3 Questions on…

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

Monday, May 21, 2018

With Mark Burkard, MD, PHD, of the University of Wisconsin Carbone Cancer Center

By Sarah DiGiulio

Two individuals given the same cancer diagnosis and who end up following identical treatment plans may have identical outcomes. Or they may have very different ones. Across all cancer types, some patients survive years beyond their prognosis and some survive for far less time.

New research seeks to look more closely at why that is. Instead of starting with a specific drug or treatment, researchers at the University of Wisconsin will begin their investigation by looking at the best outcomes—by identifying exceptional survivors who have lived for a longer-than-expected time—and then looking at treatment decisions, genetics, lifestyle choices, or other factors that may have led to those outcomes.

"How do these exceptional patients survive so long with incurable cancer? We're hoping the answers can help more people live better and longer with cancer," the study's principal researcher Mark Burkard, MD, PhD, a breast cancer oncologist at Wisconsin's Carbone Cancer Center in Madison, said in a statement.

This study will focus on women with metastatic breast cancer. Though in the future, Burkard hopes the work will guide similar projects in pancreatic cancer, colon cancer, and other types of cancer, he told Oncology Times. Here's what else he said about the new project.

1. Can you walk through the steps of the study and how individuals can participate?

"In the first step, women or men with metastatic breast cancer can go to our website (bit.ly/2CiUdya); and if they are interested select 'Participate Now,' read the information, and then provide their contact information.

"Once we verify they meet eligibility requirements—an adult with metastatic breast cancer—we will email them a unique link to fill out a full web survey about their cancer history, treatment, habits, and diet. For this portion of the study, they need not be a 'long-term survivor.' We hope to have 2,000 individuals participate, of which 1,000 are long-term survivors.

"We plan to invite 50 individuals who are the longest-term survivors who have available archived tumor specimens to participate in step two. Individuals who choose to participate [in this second step] will send a saliva sample and give us permission to obtain medical records and archived tumor specimens from a surgery or biopsy in the past. We will use these to study the genes in the cancer and the genes in person.

"We hope to use this [information] to identify unique genes that control long-term survival, such as those that make slow-growing cancer or allow the immune system to restrain the growth of cancer."

2. What led you to look at these extreme survivors and how is the project different from other research?

"I met a 40-year survivor in clinic and was amazed to learn her story. I started asking my colleagues and discovered there are many more [long-term survivors] out there. I slowly came to the realization that we could learn a lot from these amazing people and use the information to help others.

"I opened a study of exceptional survivors at our hospital and found it would be helpful to identify more. At the same time, other exceptional survivors heard about some of the local news stories and asked to participate—I had emails from across the U.S. and one from the U.K. So it was clearly important to find a way for them to participate as well.

"There are ongoing projects that are working on genetic analyses of tumors in people with metastatic breast cancer. Also, there are studies on 'exceptional responders,' or people who have a surprising benefit from a particular drug. Though most exceptional survivors I have identified so far have not had such an exceptional response.

"Our study is the first comprehensive study, to my knowledge, that seeks to identify behavior, diet, treatment patterns, immune system, and genes that allow some individuals to be exceptional survivors."

3. What's the takeaway for practicing oncologists and cancer care providers about how this research will benefit their patients with breast cancer in the future?

"I'm hoping to identify the fundamental reasons why some people live so long with metastatic breast cancer. There are a number of alternative reasons that have been proposed—treatments, diets, habits, medical practices, immune system, or the genes driving the growth of the tumor. We are going to survey all these possibilities.

"Some of these [findings] could be directly used to advise other people on how to become long-term survivors. Others will not be easy for us to control (e.g., genes inside the tumor).

"However, even if the tumor genes are controlling long-term survival, we could at least identify which individuals are likely to be [long-term survivors] at the outset and develop a different treatment plan. It is possible, for example, that many of these people don't need to have harsh chemotherapies if they will outlive their cancer anyway."

Friday, May 4, 2018

With Douglas Blayney, MD, FACP, at Stanford University

By Sarah DiGiulio

How to deliver better value in cancer care is a question with a lot of different answers. In a new study, researchers took a closer look at patterns and structures within oncology practices across the U.S. to better quantify and make sense of some of those answers.

The research identified three attributes—early and normalized palliative care, ambulatory rapid response, and early discussion of treatment limitations and consequences—associated with practices that deliver the highest value care and had the highest potential for lowering spending without compromising the quality of care, according to the data published in JAMA Oncology (2018;4(2):164-171).

