3 Questions on…
Answers straight from the experts on the latest news and topics in oncology

Monday, July 10, 2017

With Angela Mariotto, PhD, Chief of the Data Analytics Branch of the Division of Cancer Control and Population Sciences at NCI

By Sarah DiGiulio

New data suggests the number of women in the U.S. living with distant metastatic breast cancer is growing. As of the beginning of this year, that number was more than 150,000, according to new research from NCI published online ahead of print in the journal Cancer Epidemiology, Biomarkers & Prevention (2017; doi:10.1158/1055-9965.EPI-16-0889).

The researchers analyzed data from the NCI's Surveillance, Epidemiology, and End Results Program to determine how many women diagnosed with breast cancer went on to develop metastatic disease. (The researchers applied a back-calculation method to breast cancer mortality and survival data.) It is the first estimate of its kind to include both women initially diagnosed with metastatic breast cancer, as well as those who progress to the disease after a first diagnosis at an earlier stage (because U.S. registries currently do not routinely collect or report on recurrence data).

The estimates suggest the number of women living with metastatic breast cancer grew by 4 percent from 1990 to 2000 and 17 percent from 2000 to 2010. The researchers project that number will increase by 31 percent from 2010 to 2020.

The growing number, however, is a favorable finding, the study's lead author Angela Mariotto, PhD, Chief of the Data Analytics Branch of the Division of Cancer Control and Population Sciences at the NCI, explained. "Over time, these women are living longer with [metastatic breast cancer]. Longer survival with [metastatic breast cancer] means increased needs for services and research. Our study helps to document this need."

The data also revealed that the median and 5-year relative survival for women initially diagnosed with metastatic breast cancer is improving—particularly among younger women.

As of Jan. 1, 2017, more than 150,000 women in the U.S. were currently living with metastatic breast cancer—and three out of four of them had initially been diagnosed with an earlier stage breast cancer. Between 1992 to 1994 and 2005 to 2012, 5-year relative survival among women initially diagnosed with metastatic breast cancer between the ages of 15 and 49 doubled from 18 percent to 36 percent. And more than 11 percent of women diagnosed between 2000 and 2009 who were younger than 64 survived at least 10 years.

"These findings make clear that the majority of [metastatic breast cancer] patients, those who are diagnosed with non-metastatic cancer but progress to distant disease, have never been properly documented," Mariotto added. "This study emphasizes the importance of collecting data on recurrence at the individual level to foster more research into the prevention of recurrence and the specific needs of this growing population."

Here's what else Mariotto told Oncology Times about the new data.

1. Why was this group of women with cancer never accurately documented before?

"Approximately 155,000 women are living with [metastatic breast cancer] in the U.S.—and three in four of these women were initially diagnosed with early-stage breast cancer and later progressed to metastatic breast cancer. The three out of four is a group that was never accurately quantified [before].

"We have very good information on incidence of how many people are initially diagnosed with metastatic breast cancer, and we also have survival information for them from linkages with mortality data. However, our data is patchy and we do not have longitudinal information on recurrence or progression of disease. So we didn't know how many women diagnosed with early-stage breast cancer progressed to metastatic disease and were alive today. Using the methods in the paper, we estimated that they represent approximately 75 percent of all those living with [metastatic breast cancer].

"Ideally, in the future, we would like to collect data on recurrences to have better information on these undocumented population of cancer patients."

2. How were you able to quantify this group of patients living with metastatic breast now— including the women initially diagnosed with an earlier-stage cancer?

"We looked at data from cases initially diagnosed with [metastatic breast cancer] from the SEER registries. We also looked at published data from an MD Anderson study that reported survival from recurrence [metastatic breast cancer] to be lower than survival of women diagnosed with de novo (at diagnosis) [metastatic breast cancer]. The information was used to adjust our survival estimates.

"Then we used U.S. breast cancer mortality data. The method is called 'back calculation' and is often used to estimate an event in the past using information about an event in the future—for example, to estimate the number of HIV infections from the number of AIDS diagnosed cases. In our case, we assumed that each breast cancer death transitioned through [metastatic breast cancer]."

