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

Thursday, August 10, 2017

With Carol Parise, PhD, Research Scientist at Sutter Institute for Medical Research

By Sarah DiGiulio

On the list of factors that affect a patient's outcome after being diagnosed with cancer is marital status. Research that looked at more than 730,000 patients with any one of the 10 leading cancers in the U.S. suggests that being married yields an advantage for patients with cancer in terms of having a lower risk of having metastatic disease, under-treatment, and death from cancer (J Clin Oncol 2013;31:3869-3876). But now new research suggests the story might be different for some people, depending on their race.

The new data included 23,493 women who had been diagnosed with triple negative breast cancer. The findings were presented during a poster presentation at the 2017 ASCO Annual Meeting (Abstract 1098).

"Being married at the time of diagnosis of triple negative breast cancer provides a survival advantage for women who are white and Asian/Pacific Islander, but not for black or Hispanic women," study author Carol Parise, PhD, Research Scientist at Sutter Institute for Medical Research, Sacramento, Calif., shared with Oncology Times.

The data also showed that the single white and Asian/Pacific Islander women with triple negative breast cancer had worse survival than women who were white and Asian/Pacific Islander and married at the time they were diagnosed with the disease.

Of the women in the study, 13,241 were white, 2,775 were black, 5,059 were Hispanic, and 2,418 were Asian/Pacific Islander. The researchers used Kaplan-Meier survival analysis and Cox regression to assess the risk of mortality associated with marital status (married, single/never married, separated, divorced, or widowed). The models were adjusted for cancer stage and grade, age, socioeconomic status, and treatment type.

Here's why Parise says these findings are significant and what implications they have for addressing disparities in cancer care outcomes.

1. What led you to specifically look at how marital status affects breast cancer outcomes among different races?

"Our research in breast cancer has centered on the topic of disparities in incidence and mortality due to race/ethnicity and socioeconomic status. Since marital status has been shown to be an advantage for cancer survival, we wanted to know if this was true for all race/ethnicities for the subtype of breast cancer with the worst survival.

"We investigated whether there was a survival advantage [in triple negative breast cancer] for women of the same race/ethnicity who were married versus single, divorced, and widowed. No other study has compared differences in risk of mortality of [triple negative breast cancer] associated with being married within a single race."

2. Why do you suspect that race played a role in whether or not being married provided a survival advantage for the women in this study with triple negative breast cancer—and do you suspect the same pattern would exist for patients with other types of cancer, too?

"We cannot draw conclusions given the nature of our data, but we can speculate that since social support is a correlate of survival for breast cancer that this could account for why marital status is associated with improved survival. This area deserves further research.

"We focused on [triple negative breast cancer] because it is the subtype with the worst survival. ... While we did not conduct the analysis with the combined subtypes for each race, we believe the results would be similar for all cancers."

3. What is the next step given these findings?

"This study was an epidemiologic investigation. These types of studies tend to raise more questions than answers since they are correlational in nature.

"While we do not have the resources to further pursue this topic, a next step would be to determine the social support factors that are important for women with [triple negative breast cancer] and determine if there are differences in what constitutes support for women of different races. It appears as if there are other factors associated with survival besides surgery, radiation, [chemotherapy], and hormonal therapy—and these should be explored."

Tuesday, July 25, 2017

With Fedro A. Peccatori, MD, PhD, Director of the Fertility & Procreation Unit in the Division of Gynecologic Oncology at the European Institute of Oncology

By Sarah DiGiulio

Treating pregnant women with cancer is a balancing act. Aggressive treatment may be the best course for the mother with highest chance of survival—yet too much treatment poses severe risks to developing fetuses.

New data collected from Sweden's nationwide health registries showed that maternal cancer during pregnancy is associated with increased risks of fatal outcomes (though rare), including stillbirth and neonatal mortality. The data included 984 women who were diagnosed with cancer during pregnancy and 2,723 women who were diagnosed with cancer the year after pregnancy. (The data was collected from more 3,947,215 singleton births included in the registries between 1973 and 2012.)

Another significant finding from the research: preterm birth explained 89 percent of the association of maternal cancer during pregnancy with neonatal mortality. The data was recently published in the Journal of Clinical Oncology (2017;35:1522-1529).

"The correlation of preterm birth with impaired neonatal outcome, confirmed also by the current study, underlines the need for true multidisciplinary management of any pregnant woman with cancer," wrote Fedro A. Peccatori, MD, PhD, of the European Institute of Oncology, Milan, Italy, and Monica Fumagalli, MD, of the University of Milan, in an editorial accompanying the new research (J Clin Oncol 2017;35:1499-1500).

The safety and outcomes for expectant mothers with cancer and their fetus depends on the cancer type, the stage of the disease, the health of the mother and the fetus, and other factors, Peccatori and Fumagalli explained. But the new data suggest there's a need to increase collaborative research initiatives that address the still unknown questions about treating expectant mothers with cancer—and there needs to be better awareness on the part of providers and their patients about current guidelines.

Peccatori, who is Director of the Fertility & Procreation Unit in the Division of Gynecologic Oncology at the European Institute of Oncology, explained further why more work on this topic is needed.

1. Why would you say these new findings from the Swedish cohort by Lu, et al., are significant?

"[The paper] underlines, for the first time, that patients who suffer from cancer during pregnancy may have higher stillbirth and infant mortality rates compared to the reference population. The study comes from Sweden, where stillbirth and infant mortality rates are very low, but it was quite clear that the main determinant of morbidity and mortality was prematurity, which is avoidable in most of the instances in this group of patients.

"Cancer during pregnancy is increasing, as the age at first and subsequent births are increasing. Thus, speaking of cancer during pregnancy is not trivial. It is estimated that one [in] 3,000 pregnancies may be complicated by cancer. Most of these are curable and can be treated during pregnancy with surgery and chemotherapy, the latter from the second trimester. Baby health for most of these mothers is of utmost importance and all the variants that may influence it are surely worth reporting."

2. What would you say are some of the biggest unknowns when it comes to how to treat cancer in pregnant women—and the challenges in delivering high-quality care to these patients?

"As said, cancer can be treated also during pregnancy. Nonetheless, you need a really multidisciplinary and multi-professional team to take care of the pregnant mother with cancer. In my institute, we have set up a collaboration with the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Milan University where we found the best possible obstetricians, perinatologists, and neonatologists to take care of these women.

"Still, many questions remain. The effect of the disease on the pregnancy evolution, the placental toxicity of drugs, and the different models of baby attachment after a diagnosis of cancer during pregnancy are still unanswered questions that our group is investigating. Chemotherapy can be safely administered starting from the second trimester, but we are still missing comprehensive and detailed information about long-term outcome on the offspring."

3. What is most important to know about this recent research and how to care for pregnant women with cancer?

"Too often, cancer during pregnancy is considered an oxymoron and many physician advise for pregnancy interruption. Unfortunately, the data that support an active management of cancer during pregnancy are not well-known. The issue is also underserved in medical education.

"When we say 'need for action,' we mean more humbleness, more knowledge, more collaboration, and more research. All this can be done if we share data within collaborative initiatives, as the multinational International Network on Cancer Infertility and Pregnancy, which was launched in Europe, but includes also U.S. centers.

"Treating cancer during pregnancy is possible, but not trivial. To achieve the best results for the mothers and their babies, you need to understand this unique situation and act accordingly."

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."