3 Questions on…

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

Thursday, September 7, 2017

With Adam Godzik, PhD, at Sanford Burnham Prebys Medical Discovery Institute

By Sarah DiGiulio​

Sophisticated new algorithms offer opportunities when it comes to understanding why cancers develop and finding treatments that work. The idea is to look at a patient's genome and look for genes where cancer mutations cluster in some specific regions of the gene (standard algorithms look for genes that have more mutations than would be expected according to the average mutation rate for that gene)—and that might be linked to a specific type of cancer or cancer drug known to work for other patients with that mutation.

But not every algorithm shows the complete picture. It's only when insights are combined from several algorithms that it becomes clear whether or not the right mutations are being correctly linked to the cancers they lead to or drugs that work for patients with those cancers, explained Adam Godzik, PhD, Director and Professor of the Bioinformatics and Structural Biology Program at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Calif.

Those were the findings of a paper Godzik and his colleagues recently published in Nature Methods (2017;14:782-788).

"The point here is that when results from various cancer genomic studies are presented, people usually see the final result of two actually independent things: data from the patients and the algorithm used to analyze these data," Godzik said. "When results from different studies are compared—with both data and algorithms being different—at the end we don't know what contributed to the difference."

This new research was designed to compare the effectiveness of multiple algorithms on the same set of data to reveal the difference each algorithm was finding.

"The key finding is that each algorithm in the group we compared is adding something unique, missed by other algorithms," Godzik noted. "The picture we get from using all of them is more complete than that obtained using just one algorithm."

In an interview with Oncology Times, Godzik elaborated about why these findings are significant, and what they reveal about the future of using algorithms for cancer diagnoses.

1. Why is this research important—especially as more and more algorithms for cancer are being developed?

"When you see two papers [that evaluate an algorithm for pinpointing a gene mutation that could lead to cancer], each of them have a different dataset and a different algorithm. So you may not actually be so sure what is causing the differences. Is it the difference in the data or is it the difference in how people analyze it, the algorithm?

"So in this case, these algorithms that we looked at—each of them is giving us part of the truth. And the best insights we get is that, when we combine all these algorithms together, we see the global picture."

2. So you're not saying your data shows any one algorithm is necessarily wrong? What's the takeaway about each specific algorithm you looked at?

"Each of the observations might be true. If you have a group of people who are looking at people with breast cancer, somebody analyzes that and says there's a group that has mutations in [a specific] gene and this group has low survivability and should get more aggressive treatment. We're saying, well if you use another algorithm you might see another group [that has that gene but needs another type of treatment].

"It's not like one algorithm is correct and another algorithm is wrong. Each algorithm is showing you part of the truth and you would be missing something if you don't use multiple algorithms. Most observations they would make would be correct, but it wouldn't be all of the truth. Some algorithms would miss some of those subgroups. And we still don't know, in most cases, what it means. But in the future, we anticipate we'll know how the different subgroups could be treated differently.

"For instance, a big drug trial may fail because they take 1,000 people and give the drug to these people and it only helps 20 people. So, they say it's not good enough and the drug is not approved. But with tools like [these algorithms] we can say yes, it only helped 20 people, but it helped 100 percent of people who have a certain feature or a certain set of mutations. And this could be very useful because now we can say, well, the drug is not for everybody, but the drug can work for this one specific group.

"So this is the big picture here. This is the dream."

3. What is most important for oncology clinicians to know about your findings—and the future of using algorithms to diagnose and classify cancers?

"Doctors: Pay attention to how the data was analyzed, it could be as important as what is being analyzed.

"I think it would be too early to say these tools are usable now—or give a lot of insights for practicing clinicians. At this point in day-to-day clinical practice, genomic information is very rarely used or may only focus on one or two specific genes, like BRCA1/2. But this research is part of a bigger trend of more and more detailed analyses coming from cancer genomes."

Friday, August 25, 2017

With Betty Ferrell, RN, PHD, in the Department of Population Sciences at City of Hope

By Sarah DiGiulio

It was as recently as 2012 that ASCO issued its first guidance on integrating palliative care as a standard part of oncology care. And in a clinical practice guideline update released earlier this year, ASCO revised its recommendations based on new evidence (J Clin Oncol 2017;35:96-112).

"A key emphasis is the need to integrate palliative care much earlier in the course of illness and treatment," explained the update's lead author Betty Ferrell, RN, PhD, Director and Professor in the Division of Nursing Research and Education in the Department of Population Sciences at City of Hope, Duarte, Calif. "These guidelines reflect a growing body of solid evidence for the benefits of palliative care to improve patient quality of life. "This version also emphasizes that [palliative care] should be provided by the oncology team as well as the [palliative care] specialty service," Ferrell said.

Key recommendations from the expert panel who wrote the guidelines (based on a systematic review of literature) that were included in the updated guidelines include the following:

  • All patients with advanced cancer—whether patient or outpatient—should receive palliative care services early in the course of their treatment, concurrent with active treatment.
  • For newly-diagnosed patients with advanced cancer, referral to palliative care services should happen with 8 weeks of diagnosis.
  • Essential components of palliative care services may include symptom, distress, and functional status management (such as pain, dyspnea, fatigue, sleep disturbance, mood, nausea, or constipation); clarification of treatment goals; exploration of understanding and education about illness and prognosis; assessment and support of coping needs; coordination with other care providers; and referral to other care providers, if needed.

The new guideline makes it clear that these palliative care services can be provided by an interdisciplinary palliative care team or by the patients' nurses, social workers, or other providers. What's important is that all patients with advanced cancers have access to these services.

Ferrell elaborated on why the revisions are important and the barriers still standing in the way of more comprehensive palliative care services for patients with cancer.

1. Why were these palliative care guidelines updated most recently?

"The health care system is so burdened with limited resources, and we need new models of care. In previous years, [palliative care] was seen as only indicated at the end of life. However, there is growing awareness that all patients experience symptoms and [quality of life] concerns that would benefit greatly from [palliative care].

"There is also an important issue of the aging of our population. Our cancer patients are older and they come with many comorbidities [that are] also compromising their quality of life. And finally, improved cancer treatment means that patients live much longer, even those with advanced disease. We need to support our patients who now are living years with significant quality of life concerns."

2. The oncology community has been talking about the importance of palliative care for several years—are we there yet, and what are barriers that still impede efforts to make these services more widely available?

"We have made significant progress. There is broad acceptance across most oncology settings that palliative care is essential to quality oncology care.

"Barriers remain, however. Patients and families are often reluctant to accept palliative care as they associate it with end-of-life care. Unfortunately, patients are often not referred for palliative care until very late, and referrals to hospice come even later. There is a major need to increase palliative care knowledge and skill in the entire oncology workforce as all clinicians practicing in the field of oncology need [a] generalist level of competence in palliative care.

"The key paradigm shift [over the past 5 years, since the first guidelines were developed,] is that palliative care is now firmly established as a specialty in medicine, nursing, and other disciplines. There is also a very substantial body of evidence supporting the benefits of palliative care to health systems and to patients."

3. What is the bottom line about these updated guidelines and providing palliative care services to patients with cancer?

"Palliative care improves quality of life for patients, supports family caregivers, extends survival, and benefits health care systems.

"Palliative care is important for all cancer patients across the care trajectory."

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."​