3. What would you say is the takeaway message about these data and the treatment and care of women living with metastatic breast cancer?

"That survival for women initially diagnosed with [metastatic breast cancer] has been improving. Showing the increasing burden of [metastatic breast cancer], we hope to highlight the importance of documenting recurrence to foster more research into the specific needs of this understudied population.

"This study is part of a larger effort at NCI, trying to develop more automated processes and methods to collect recurrence data—possibly using electronic documents, such as claims data, pathology reports, lab tests, and imaging results to point to cancer's return. These data may provide better information on prevention of recurrence."​

Thursday, June 22, 2017

With Deborah V. Novack, MD, PhD, of Washington University in St. Louis

By Sarah DiGiulio

Breast-conserving lumpectomies are a mainstay of invasive breast cancer treatment. And although they often lead to positive long-term outcomes and survival rates, many patients require multiple surgeries to get rid of all the cancerous tissue because surgeons only know for sure that they've removed all of a tumor after the extracted samples are sent to a lab for analysis.

But a new imaging technology could change that, according to Deborah V. Novack, MD, PhD, Associate Professor of Internal Medicine, Bone & Mineral Diseases, and Pathology and Immunology in the Division of Biology & Biomedical Sciences at Washington University in St. Louis.

Novack and her team are developing a microscopy technique that would allow surgeons to analyze a patient's tumor in the operating room and know immediately whether they've removed the entire tumor—or if they need to take more breast tissue out of a patient.

"Photoacoustic microscopy uses light (in our case UV light to excite DNA/RNA in cell nuclei) and detection of its absorption to visualize tissues 'as is' without adding any extra dyes or stains," she explained.

"The absorption of light by molecules generates ultrasonic waves, which are then detected—rather than detecting the light itself—thus overcoming the lack of returned light due to strong absorption and the high degree of photon scattering in thick tissue."

The bottom line is that margin status for removal of primary tumors is still an important determining factor of a patient's prognosis and need for further treatment, Novack noted. "And there are new technologies on the horizon to determine margin status intraoperatively."

The team recently published a study in Science Advances demonstrating that this new technique works (2017; doi:10.1126/sciadv.1602168).

Here's what else Novack said about that research and the next steps for developing this technique and making it available for surgeons in the operating room.

1. Could you explain how the microscopy technique you are developing would improve lumpectomies for patients with breast cancer who undergo the surgeries?

"Currently, the method used to assess surgical margins during an operation involves freezing tissue, cutting thin sections, and looking under a microscope. This does not work well for fatty tissues, such as breast—so margins cannot be checked during breast surgery, leading to a large number of repeat operations that are expensive, stressful, and potentially painful for the patient and also delaying adjuvant therapies such as radiation and chemotherapy. Therefore, use of this technology could decrease the number of procedures needed for each patient, and shorten the time until the additional therapies can be completed.

"The advantage of [photoacoustic microscopy], once fully integrated with software to identify malignant cells, is that it could scan a large surface area quickly. It could potentially be used to evaluate margins for several types of larger specimens including soft tissue, pancreas, or lung, which have a fairly extensive area that represents the margin (the surface cut by the surgeon in direct contact with the part of the organ or tissue still in the patient)."

2. What are the key findings from the new research you and your colleagues just published?

"Using [photoacoustic microscopy], we were able to generate images of breast tissue, including tumor and adjacent normal areas, that closely approximated the same areas visualized with standard optical microscopy following processing for paraffin-embedding, sectioning, and staining.

"Because there are features such as nuclear size and internuclear distance (the distance between the centers of nuclei of adjacent cells), we can adapt methods currently being designed for computer-based analysis of histological slides to the [photoacoustic microscopy] images in our development of algorithms to automate the determination of clear or involved margins."

3. What is the next step for this technology and what else needs to happen before these tools are available in operating rooms?

