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3 Questions on…

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

Tuesday, May 21, 2019

With Ralph Salloum, MD, of Cincinnati Children's Hospital Medical Center

By Sarah DiGiulio

New cancer treatments and therapies pose exciting opportunities when it comes to improving care overall. But understanding the side effects, as well as the long-term late effects of those new and improved therapies, takes time.

A new study that analyzed long-term health outcomes in a group of 1,311 survivors of childhood medulloblastoma, who were diagnosed before turning 21, is an example. The data, published online ahead of print in the Journal of Clinical Oncology, follows patients diagnosed from 1970 to 1999 with a median follow-up of 21 years, ranging from 5 to 44 years (2019; https://doi.org/10.1200/JCO.18.00969). The researchers found that, while changes in medulloblastoma treatment over those 3 decades have improved survival rates, the rates of subsequent neoplasms and other severe health conditions have increased in modern survivors.

The researchers noted that survivors of medulloblastoma need to be closely monitored for these debilitating late effects and that more survivorship research and follow-up data are needed to better understand the longer-term effects of the newer modalities of medulloblastoma treatments used.

In an interview with Oncology Times, lead author Ralph Salloum, MD, Program Leader of the Young Adult Neuro-Oncology Program and Director of the Brain Tumor Survivorship Program at Cincinnati Children's Hospital Medical Center, stated: "Because of the inherently shorter follow-up of survivors from the 1990s, most comparisons in this study were limited to 15 years of follow-up. So, one question that remains unanswered is: what happens later as this survivor population ages?"

Salloum explains more about this study and why studying long-term and late effects of cancer treatment even decades later is important.

1. Your research analyzed patient data going back to the 1970s, which seems to speak to the value of tracking patients' outcomes over the long-term (via registries and cohorts). Is your research illustrative of this point?

"High-quality data regarding diagnosis, cancer treatment, and longitudinal follow-up of cancer survivors are essential in survivorship research. In this context, the Childhood Cancer Survivor Study with its expansion to include survivors across 3 decades (1970-1999) not only allowed us to evaluate long-term health outcomes of medulloblastoma survivors, but also offered a unique opportunity to explore the impact of temporal changes in therapy on major late effects among more than 1,000 survivors of medulloblastoma in a period when pivotal changes in treatment were made.

"A previous Childhood Cancer Survivor Study had shown an overall temporal reduction in late mortality attributable to late effects in survivors of childhood malignancies across 3 decades (1970-1979, 1980-1989, 1990-1999). Given that central nervous system tumor survivors are at the highest risk for late morbidity and mortality among pediatric cancer survivors, we aimed to focus this analysis on medulloblastoma survivors specifically in order to better understand these temporal trends and their association with treatment evolution during that era."

2. The data you analyzed revealed some underappreciated risks that patients with medulloblastoma face over the long term. Why is this finding important?

"The evolution of medulloblastoma therapy from the 1970s to the 1990s (to include adjuvant chemotherapy and incorporate risk stratification) aimed to improve survival and minimize the risk for late effects of treatment. The key finding from this study is that, while survival of medulloblastoma has improved across these decades, historical changes in medulloblastoma therapy failed to minimize the risk for late effects.

"In fact, we found that more modern survivors have significantly increased risk for severe and life-threatening chronic health conditions and subsequent neoplasms. Fortunately, special education needs were lower for a subgroup of patients treated with reduced doses of craniospinal radiation.

"Currently, most children with medulloblastoma are cured as a result of the tremendous improvements in therapy that the pediatric oncology field has witnessed over the last 50 years. Unfortunately, we show that this cure comes at the cost of a spectrum of adverse outcomes that are experienced by survivors beyond 5 years from diagnosis.

"These late effects are rarely reported by pediatric cooperative groups and consortia whose primary goals are often cure rates, as they don't have the ability to follow their patients past 5 years from diagnosis. It is therefore our responsibility to report more consistently the delayed sequelae of treatment, including quality-of-life outcomes through studies like the Childhood Cancer Survivor Study. This is particularly important considering the longevity of pediatric cancer survivors and the potential implications that long-term follow-up research can have on frontline clinical trials and treatments."

3. What's the bottom line practicing oncologists and cancer care providers should know about this research—particularly for those treating patients with medulloblastoma?

"Our research shows that medulloblastoma survivors remain at a high risk for late effects of treatment. We therefore need to focus modern therapy efforts on reducing risks for late effects for future generations. For example, this could be accomplished by reducing therapy in patients with favorable molecular and clinical features, introducing otoprotective agents in treatment regimens and using advanced radiation modalities such as proton beam therapy.

