung nodules, perhaps along with several enlarged right hilar and mediastinal lymph nodes. The effusion is drained, and the pathologist gives my doctor and me the immediate feedback that this is a carcinoma, and we quickly learn that the immunohistochemistry profile is consistent with an adenocarcinoma. Where do we go from here?

My next step is to order broad next-generation sequencing, which may entail a new biopsy, either CT-guided or an endobronchial ultrasound and biopsy of whatever is accessible. We need sufficient tissue to send off for broad molecular testing that includes a look for all of the growing collection of lung cancer “driver mutations.” These include long-established markers like a mutation in the epidermal growth factor receptor (EGFR) gene or a rearrangement in the anaplastic lymphoma kinase (ALK) gene, but now also a rearrangement in ROS1, mutation of BRAF V600E, a MET exon 14 skipping mutation, RET fusion, or fusion in the TRK gene. These genetic alterations are found in approximately 0.5% to 10% each in patients with non-small cell lung cancer (NSCLC) and far more commonly in patients with a non-squamous NSCLC tumor. They all have FDA-approved oral targeted therapies with efficacy that generally exceeds what we could expect with our best standard non-targeted approaches involving immunotherapy with or without chemotherapy. Most of these targeted therapies also better tolerated and can work for a prolonged period that may reach the range of years.

This mutation testing typically takes at least 2 to 4 weeks, but the importance of identifying one of these mutations, when present, makes it critical to seek this information at the time of initial diagnosis. Moreover, in addition to the array of markers we currently have targeted therapies for, we expect an FDA approval for an inhibitor of KRAS G12C-mutated NSCLC, seen in about 12% to 13% of advanced NSCLC, in the coming months; all in all, comprehensive molecular testing guides us to an optimal targeted therapy for at least 20% of patients, and that proportion will continue to increase as new targets with effective therapies become available.

In the hypothetical scenario of my own diagnosis, as this testing is being done we’re also testing for tumor PD-L1 expression, which identifies tumors most likely to respond well to immune checkpoint inhibitors, potentially sparing patients first line chemotherapy if they don’t receive a targeted therapy. And I’d seek to complete imaging with a PET/CT and brain MRI, in order to identify whether the cancer has spread to other sites beyond those already identified.

Once these tests are completed, I’d prioritize a targeted therapy if my tumor harbors a driver mutation. If not, I’d generally favor pembrolizumab monotherapy if my cancer is among the approximately 28% to 30% that demonstrates high tumor PD-L1 expression (greater than 50%). Otherwise, if my cancer has neither a driver mutation nor high tumor PD-L1 expression, I’d generally favor a platinum-based chemotherapy doublet with pembrolizumab—an option I would also favor in a patient with a tumor that doesn’t harbor a driver mutation and with high tumor PD-L1 if that patient had many cancer-related symptoms or otherwise showed a pattern of rapid progression in the early weeks of the workup. Though I’d be happy to sequence the immunotherapy with subsequent chemotherapy in patients in whom I’m confident they will still have the performance status to tolerate platinum doublet chemotherapy after progressing on chemotherapy, I’d favor “front-loading” with chemo-immunotherapy together in patients in whom I’m concerned I may only have “one shot on goal.”

Dr. West can be reached at JackWestMD@gmail.com or on Twitter at @JackWestMD.

Related Links:

Molecular Testing Guides Treatment for Claudius’s Lung Cancer

What’s New in Immunotherapy for Non-Small Cell Lung Cancer?

Comprehensive Molecular Testing Needed for Stage IV Lung Cancer

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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

How an Expert Would Manage Her Own Advanced Ovarian Cancer

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

Summer Dewdney, MD
Director of the Division of Gynecologic Oncology at Rush University Medical Center

Cancer patients often ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks oncologist Summer Dewdney, MD, how she would handle her own diagnosis of advanced ovarian cancer. Dr. Dewdney is Director of the Division of Gynecologic Oncology at Rush University Medical Center in Chicago, Illinois.