"There are two important steps needed to bring this technology into the operating room. One is to design a larger, faster detector that can accommodate specimens with a real-life 3-D shape. Right now, our apparatus is slow due to use of a single laser and only visualizes a flat cut surface.

"We also need to work with the images from [photoacoustic microscopy] to develop the computer programming to detect the areas involved by cancer. Then, a clinical trial will be needed to establish that the system (the detector and software) are sensitive and specific enough to be used on patients.

"One advantage of the technology is that it is non-destructive. After being imaged by [photoacoustic microscopy], the samples can be treated exactly as they are now for standard histological analysis of tumor margins, giving a good margin of safety with a 'gold standard' method to back up the findings.

"We don't have an exact time frame, but it will still be several years."​

Monday, June 12, 2017

With Agnés Dechartres, MD, PHD, Assistant Professor in Clinical Epidemiology at Paris Descartes University

By Sarah DiGiulio

When it comes to evaluating cancer immunotherapy treatments, progression-free survival and overall survival are not interchangeable. That was the bottom line from a new study published online ahead of print in the Journal of Clinical Oncology (2017; doi:10.1200/JCO.2016.71.2109).

The study analyzed 51 other clinical trials that had assessed 14 cancer immunotherapy drugs for the treatment of 15 different conditions. All the trials were phase II through IV and included approved drugs. Nearly one half of the drugs in all the trials included in this research showed statistical significance for progression-free survival, but not for overall survival. Results varied for the different drugs, but on average the treatment effect size was 17 percent greater for progression-free survival than for overall survival, with important differences for some drugs, the authors noted in the study.

"Given the growing pressure for faster patient access to innovative therapies, regulatory authorities are relying increasingly on primary surrogate outcomes such as [progression-free survival] instead of final patient outcomes such as [overall survival] for making decisions regarding drug approval and licensing," the researchers stated. "However, for these therapies, whether [progression-free survival] is a valid surrogate for [overall survival] is unknown."

While the study authors acknowledge this research is not representative of all cancer immunotherapy drugs, they note the results highlight an important limitation of using progression-free survival as a primary outcome—and, more importantly, that differences between progression-free and overall survival should be considered when evaluating new drugs.

The next step of this work is looking closer and focusing on different types of immunotherapies and different types of cancer, study author Agnés Dechartres, MD, PhD, Assistant Professor in Clinical Epidemiology at Paris Descartes University, told Oncology Times.

The debate over progression-free versus overall survival is not a new one. Others have argued solely relying on overall survival as a reliable endpoint for proving a drug's efficacy slows down the approval of beneficial drugs and wastes financial resources for research.

But this data is an important step in gathering more evidence to answer that question, Dechartres said. Here's what else she told Oncology Times about the work.

1. What led you to conduct this research now and focus on immunotherapies?

"We decided to do this study because progression-free survival is a commonly used surrogate outcome in cancer clinical trials. Cancer drugs are evolving a lot, especially with immunotherapies. Regulatory authorities are relying increasingly on primary surrogate outcomes such as [progression-free survival], but whether [it's] a good surrogate for overall survival was not clear.

"We decided to look at all immunotherapies (using a broad definition for immunotherapies) to provide an overall picture on these drugs. In future studies, we are going to look more in depth to the different types of immunotherapies and different cancers."

2. What would you say was the most important finding from this research and conclusion that you reached?

"We found a larger apparent benefit with progression-free survival than with overall survival for immunotherapies. In some cases, there was a benefit for [progression-free survival], but no benefit at all for [overall survival]. These results were consistent with surrogacy metrics suggesting [progression-free survival] cannot be considered as a good surrogate for [overall survival] for immunotherapies.

"Our research says it is important to look at both types of outcomes to have a transparent and complete information on the benefit of these drugs. Relying only on [progression-free survival] can give an incomplete picture of the benefit."

3. What is the bottom line that all practicing oncologists, cancer care providers, and cancer researchers should know about these findings?

"It is not the same message when you have a drug that improves both progression and survival—and when you have one with a benefit on progression, but no evidence of an impact on survival.