"Given that the risk for chronic health conditions from late effects of therapy remains very high even in modern survivors of medulloblastoma, we hope that this study also serves as a siren call to closely monitor these survivors and improve rates of screening and guideline-based follow-up."

Friday, May 3, 2019

With Robert J. Hayashi, MD, of Washington University School of Medicine

By Sarah DiGiulio

Compared to the general population, people who have survived cancer at any point in their lives tend to be at higher risk of certain complications and overall early mortality. A recent study published online ahead of print in Cancer finds that individuals diagnosed with cancer when they were adolescents or young adults (between the ages of 15 and 39)—a population historically less studied than those diagnosed as young children or older adults—were at a significantly higher risk of death from something other than cancer decades after their diagnosis (2019; https://doi.org/10.1002/cncr.32063).

The research is significant because it's one of the first studies to investigate this question of mortality risk from non-cancer causes in the adolescent and young adult population, according to the study authors.

In an editorial accompanying the research, Robert J. Hayashi, MD, Professor of Pediatrics in the Division of Pediatric Hematology/Oncology at Washington University School of Medicine, argues that the new data illustrate why more research is needed to better understand the late effect of anti-cancer treatment in this population of survivors, and the particular long-term risks they have (2019; https://doi.org/10.1002/cncr.32064).

"To date, there's relatively little published data about the complications that may be unique to this particular [adolescent and young adult] age group," Hayashi told Oncology Times.

The data shows that this population is not only at increased risk of early death, but likely for other long-term side effects because of having cancer. "We should not be presumptuous that the scope of problems that young children experience or the scope of problems that older adults experience are readily transferrable to this age group," Hayashi said. "I think there's something unique about their problems."

Here's what else Hayashi said about what research he thinks is needed in this cancer survivor population, what steps are needed to change outcomes for these individuals, and why he calls this gap in research "a new frontier."

1. What are some of the key questions that future research needs to answer?

"First of all, there would be utility in forming more structured, long-term continuity clinics for this population. So-called 'late effects clinics' have been well-established in pediatrics for many years. They're beginning to take hold in adult oncology. And I think there needs to be a culture for oncologists to both support and transition patients to survivorship clinics where there is expertise on potential complications so that we can start to assemble larger populations that would be readily available for further investigation.

"These clinics serve multiple purposes. They provide a service to the patient in terms of giving them education and in terms of maintaining their own wellness and [managing] their risks for subsequent complications. They also give clinicians insights in terms of potentially the unique features of a population that has been relatively understudied.

"If we're successful at the national level assembling these patients into specialized clinics, I think we'll see insights into what are going to be the most obvious and pertinent questions for this group.

"And then we need to start to develop research groups that specifically focus on this age population. The two kind of go hand-in-hand because you can't really do research unless you have a critical number of patients, and it's difficult to assemble these types of populations [to study] if you don't have some mechanism to assemble them and study them systematically."

2. What are the challenges of pursuing this research and moving the needle to actually answer these types of questions?

"Funding is an issue. I think developing infrastructure and networks of survivorship clinics to assemble these populations [is an issue]. I think there needs to be an assemblage of investigators who have an interest and can commit time to start to network together and develop standardized workflows. I think they're going to be very important because the more fragmented the evaluations of the patients, the more difficult it is to try to discern what is the true prevalence of complications of this population.

"To the extent that clinicians who serve this population can learn from the past experiences from how both pediatric oncologists and some of the adult and older populations are beginning to advance, they can hopefully leapfrog on those experiences and establish the momentum, so they can then move their investigation forward.

"And I think what is going to be very important is that we're not presumptuous about what to expect. There are many features of this population that makes them very unique.

"One of the aspects of labeling this as a new frontier is not just the population, but also the rapidly evolving anticancer therapy that's developing with newer targeted therapies. We have whole classes of agents that literally have not been used long enough to know what the long-term toxicities are. So there's going to be a great need to further investigate that, not just for the adolescent and young adult population, but for all populations."

3. What's the bottom-line takeaway message about this new frontier in adolescent and young adult cancer survivorship care?

"We are obviously moving to an age in which winning the battle of cancer is now becoming a much more realistic and prevalent success story, and we can't lose sight of the fact that our obligations to the patient extend beyond achieving a cure for their primary malignancy. As clinicians who are responsible for administering these therapies, we need to at least facilitate access to care, so that [patients] not only remain cancer-free but that they are able to have a long and also functional life."