Curious Dr. George: You are an expert clinical oncologist treating patients with gynecological malignancies. Imagine that you personally began to experience vague abdominal symptoms and were found to have ascites (excess fluid in the abdomen) with positive cytology for malignancy cells. How would you proceed to manage your own likely ovarian malignancy?

Summer Dewdney, MD: Ovarian cancer is the leading cause of death from a gynecologic malignancy in the United States. However, we have made great strides in the treatment of ovarian cancer in the past couples of years, and this has really become a cancer that can be treated chronically. Each patient’s treatment is individualized, and knowing specific information about genetics and molecular analysis is very important.

Initially, I would get a CT scan of the chest, abdomen, and pelvis to look for evidence of metastatic disease and tumor burden. The majority of the time this cancer is found at stage III or IV, and patients usually present with minimal symptoms despite advanced disease. I would have my tumor markers checked, including CA-125 and CEA, depending on which ones are elevated (mostly likely CA-125); these could be monitored moving forward through treatment and surveillance. Depending on the exact pathology and CT results we would then determine if I would undergo a debulking surgery versus neoadjuvant chemotherapy first. I would ensure my care was being managed at a tertiary care center by a gynecologic oncologist. Having an optimal tumor debulking done by a gynecologic oncologist would be very important as this would impact my overall prognosis. I would also see if there were any clinical trials available for me in an upfront setting and make sure I was at an institution that offered clinical trials. If I was not enrolled in a clinical trial, I would receive carboplatin and paclitaxel either before surgery or after surgery, which would likely be the backbone of any clinical trial too.

I would want information on my BRCA status, both germline and somatic as soon as possible to see if I would need maintenance therapy with a PARP inhibitor after treatment. In addition, my surgical pathology would also be tested for molecular analysis. If my germline testing was negative, my tumor would be tested for HRD (homologous recombination deficiency) and BRCA, and if either was positive this would also help inform the decision on PARP inhibitor maintenance. I know my risk of recurrence would be high if I was found to be at stage III or IV, and therefore would want some sort of maintenance therapy after initial surgery and treatment.

If a recurrence was ever found, it would be important for me to be in a clinical trial. If my recurrence didn’t occur for years after treatment and was isolated or only minimal disease, I would consider undergoing a secondary debulking surgery first, followed by systemic treatment (hopefully a clinical trial). My hope would be that the recurrence occurred more than 6 months from the end of treatment and define me as platinum-sensitive, as this prognosis is better.

Personally, quality of life and time with family would be very important, and I would have palliative care involved earlier than later. I would make sure if I did succumb to this disease after hopefully years of living with it, that my last days were not in a hospital and spent with my family.

In summary, ovarian cancer is a tough disease but can be treated for years. Some patients may even be “cured” and not experience a recurrence, but this is the exception rather than the rule. I want to emphasize that many patients are able to have this disease controlled for “years” and often patients experience times of remission.

I want to recognize all the work that scientists have done to move the mark and improve the treatment of ovarian cancer over many years. More importantly, I would like to thank all the patients and families that have participated in clinical trials to get us this information so we can continue to advance the treatment of ovarian cancer.

Requests for Dr. Dewdney’s email address can be sent to Curious Dr. George at gdlundberg@gmail.com.

Related Links:

New Treatments for Ovarian Cancer in 2020

Behind the Scenes at Cancer Commons: Working with Patients

How an Expert Would Manage Her Own Advanced Colorectal Cancer

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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

Behind the Scenes at Cancer Commons: Working with Patients

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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.

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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

How an Expert Would Manage Her Own Advanced Colorectal Cancer

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

Christina Wu, MD Associate Professor of Hematology and Medical Oncology, Emory University

When facing a new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Cancer Commons Expert Physician Advisor Christina Wu, MD, how she would handle her own diagnosis of metastatic colorectal cancer. Dr. Wu is Associate Professor of Hematology/Oncology and Associate Division Director of Medical Oncology at Winship Cancer Institute of Emory University.

Curious Dr. George: As an experienced academic and practicing clinical oncologist at Emory University, you have particular interest, training, and experience in colorectal cancer. What would you do if you personally were discovered to have an asymptomatic, unsuspected, non-obstructing adenocarcinoma of the ascending colon that had already metastasized to your liver?

