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Tuesday, October 25, 2016

With Sriram Yennu, MD, MS, of MD Anderson Cancer Center Department of Palliative Care and Rehabilitation Medicine

By Sarah DiGiulio

While research shows there is a long way to go to successfully making palliative care part of standard care for patients with advanced cancer treated at cancer centers across the U.S., a new study reveals there is an even longer road ahead when it comes to making palliative care a global standard of cancer care.

The main goal of the new research was to look at the characteristics of patients receiving palliative care that were associated with a poor perception of curability, explained the study's lead author Sriram Yennu, MD, MS, Associate Professor in the Department of Palliative Care and Rehabilitation Medicine in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston.

"This was the first study that had the presentations from so many different continents," he said. The research was presented at this year's Palliative Care in Oncology Symposium and analyzed data from 1,390 patients with advanced cancer receiving palliative care from countries in North and South America, Europe, Asia, and Africa (Abstract 05). Among all of the patients, 49 percent reported that their cancer was curable, 60 percent perceived the goal of their therapy was "to get rid of their cancer," 79 percent perceived that the goal of their therapy was to "make them feel better," and 62 percent perceived they were relatively healthy.

Additional analysis revealed the patients from France and South Africa were more likely to have an accurate perception of the goal of their treatment, while patients from the Philippines, Brazil, and Jordan were more likely to have the misperception that the goal of their treatment was to cure their cancer. What's more: these regional differences were more significant in explaining the gaps in the patients' misperceptions about the curability of their cancers than age, gender, marital status, religion, and passive decision control preferences.

In an interview with Oncology Times, Yennu elaborated on what these findings mean and how the researchers plan to use the new data.

1. What would you say are the key findings from this research? And were you surprised by the findings?

"Many advanced cancer patients have confusion. They have poorly answered questions regarding their disease, treatment goals, and decision-making.

"The main goal [of our study] was to look at the patient characteristics associated with a poor perception of curability.

"We found there was a really significant role of culture in how patients perceive the curability of their cancer and the goals of their treatment.

"Patients belonging to countries such as the Philippines, Brazil, and Jordan had a poor perception of curability, and patients belonging to countries such as France and South Africa had more accurate perceptions of curability, compared to the United States. Interestingly, age and marital status, religion, and the way they are making decisions showed no significant [role] in patients' perception of curability.

"Education, which is a surrogate for socioeconomic status, [also played a role in patients' perception about their disease]. Patients who were highly educated (having a college or advanced degree) were more likely to have an accurate perception of the goals of their palliative care compared to others who had a high school education or less.

"But what exactly causes people to have these varying perceptions about their cancer and care is not clear from the results of this study. We need further studies to investigate what is modulating what."

2. What should practicing oncologists (in any country) know about this research?

"Communication—patient-physician communication—is a really critical aspect of what physicians do in the management of the disease. That includes reviewing different treatment regimens and the traditional approach, discourse about the disease, and the goals of therapy to help patients get the appropriate treatment.

"Asking a patient what they understand about the perception of curability is the first step physicians need to do to help that patient.

"Then they need to explain what the goals for therapy are. And once that is explained, we need to reiterate during subsequent visits all of those points."

3. How will you continue this research? What are the next steps?

"The questions that were answered were very straightforward. The next step would be doing some qualitative studies to understand why this is and developing a grounded, theoretical framework so that we can develop interventions using modalities like decisional aids and checklists to help patients have the correct perception of curability—and thereby help them make the right decisions."

Monday, October 10, 2016

With Heather Greenlee, ND, PHD, Epidemiologist at Columbia University

By Sarah DiGiulio

Obesity has long been known to complicate cancer treatment—and in specific cancers has been associated with worse prognoses. That's what led Heather Greenlee, ND, PhD, Assistant Professor in the Department of Epidemiology at the Mailman School of Public Health at Columbia University, New York, N.Y., and her colleagues to take a closer look at the prevalence of obesity among patients with a history of cancer, as well as how those rates have changed in recent years.

The researchers analyzed rates of obesity from 1997 to 2014 in 538,969 adults in the U.S. between 18 and 85 who were part of the National Health Interview Survey (NHIS) for a study that is now published online ahead of print (JCO DOI: 10.1200/JCO.2016.66.4391). Within the sample, 32,447 patients had survived cancer.

The data show obesity rates were higher for patients with cancer compared to individuals without a history of cancer, and obesity rates also increased quicker among the individuals who had had cancer. Prevalence of obesity had increased from 20.9 percent to 29.5 percent during that period for the individuals who had no history of cancer—and from 22.4 percent to 31.7 percent for the individuals who had had cancer.