"As a physician, I would expect to be informed on that. It is important the information on both types of outcomes are available to be sure the practicing oncologists, cancer care providers, and patients can rely on transparent and complete information so their interpretation can be appropriate and not overoptimistic."

Thursday, May 25, 2017

With Jennifer Griggs, MD, MPH, of the University of Michigan

By Sarah DiGiulio

In 2015, the ASCO Health Disparities Committee outlined the need to develop a strategy to specifically address the needs of sexual and gender minority patients with cancer—the risk of those patients for receiving disparate care and having suboptimal treatment experiences. In April, ASCO published its first position statement on the topic online ahead of print in the Journal of Clinical Oncology (2017; doi:10.1200/JCO.2016.72.0441).

"It is hoped that these recommendations can also be used to help other stakeholders in the oncology community to address the needs of [sexual and gender minority] populations in the cancer care setting," the position statement reads.

The statement's recommendations fall under the following categories: patient education and support, workforce development and diversity, quality improvement strategies, policy solutions, and research strategies. They call for the following steps to be taken, among others: enhance patient navigation and care coordination (that encourages safe disclosure of sexual and gender minority identities), integrate a focus on sexual and gender minority physicians in oncology workforce diversity efforts, ensure adequate insurance coverage to meet the needs of sexual and gender minority individuals affected by cancer, and ensure policies prohibiting discrimination.

Jennifer Griggs, MD, MPH, Professor in the Department of Health Management & Policy and in the Division of Hematology & Oncology within the Department of Internal Medicine Hematology & Oncology at the University of Michigan, Ann Arbor, and one of the position statement coauthors, explained why the recommendations are important and what ASCO and others hope they will accomplish.

1. What would you say are some of the biggest cancer health disparities among sexual and gender minorities—and the biggest barriers to overcoming them?

"There are many gaps in knowledge vis-à-vis disparities among sexual and gender minorities, but we do know that there are higher rates of some cancers and risk factors for cancer. For example, lesbian and bisexual women have higher rates of obesity, [which is] associated with many cancers, including breast cancer; gay men have a greater risk of anal cancer; and people who are [lesbian, gay, bisexual, transgender, and intersex] are more likely to smoke cigarettes than their heterosexual cisgender counterparts.

"Sexual and gender minorities also have lower rates of cancer screening, in part due to lower rates of insurance coverage, exclusion from standard cancer screening and outreach campaigns, and experiences of discrimination when interacting with health care systems and providers.

"Among medical providers, there is a lack of knowledge and barriers to high-quality patient-provider communication that inevitably lead to suboptimal care and survivorship care planning.

"Finally, some people who identify as [sexual and gender minorities] may not disclose their sexual orientation or gender identification due to concerns about discrimination and stigmatization.

"The biggest barriers [to overcoming these disparities] are most likely lack of awareness among health care providers, lack of training in communication, lack of insurance, and historical discrimination that leads to lack of trust."

2. This is the first ASCO position statement on cancer care for LGBTI patients—why now?

"We have previously focused on racial and ethnic disparities in care, then policies that impact socioeconomic disparities, and the science of disparities measurement. This statement, in particular, was prompted by the 2015 curricular reform statement of the Association of American Medical Colleges. I read a summary of this report in which the authors were quoted as saying they would like to see efforts to expand their work to specialty societies.

"Our immediate response was that [ASCO] should address disparities in access and quality of care in [sexual and gender minority] patients, their loved ones, and in our workforce.

"We always try to put the patient needs first. The main goal and purpose was to raise awareness of the needs of [sexual and gender minority] populations and to make a plan for addressing these


"Developing educational and training materials for medical providers to improve patient/provider communication and patient education and support materials is the right next step. … [And] to make the greatest impact, we will need to engage patients, caregivers, medical providers, and other health care leaders, policy makers, researchers, funding agencies, insurers, and advocacy communities."

3. What is the bottom-line takeaway all practicing oncologists and cancer care providers should know about this position statement and these ASCO recommendations?