Dr. Wu: Colorectal cancer is the third most common cancer in the U.S., and one of the leading causes of cancer deaths. However, every patient with metastatic colon cancer to the liver is treated individually because there are various systemic and liver-directed treatment options. If I were diagnosed with colon cancer and liver metastasis, I would want a multi-pronged approach to include the following:

Next-generation sequencing: First of all, I would want to know if I could benefit from immunotherapy so that I could be spared the side effects of chemotherapy. I would test for mismatch repair protein status or microsatellite instability. I would want to know the tumor’s KRAS/NRAS/BRAF mutation status, because I would be a candidate for anti-EGFR therapy if my tumor was RAS wild-type and the primary cancer was left-sided. The presence of a BRAF mutation would direct me to targeted therapies, such as encorafenib and an anti-EGFR antibody or vemurafenib, irinotecan, and an anti-EGFR antibody. If the tumor was RAS wild-type with HER2 amplification, I would be interested in HER2-targeted therapies. In addition, if I had the rare NTRK fusion mutation, I would be a candidate for larotrectinib. There are also ongoing clinical trials testing drugs that target KRAS mutations, such as KRAS G12C.

Multi-disciplinary tumor board: I would want high-quality imaging and experts from medical oncology, surgical oncology, radiation oncology, gastroenterology, radiology, and interventional radiology reviewing my case in a tumor board. It would be meaningful to know upfront whether the liver metastasis was surgically resectable, because I may opt to receive systemic chemotherapy followed by surgical resection. If I required conversion therapy, I would consider triplet chemotherapy (FOLFOXIRI) to get more of a response so that I could get to surgery. However, if I had clearly unresectable disease, I would choose doublet chemotherapy such as FOLFOX or FOLFIRI with a biologic agent to improve my quality of life. With unresectable disease, I could also consider radiation, Y90 treatment, or ablation to the liver tumors, should I have good control or surgical resection of the extrahepatic disease.

Genetic counseling: There are hereditary syndromes that lead to colon cancer development, including Lynch syndrome, familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis. All patients with a new diagnosis of colorectal cancer are recommended to have universal screening for Lynch syndrome, and identifying a hereditary syndrome may help family members with early detection.

Palliative care: This is such an important team that treats the symptoms patients have from their cancer as well their cancer treatment. They also provide great support to patients and their caregivers in navigating their way through their cancer diagnosis.

Clinical trials: I personally would want to be part of clinical trials that could help move new drugs forward for colorectal cancer patients, and thus I would consider this an essential team in my cancer care.

Final thoughts: As I reflect on all the teamwork and different moving pieces that have to come together for one cancer patient, I am certainly grateful for all the multi-disciplinary clinical staff and physicians who are caring for cancer patients.

Dr. Wu can be reached at Christina.wu@emoryhealthcare.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

What Is a Cancer Commons Options Report?

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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

Hydrogen Peroxide Appears to Treat Pre-Cancerous Oral Lesion in “N-of-One” Experiment

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Ronald Piana
Freelance science writer, specializing in oncology

Numerous patients come to Cancer Commons because they wonder if their best cancer treatment option may lie beyond standard care. For many patients, this will mean receiving treatment through a clinical trial. However, with the input and supervision of their medical care team, a select number of patients may arrange to try a non-standard treatment outside of a normal clinical trial. This approach is often called an “N-of-one” experiment, because it is like a clinical trial where the number of participants (N) is just one—the patient.

Here, our Curious Dr. George speaks with Ronald Piana about an N-of-one approach he took to treat his own oral leukoplakia, a condition that can develop into oral cancer. Ronald Piana is a freelance science writer specializing in oncology.

Curious Dr. George: In a recently published study, Neil Mundi, MD, of the University of Western Ontario and colleagues reported success in minimizing or even eradicating biopsy-proven non-melanoma cutaneous malignancies by the topical application of concentrated hydrogen peroxide. You had a similar recent experience with an oral premalignant lesion in an N-of-one clinical trial. What was your experience?