The study coauthors explain why these findings are so significant in the paper: "It is well established that obesity can influence other medical conditions such as diabetes, heart disease, hypertension, and hypercholesterolemia, which may affect overall survival. In addition, specific chemotherapy agents have cardiac adverse effects that can be compounded by higher BMI. … Studies of breast, colon, and prostate cancer showed comorbid conditions increase 5-year all-cause and cancer-specific mortality. Therefore, it is important to consider obesity among cancer survivors not only in relation to cancer outcomes, but also in relation to other comorbid diseases."

Greenlee, the study's lead author, elaborated on how these findings should influence practice.

1. What is new about these findings that was not previously known about the prevalence of obesity among patients who had survived cancer?

"To our knowledge, this study is the first to use a nationally representative dataset to look at the trends over time. We examine annual data from 1997 to 2014.

"NHIS is a nationally representative dataset, which is an ongoing cross-sectional survey of health status, health care access, and behaviors of the U.S. population. We think that this dataset can provide a largely unbiased estimate of obesity among the sampled population.

"This paper clearly shows that obesity rates have been increasing over time for cancer survivors, that this rate is higher than the rate in the general populations, and that there are specific subgroups where the rates of obesity are the highest.

"Obesity is a growing public health issue. It is on a trajectory to get worse over time. And we need to develop effective programs and interventions to change the course of what is happening at a population level."

2. What should oncologists and oncology care providers know about the prevalence of obesity rates among their patients with cancer—as well as about the resources that are currently available to patients with cancer to treat, manage, and prevent obesity?

"Obesity among cancer survivors is common, and is a growing problem. There are subgroups of patients who are at particular risk of obesity, which puts the patients at risk for a multitude of chronic health issues. Clinicians need to work with their patients to effectively treat and manage obesity.

"Currently, there are not good insurance reimbursement streams for nutrition, physical activity, weight loss, and weight management programs for cancer survivors. If patients want to engage in these, they largely need to pay out of pocket, which is a huge barrier. We know that simply handing patients a booklet on food, physical activity, and weight goals is not enough to effectively change behaviors. Patients need education, skill building, and support to effectively make lasting changes—most people can't do this on their own."

3. So what is the next step? Who develops those interventions and how do they get implemented?

"Our research program is examining and testing strategies to prevent and manage obesity in the oncology setting. In my opinion, the main barrier to implementing effective weight management programs is financial resources.

"There is not going to be a 'one-size-fits-all' approach to manage obesity among cancer survivors. Survivors need to have options that work with their lives and their learning styles. They also likely need ongoing support. We are testing various methods that use in-person, written, and mobile health formats to understand which formats will work best."​

Wednesday, August 24, 2016

With Lauren Wallner, PhD, MPH, Assistant Professor of General Medicine at the University of Michigan Medical School

BY Sarah DiGiulio

Patients with cancer can get all sorts of information about what their diagnoses might mean and what their treatment options are online—via email, social media, and web-based support groups. But whether or not such communication helps patients make better decisions, or leaves patients happier with the decisions they do make, is a debated question. New research published online ahead of print in JAMA Oncology offers a few insights on the topic.

"Our study suggests that there continues to be an unmet need in patients for more decision-making support," explained the study's lead author Lauren Wallner, PhD, MPH, Assistant Professor of General Medicine at the University of Michigan Medical School.

Wallner and her colleagues looked at data from 2,460 women who had had a diagnosis of breast cancer who answered survey questions for the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles County from July 2013 through September 2014 about their online communication use and their own appraisal of their treatment decision-making (doi:10.1001/jamaoncol.2016.2070). The data shows that the women who were more frequent users of online communication—including social media, online support groups, email, and text messages—more positively appraised their decision making about their cancer treatment compared with the women who did not report using methods of online communication.

Wallner told Oncology Times more about the research and how it might affect how oncologists help their patients make decisions about their treatment options.

1. Why did you and your colleagues decide to look at social media use among patients with breast cancer and how can practicing clinicians use findings like these?

"The use of online communication, particularly social media, has rapidly grown among cancer patients and survivors in recent years—particularly in breast cancer. Yet we knew very little about what types of patients are using it, why they are using it, and whether or not using it results in improved outcomes.

"We, therefore, asked women about their use and reasons for use to better understand whether social media and other online communication tools could be used to communicate and support patients through the treatment decision-making process and [their] ongoing care.

"While this was a large and diverse population-based sample of newly diagnosed patients with breast cancer in Los Angeles and Georgia, it is possible that these results may not be generalizable to patients in different geographic areas. Also, it is possible that use among patients with different types of cancer may differ."