Friday, April 19, 2019

With Norman Sharpless, MD, former Director of the NCI

By Sarah DiGiulio

Cancer therapies and cancer care are more advanced today than ever before. And cancer researchers are continuously learning how to grow what we know. But to do that effectively, two thought leaders in cancer research say the clinical trial process that validates new treatments and delivery of care needs a revamp.

Norman Sharpless, MD, and James H. Doroshow, MD, coauthored a Viewpoint editorial that was published earlier this year in JAMA highlighting the different ways they suggest cancer clinical trials need to be modernized (2019;321:447-448). At that time, Sharpless was Director of the NCI; in April, he became acting Commissioner of the FDA. Doroshow is NCI's Director of the Division of Cancer Treatment and Diagnosis.

"The approaches we laid out are designed to reduce the financial pressure of clinical trials, conduct trials that complement those of industry, facilitate access to investigational agents, base trials on molecular alterations, and improve accrual rates," Sharpless told Oncology Times.

"Rethinking clinical trials is also about finding ways to overcome barriers that can get in the way of executing the most efficient trials," he noted. Here's what else Sharpless shared about the potential future of cancer clinical trials.

1. What prompted you and Dr. Doroshow to write this JAMA Viewpoint article now?

"With so many new and promising cancer treatments being developed, the importance of clinical trials to test them has never been more important. The past 10 years, in particular, have seen a transformational reworking of the NCI's clinical trials infrastructure.

"Clinical trials are the fundamental means for making progress in cancer treatment and prevention, but we need a shift in how we think about and design clinical trials to make them work better for researchers, clinicians, and patients.

"These changes must address such challenges as cancer heterogeneity, poor accrual rates, the difficulty patients have in finding trials, unnecessary exclusion criteria, and onerous costs. In short, we need to modernize clinical trials, moving towards smaller, more focused, more rapid trials that can often be deployed in a community setting."

2. The editorial talks about "right-sizing" trials as a way to drive down costs. What does it mean to "right-size" a clinical trial?

"'Right-sizing' clinical trials involves looking at the efficiency of trials, including decreasing the number of patients required to test the treatment under investigation. For example, as we say in the article, with some trials of highly active agents, it may be possible to forgo traditional control group interventions in favor of well-annotated 'synthetic' control arms that are created with data from previous trials.

"NCI is also exploring the use of novel endpoints that reflect the mechanism of action of the drug under study through pragmatic trials that are conducted in clinical practice settings, and through augmented annotation and aggregation of new and existing trials data. Such approaches would make it possible to answer relevant clinical questions without additional enrollment.

"Having said that, I am certain the NCI will need to continue to support large randomized trials of certain types of clinical questions. Such trials are sometimes the only appropriate way to answer certain key questions related to oncologic clinical practice. A recent NCI-sponsored example of such a trial is the TAILORx trial, which evaluated therapeutic de-escalation in women with estrogen receptor-positive breast cancer. The key for the NCI is to figure out the smallest appropriate trial design needed to address the clinical question being addressed."

3. You also talk about improving clinical trial accrual rates. What efforts are currently being made at NCI to do this? What will actually push the needle on changing this issue?

"One of our most promising efforts to improve accrual rates among our underserved populations is the NCI Community Oncology Research Program (NCORP) that brings cancer clinical trials to community settings. NCORP also allows us to reach more minority and underserved persons in the communities where they live. NCORP gives patients access to trials they might not otherwise have access to.

"The program not only increases the generalizability of study findings, but also illuminates potential disparities in outcomes. The NCI-MATCH trial, for example, is available at 1,100 sites across the country through NCI's National Clinical Trials Network and NCORP, leading to enrollment that better reflects the overall patient population.

"Maximizing accrual rates to clinical trials while still ensuring patient safety is a priority for NCI. For more than a decade, NCI has been committed to expanding the eligibility criteria for NCI-funded clinical trials, including decreasing the use of upper age limits in adult trials and making it possible for cancer patients who are also HIV-positive to participate in more trials.

"We've also revised our clinical trial protocol template to ensure participation by certain patients with brain metastasis and patients with altered organ function. The goal is to ensure that the results of clinical trials are broadly generalizable, so that as many patients as possible can benefit from new targeted cancer treatments and immunotherapies."