"The bottom-line is that this statement is a roadmap for improving the care of patients who identify as sexual and gender minorities, along with their loved ones, as well as to create safe workplaces for a diverse workforce. Cancer providers are committed to providing the best care for their patients, and all of us can improve our knowledge and skills in this area. In addition, expanding our knowledge base and policies that prevent discrimination will help us achieve our goals of providing equitable care."

Wednesday, May 10, 2017

With Kostas Tsilidis, PhD, of Imperial College, London

By Sarah DiGiulio

Cancer researchers have long studied the link between obesity and cancer, but there is still a lot of uncertainty about what drives that link and for which cancers the link is the strongest. A new study has investigated the strength of the research supporting that connection between being overweight and developing or dying from cancer, finding a significant amount of evidence is low quality.

The new umbrella review analyzed 204 meta-analyses in total and found that 77 percent reported a statistically significant link between obesity and the incidence of or mortality from cancer (BMJ 2017;356:j477).

Yet, of 95 meta-analyses that investigated the link between continuous obesity measures and the risk of developing or dying from 36 different cancers (or cancer subtypes), only 12 of those analyses (13%) were supported by strong evidence. The other studies were found to either have highly suggestive (18%), suggestive (25%), weak (20%), or no (25%) evidence of an association between the obesity measures and cancer.

"This potentially makes excess body fat the second most important modifiable cancer risk factor after tobacco use," noted Yikyung Park, ScD, Associate Professor of Surgery, and Graham A. Colditz, DrPH, MD, MPH, Deputy Director of the Institute for Public Health, Chief of the Division of Public Health, and Professor of Surgery, both at Division of Public Health Sciences at Washington University School of Medicine (BMJ 2017;356:j908).

The evidence suggests that better data on the link between being overweight and cancer risk is needed, the authors of the umbrella review concluded.

"As obesity becomes one of the greatest public health problems worldwide, evidence of the strength of the association between obesity and cancer may allow finer selection of people at high risk, who could be selected for personalized primary and secondary prevention strategies," the researchers noted in the original paper.

Study co-author Kostas Tsilidis, PhD, Senior Lecturer in Cancer Epidemiology in the Department of Epidemiology and Biostatistics within the School of Public Health on the Faculty of Medicine of Imperial College, London, explained more about what the data showed and what additional research in this area is needed.

1. Cancer researchers have been talking about the link between cancer and obesity for a long time. What does this new review you and your colleagues published in BMJ add to what is known about this link?

"These findings are complementary to what we already know about obesity and cancer risk. Obesity leads to lots of disruption of hormonal and metabolic pathways. Excess fat has been linked to higher estrogen levels, higher insulin levels, and increased inflammation, all of which can affect cell division, but different cancers may be more or less susceptible to the aforementioned mechanisms.

"We found that strong evidence supports the association between obesity and 11 cancers (esophagus, stomach, colon, rectum, biliary tract system, pancreas, breast, endometrial, ovary, kidney, and bone marrow). There could be associations between obesity and other cancers, but substantial uncertainty remains in the biomedical literature. These findings are important because cancer is a leading cause of death worldwide, and the prevalence of obesity has more than doubled over the past 40 years."

2. Where are the most urgent gaps—and what additional research is most important in terms of better understanding the link between obesity and cancer? And what are the challenges standing in the way of that research?

"Future large prospective observational studies and consortia thereof with better assessment of the dynamic nature of body fatness could assist in complementing the current literature evidence. But, since we need to start acting to reduce the obesity epidemic, we especially need better research to evaluate potential effective guidelines and public health interventions for weight management in children and adults.

"Randomized controlled trials of potential weight management interventions will be expensive. It also would be difficult to identify effective interventions with weight management results that are sustainable. Working with children and their parents is also challenging, but it is paramount to evaluate weight management programs at young ages."

3. There are a few conclusions that can be drawn from this research. What is most important for oncologists and oncology care providers (and everyone) to know about this work and the findings from this large-scale analysis?

"Strong evidence supported the association between obesity and 11 cancers. We should probably start to seriously act to reverse the obesity epidemic."​