3 Questions on…

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

Monday, November 13, 2017

With Gil Bar-Sela MD, at Rambam Health Care Campus in Haifa, Israel

By Sarah DiGiulio

Previous research offers some fairly strong evidence that cannabis use has the potential to suppress immune system functioning (Eur J Immunol 2010;40:3358-3371). That could be a problem if the increasingly commonly used drug is being taken by cancer patients on immunotherapies. And that's why Gil Bar-Sela, MD, Head of Supportive and Palliative Care at Rambam Health Care Campus in Haifa, Israel, and his colleagues decided to investigate potential interactions between cannabis and the immunotherapy nivolumab. They presented their data at the ESMO 2017 Congress in Madrid in September (Abstract 1545PD).

The researchers led a retrospective, observational study that analyzed records of 140 patients treated with nivolumab at Rambam Health Care Campus between 2015 and 2016. Eighty-nine patients reported only taking the cancer drug, and 51 patients reported taking the cancer drug, as well as using cannabis. The patients in the trial were taking nivolumab to treat either advanced melanoma, non-small cell lung cancer, or renal clear cell carcinoma.

The analysis showed that cannabis use was the only significant factor that reduced the patients' response to nivolumab for the group: 37.5 percent of the patients not using cannabis had a response to the drug, while 15.9 percent of the patients having reported using cannabis had a response to taking nivolumab. Though, cannabis use did not significantly affect progression-free survival or overall survival among the patients.

Bar-Sela said the results, while not conclusive, are noteworthy for patients taking immunotherapies—and warrant further prospective clinical study.

1. What were the key findings from this research—and which, if any, of the findings were surprising?

"The key finding was the lower response rate to immunotherapy in the group of patients that had taken cannabis [at] the same time. The only parameter that influenced the response rate to immunotherapy was cannabis. Other parameters [including smoking, hypertension, brain metastases, and more] influenced survival and that was not surprising.

"In retrospective data, we collect all available data from the files and run them in the multivariate regression model. Of course, not all of [the results] have meaning. For example, smoking is higher in the lung cancer patients, resulting in lower progression-free survival compared [to patients with] renal cell carcinoma, and so on. These other parameters are related directly to the patients' illnesses and general situations.

"This topic [has not been] reported before. It is the first time. However, some concern was raised in the '90s when some patients with AIDS took cannabis for symptom relief.

"The finding [supports] the hypothesis that such interaction is possible. Cannabis depressed the immune response, according to several basic [studies]."

2. What conclusive were these findings and what implications do these findings have for how cannabis use might affect the effectiveness of other immunotherapies besides nivolumab?

"The data is retrospective, and results should be taken with caution. [Currently], we are prospectively collecting blood samples from patients undergoing immunotherapy [who are either cannabis users or not] to better understand the specific influence on the immune system.

"The prospective trial is collecting data from all patients using immunotherapy drugs, [either] as single medications or in combination. The main difficulty of such a study is the heterogeneous population of the study and the unknown differences in the immune system we are looking for. So, [this research] probably will serve as a search for differences that will lead to proper laboratory study of the interaction.

"An interaction [with cannabis] is possible for all immunotherapy drugs and is not specific to nivolumab. As far as I know, there is no negative interaction with chemotherapy."

3. What should all practicing oncologists and cancer care providers know about your research and how cannabis use among their patients might be affecting treatments?

"According to basic studies, cannabis probably is immunosuppressed—and in this one study of retrospective data, there was a negative interaction with immunotherapy drugs. Personally, I give this information for patients who are on cannabis and starting immunotherapy or vise versa. I think it is important information for the patients to make the right decisions regarding their treatment.

"This information should be studied more. However, I think it is important for the patients now, not just in a year or two when the data from the prospective trial will be available."

Tuesday, October 24, 2017

With Walter F. Baile, MD, of The University of Texas MD Anderson Cancer Center

By Sarah DiGiulio

Better communication means better outcomes when it comes to medicine. That's something doctors and health care researchers have known for a long time. But implementing strategies to improve health care provider-patient communications is easier said than done.