2. Were you surprised by the findings? What was most significant?

"I was surprised that the use of online communication was not higher in this population, as breast cancer patients are a very engaged and active on social media sites like Twitter and Facebook. But in our large and diverse population, only 41 percent of women reported some frequent use of online communication and only 12 percent of them were using social media sites.

"While use of social media and other online tools in the context of cancer has been increasing in the past decade, and past studies have shown that, ours is the first (to my knowledge) to assess whether use of these online communication tools was associated with more positive appraisals of cancer treatment decision-making.

"Our study suggests that women newly diagnosed with breast cancer who frequently used online communication—such as email and social media—were more likely to deliberate longer about their breast cancer treatment decision and be more satisfied with their decision."

3. In the paper, you and your coauthors explain: "The presence of variation across age, race and education reinforces that barriers exist to incorporating these modalities broadly across patients with cancer. Additional research is needed before these modalities can be leveraged to improve patient care experiences." Could you elaborate on where your research showed these barriers exist?

"We found strong gradients in online communication use across age, race, and education. Older women, black and Latina women, and those with less education were less likely to be using these forms of online communication.

"These barriers in use need to be considered [to be able] to leverage social media and other forms of online communication to support women through their treatment decision and ongoing breast cancer care. At least in our sample, using these forms of communication would not currently reach all patients who need support."

Tuesday, August 9, 2016

With Ton Schumacher, PhD, of Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital and Leiden University

By Sarah DiGiulio

Cancer immunotherapies have led to some of the best outcomes when it comes to anticancer drugs. Except, that is, when they don't work.

But new findings suggest there may be another way to make cancer immunotherapy drugs a lot more effective more of the time. The new study suggests some T cells from healthy donors may be able to specifically recognize neoantigens present on human tumors and mount effective attacks against those tumors (Science 2016;352:1337-1341).

"[The study] showed that neoantigen-specific T cells from healthy donors could recognize and kill melanoma cells harboring the relevant mutation in vitro," Mahesh Yadav and Lélia Delamarre, both of the Department of Cancer Immunology at Genentech, wrote about the new research in an accompanying editorial (Science 2016;352:1275-1276). "The findings point to a new individualized approach for expanding immunotherapies."

The difference between this approach and previous T-cell therapies, they argue, is that this approach might be a way to systematically identify allogeneic T-cell receptors directed against neoantigens to build effective therapies.

"A systematic approach for identifying immunogenic neoantigens in a high-throughput manner is needed to advance neoantigen-based approaches in cancer immunotherapy. The findings of Strønen et al. now put us more firmly on that path," they write about the new research.

The approach has only been tested in the lab, so much more research is still needed to know if and/or how well the approach will work in developing new cancer drugs.

Study author Ton Schumacher, PhD, Senior Member at the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital and Professor of Immunotechnology at Leiden University, told Oncology Times more about the research and why it might be so promising.

1. For oncologists without expertise in translational research, what are neoantigens and what do they (or might they) play in cancer immunotherapies?

"Recent research by others and us has shown that the DNA damage that, on the one hand leads to oncogenic transformation, also leads to the formation of aberrant peptides (neoantigens) that can be recognized by T cells. T-cell recognition of such neoantigens appears to explain much of the clinical activity of the cancer immunotherapies, such as PD-1 blockade, that are now revolutionizing cancer treatment for a number of human malignancies.

"A surprising finding in the prior research on T-cell recognition of neoantigens has been that in most patients the number of neoantigens to which a T-cell response is mounted is very modest, even for tumors with large amounts of DNA alterations. Here we wanted to determine whether the T-cell based immune system might perhaps not respond to 'all that is foreign' on the tumor cells.

"To address this, we first determined which neoantigens would be predicted to be present on the tumors of three patients. We then showed that the vast majority of these predicted neoantigens were not seen by T cells from the patients. But, when we used T cells from healthy donors, we could induce T-cell recognition of a large set of these neoantigens in an in vitro system.

"The research can be seen as further evidence that even though tumors arise from our own tissues, the DNA damage that they often carry offers an opportunity for attack by the immune system, and that therapies that aim to exploit this 'foreignness of human cancers' are of high interest."

2. So how do these findings change the way researchers currently think about immunotherapies?

"The key finding of our research is that there are many tumor antigens on human melanoma that can be recognized by T cells, but to which the T-cell pool of the patient did not mount a measurable response.

These data thereby indicate that it should be feasible to broaden the tumor-specific T-cell response in cancer patients.

"Most current cancer immunotherapies rely on the endogenous T-cell pool of the patient to recognize cancer cells. The current data suggest it may actually be feasible to exploit an 'outsourced immune response,' using T cells from healthy donors as a starting point, to boost tumor-specific immunity."