"We tried to find out what the distinguishing difference was [among the practices that delivered high-value care]," Douglas Blayney, MD, Professor of Medicine (Oncology) at Stanford University, told Oncology Times. "Early integration of palliative care, discussing limitations, and ambulatory rapid response of outpatient treatment problems before they became emergent were important."

For the study, the researchers looked at the top seven oncology practices in the Midwest and Pacific Northwest regions that consistently scored the highest on either QOPI measures or Choosing Wisely measures, and for which cost data was available, as measured by insurance claims data. Staff in those practices (including doctors, nurse practitioners, nurses, front office staff, and others who worked in the practice) completed questionnaires about what factors they felt allowed them to deliver high-value care. The researchers also conducted site visits to each of the practices, observed the staff 's actions, and asked additional questions of staff. The researchers grouped the responses into themes and then identified 13 attributes overall that helped the teams deliver high-value care. Of those 13, researchers ranked each in terms of the attribute's potential to improve quality of care and lower cost.

The aforementioned attributes were the ones most able to push the needle in both directions. Here's what else Blayney said about the findings.

1. Your research identified three attributes that distinguished the highest-value oncology practices in the subset of practices you reviewed. Can you explain those attributes in more detail?

"The high-value practices seemed to have three things that really stood out. The first included early incorporation of palliative care; and importantly, palliative care was a normal part of the practice and patient care. It wasn't anything that only happened at the end of life. The second thing was what we called ambulatory rapid response, which was ability to rapidly evaluate and care for patients who are having urgent problems before they turned into emergent problems and have to go to the emergency department or be hospitalized. [The third] was that the consequences and limitations of cancer treatment were discussed with patients and their families. And this was an early discussion [in the course of a patient's cancer care].

"Many of the high-value attributes represent a cultural shift in the way oncologists and medical oncologists practice, including early implementation of palliative care and making sure patients understand that, even though we're trying to cure them, some of the treatments we use do have limitations. Those are difficult cultural shifts, but they don't require huge investment in equipment or expensive changes."

2. There were other attributes you identified as being helpful in terms of delivering value. Can you explain those attributes and if any were unexpected?

"There was support for the patient. [Another attribute was that] care team members functioned at the highest level of their license and training. All of the practices, for instance, utilized the nurse practitioners and nurses to deal with symptom management within the scope of their licenses.

"[Another attribute was that] the physical layout and technical support facilitated high-value care. There was a team approach around the patient throughout the care trajectory—meaning, for instance, it wasn't just tech at the infusion center. It was the doctor and the team around the doctor.

"And, finally, we found that practices that function as a small unit, even if they work within a large health care system, tend to deliver higher-value care. And practices where EHRs were effectively used for communication among various components of the practice was foundational.

"I was surprised that there were no major academic medical centers—at least by our standards for this study—that were 'high value.' That's a disappointment to me because I work in one and I think we do deliver high-value care. But it points out that we all have work to do."

3. There's been a lot of research on how to deliver value in oncology. Why is this research important and why are these findings important and relevant now?

"If we move into a prospective payment system, much of the economic risk that was formerly born by insurance companies will be pushed downstream to patients and practices. So it's particularly timely that this research be highlighted so these systems are constructed and these payment models that we build implement these attributes.

"There may be more [attributes] that we have missed or we may be wrong. We've incorporated measures of quality and measures of cost into these questions in asking and answering questions about value. The next thing I think we need to [do is] incorporate the voice of the patient into the discussions around value and the procedures and processes that deliver high-value care.

"I think we have a good start, or [have proposed] a good start, to research methods to answer these questions."

Friday, April 20, 2018

With Paul C. Nathan, MD, MSc, FRCPC, of The Hospital for Sick Children in Toronto

By Sarah DiGiulio

Survivors of childhood cancer are known to be at higher risk for physical health problems later on, but whether or not (or how much) an early cancer diagnosis affects their mental health risks later on is not so clear. That's according to Paul C. Nathan, MD, MSc, FRCPC, a clinician investigator, staff oncologist, and Director of the Aftercare Program in the Division of Haematology/Oncology at The Hospital for Sick Children in Toronto, who recently investigated the question with his colleagues (Cancer 2018: doi:10.1002/cncr.31279).

"A lot of the risk factors were the same things we see in the general population," Nathan told Oncology Times. "The problem is that we tended to see these problems more frequently in childhood cancer survivors."