Friday, April 5, 2019

With Nathan R. Handley, MD, of Sidney Kimmel Cancer Center at Thomas Jefferson University

By Sarah DiGiulio

In the year following diagnosis with an advanced cancer, nearly three-quarters of patients are hospitalized. Some of those hospitalizations are necessary and some could be avoided with better management of symptoms throughout the treatment process.

In a recent "Comments and Controversies" article in the Journal of Clinical Oncology co-author Nathan R. Handley, MD, Assistant Professor of Medical Oncology at Sidney Kimmel Cancer Center at Thomas Jefferson University, explains why the "Hospital at Home" model could lower the number of those avoidable hospitalizations, lower costs to health care systems, and improve the quality of care for patients with cancer overall (2019;37(6):448-452).

Importantly, he also acknowledges the several challenges that must be addressed to implement such models of care (in the U.S. and elsewhere): selecting appropriate patients for such models of care, staffing and resource allocation (so that high-level care is available to patients in a timely manner), and reimbursement. But he argues that these challenges are surmountable.

"Logistics of care delivery are a barrier. Getting care to the patient, rather than having the patient come to care, changes the way we think about health care in general," Handley told Oncology Times. But he believes the benefits will be worth it.

1. Can you start by defining what "hospital at home" means—and when it comes to cancer care, what types of patients would benefit most from utilizing it?

"'Hospital at home' is a mode of care delivery in which hospital-level care is delivered in the home setting, rather than in the traditional inpatient unit. For something to be considered hospital at home, the quality and level of care received at home should be at least equivalent to what the patient would receive in the hospital.

"Hospital at home exists in the U.S. for general medicine conditions, with major active programs at Johns Hopkins [Medicine], Mount Sinai [Health System], and Cedars Sinai [Medical Center]. In these programs, commonly treated [conditions] include pneumonia, chronic obstructive pulmonary disease exacerbations, congestive heart failure exacerbations, and cellulitis (or similar infections requiring IV antibiotics).

"Most [hospital at home] programs have generally seen significant decreases in total costs of care. Quality of life is as good or better. Patients tend to be significantly more mobile in the [hospital at home] environment than the hospital environment. Hospital-acquired infections are less of a problem. Patient satisfaction tends to be as good or better as well.

"Many of the potentially preventable causes of admission described in OP-35 (a quality metric for outpatient care recently added to the CMS Hospital Outpatient Quality Reporting Program that will impact payments in the 2020 [financial year] and beyond) could likely be managed in a hospital at home program. These include things like anemia, nausea, dehydration, neutropenia, diarrhea, pain, emesis, pneumonia, fever, and sepsis. I would anticipate a significant amount of overlap in the selection criteria used by existing hospital at home programs.

"[But] the logistics are more challenging for a hospital at home model—it moves more of the work to the provider and the health system. And it's not right for every patient. A patient requiring advanced imaging, multispecialty consultation, or procedures would not likely be a good candidate for a program like this."

2. This model is being utilized outside of the U.S. already. Is it feasible in the U.S., too?

"A great example of a robust hospital at home program comes from Australia. In the state of Victoria, about 5 percent of all acute care bed-days actually occurs in the home setting. Examples exist through much of Europe as well. Some programs with a cancer focus also exist. For example, intensive chemotherapy can be given at home in Switzerland.

"The advantage all these programs have is that they either exist in fully capitated single-payer systems or they have arranged reimbursement equivalent to that received for traditional inpatient admissions. The challenge in the U.S. is that reimbursement mechanisms are lagging.

"It could be feasible in the U.S. Reimbursement makes it a bit challenging at present. That being said, some health systems that operate under a global risk model are already positioned to succeed in a hospital at home program (e.g., places like Kaiser Permanente or Geisinger). And policy is moving toward increasing reimbursement for home-based services. For example, CMS has proposed reimbursing providers for remote patient monitoring, which could be an important component of an effective hospital at home model. And Mount Sinai submitted a payment model (HaH-Plus) for their program to CMS; the Physician-Focused Payment Model Technical Advisory Committee recommended it be implemented, so that may happen.

"[But] it will require a significant mental shift. Reimbursement is still a barrier—hospitals are generally not going to be excited about moving patients out of the hospital if the total revenue decreases.

"I would say that the logistics of a program such as this may be simpler in an urban setting due to the geographic localization of patients. The biggest barrier in rural settings might be the time required for a provider to get to a patient—it would not be ideal if the patient were declining and the nearest provider was 3 hours away, for example."