Now ASCO has taken an important step forward by issuing the organization's first set of guideline recommendations to outline best practices for cancer clinicians when communicating with patients and their loved ones (J Clin Oncol 2017:doi:10.1200/JCO.2017.75.2311).

"Communication skills are essential to providing patient-centered, comprehensive oncology care and should be a key competency for all oncologists," said Walter F. Baile, MD, Professor of Behavioral Science and Psychiatry in the Department of Behavioral Science, Division of Cancer Prevention and Population Sciences at The University of Texas MD Anderson Cancer Center, Houston, who served as Co-Chair of the ASCO expert panel that authored the guidelines.

ASCO has always taken an interest in promoting good clinician-patient communication, though these are the first clinical practice guidelines that have been issued, Baile told Oncology Times. "More recently, however, we have come to recognize how profoundly important [such communications] are to the patient and family—and are associated with important outcomes, such as end-of-life decisions.

"In addition, we now have evidence that [these skills] can be taught and learned," said Baile, who is also Director of the Interpersonal Communication And Relationship Enhancement (I*CARE) program in the Department of Faculty Development at MD Anderson.

The guideline expert panel conducted a systematic review of previous guidelines, research, and reviews published in the past decade to draft and finalize the recommendations. Key recommendations from the new guideline include the following:

  • communication skills training programs should be available to oncologists at every level of practice;
  • clinicians should clearly establish care goals with their patients and make sure their patients understand their prognosis, as well as their treatment options;
  • clinicians should encourage patients to discuss their concerns and guide conversations;
  • clinicians should initiate conversations about patients' end-of-life preferences early in the course of incurable illness, as well as throughout their care;
  • clinicians should discuss patient concerns about cost of care; and
  • clinicians should make patients aware of all their treatment options, which may include clinical trials or palliative care for some patients.

Here's what else Baile said is important for oncologists and all cancer care providers to know about the new recommendations.

1. The new guideline notes: "Good interpersonal skills are not a substitute for strong health care communications skills." Can you elaborate on what that means and why it's important in these recommendations?

"Communication skills should not be confused with being 'charming' or having good 'bedside manners'—although these may help in establishing rapport with patients and families. Beyond this, many conversations with patients and families can be very challenging, including giving bad news and discussing complex treatments and end-of-life conversations. These require specific skills that can be learned and taught. Moreover, patients value their relationship with their oncologist, which is anchored in good communication skills. In fact, these skills are recognized as an essential component of patient satisfaction with care."

2. How do you intend for clinicians to use these guidelines?

"First of all, we hope they can serve as a guide to help our training programs define what communication skills are essential for our fellows to master as part of their training.

"Secondly, we feel they serve as a tool for how to, not only establish a collaborative relationship with the patient and family, but make recommendations as to when and how to approach difficult communications, such as talking about prognosis and cancer recurrence.

"[And,] they are important guidelines, but providers must remember that every patient and family is different. The guidelines are meant to provide flexibility and a 'patient-centered' or better yet a 'relationship-centered' approach so they can be adapted to the needs and concerns of each patient resulting in truly personalized care."

3. What else needs to happen to actually make these changes (and improvements) in patient-doctor communication happen?

"Communication skills training needs to begin in fellowship and use methods such as simulation and role-play so learners can master specific skills. Barriers are always time and competition with other learning in the curriculum. [But], beginning early during formative years can allow oncologists to master skills that will serve them during the more than 30,000 encounters with patients and families they are likely to have over the course of their career. For more senior clinicians, learning to use communication protocols for giving bad news is useful."