Ronald Piana: In 2018, during a routine dental examination my dentist discovered a small whitish patch on the left lateral border of my tongue. He ordered a biopsy, and the lesion was diagnosed as benign leukoplakia. The lesion recurred and progressed, and approximately 1 year after the initial diagnosis presented as a raised, red-white lesion about 3 cm in diameter that was causing discomfort. On follow-up, my dentist found the lesion “very concerning” and scheduled a consultation with an oral surgeon.

I’m a 25-year veteran science writer in the oncology sector, and I’d chanced to read Mundi’s study, in which he and his colleagues successfully treated non-melanoma skin cancers with topical 33% hydrogen peroxide (H2O2). I decided to do an N-of-1 experiment on my oral lesion. I brushed the lesion until blanching with a cotton swab soaked in a solution of 35% H2O2 twice a day for 2 days prior to my appointment. At the appointment, the oral surgeon viewed a digital image of the lesion obtained by my dentist and prepared for excision. Upon oral examination, however, he found no evidence of the 3 cm lesion. On 3-month follow-up, no visual indication of recurrence could be detected.

Curious Dr. George: What biological effects might explain the result?

Ronald Piana: Hydrogen peroxide is a well-established apoptosis-inducer with broad cytotoxic activity in a range of cell types. Other H2O2 cytotoxic pathways have been identified, such as lysosomal membrane permeabilization (LMP). In LMP, the lysosome (described as a “suicide bag”) is compromised by H2O2-driven oxidative stress, during which large amounts of H2O2 enter the lysosomal compartment, forming abundant hydroxyl radicals, or highly reactive iron-centered radicals, which leads to degradation of cellular structures and, ultimately, cell death. Yet another intriguing explanation considers the Warburg effect, wherein transformed cells, such as those in cutaneous malignancies, undergo a shift from oxidative to glycolytic metabolism, rendering cells more susceptible to H2O2-induced oxidative stress. H2O2 has other cytotoxic pathways, yet, in short, this potent agent kills cancer cells by inducing oxidative stress.

Curious Dr. George: What do you propose as next steps?

Ronald Piana: Mundi’s study is the first in the literature to evaluate high-concentrate H2O2 as a topical treatment for cervicofacial cutaneous malignancies. The results have broad health implications for the millions of Americans diagnosed each year with skin cancers, and further indicate that topical H2O2 treatment could be a valuable clinical option for a variety of healthcare professionals including surgeons, dermatologists, and primary care physicians. Therefore, I hold that prior investigative work coupled with findings from Mundi, et al., should be viewed as proof-of-concept in safety and efficacy leading to larger scale evaluation and recognition of topical H2O2 as a treatment option for select carcinomas and, equally important, opening the investigative door into other exciting clinical opportunities.

My concern is that further serious investigation of this cheap and readily available agent, for various reasons beyond the scope of this post, will be ignored or rebuffed by the research and medical communities. To that end, I encourage others in the healthcare community not to let this valuable clinical opportunity pass.

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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.

American Health Care: What’s Left After COVID-19?

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

How to Learn About Cancer in a Classroom: Shaping Compassionate Doctors

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Marin Langlieb
Clinical Research Coordinator at Massachusetts General Hospital

The patients and caregivers we serve here at Cancer Commons rely on their doctors to provide expert, compassionate care. Building the skills to give such care can begin early in a doctor’s education. Here, for a change of pace, our Curious Dr. George asks a future doctor about a unique experience that helped her learn how to connect with cancer patients. Marin Langlieb is a Clinical Research Coordinator at Massachusetts General Hospital in Boston, Massachusetts.

Curious Dr. George: As a recent college graduate in pre-med now working in Boston in research, and as a student interacting with cancer patients, how would you rate your educational experience in preparation for medical school and for a lifetime of work as a physician?

Marin Langlieb: The answer to this question lies in a seminar I took as an undergrad that exemplifies why teaching both the sciences and the humanities to pre-meds is so critical.