The researchers looked at the medical records of 4,117 5-year survivors of childhood cancer treated in any of the five pediatric cancer centers in Ontario, Canada, between 1987 and 2008. Everyone was diagnosed and treated before they were 18. The study cohort also included a control group of 20,269 healthy individuals matched for age, gender, and where they grew up geographically. (Because Canada has a publicly funded health care system, information about medical diagnoses, cancer treatments, and health care visits are available from cancer registries and administrative databases.)

The data showed that the childhood cancer survivors had a 34 percent increased risk for a medical visit for a mental health complaint than the general population. More than 40 percent of the survivors in the group studied had at least one visit for a mental health complaint. And the cancer survivors had a 13 percent increased risk for a severe mental health event, which included emergency room visits or hospitalizations due to a mental health complaint or problem. And childhood cancer survivors who were treated at the youngest ages (between 0 and 4 years) were at the highest risk for these severe mental health events.

Nathan said he and his colleagues were not surprised by the findings, as some previous evidence and their own clinical experience suggested they would find these elevated rates of mental health problems in survivors of childhood cancer. But, he added that the findings point to some very important implications. Here's what else he told Oncology Times.

1. There's a lot of research when it comes to survivors of childhood cancer—what's new about the question you asked and what you found?

"I think much of the focus in some of the survivor outcomes has been on the long-term physical consequences of cancer therapy. We know survivors have an elevated risk for chronic health conditions, such as cardiac disease, new cancers, and endocrine problems. There has been some work in mental health and psychological outcomes, but there's definitely been far less of a focus on that than there has been on the physical manifestations and the physical consequences of therapy.

"This study adds to the small, but growing, body of literature that [shows] surviving childhood cancer can impact long-term emotional and psychological health. And [it suggests] that risk-based care for cancer survivors—which considers previous cancer diagnoses, treatments received, and physical consequences—has to focus on mental health consequences as well."

2. Your data found one of the groups at the highest risk for mental health problems later on were survivors of childhood cancers who were treated at the youngest ages. Do you any suspicions why that group was at the highest risk?

"That finding was novel in that survivors who were treated for their cancer at a really young age (4 years or younger) seemed to be at a particularly higher risk for developing a severe mental health problem later on (requiring either hospitalization or an emergency room visit). And we don't really know why. Is there something about having had the traumatic experience of cancer at a very young age that somehow predisposes you to problems later? Is it possible that parents change how they parent their kids who have had cancer?

"They may not remember the actual experience of having had cancer. But maybe there's something about the trauma of having cancer—even if you can't remember the details—that has an impact.

"Maybe it's that we haven't historically thought about mental health care in these very young patients, so no attention is paid.

"These are all potential explanations. But, we would need to do more research in these younger patients to understand why we saw this. But it was a pretty striking finding about how much this risk was elevated."

3. What are the most important implications of this research?

"Message one: The complete care of survivors of childhood cancer must expand beyond just thinking about physical consequences, such as new cancer and heart disease. There needs to be a focus on the mental health of these survivors. And that means that those practitioners looking after them as adults, very often family doctors, need to be aware that they should be screening for things like anxiety, depression, PTSD, substance abuse, [and other problems]. Realizing now that this is a population at risk, there needs to be some focus on that risk.

"Two: [We need to look at] whether mental health care resources need to be available or offered more broadly during the pediatric years. Perhaps a more proactive pediatric approach will save patients from running into these mental health issues in adulthood.

"And lastly, another important message is [also] that, though the [mental health] risks are higher for survivors of childhood cancer, many of these survivors are also doing absolutely fine. We can be reassuring [to parents and others] that most kids and adults do absolutely fine, but we do need to be on the lookout for those who are struggling and have a means to get them help sooner rather than later."

Thursday, April 5, 2018

With JUAN FUEYO, MD, at MD Anderson Cancer Center

By Sarah DiGiulio

Recurrent glioblastoma is a tough cancer to treat. Glioma cancer cells at the outset are very resistant to treatments, such as chemotherapy and radiation therapy that tend to traditionally work in fighting and killing other types of cancer cells. "The FDA has only approved three drugs to treat malignant gliomas and one of them does not improve survival," explained Juan Fueyo, MD, Professor in the Department of Neuro-Oncology at MD Anderson Cancer Center, Houston. "Other therapies, including biological therapies, needed to be developed."