Tuesday, October 10, 2017

With Paolo Tralongo, MD; Mary S. McCabe, RN, MN; and Antonella Surbone, MD, PhD, FACP

By Sarah DiGiulio

The field of cancer survivorship care has grown significantly in the past 2 decades—yet there are still many very real challenges in the delivery of cancer survivorship care and meeting the needs of cancer survivors. That's the bottom line from three experts in the field: Paolo Tralongo, MD, Chief of the Medical Oncology Division at RAO Umberto I Hospital, Siracusa, Italy; Mary McCabe, RN, MN, Director of the Cancer Survivorship Initiative at Memorial Sloan Kettering Cancer Center, New York City; and Antonella Surbone, MD, PhD, FACP, Professor in the Division of Hematology and Medical Oncology at New York University School of Medicine, according to their recent editorial (J Clin Oncol 2017; https://doi.org/10.1200/JCO.2017.74.3450).

"Although significant success is certainly true for advocacy, it may be best to limit any celebration regarding the success of the medical management and care delivery aspects of survivorship care," the three noted. "Furthermore, the unique individual and sociocultural factors that play a major role in the delivery and acceptance of survivorship care are yet to be fully addressed."

They argue that better "categorization" of cancer survivors would help tailor care to better meet the very different needs for more patients on the spectrum of their post-cancer journeys.

1. What area of care for cancer survivors still needs attention and improvement?

Tralongo, McCabe & Surbone: "We wanted to make the point that survivorship care shouldn't have a one-size-fits-all approach. Rather, we now understand that care can and should be tailored based on treatment exposures. And, even though many survivors do very well, we should focus on assuring the highest quality of care for all individuals after treatment ends.

"Much progress has been made in terms of care and medical care in survivors. However, much still needs to be done to create the best survivorship care model. Many of these patients suffer from the late effects of active treatments—surgery, chemotherapy, radiotherapy—that are not only intended as physical disturbances, but also as psychological discomfort.

"Individual and sociocultural factors that play an important role in accepting survivorship care need to be taken into account. As the number of cancer survivors continues to increase, it becomes more and more important to educate health providers about the care standards that have been developed so to assure that survivors receive quality care internationally. Patient categorization is a further step forward."

2. How does patient categorization work when it comes to cancer survivorship care?

Surbone: "The categorization of cancer survivors that we have proposed in the present and past JCO articles requires a paradigm shift in the culture of cancer survivorship care, whereby we abandon a common, general approach to all cancer survivors in favor of the application of our epidemiologic knowledge and the developing risk assessment tools to tailor follow-up and recommendations to each individual cancer survivor. Cancer and survivorship care should both move to personalized precision approaches, as it is done in other chronic diseases.

"Personalizing follow-up will improve the medical and psychosocial care for each individual survivor and will help reduce the stigma of disease that still persists in many cultures."

Tralongo & McCabe: "The key thing to understand is that cancer survivorship is a formal period of care with a developing set of care guidelines that are specific to categories of patients, allowing for tailored, patient-centered care. Indeed, knowledge of these topics will help improve the care patterns, enabling better identification of individual disorders and individual risk."

3. What's the next step to developing better survivorship care models?

McCabe: "Research is still needed to evaluate the effectiveness of various models of survivorship care that have been developed, but not evaluated. Related research is needed to understand the most relevant models of care for underserved survivor populations. In addition, health services research is needed to evaluate the degree of dissemination of interventions developed for the management and prevention for long-term and late effects of treatment."

Tralongo: "At the same time, it is important to start rehabilitation pathways that should be considered as multidimensional/comprehensive rehabilitation, focused on improving or regaining both physical and psychosocial abilities, as needed from diagnosis onward."

Tralongo, McCabe & Surbone: "At the national level, ongoing efforts are needed by key organizations such as ASCO, American Cancer Society, National Comprehensive Cancer Network, and Institute of Medicine to continue their leadership in developing guidelines for clinical care of survivors.

"At the local level, a commitment is needed by the oncology community and primary care community to focus on the needs of survivors with attention to implementation of what we know along with researchers across the spectrum of medical, psychosocial, health services, and epidemiologic specialties, as well as to evaluate genetic mutations and environmental exposure."