After losing my pediatrician to cancer during college, I knew that I wanted to understand more about the disease. From a scientific perspective, my pre-med classes prepared me very well. In biology, it seemed like every semester I had a lecture about p53, a protein that regulates the cell cycle to prevent unregulated cell division. Yet, although I knew all this information about cancer at the micro-scale, I still wanted to understand cancer in the context of real human experiences. In other words, what was it like to actually live with cancer?

At most universities this is a topic that is probably not taught in a classroom. But my junior year, I enrolled in a seminar course called “Community Based Cancer Research Presentations and Discussions” that was part of a broader partnership between cancer researchers at my university and the local cancer resource center. Each class we would have lectures from people with a wide variety of science and humanities backgrounds—such as communication professors, physicians, ethicists, and community participants who were cancer patients themselves—all on cancer-related topics.

The lectures were extremely interesting (for example, one was on the importance of patient advocacy from “Congress to the Bedside”), but the primary goal of this unique program was the connections it fostered. For the scientists, who were researching cancer with cells or mice, it helped connect them to those who would be most affected by their work. For the community participants, they told me they joined the class because they wanted to better understand and communicate the science behind their disease. For example, many of the people I talked to wanted to be able to read complex scientific literature and understand some of the treatments they were receiving. Even more so, they stated that understanding the mechanisms and pathways behind their disease helped give them a sense of reassurance—people actually understood some of what was happening inside their body.

I think my pre-med classes did prepare me for a future career in medicine, although opportunities that connect students and members of the community are critical. For example, this class taught me how to actually apply what I was learning in my science classes to scenarios I might experience as a physician. That is, speaking with the community members taught me that being a good physician goes beyond using science solely to treat patients, but also to help patients clearly understand their diagnosis, their treatment, and their disease. In addition, learning how to communicate science effectively has been crucial to my current work in clinical research, from conducting informed consents to helping write grants.

However, the most important thing the class did was introduce me to some of the kindest people I have ever met. Even now, they push me to study harder, think bigger, and realize just how much of an incredible privilege a career in medicine is.

Marin Langlieb can be reached at mlanglieb@mgh.harvard.edu.

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

How an Expert Would Manage His Own Stage 4 Pancreatic Cancer

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John Strickler, MD
Associate Professor of Medicine at Duke University, Cancer Commons Advisor

When confronted with a new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Cancer Commons Expert Physician Advisor John Strickler, MD, how he would handle his own diagnosis of metastatic pancreatic cancer. Dr. Strickler is Associate Professor of Medicine in the Division of Medical Oncology at Duke University and Co-Leader of the Duke Molecular Tumor Board.

Curious Dr. George: Cancer Commons provides information about treatment options to patients with advanced cancer, usually beyond the standard of curative care. As an experienced academic and practicing clinical oncologist at Duke University, you have particular interest, training, and experience in gastrointestinal cancer. What would you do if you personally were diagnosed with asymptomatic, unsuspected, ductal adenocarcinoma of the tail of the pancreas that had already metastasized to your liver?

Dr. Strickler: Pancreatic cancer is one of the most lethal malignancies. In most cases the disease presents as surgically incurable (locally advanced) or metastatic. Despite the grim survival statistics and poor prognosis associated with this disease, there is reason to have hope. In the past decade, advancements in supportive care, chemotherapy, and molecular diagnostics have allowed patients to live longer and live better. While we have a long way to go, finally progress is being made.

If I were diagnosed with metastatic (stage 4) pancreatic adenocarcinoma, the first thing I would do is find an experienced multi-disciplinary team with pancreatic cancer expertise. This team would give me the best outcomes possible. Members of this team would include experts in the following fields:

Medical Oncology: Although the primary function of a medical oncologist is to provide chemotherapy, typically he or she formulates the treatment plan and coordinates care. In my hypothetical case, the medical oncologist would recommend either gemcitabine alone, gemcitabine with nab-paclitaxel, or FOLFIRINOX. All of these treatments are reasonable, but combination chemotherapy (gemcitabine + nab-paclitaxel or FOLFIRINOX) offers the greatest disease control and longest survival.

