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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

(radiotherapy).

"[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."​


Friday, July 8, 2016

With Mahiben Maruthappu, MD, Senior Fellow to the CEO of NHS England

By Sarah DiGiulio

 With global economic crisis comes increased unemployment, as well as reduced public sector spending on health care, and—according to new research—a rise in cancer mortality.

"Rise of unemployment was associated with increased cancer deaths -- and particularly in treatable cancers, which suggests that access to health care is ultimately important (because rates of non-treatable cancer deaths remained indifferent)," the study's lead author Mahiben Maruthappu, MD, Senior Fellow to the CEO of England's National Health Service and a practicing physician, explained about the research, which was published online ahead of print in The Lancet  (dx.doi.org/10.1016/S0140-6736(16)00577-8). "We were surprised by how neatly it fit together."

Other studies have compared socioeconomic change and socioeconomic status with cancer outcomes, but this is the first study Maruthappu said he is aware of that demonstrated these findings on this scale across so many countries.

Maruthappu and his colleagues gathered data from the World Bank on unemployment rates for 75 countries (representative of 2.106 billion people) and public-sector expenditure on health care for 79 countries (representative of 2.156 billion people). They compared those numbers to cancer mortality data from the World Health Organization between 1990 and 2010. In an interview with Oncology Times, Maruthappu discussed what the data showed and their implications for practicing oncologists.

1. What were the key findings from this study?

"We found that public spending in health care systems were associated with reduced cancer mortality and that rise in unemployment was associated with increased cancer mortality. Interestingly, in this analysis controlling for universal health coverage removed the association between unemployment and cancer mortality.

            "And we also found that treatable cancers are far more sensitive in these analyses to macroeconomic changes than non-treatable cancers.

            "We then conducted a time trend analysis that aimed to estimate the number of excess cancer deaths that occurred in countries with universal coverage and without universal health coverage. We found that in the full group of countries [the data covered] there was a significantly increased number of cancer deaths from 2008 to 2010. But those deaths were largely in countries without universal health coverage. We estimate that there were 260,000 additional cancer deaths between 2008 and 2010 alone.

            "Universal health coverage protected, and people who were unemployed [in those countries with universal health care coverage] therefore had potentially greater access to the health care services they need. And when we did an actual experiment looking at the recent economic crisis these trends all stood true.

            "That is quite a powerful indicator that universal health coverage has quite a significant role to play in the mechanism that link these economic changes to cancer outcomes."

2. Could you explain why and how you separated out treatable versus non-treatable cancers? What did you learn from those analyses?

"We labeled cancers as treatable or untreatable based upon whether they had survival rates that were comparatively low compared to those that were quite high. And the cancers that were categorized as treatable were breast, prostate, and colorectal cancers, which are also the most common. And the ones that were categorized as untreatable in this context were lung cancers and pancreatic cancers.

            "We found that the sensitivity of treatable cancers to economic changes were far greater and had a much stronger association in unemployment and spending cuts than non-treatable cancers. And in turn the protective role that universal health coverage played was much stronger for cancers that were treatable, which logically and intuitively made sense given our rationale for what's going on.

            "We believed that if people become unemployed or are in economic hardship they may have reduced access to health care services, which means that their cancer may not be picked up as early on or may not be treated as well—which in turn means that they may be more likely to die.

            "And if a cancer is treatable that means that like for breast cancer or colorectal cancer, having access to health care resources you need generally plays a big role, whether it be chemotherapy, radiotherapy, or surgery that you need. In contrast, if your cancer is largely untreatable having access to the health care resources you need probably won't make that big a difference or as big a difference. And that's exactly what we found."​

3. What should practicing oncologists and oncology care providers know about these findings?

"Oncologists need to be quite proactive if they are providing care to people who are potentially unemployed. In the same way that we consider other risk factors for certain types of cancers, we need to be looking at socioeconomic status and employment status and factor that into our equation. And that's because if they are unemployed they will be less likely to continue a treatment or have compliance with treatment. We, as healthcare professionals, need to be aware of that and have a proactive response."