Monday, September 25, 2017

With Skyler Johnson, MD, of Yale School of Medicine

By Sarah DiGiulio

Skyler Johnson, MD, a resident in the Department of Therapeutic Radiology, and his colleagues at Yale School of Medicine, New Haven, Conn., were bothered by a certain trend they noticed: their patients were refusing conventional cancer treatments at the time of diagnosis. They also were seeing that patients with advanced cancers who had been diagnosed much earlier had refused conventional treatment to try alternative medicines. After those therapies didn't work, they came back to receive conventional therapy.

Johnson's group used the National Cancer Database to look at patients diagnosed with the four most common cancers in the U.S. between 2004 and 2013 (breast, lung, prostate, and colorectal cancers). They compared outcomes for patients who chose an "unproven medical therapy delivered by a nonmedical professional" at the time of diagnosis with matched patients who chose conventional therapies. The data was stark.

Overall, the patients who chose alternative therapies had a 2.5-fold increased risk of death compared with patients who chose conventional therapy after 5 years. Looking only at patients with breast cancer, risk of death after 5 years was five times higher among the patients who chose alternative medicine. For patients with colorectal cancer, risk of death was four times higher for patients who chose alternative medicine. For patients with lung cancer, risk of death was two times higher among those who chose alternative medicines. And there was no statistically significant increased risk of death at 5 years for patients with prostate cancer who chose alternative medicine over conventional therapy, which Johnson noted was expected.

The data was published online ahead of print in the Journal of the National Cancer Institute (doi:10.1093/jnci/djx145). Here's what Johnson said cancer care providers and patients should know about these findings.

1. Were you surprised by the findings?

"I was surprised initially that [the increased risk of death with alternative medicines] weren't higher. Two-point-five sounds like a high number, but based on our anecdotal experience in clinic we thought it might be much worse.

"The data we collected was for initial treatment only, that first treatment decision that patients make [after they are diagnosed with a cancer]. Just like we were seeing patients whose cancers had advanced, gotten worse, and then they were coming [back] in for conventional therapies—that's perhaps what was happening in our dataset. So we likely under-ascertained for the true treatment affect. Some of these patients [who initially chose alternative therapies] may also have received a conventional cancer therapy later, which may have improved their survival.

"Plus the National Cancer Database only collects from accredited cancer centers. A lot of patients who were coming to see us after they had tried these alternative medicines were coming from different centers as well. So, there are a lot of patients treated at places where their data was not likely collected."

2. Is there clear data overall on how many patients choose alternative therapies over conventional treatment—and why?

"This is a really hard question to answer because we know there's a hesitancy on behalf of patients to tell their physicians this is the decision that they're going to make. So we really don't know how to quantify the exact number of patients doing it. Our dataset is small and it's only about 0.02 percent of the total patients in the dataset, but that likely underreports [the true number of patients who choose alternative medicines].

                "There was another code in the dataset where patients were refusing conventional cancer therapies and they didn't give a reason. We didn't include those patients because we didn't know what they were doing or why they were refusing, but it's likely that at least a majority or at least a portion of those patients were doing some form of alternative medicine, too. It's an area of further research that's needed.

"And it's hard to know why patients choose alternative over conventional therapies. There's marketing [from the alternative medicine industry]. It could be physicians not doing a good enough job explaining why to choose evidence-based treatment. It could be the patients themselves who feel that alternative medicines might be more effective or less toxic despite the lack of evidence for that claim."

3. What would you say is the bottom-line message about this work and alternative medicines for cancer treatment?

"Alternative medicines can be defined as unproven therapies. They may be being researched in preclinical settings or laboratory settings, but if they're unproven to work, they are not medicine. The discussion becomes more nuanced when talking about some complementary therapies. Someone who receives acupuncture or a botanical or other type of medicine as a complementary medicine may be able to safely do that—but they to do it under the guidance of their physicians in addition to their conventional therapies, not in lieu of conventional therapy.

"The long and short of it is that, if a person chooses alternative medicine for their curable cancer as their initial treatment choice, they are at greater risk of death than if they were to choose conventional cancer therapy. [How great that increased risk is] is dependent on which cancers they have. But there's a real risk associated with taking that decision that can affect their chance at cure and survival."

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."