Additionally, the medical oncologist would be responsible for ordering next-generation sequencing (NGS) on my tumor tissue to determine if my tumor harbors an “actionable” genetic alteration. Although these actionable genetic alterations are rare, they may make me eligible for immunotherapy or other targeted therapies.

Genetic counseling: Approximately 5% of all patients with pancreatic cancer have a germline (hereditary) mutation in BRCA1/2 or PALB2, and these hereditary mutations predict benefit from platinum-based chemotherapy and PARP inhibitors. Other rare germline mutations can also predispose a patient to pancreatic cancer. Current national guidelines advise germline testing in all patients diagnosed with pancreatic cancer, regardless of family history, age, or stage at diagnosis. Genetic counseling is advised for any patient who tests positive for a pathogenic germline mutation or has a strong family history.

Palliative care: Many patients are hesitant to consider palliative care. There is a misconception that palliative care represents end-of-life care. I hope that we can change this misconception. Pancreatic cancer often presents with complicated symptoms that are difficult to manage. Even if I present completely pain free, symptoms from pancreatic cancer can change rapidly. Given the incurable nature of this disease, it is helpful to have a team of doctors who can help me and my family prepare for the future. I view palliative care as a critical “extra layer of support” to fight a very difficult illness.

Other important members of the team: As a medical oncologist, I have learned that I am only as good as the people around me. I cannot overstate the importance of having experienced and dedicated nurses, advanced practice providers (NPs and PAs), and clinic staff to provide extra support. Additionally, by finding a skilled multi-disciplinary team for my hypothetical diagnosis, I would have access to other experts, including radiologists, pathologists, surgeons, radiation oncologists, and gastroenterologists. All of these physicians would be key to my health and symptom management.

Final thoughts: As a gastrointestinal medical oncologist, I have seen how difficult pancreatic cancer can be for patients and their loved ones. If I were facing this disease myself, I would recognize that it takes a community of dedicated clinicians to keep me living longer and living better. As a patient, I would make myself available to clinical trials and other research. It is through these research efforts that we will change the course of this terrible disease and improve outcomes.

More details about ways to support pancreatic cancer research and support patients and families fighting this disease can be found at the Pancreatic Cancer Action Network.

Requests for Dr. Strickler’s email address can be sent to Curious Dr. George at gdlundberg@gmail.com.

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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

How an Expert Would Treat His Own Glioblastoma

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Al Musella, DPM
President, Musella Foundation For Brain Tumor Research & Information, Inc.

Two years ago, our Curious Dr. George asked Al Musella, DPM, what he would do if he were diagnosed with glioblastoma multiforme (GBM). Here, he revisits that question. Dr. Musella is President of the Musella Foundation For Brain Tumor Research & Information, Inc.

Curious Dr. George: You direct an established foundation that supports research and information about brain tumors. What would you do if you yourself were diagnosed with GBM?

Dr. Musella: Now that GBMs are in the news again, I would like to discuss what I would do if it happened to me—a newly diagnosed GBM in an adult in otherwise good shape. There are several choices:

Standard of Care: Surgery, radiation, and the drug temozolomide; with this standard approach, the chance of 5-year survival is about 5%. However, standard of care plus Optune—a wearable device that uses electrical fields to treat GBM—bumps my chance of 5-year survival up to 24.9% (if used over 90% of the time) with no added toxicity.

Phase 3 Clinical Trials: There are now about four phase 3 trials for newly diagnosed GBM in the U.S. One involves intraoperative radiation therapy at the time of the initial surgery and looks worthwhile. The others involve treatments that in earlier trials improved survival by just a few months. They may be worth a try if they did not have two big downsides: 1) Most have a control group of patients who receive the old standard of care so that some of the participants do not get the experimental treatment. 2) Some do not allow you to use Optune, so you are trading a known benefit for a chance at an unknown benefit.

Historically, over the last 50 years or so, only a handful of phase 3 trials have been successful. Optune was the most successful phase 3 trial, and no other phase 3 trial has yet come close, so the chances of doing better in a phase 3 trial than Optune is low. What we thought were the most promising phase 3 trials over the last few years all failed. We are waiting for results from the phase 3 trial of DcVax—that may be a game changer, but this therapy is not available to the public right now.

