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

Friday, January 18, 2019

With Wynne Norton, PhD, Program Director in the Division of Cancer Control & Population Sciences at NCI

By Sarah DiGiulio

Health care providers across all disciplines are struggling to provide better care and cut costs. And in oncology, the issue is becoming ever more prescient. New drugs are more effective, but more expensive to make. Better tests and screens are available, but may not be worthwhile for everyone. And the consequences of not delivering sustainable, high-quality cancer care are life-threatening.

That's why Wynne Norton, PhD, Program Director in the Division of Cancer Control and Population Sciences at the NIH, along with her NCI colleagues, wrote a Comments and Controversies article in a recent issue of the Journal of Clinical Oncology outlining a better strategy for studying and de-implementing overuse in cancer care (2018; doi:10.1200/JCO.18.00589).

There are two bottom-line messages from the article, Norton shared with Oncology Times. "First, we wanted to encourage researchers and practitioners to develop and test approaches for effectively de-implementing various cancer-focused practices.

"Second, to support this type of work, we tried to highlight some of the key factors that are likely to play a role in this process, and therefore are likely targets of change needed to facilitate de-implementation," she said.

Norton and her coauthors recognize that de-implementation—especially when you're talking about doing it in cancer care where the stakes are so high—is a "difficult enterprise," they noted in the article. But it's also critical to helping cancer care evolve and improve.

Here's why Norton said establishing a process to accomplish it matters.

1. Why did you and your colleagues decide to write this article now?

"Over the past several years, there has been increasing attention to the issue of overuse of ineffective, low-value, harmful, and unproven practices, interventions, and treatments in the scientific literature—and among professional societies, funding agencies, and research-based organizations.

"Of course, this is a very important issue to patients, providers, and payers, as it cuts across many health conditions, delivery settings, and patient populations.

"We've been involved in several efforts recently to better understand the issue of overuse (e.g., review and summary of grants funded by the NIH on this topic; presentations at the Preventing Overdiagnosis Conference), and to begin to identify ways in which we may either prevent or de-implement the use of these types of practices. Recent high-profile studies in cancer—the TAILORx trial in particular—signaled a timely opportunity for us to summarize issues related to de-implementation.

"Ultimately, we wanted to encourage the research and practice communities to move beyond describing the problem of overuse toward developing and testing ways to de-implement ineffective, low-value, harmful, and unproven practices in cancer care delivery. The overarching goal is to achieve the optimal balance of implementation of beneficial interventions along with de-implementation of harmful or low-value interventions."

2. How would you define what a "de-implementation framework" is and how you came up with this one?

"The de-implementation framework is a conceptualization of multi-level factors that are likely to influence and impact the de-implementation process. We wanted to propose a way of thinking about de-implementation that would simultaneously guide providers, clinic managers, and quality improvement specialists in their practice-based efforts and help researchers identify and test strategies to facilitate de-implementation. We hope it serves as a blueprint for advancing the science and practice of de-implementation.

"[To develop it], first we reviewed the research and practice landscape on overuse, medical reversals, inappropriate use, and low-value care, including seminal work by Drs. Carrie Colla, Deborah Korenstein, Daniel Morgan, Daniel Niven, and Vinay Prasad (among others), prominent campaigns (e.g., Choosing Wisely), and various organizations and agencies (e.g., National Academy of Medicine, Canadian Deprescribing Network).

"[My co-authors] and I had many conversations about these issues and solicited feedback from our colleagues at various conferences and meetings. Along the way, we developed, edited, and refined the de-implementation framework until we had the final version, which is now published in Journal of Clinical Oncology.

"Although we are happy with the framework in its current version, we anticipate that it will need to be revised over time as practice experience and scientific evidence accumulate. We look forward to seeing how others may contribute to this work."

3. What's next and how do you envision cancer care providers and the cancer care community using this framework?

"For providers, clinic managers, quality improvement specialists, and other key players involved in cancer care delivery, we hope this framework will provide an outline for how to identify, prioritize, and facilitate de-implementation.

"For researchers, we hope that the framework highlights many of the key factors that are likely to facilitate or impede the de-implementation process, and leverage this information to develop and test strategies to effectively drive de-implementation (where appropriate) in cancer care delivery settings."

Monday, January 7, 2019

With David F. McDermott, MD, of the Dana-Farber/Harvard Cancer Center

By Sarah DiGiulio

The Journal of Clinical Oncology recently published a special series on new advances and ongoing research in kidney cancer. The journal regularly rotates through topics for its special series collections (to cover practice updates and forthcoming research clinicians should be aware of), but this new series on kidney cancer is particularly timely, noted David F. McDermott, MD, Director of the Cutaneous and Immuno-Oncology Programs at Beth Israel Deaconess Medical Center, Leader of the Dana Farber/Harvard Cancer Center Kidney Cancer Program, and Professor of Medicine at Harvard.