3. What would you say is most important to know about the hospital at home model and its potential role in cancer care?

"The hospital at home model could have several compelling advantages over traditional inpatient care. Many patients with cancer spend a significant amount of time seeking and receiving care. By delivering care in the home setting, we can allow them to spend more time where many of them would prefer to be: at home. Hospital at home has the potential to deliver care in a safe, cost-effective manner while driving patient satisfaction."

Wednesday, March 20, 2019

With Ronald R. Barkley, MS, JD, President of the Cancer Center Business Development Group

By Sarah DiGiulio

Few disagree that high health care costs are a growing problem and solutions need to be developed. One solution is a system management and triage pathway protocol. The goal of these protocols is to reduce costs and deliver high-value care by better managing patient symptoms and side effects of treatment to reduce unwarranted emergency room visits.

A recent study examined the cost-savings potential of using such a strategy. Researchers identified likely emergency room visits that were avoided (as documented in the triage program) at two practices participating in the Center for Medicare & Medicaid Innovation's (CCMI) Oncology Care Model program over a 6-month period. They calculated an estimated cost savings based on the average emergency room and hospitalization costs for such events (J Oncol Pract2019;15(2):e91-e97).

The results revealed 222 emergency room visits were avoided—an annual cost savings of $3.85 million between the two practices.

"In addition to improved patient care and satisfaction, [this data provides] further evidence that cancer care costs can be reduced through a routine system of symptoms management and nurse triage of symptoms," noted study co-author Ronald R. Barkley, MS, JD, President of the Cancer Center Business Development Group, a company that advises oncology practices in transitioning to and implementing value-based care systems.

The researchers noted the study's limitations. For instance, it is impossible to know with certainty—based on the predictive design of the study—whether or not the emergency room non-events identified as being avoided because of the symptom triage program would have actually turned into emergency room visits or hospitalizations without the program.

The study authors also noted the time period used to look at such events was limited to 6 months, and the figures they reached do not include operating expenses incurred by the practices to provide the symptom management and triage program services, nor did the study attempt to identify any amounts of alternate payment model reimbursements earned by the practices associated with the cost savings achieved for payers. Follow-up research will analyze data from a larger number of practices and factor in operating cost data, Barkley said.

Here's what else he said about the significance of these findings and the potential of such symptom triage pathways.

1. What is a symptom management and triage pathways program and how do they help save money?

"A software service documents incoming patient calls and diverts high-acuity calls to a nurse call center for intervention. The system allows providers to manage a high volume of patient inquiries. Without it, a high volume of patient calls can slip through the cracks."

2. Why is value-based care and implementing strategies that save important in cancer care?

"There is heightened public awareness and government scrutiny with regard to the high costs of health care. It is well-known and documented that health care services are provided that are unwarranted, unnecessary, and could be avoided. This is true in oncology care.

"So, if we can avoid unnecessary services through care management and cost consciousness, why shouldn't we do so?

"Reduced units of service equal reduced costs (claims) to the system. Why is reducing emergency room events and associated hospitalizations an important part of overall cost-saving strategies (in addition to looking at other factors, like drug costs, etc.)? One of the three primary sources of reduced services and costs in oncology is in precluding unwarranted emergency room trips and subsequent emergency room-related hospitalizations.

"Cancer patients undergoing active treatment (chemo in particular) experience dizziness, nausea, vomiting, and dehydration. When a patient is at home and experiences these side effects, the natural tendency is to call 9-1-1 or run to the ER. However, if the patient and/or caregiver had an alternative, such as a nurse call service to walk them through their symptoms and see them at home, or an in-office physician instead, most of the emergency room trips could be precluded.

"Avoid an emergency room trip and emergency room-related hospitalization and you just precluded generating the associated costs.

"Note that chemo patient emergency room visits result in hospitalization a high percent of the time (50-75% in some instances). Emergency room staff are trained in trauma, not cancer care, so the tendency is to get the cancer patient out of the emergency room and into a bed to free up space for the trauma cases."

3. What is the key takeaway message from this research?

"Reduce costs to health care systems and payers through symptom management. However, there are operating costs to the provider associated with providing such enhanced care. Absent an innovative or alternative payment model to incentivize and compensate for the increased operating costs to providers and costs reduced (savings achieved for the payer), the only winner is the bottom line of the payer.

"Examples of [alternative payment models] in oncology that financially reward a provider for the extra effort are the CMMI Oncology Care Model program, Anthem Cancer Care Quality Program, and Aetna oncology medical home—all with economic features built in to incentivize providers to preclude unwarranted services and costs."