Phase 1 or 2 Trials: About 150 phase 1 or 2 trials are currently active in the U.S. There are many interesting choices here, but we do not have enough data to make an informed decision on which one to try. We do have early results from some phase 1 trials, some of which are better than those seen with standard therapies, but it is not likely that any one of these alone will make a big difference in survival for most patients. We do not (under the current system) have the ongoing results of these trials—we only get the results a few months after the trial is over. And while inside the trial, we cannot combine them with other treatments.

Off-Label Use of Drugs Approved for Other Diseases: There are many choices here, and a rational approach might be to select a “cocktail of drugs” based on a genomic analysis of my tumor.

Cocktail Approach Involving Experimental and FDA-Approved Treatments: Right now, this is impossible or very difficult to obtain. However, if it were possible, this would be my approach. Especially if we had a registry of all of the patients, the treatments tried, and the outcomes so we can learn from every patient.

Getting Access to Experimental Therapies: There are a few pathways to getting experimental therapies. Currently, none are really practical on a large scale. I have tried to get expanded access/compassionate use/right-to-try access on the most promising experimental treatments, and it is very hard. Getting multiple drugs this way for a cocktail is just about impossible. We had high hopes for the Right To Try Act, which was passed last year, but it turned out not to help at all. Drug companies are not willing to use this pathway for brain tumor patients. However, even if we could get them, without tracking the results, we are not learning and are doomed to repeating the same failures.

My foundation is  working on a new bill that will solve this problem and speed up the search for the cure. Click here to learn more.

So, bottom line: What would I do?

Surgery: I would begin with surgery, trying for maximal safe resection, possibly using Gliolan (a dye that helps surgeons see small clusters of GBM cells) to increase chances of maximal resection. I would also consider insertion of Gliadel wafer (intraoperative chemotherapy) if the resection cavity is not up against the ventricles (and we are not planning on entering a trial that excludes prior use of Gliadel) or some type of intra-operative radiation.

Radiation: I would receive standard radiation or possibly proton beam radiation. This may be followed by some type of boost, possibly “leading-edge” radiosurgery.

Temozolomide: I would receive this drug during and after radiation, only if molecular testing of my tumor sample detects methylated MGMT. If the tumor is unmethylated, I would seek treatment with the drug Val-083, either in a trial or through a compassionate use/right-to-try program. The length of time to use temozolomide is controversial. The most commonly uses length of treatment is 6 months after radiation (as well as during radiation).

Immunotherapy: There are a few immunotherapies that have shown remarkable results in a minority of patients. A few of the early vaccine and gene therapy trials have tails of 20% or more of patients living over 5 years and with minimal or no side effects. I would try to get one (or maybe two) of these drugs. The polio vaccine trial (PVSRIPO) looks promising, as does the CMV vaccine, the Survaxin vaccine, and Gliovac.

Optune: We are put into a very tricky situation here. Many trials will disqualify you if you use Optune, but Optune has the highest survival rates in large trials. So as I said before, you are being asked to gamble a known benefit for an unknown experimental treatment that might or might not help, and you might even be assigned to a control group. The results with Optune alone are still not good enough. The results shown above were for newly diagnosed GBMs. For recurrent GBMs, they are not nearly as good, so it is important to use it early in the course of the disease. Ideally, I would combine Optune with one of the immunotherapy treatments in phase 2 or 3, but that is not possible yet. We really need to fix that. Why should I be allowed to die just to appease an archaic tradition of requiring standard phase 2 and 3 trials?

…The choices are overwhelming for me. And for someone new to brain tumors, it is impossible to decide. We—the Musella Foundation—have formed a collaboration with Cancer Commons to create a program to help patients find the best treatment options for their individual case, then help them get access. We track how these patients do so that we learn from every patient. To take advantage of this free program, click here.

Dr. Musella can be reached at musella@virtualtrials.com.

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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.