3. This study looked at melanoma cells. How broadly do you expect this approach to work outside of melanoma?

"We expect that this approach may also be effective for other tumor types with similar amounts of DNA damage, such as lung cancer or bladder cancer.

"The next step [of our research] is to further optimize the technology we have developed to create neoantigen-specific T-cell responses in vitro and to develop efficient strategies to transfer the neoantigen specific T-cell responses from these T cells into patient T cells. Together, this would allow us to test the concept within the clinic."

Wednesday, July 27, 2016

​​With Daniel Heller, PhD, Molecular Pharmacologist at Memorial Sloan Kettering Cancer Center

By Sarah DiGiulio

P-selectin—a molecule on the inner walls of blood vessels—plays an important role in allowing tumors to metastasize. Researchers say they have now found a way to target the molecule using nanoparticles that they say may be key to better delivering anticancer drugs to stop those metastases.

"The nanoparticles that we synthesized have affinity for P-selectin, which is present on or can be induced (via radiotherapy) to appear in the walls of tumor vasculature," noted researcher Daniel Heller, PhD, Molecular Pharmacologist at Memorial Sloan Kettering Cancer Center, New York, N.Y. "The nanoparticles bind to the P-selectin, causing them to localize within the tumor microenvironment and deliver drug cargoes there, including precision medicines.

"The drugs which we load into the nanoparticles are not new, but this technology may allow the development or rescue of drugs which have good anti-cancer properties but have poor pharmacologic properties," Heller explained.

This drug delivery process has a lot more testing to go before it reaches the bedside, including being tested in clinical trials. But the researchers say the strategy could be effective across almost any tumor type. The data were recently published in Science Translational Medicine (2016;8:345ra87).

Here's what else Heller told Oncology Times about their findings.

1. Why target P-selectin?

"It's not a conventional 'drug target,' but a new target that can be used to cause a drug carrier (i.e., the nanoparticle that carries drugs) to stick to a tumor site. This is true because the target appears in tumor blood vessels (that feed metastatic tumors). P-selectin often facilitates the metastatic process by causing circulating tumor cells to adhere to blood vessel walls, extravasate, and form new metastases.

"We used P-selectin as way to target drugs to these metastases. We developed a new class of nanoparticles composed of the polysaccharide fucoidan, which has specific affinity to P-selectin. The

fucoidan-based nanoparticles can be loaded with many different classes of drugs.

"And we showed, using two metastatic tumor models, that doxorubicin-encapsulated nanoparticles targeted to P-selectin are much more effective than untargeted nanoparticles, or the same amount of doxorubicin given conventionally. A single injection of the nanoparticles resulted in complete tumor inhibition in 50-80 percent of the mice, depending on the metastatic model."​

2. What advantages would this type of drug delivery have over existing modes of anti-cancer drug delivery?

"New 'targeted' therapeutics and precision medicines, like MEK inhibitors, can be targeted using these nanoparticles, which can significantly reduce the side effects of these drugs.

"Not only did we show that the nanoparticles allow us to give much greater doses of chemotherapeutic drugs to a tumor than could normally be administered, we also showed (in collaboration with the José Baselga Lab) that the pharmacokinetics, pharmacodynamics, toxicity, and efficacy of a personalized drug can be much improved by physically targeting these 'targeted' drugs.

"We found that the tumor-targeted nanoparticles can localize MEK inhibitor in the tumor site, resulting in prolonged inhibition of pERK. MEK inhibitors can cause serious dermatologic side effects. We

showed that the drug doesn't get to the skin and doesn't affect the skin when it is administered using the nanoparticles, but it is much more effective against the tumor."

3. Your paper notes this strategy could be effective against almost any tumor type. Why?

"This approach would work for any tumors that express P-selectin, which includes both primary and metastatic tumors. This would also work for any tumor that could be irradiated via ionizing radiation


"[We also found that] radiation can be used to 'guide' these nanoparticles to the blood vessels of nearly any tumor, even if the target (P-selectin) doesn't naturally appear in the tumor because

P-selectin is produced in blood vessels upon exposure to radiotherapy. Therefore, radiotherapy can be used to produce the target in the tumor before the nanoparticles are administered, ensuring that the target is present for the nanoparticles to stick to.

"We don't have any indications whether this technology would work better or worse in metastatic tumors, but we found that metastatic tumors are good targets."​

Do You Have a Question?

Sarah DiGiulio
The “3 Questions on…” blog asks oncology’s thought leaders for their perspectives and takes on the field’s current news and controversies. Want to get answers to your questions? Add a comment or email Pam Tarapchak at pam.tarapchak@wolterskluwer.com or Catlin Nalley at catlin.nalley@wolterskluwer.com to suggest a topic for a future column. We want to hear from you!

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