So Fueyo and other investigators developed the "smart bomb" virus or Delta-24, an adenovirus that is genetically engineered to replicate selectively in tumor cells. "The fact that the virus will identify a pathway abnormal in cancer cells to replicate and kill is the 'smart' component of the strategy," he told Oncology Times.

The team has published results of a phase I clinical trial that evaluated the therapy in 37 patients with malignant brain tumors (J Clin Oncol 2018; doi:10.1200/JCO.2017.75.8219). The trial was designed to assess toxicity and help determine an appropriate dose, not test efficacy, Fueyo said.

Twelve patients were treated with the virus and subsequently had their tumors removed surgically (patients in this arm had to have tumors that were manageable by surgery, which would have been standard treatment for these patients had they not be part of the study). The other 25 patients in the second arm of the study were treated with the virus and followed (and did not have their tumors surgically removed). The first group that underwent surgery gave the researchers the opportunity to observe how the virus had infected the tumor cells after the tumors were removed, Fueyo explained.

More than half of the patients receiving the therapy had some response and, of the group who did not have their tumors removed surgically, five patients survived more than 3 years with three patients showing a complete response (meaning they had clear radiological images and survival of more than 3 years). Toxicities among all patients on the trial were minimal, with two patients experiencing low-grade side effects related to treatment.

From the resected tumors, researchers observed that the virus could replicate in human tumors, noted Frederick Lang, MD, Professor and Chairman in the Department of Neurosurgery at MD Anderson. "Our trial was unique for brain tumor trials because of this arm. We didn't just look at clinical and radiographic outcomes. We actually looked at the biological effects of the virus on the tumor."

"And the patients eligible for this trial had already failed surgery, radiotherapy, and chemotherapy," Fueyo added.

More testing in a larger group of patients is needed before the therapy is ready for primetime, Fueyo said. Here's what else he told Oncology Times about the new treatment.

1. Why were you so surprised by the findings from this research?

"First, we did not expect to have long-term survivors—that a patient whose survival was statistically measured in weeks was capable to live for 5 years with great quality of life was a wonderful surprise.

"The second surprise came after the realization that the pathology and radiologic evidence pointed out that infection of the tumor with Delta-24 elicited an anti-tumor immune response that was probably responsible for the elimination of the tumors. This is a paradigm shift in virotherapy. As a result, virotherapy is now considered one of the strongest forms of immunotherapy for solid tumors.

"The trial also showed that Delta-24 is not toxic and can be safely administered by injection into solid tumors. The fact that the response to the therapy is not accompanied by the common and serious side effects of the chemo and radiotherapy is a big plus."

2. What's next for this therapy?

"We are now focused in improving the immune arm of the therapy. To this end, we have modified the Delta-24 to express immunomodulators. This new generation virus, called Delta-24-RGDOX, should be more powerful than the parental virus in the awakening of the immune system. Our lab published these results a few months ago in Cancer Research. In addition, the combination of Delta-24 with antibodies against anti-PD-1 is currently being tested in a multi-center clinical trial (the CAPTIVE trial). In 1 year, we should be able to know if the combination of these two treatments increases the percentage of long-term survivors [thanks to the use of] Delta-24 as single treatment.

"Also, the Delta-24 virus is now in a phase II clinical study and, if this trial is successful, that pathway for commercialization should be very fast.

"The virus is easily produced and vialed. It can be used in any hospital with a department of neurosurgery. [It's] a sophisticated treatment because its inception required knowledge of fundamental cancer biology and virology. But the process for the clinical grade manufacture is not complex—and the administration requires technology that is available in the majority of the hospitals.

"In a matter of few years the 'smart bomb' virus would be available to cancer patients. Delta-24 is targeted to a pathway that is abnormal in the vast majority of cancers and, therefore, the treatment can be applied to the majority of patients with solid tumors, including melanoma, breast, and lung cancers. The new generation Delta-24-RGDOX induces not only local anti-tumor effect, but it is also useful to treat metastases."

3. What's the takeaway for this new therapy?

"We should probably accept that, in addition to conventional therapies, new biological therapies including CAR-T cells, immune checkpoint antibodies, and oncolytic viruses are knocking on the door to be included in the current armamentarium of cancer therapies. Clinical studies are demonstrating these therapies work [based on] the new and more complete knowledge that we have of the immune system and the immune characteristics of the tumor. Immunotherapy is currently leading a revolution in cancer therapy that results in long-term survivors and should be kept in mind at the moment of planning any treatment regimen for cancer patients."