Wednesday, June 22, 2016

With PAUL SABBATINI, MD, Deputy Physician-in-Chief for Clinical Research at MSKCC[NC1] 

By Sarah DiGiulio

The medical and research community knows that clinical trial patient enrollment is low, Deputy Physician-in-Chief for Clinical Research at Memorial Sloan Kettering Cancer Center (MSKCC), Paul Sabbatini, MD, explained. For adult cancer patients, the enrollment rate is just three percent, according to the Institute of Medicine's 2010 "Transforming Clinical Research in the United States."

That's a problem, Sabbatini said. "Every advance in the way we approach cancer treatment today has come from a past clinical trial--and tomorrow's advances will be generated by today's clinical trials."

To better understand some of the dynamics behind those low clinical trial enrollment rates, MSKCC commissioned a national survey of consumers, as well as of practicing physicians late last year. The survey data included 1,511 consumers 18 to 69 and 694 practicing physicians who had previously discussed clinical trials with patients across the specialties of oncology/hematology, obstetrics/gynecology, urology, ear/nose/throat medicine, neurology, pulmonology, or dermatology. MaPS/Millward Brown Analytics conducted the survey; Sabbatini and his colleagues have submitted an abstract with the data for publication.

Sabbatini walked through the key findings from those data (available online: www.mskcc.org) and the implications for oncology in an interview with Oncology Times.

 

1. What would you say were the key findings from this survey and were they surprising?

"One of the most significant things we learned through the survey was that only 40 percent of American consumers have a positive overall impression of clinical trials, and only 35 percent are likely to enroll. This was extremely alarming to us.

            "Yet after reading a brief statement that helped them to better understand clinical trials, positive impressions among consumers increased to 60 percent. Their likelihood to enroll increased to 44 percent. This points to a desire for education, which is both an opportunity and a challenge that we must embrace.  

            "Additionally, when we asked about top barriers for clinical trial participation, we found that consumers and physicians share similar concerns. When asked about their main deterrents when considering participating in a clinical trial for cancer treatment, consumers surveyed pointed to side effects/safety (55%), potential costs (50%), location of treatment (48%), and worries over getting a placebo (46%). When physicians were asked what they believe are their patients' biggest concerns when considering participation in a clinical trial for cancer treatment, they cited side effects/safety (63%) and concern about getting a placebo (63%).

            "Finally, of the almost 600 physicians polled, more than half (56%) of physicians said they considered clinical trials late in treatment, with 28 percent noting them 'as a treatment of last resort.' Only one-third (32%) said they discuss the topic with their patients at the beginning of treatment. However, it is important to evaluate clinical trial enrollment every time a change in treatment is considered."

 

2. How do these results inform how to actually increase clinical trial participation?

"The survey findings signal to us that we must do a better job educating people on what clinical trials are and what they are not--this includes consumers and physicians.

            "We also need to be communicating about the importance of clinical trials of all kinds, but especially with cancer. Thanks to the many advances in precision medicine, researchers are now able to sequence more and more genes and to do it at a faster rate. But we must start by having the necessary volume, and that comes from patients feeling they are armed with the information they need to opt in to a clinical trial."

 

3. What would you say is the bottom line that practicing oncologists everywhere--whether they are involved in clinical trials research or not--need to know about these findings?

"Education is our biggest barrier to enrollment. We were pleased to see that when we shared some basic information about what trials are, the overall positive impression of consumers jumped from 40 percent to 60 percent. Physicians also reviewed the statement and the majority responded in a positive way, noting that this type of statement could be helpful/useful--68 percent said they would be likely to use the statement with patients and 69 percent felt it would be effective in educating patients.

"We need to commit to starting a national dialogue on the importance of clinical trials--one that involves oncologists and institutions around the country. Speaking with a collective, collaborative voice is the best way to ensure that the message is being heard."

 

Sarah DiGiulio is a contributing writer.

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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