"Over the last 3 years, investigators have leveraged a growing understanding of kidney cancer biology to target critical pathways and produce durable benefits, even rare remissions, for patients with advanced kidney cancer," McDermott wrote in an overview article he co-authored in the series (2018; doi:10.1200/JCO.18.01198).

McDermott served as a guest editor for the series, helping select the topics covered, recruiting researchers to write the reviews about those topics, and reviewing the articles featured in the series.

McDermott is also co-principal investigator of the NCI Specialized Programs of Research Excellence grant focusing on kidney cancer.

"There are quite a number of new options for patients [with kidney cancer] that are improving survival and, in rare cases, even leading to remission," McDermott told Oncology Times. The articles in this special series cover those advances, as well as the new questions and challenges those advances come with. The series covers new therapy targets that may lead to future improvements, as well as advances in prevention, early detection, and surgical interventions.

"It's really a soup-to-nuts overview on where the treatment of kidney cancer is in 2018," McDermott said. He shared some highlights of the coverage.

1. What makes this special series so timely? What are the highlights in the coverage?

"I think the biggest advance in kidney cancer over the last few years—this is true in all cancer types, but especially in kidney cancer this was the case—is the better understanding of how tumors evade the immune response and how you might be able to overcome those by applying immune checkpoint inhibitors (like PD-1 and PD-L1).

"They were first introduced in the kidney cancer clinics a few years ago for patients who failed kidney cancer treatment and now we're bringing them into the frontline in combination—either combinations with older therapies like VEGF blockades (fusing first-line and second-line therapies). Or we're using [these immune checkpoint inhibitors] in combinations with other immune therapies. And the early results are encouraging.

"We had [nivolumab plus ipilimumab] FDA-approved in April (N Engl J Med 2018;378:1277-1290). And since we started [this article series] a year ago, there have been three other randomized phase III trials that have met their primary endpoint that combine VEGF blockade and PD-1. So in the coming year, there will be several FDA approvals of those combination, which is essentially fusing first- and second-line therapies together."

2. What are some of those still unanswered questions and gaps in the research and evidence?

"The benefits [and new data] are encouraging to patients, but it also presents new questions and challenges. How do you manage the cost? Toxicities? Which patients should receive which combinations? What do you do when patients fail a combination therapy? And I think the average practitioner will be faced with the dilemma of which should I use first? Should I stick with my old standard therapy or should I try these new combinations—and if so, why?

"Also, what are the new targets? Can you bring these new approaches into the adjuvant setting? (That's an area of active research.)

"And decreasing kidney cancer incidence is important. What risk factors can we modify that might reduce the incidence, which is particularly important around the world where they don't have access to any of these treatments. What are the new imaging techniques that are useful?

"What are the genetic predispositions of kidney cancer and the implications for screening and the management of those patients? How can we better stage patients? What are we learning about the different subtypes of kidney cancer and what are these molecular pathways that drive them?

"How do you manage small renal tumors, which are common but not always lethal? How do you manage advanced disease after surgery?

"It's a fast-moving field and we need to focus on the rational application of these new treatments (not just broadly give them to every patient). We need to do a better job of appropriately selecting patients for treatments.

"We want [kidney cancer care providers] to stay focused and tuned in on what's new and what's coming out in journals and at medical meetings, too. The new therapies are not just making statistically significant differences in clinical trials, but they're making clinically meaningful differences for our patients."

3. Are there any takeaways in these articles?

"I think it is important, not just for kidney cancer but for all tumor types, that we balance our approach, not just in the clinic, but also focusing on funding and supporting good basic science research.

"Too often we get focused on new drugs and new targets—which is important. But we still need innovative new ideas that often come from the laboratories. We need to fund those creative scientists who will make the next big discoveries. We're now benefiting from discoveries from 10 and 20 years ago. But we need to keep funding the basic work that may come from many different areas."

Thursday, December 20, 2018

With Beverly Moy, MD, Clinical Director of the Breast Oncology Program at Massachusetts General Hospital

By Sarah DiGiulio

When a patient participates in a clinical trial, costs of medications and/or interventions are covered by the funding for the trial as a way to ensure that clinical trials get fair and equal participation. But there are other costs associated with participating in a clinical trial that go beyond whatever intervention is being administered or tested in the trial. There are supportive care costs that aren't covered by the clinical trial, and there may be travel and/or lodging costs to make it possible to participate in a clinical trial.