Tuesday, March 20, 2018

With Rakesh Patel, MD, at Good Samaritan Hospital, Los Gatos, Calif.

By Sarah DiGiulio

Several studies have investigated how outcomes and costs compare when it comes to choosing intraoperative radiation therapy versus external beam radiation therapy (EBRT). There are pros and cons to each treatment approach and, for some women, one or the other may be medically necessary.

But data that has been missing includes a comparison of the financial costs and the quality-of-life benefits and costs for each therapy over women's full lifetime.

A group of researchers recently collected such data and found that intraoperative radiation therapy did have lower lifetime costs compared with EBRT, as well as improved quality of life for the women receiving the treatment, according to a new study published online in Cost Effectiveness and Resource Allocation (2017; doi:10.1186/s12962-017-0084-5).

"Our analysis demonstrated that intraoperative radiation therapy could result in a direct cost savings for the U.S. health care system of more than $630 million over the lifetime of patients diagnosed annually with early-stage breast cancer, as well as significantly benefit patient health by minimizing radiation exposure and offering a better quality of life," the study's lead author Rakesh Patel, MD, Radiation Oncologists at Good Samaritan Hospital in Los Gatos, Calif., shared with Oncology Times.

The researchers used a Markov decision-analytic model using data obtained from peer-reviewed literature to compare the use of the two types of radiation therapy in women with early-stage (stages I-IIA/IIB) breast cancer. (That means that estimates of adverse events, quality of life, and incidence of death were based on probabilities extrapolated from the best available data in the literature to predict long-term outcomes for women receiving each type of treatment.) For EBRT, the researchers looked at data from 6-week treatment courses.

Here's why Patel said this data is significant.

1. This topic and the question you looked at is not necessarily one that's been ignored in other literature and research. Why was this study important and why now?

"This study examined the quality of life and direct costs of care in treating early-stage breast cancer with intraoperative radiation therapy versus EBRT over the life of the patient.

"In today's value-based health care landscape, it is important for clinicians to evaluate therapy options that deliver optimal outcomes for their patients while ensuring that health care dollars are invested most efficiently. So, the key findings of this study show that intraoperative radiation therapy allows a balance between these two critical factors for selected patients. It can potentially drive down the cost of breast cancer treatment while maintaining the patient's overall outcome and quality of life.

"In the U.S., there are approximately 60,000 new cases annually of in situ breast cancer. That is a daunting number. As a doctor, it is my responsibility to guide and treat these patients throughout their course of care, and that also includes educating them on all of their available treatment options. EBRT, considered to be the most common form of radiotherapy, is a lengthy treatment course (from 3 to 6 weeks), and quite frankly, some patients may be unable to commit to this; some may find it stressful; some may be looking for a different, improved patient experience. Therefore, conducting this research to determine the value of intraoperative radiation therapy as a meaningful treatment option for early-stage breast cancer was important."

2. Besides costs, what were some of those health benefits and quality-of-life benefits that women who underwent intraoperative radiation therapy had?

"Because EBRT delivers radiation to the whole breast, it can potentially cause radiation damage to surrounding healthy tissues and critical structures, such as the heart, lungs, and ribs. The study found that external beam radiation potentially exposed patients to four times more radiation than intraoperative radiation therapy, which could translate into greater than 15 times relative risk of longer-term complications.

"In addition, intraoperative radiation therapy treatments are shorter and, because of the more targeted radiation delivery, there are fewer patient side effects. These factors enable patients to return to their normal daily lives more quickly, reducing emotional stress, travel to and from doctors' appointments, days off work, and more.

"We hope this information will create awareness and better educate affected women about all of the treatment options available to them so they can make informed decisions. While not everyone will be a good candidate and approved to receive treatment for intraoperative radiation therapy, for those who are, they should fully understand this alternative, [and] its potential benefits and cost savings."

3. So what is the bottom line that practicing oncologists and cancer care providers should know about this research?

"As the U.S. health care system continues to move from a payment system relying on volume to one that relies on value, it's important for all clinicians to continue enhancing their quality of care [by] evaluating and identifying which therapies provide the best overall value and benefits for their patients, while also ensuring that health care dollars are being invested efficiently.

"By implementing highly effective, state-of-the-art technologies that save the health care system money while simultaneously providing effective patient outcomes, [like] targeted therapies such as intraoperative radiation therapy, clinicians are on the right track to achieving unprecedented success in this new era of value-based care."