Tag Archive for: BRCA

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

How an Expert Would Manage Her Own Advanced Ovarian Cancer

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


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

Serious Caveats in Screening for Pancreatic Cancer

A Q&A with Rama Gullapalli, MD, PhD; a a physician-scientist in the departments of Pathology, Chemical and Biological Engineering at the University of New Mexico. His research lab focuses on the role of the environment in hepatobiliary cancers. He is also a practicing molecular pathologist with an interest in emerging molecular diagnostics, next generation sequencing and bioinformatics. Email: rgullapalli@salud.unm.edu 
Q: A recent New York Times op-ed piece from an NYU Langone Health professor urged an aggressive approach to screening for early-stage pancreatic cancer. Despite optimism, the history of cancer screening is rife with trouble, the harms often exceeding the benefits. What do you think is the best way to proceed?
A: Imagine a scenario.
A new cancer test hits the market with some impressive characteristics: a detection sensitivity of 95% and a specificity of an equally impressive 95%. If you were asked the question, “Given a positive test result, what are your chances of actually having cancer?” and you guessed a number of 80 or 90%, you would not be alone. But you’d be wrong.
The key missing information necessary to answer this question is the disease probability among the general population. The number of new cases of cancer detected every year in the U.S. is about 462 cases per 100,000 people. This means that the probability of a new cancer being detected in a member of the U.S. population annually is roughly 0.00462%. Incorporating this information leads to only an 8.1% chance of having cancer for a test that is positive! This is what is called an inverse probability problem.
Puzzled? Let me explain it in a different way. Statistics show that, in the U.S., about 462 people are newly diagnosed with cancer for every 100,000 people among the general population each year. The new test will correctly pick up 95% of these new cancer patients (i.e., about 439 patients). Of the remaining 99,538 people who do not have cancer, the test will incorrectly diagnose cancer in about 4,977 individuals! This is what pathologists would refer to as a “false-positive” diagnosis. The key point to remember is that cancer is a relatively rare disease. This basic fact enormously influences the value of any given cancer-screening test available in the market.
There has been much optimism and hype associated with cancer screening. Some cancer screening tests, such as tests for colorectal cancer or cervical cancer, have indeed made a dent in our ability to detect and treat the disease at an earlier stage. But in other cancers, such as breast cancer and prostate cancer, the results have been a mixed bag. For instance, screening for cancer in hard-to-access organs, such as ovarian cancer, led to an increase in complications due to surgery with no difference in the cancer outcomes.
A screening test with an increased false-positive rate (think of the 4,977 people in our imagined scenario who had a false-positive test result, but no real cancer), results in unnecessary and invasive testing that is ultimately of no clinical value. However, the societal costs of following up false-positive test results are enormous and include increased downstream testing and increased patient interventions. For patients, an enormous amount of anxiety and stress is expended in resolving false-positive screening test outcomes.
recent New York Times op-ed piece discussed the issue of cancer screening in one such hard-to-treat disease: pancreatic cancer. In response to beloved TV host Alex Trebek’s diagnosis of stage 4 pancreatic cancer, author Diane Simeone, MD, suggests DNA testing as a first step to identify high-risk BRCA gene mutations in potential pancreatic cancer patients. BRCA gene mutations are associated with a higher risk of some types of cancer, including breast, ovarian, and pancreatic cancers. In her op-ed, Dr. Simeone reports that her clinic identified BRCA gene mutations in roughly 15% of the pancreatic cancer patients treated there. The key point is that these mutations were detected in patients who already had pancreatic cancer.
The op-ed piece correctly states the importance of identifying individuals at a higher risk for pancreatic cancer. While it is indeed optimal to screen for these high-risk pancreatic cancer patients, the means by which we can identify these patients beforehand is unresolved and very much a work in progress. One must be especially careful in the context of hard-to-diagnose and hard-to-treat diseases, such as pancreatic, liver, and ovarian cancers.
With the dramatically falling costs of DNA testing, one may be tempted to view it as the silver bullet for early cancer detection. However, the utility of DNA testing for screening purposes in different cancers is unproven currently and needs further research. Patients and physicians must be fully aware of the potential harms of unnecessary downstream testing due to the false positive outcomes of DNA testing. DNA testing may be cheap, but the consequences of DNA testing may prove to be very costly.
Caveat emptor!
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.