It's a topic that has gotten the attention of medical ethicists, including two at the University of Pennsylvania, who penned a viewpoint article in JAMA Oncology earlier this year calling for the FDA to allow for incentives to encourage participation in clinical trials, such as reimbursement for participation expenses, as well as compensation for patients' time and effort (Oncology Times 2018;40(19):66). They say such incentives are not coercive, but instead facilitate fairer participation.

ASCO also recently took a stand on the issue, releasing a policy statement with recommendations to lessen financial barriers to cancer clinical trial participation (J Clin Oncol 2018;36(33):3331-3339).

"Cancer researchers have seen consistently low patient participation levels—especially among underserved patient populations—in part due to the financial burdens facing many patients with cancer," ASCO President Monica M. Bertagnolli, MD, FACS, FASCO, said in a press release accompanying the statement. "Addressing financial barriers will help improve the enrollment rate and the efficiency, quality, and applicability of cancer research. By including more—and more diverse—participants in our research studies, we expand our ability to care for all patients."

The recommendations (which include more specific directives) include the following:

  1. Clinical trial cost payment policies should be revised to be made more consistent, streamlined, and transparent to all stakeholders.
  2. Patients should be provided clearer information about potential trial-related expenses during the development and enrollment process.
  3. Financial compensation for out-of-pocket costs should not be considered undue inducement and impediments to such reimbursement should be removed.
  4. Research to better understand patient costs of clinical trial participation should be incentivized, as well as investigations of tools to mitigate the risk of trial-associated financial hardship.

In an interview with Oncology Times, one of the ASCO statement co-authors, Beverly Moy, MD, Clinical Director of the Breast Oncology Program at Massachusetts General Hospital in Boston, explained why addressing this issue in cancer care is so important now.

1. What prompted ASCO to issue this statement now and what's most important to know about this topic?

"Among ASCO's most important priorities are to ensure access to quality cancer care and to promote research. Underserved patients, including racial and ethnic minorities and poor patients, face nearly insurmountable obstacles to clinical trial enrollment. Therefore, in line with ASCO's mission, the removal of financial barriers to clinical trial enrollment is a topic where ASCO advocates vigorously.

"The recommendations include the improvement of payer clinical trial policies; providing patients with clear, transparent information about potential trial-related out-of-pocket costs; removal of impediments to ethically appropriate financial compensation for out-of-pocket costs; and incentivized research to better characterize the financial burden of trial participation.

"Oncologists should be aware of the added financial burden of clinical trial participation—and demand policy changes to make it possible for our underserved patients to participate. This is an important social justice issue. Patients should not be deprived of these important cancer treatment options due to financial barriers."

2. There are a lot of groups and stakeholders that need to act to fix this problem. How will these recommendations accomplish that?

"Our specific recommendations provide some concrete solutions to some of the various reasons why there are financial barriers to clinical trial participation. Removing perceived impediments to reimbursing patients for their out-of-pocket costs will make it possible for patients to incur more financial burden by participating in a cancer clinical trial. Increasing the transparency from the payer and sponsor perspective as to who is responsible for specific costs will provide patients reassurance and clarity about the financial implications of clinical trial participation.

"This statement stems from a multi-stakeholder roundtable and summarizes their comments and input. These stakeholders included the FDA, NCI, industry, payers, patient advocates, the Moonshot initiative, private cancer foundations, and academia. With increased recognition of this problem, we are hoping to bring attention to this critically important matter so that stakeholders will make meaningful changes to remove financial barriers to clinical trial participation."

3. Two ethicists recently published an editorial in JAMA Oncologyarguing that the policy banning financial compensation for clinical trial participation for ethical reasons plays a big part in financial barriers limiting clinical trial participation. Does the ASCO statement address their concerns?

"[These ethicists] thoughtfully discussed the important ethical issues behind this critically important issue. I'm glad that they supported many of the points that we made in the statement. Our third recommendation explicitly discusses the removal of impediments of ethically appropriate financial compensation for costs and brings up many of the same points made by the authors of the JAMA Oncology paper."

Wednesday, December 5, 2018

With Jessica Scott, PhD, of Memorial Sloan Kettering Cancer Center

By Sarah DiGiulio

Exercise is one of the top health-promoting behaviors an individual can adopt. It's known to lessen risk of heart problems, cognitive decline, some cancers, and mental health disorders, as well as all-cause mortality (death by any cause). And new research suggests those benefits are also true for survivors of childhood cancer survivors.

"Childhood cancer survivors remain at substantially elevated risk of mortality with life expectancy shortened, on average, by 10 years compared with the general population," noted Jessica Scott, PhD, Assistant Member in the Department of Medicine at Memorial Sloan Kettering Cancer Center, New York City, and a coauthor of the new research. "This is primarily due to treatment-related effects (such as, subsequent malignant neoplasms and cardiovascular disease, [among others]). Given this excess risk, we know that strategies that can offset treatment-related effects are of major clinical importance."

The study, published online ahead of print in JAMA Oncology, was a multicenter cohort analysis of 15,450 adults who had been diagnosed with cancer before age 21 from pediatric hospitals in the U.S. and Canada between 1970 and 1999 (2018; doi:10.1001/jamaoncol.2018.2254). The individuals were all part of the Childhood Cancer Survivor Study and were followed through 2013. The researchers looked at the association between weekly self-reported vigorous exercise and mortality (including overall death rates and cause-specific death rates).

The data showed in a median analysis after 10 years and in the full analysis after 15 years that the cumulative incidence of all-cause mortality was in fact higher for those with lower weekly vigorous exercise and lower for those who did more vigorous exercise on a weekly basis.

After 15 years, there was a significant inverse association between exercise and all-cause mortality such that, compared to those reporting no weekly vigorous exercise, those reporting approximately 1.5-2 hours per week of vigorous exercise had a 42 percent reduction in mortality, Scott said.

Another analysis of the data showed that after an 8-year period, those who increased weekly exercise by as little as 40 minutes per week saw a 40 percent reduction in all-cause mortality, compared to those who kept their exercise at about 30 minutes or less per week over that time.

The amount of exercise that conferred the most benefit to survivors of childhood cancer (in terms of reducing risk of all-cause mortality) was equivalent to about 1.5-2 hours of brisk walking per week. "However, benefits were observed even with approximately 40 minutes per week of vigorous exercise," Scott said, noting this data was observational, so randomized controlled trials would be needed to more accurately identify an ideal dose. Here's why Scott says this new data is so important.

1. What does this data tell us that we didn't already know about the late effects of childhood cancers and survivors' risks?

"In the general population, adherence to healthy lifestyle behaviors, including regular exercise, is associated with substantial reductions in cardiovascular disease mortality and mortality from any cause. Exercise also reduces the primary incidence of several forms of cancer and the risk of recurrence following a diagnosis of certain adult-onset cancers (like those of the breast, colon, and prostate).

"But whether these findings extended to adult survivors of childhood cancer with excess risk of mortality was not known. Accordingly, we wanted to evaluate the association between exercise in early adulthood and change in vigorous exercise on mortality in long-term adult survivors of childhood cancer participating in the Childhood Cancer Survivorship Study.

"This study was unique in that it included a large sample size (of more than 15,000 cancer survivors); it included a long-term duration of follow-up [including a median follow-up at approximately 10 years]; it focused on at least 5-year survivors of cancer; and [it investigated] change in exercise exposure (median interval of approximately 8 years)."

2. What types of interventions are needed to spread this message that survivors of childhood cancers need to be exercising?

"One common question by patients is 'what is the best exercise program for me?' This is one of the most important questions in exercise-oncology research and one that will likely require many years to answer. What we've found is that one size of exercise does not fit all. However, based on current evidence in oncology settings, as a first step, patients may need to check with a doctor before beginning an exercise program.

"Once cleared for activity, the exercise guidelines for cancer patients/survivors are to: 1) avoid inactivity; 2) if relatively new to exercise, perform either 150 minutes of moderate-intensity aerobic physical activity or 75 minutes of vigorous-intensity aerobic physical activity each week; and 3) if a regular exerciser, try increasing the moderate-intensity physical activity to 300 minutes or your vigorous-intensity physical activity to 150 minutes each week.

"These recommendations can be achieved by adding a few minutes of activity to a daily routine, such as taking the stairs, adding an extra 15-minute walk before/after work (or at lunch), or walking a little faster or changing a walking route from a flatter route to one with a few small hills. There are also cancer-experienced exercise specialists (clinical exercise physiologists, kinesiologists, and physiotherapists) and programs (such as LIVESTRONG at the YMCA) that can help to initiate a new exercise program following a cancer diagnosis. Small steps can make a big difference for cardiovascular health."

3. What is the takeaway message about this new work?

"There are currently approximately 16 million adult cancer survivors in the U.S., of which approximately 500,000 are adult survivors of childhood malignancies. These numbers are estimated to reach approximately 24 million [cancer survivors] and approximately 750,000 [adult survivors of childhood cancers], respectively, by the year 2030.

"Our findings support counseling all survivors, whenever appropriate, to increase participation in vigorous exercise for approximately 60 minutes a few days a week."

Tuesday, November 20, 2018

With Belle H. de Rooij, MSc, of the Center of Research on Psychology in Somatic Diseases at Tilburg University

By Sarah DiGiulio

Does an optimistic versus pessimistic outlook when it comes to a cancer prognosis (on the part of the patient) bear on the outcome for that patient? Some research has suggested illness perceptions are linked to quality-of-life outcomes and may even be linked to higher survival, too.

Now a new study adds more evidence that patients' perceptions about their cancer can provide important information to health care providers about future outcomes, better accounting for disease severity than other previous research, according to lead author Belle H. de Rooij, MSc, a PhD candidate at the Center of Research on Psychology in Somatic Diseases in the Department of Medical and Clinical Psychology at Tilburg University in the Netherlands (Cancer 2018;

"In an era of increased interest in care for cancer survivors and counselling, it is important to consider the benefits of realistic illness perceptions among cancer survivors compared to optimistic or pessimistic illness perceptions with regard to prognosis," de Rooij shared with Oncology Times.

Researchers used survey data from the population-based Patient Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship registry, along with clinical and survival data from the Netherlands Cancer Registry. The researchers analyzed data for 2,457 patients diagnosed with cancer (either colon, rectal, prostate, endometrial, or ovarian cancers, or non-Hodgkin lymphoma) at least 5 years prior.

A series of questions within the survey asked about illness perceptions. The researchers used the results from those questions to categorize patients as either having a realistic illness perception (one consistent with prognosis), an optimistic illness perception (a less threatening view than their prognosis would suggest), or a pessimistic illness perception (a more threatening view than their prognosis would suggest).

The data showed that an optimistic illness perception was linked not only to better health-related quality of life, but also to better survival.

1, What was new about the results from this data?

"Cancer survivors who have optimistic illness perceptions with respect to their prognosis at the time of the questionnaire appear to have the most favorable health-related quality of life and survival compared to survivors with either realistic or pessimistic illness perceptions. Cancer survivors who have pessimistic illness perceptions with respect to their prognosis at the time of the questionnaire appear to have the worst health-related quality of life and survival.

"Previous evidence suggests that interventions providing explicit information about the diagnosis, side effects, and prognosis of the cancer may increase illness perceptions, resulting in illness perceptions that are possibly more concordant with the disease severity or prognosis. However, it remained unclear whether these more 'realistic' perceptions about the disease were either harmful or beneficial for survivors.

"To our knowledge, this is the first study that explores illness perceptions relative to disease severity (prognosis). Previous studies demonstrated that higher (more threatening) illness perceptions are associated with worse health-related quality of life, psychological morbidities, and worse survival. However, given the findings that patients with more severe disease generally have higher (more threatening) illness perceptions, the relationship between illness perceptions and outcomes may largely be explained by disease severity. This study provides evidence on the benefits of perceptions that are realistic with respect to prognosis compared to more optimistic or pessimistic illness perceptions."

2. What are the implications of this research in terms of informing practice?

"Our findings do indeed suggest that optimistic perceptions may be more beneficial. However, it could also be true that the optimistic and pessimistic individuals were realistic, too, because their illness perceptions may be a much more inclusive reflection of their state of health than our set of objective measures regarding prognosis comprises.

"Therefore, we think it is most important that care providers acknowledge pessimistic illness perceptions among cancer survivors and try to understand why these individuals have pessimistic illness perceptions, because these they may require additional support. For patients, it might be important to find additional help when perceptions are more pessimistic than would be expected based on prognosis."

3. So what's the most important takeaway?

"Survivors with illness perceptions that are relatively optimistic with respect to their prognosis appear to have the most favorable outcomes, whereas those with pessimistic illness perceptions relative to their prognosis have the worst outcomes compared to those with realistic illness perceptions. While illness perceptions may be important predictors of health outcomes independent of prognosis, we think it is important to understand why individuals may hold pessimistic illness perceptions, and provide support that is appropriate for this group to improve their outcomes.

"It is important that care providers are aware of the potential harmful effects of diagnostic and prognostic information provision as they may increase illness perceptions, and that they should carefully monitor the perceptions of patients when providing such information.

"Perhaps there is no one-size-fits-all approach to counseling for cancer survivors, but we may need individualized approaches to prevent potential harmful effects on illness perceptions and related outcomes. Further research in this field is warranted."