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

Friday, May 20, 2022

With Luke Shenton, MPH, & Ann Klassen, PhD, of Drexel University College of Medicine

By Sarah DiGiulio​

While the link between quitting smoking and lower cancer risk is well-known, the link between quitting smoking and better cancer outcomes (even for patients who quit after a cancer diagnosis) is less talked about. But  a growing body of research shows that patients with cancer who continue smoking during cancer treatment have poorer treatment outcomes and poorer quality of life compared with never smokers—and quitting can be beneficial.

In 2017, the National Cancer Institute launched its Cancer Center Cessation Initiative, an effort to improve smoking cessation efforts in NCI-designated cancer centers. It calls for these facilities to routinely offer evidence-based smoking cessation treatment services to all cancer patients; improve electronic medical records (EMRs) to better track cessation services offered to patients and follow up to help facilitate that care; and overcome barriers to tobacco cessation efforts. To improve smoking cessation services at Sidney Kimmel Cancer Center in Philadelphia, researchers conducted qualitative one-on-one interviews with patients and clinicians.

In an interview with Oncology Times, two researchers—Luke Shenton, MPH, lead author and medical student at Drexel University College of Medicine, and Ann Klassen, PhD, Member of the Cancer Prevention and Control Program of the Sidney Kimmel Cancer Center Consortium—discussed the findings and next steps of their work.

1. What are some of the biggest barriers to better tobacco cessation outcomes?

Shenton: “We used a framework to look at three different factors in smoking cessation: factors that might predispose someone to quit, enforce them quitting, and once they're in the process, factors that reinforce them continuing down that road.

“There were really big differences in opinions between patients and providers. A lot of patients report a barrier to being able to go through this process is financial. They said programs were expensive and the resources to quit (things like medications or other products) are expensive. But when you talk to providers, they categorized those things as positive enablers because these resources are free to patients. So there's a disconnect in the financial aspect in that these resources are supposed to be free, but a lot of patients don't know how to access them.

“Another big barrier we identified was time management within the oncology visit. Even though smoking cessation counseling only takes a few minutes, a clinician might only have 20 minutes for a visit with a patient, during which they also have to talk about treatments, other symptoms, surgery results, and other things.

“And, finally, there's a difference in opinion among providers about the importance of smoking cessation during cancer treatment. Everyone thinks it's important overall, but some clinicians are more of the mindset [that] the patient is here to have their cancer treated and we should probably just focus on that."

Klassen: “I think it's also maybe not widely recognized how burdensome tobacco addiction is in terms of someone's mental health. And at the same time, patients often want to take an action during cancer treatment to improve their health. There's a lot they can't control, but we find that behavior change interventions during treatment can often be therapeutic because they offer something patients can actually do.

“We sometimes look at cancer patients and think they have so much going on and they're overwhelmed, [and] we shouldn't burden them with cessation. But often, cessation is something patients appreciate being counseled on."

2. How do you think this data should inform next steps on improving tobacco cessation?

Shenton: “Moving forward, we need to do better with education. Patients need education on where they can get the right resources and the benefits of smoking cessation. And providers need education on all the ways smoking cessation can actually make a difference in the treatment process and how they can quickly use the EMR to connect patients with these services.

“The majority of providers already do have conversations about tobacco cessation with their patients, but sometimes there's a disconnect between offering the services and then following through. Currently, much of the burden of the work of quitting falls to the patient. But we know that a multidisciplinary approach is usually best. Most patients who end up quitting do so with medication, counseling, and having family members as peer support. Sidney Kimmel is already working on this in terms of updating the workflows, so that there's an opt-out rather than an opt-in strategy for tobacco cessation for patients."

Klassen: “They're working on upgrading the EMR so that information is shared more easily, so providers can better see if a patient followed up about a smoking cessation referral. Did they go once and not come back? What can the physician do when she or he sees the patient again to keep the process moving?"

3. What do you want the cancer center community to know about this work?

Klassen: “Every cancer center sits within a community and understanding what the burden of addiction is in your community, what public health partners you have in that community, [and] what the culture of tobacco use looks like is important. And it's really important to build a comprehensive tobacco control strategy to bring all of your inpatient, outpatient, and community services under one umbrella. I think we're moving toward a bigger public health vision of tobacco control—not just [asking if we can] get you through your surgery, but can we reduce the role of tobacco in your life, your family's life, and keep your family healthier at home?"

Shenton: “Also, it's been well-known for decades that smoking causes cancer. And a lot of people really focus on that, but then once you already have cancer, some people think it doesn't really matter anymore. But there is a growing body of literature showing the effects cessation can have during treatment—better surgical outcomes, higher survival rates of actually making it through chemotherapy, lower pain severity, and higher quality of life post-cessation."

Thursday, May 5, 2022

With E. David Crawford, MD, Professor of Urology at University of California San Diego School of Medicine

By Sarah DiGiulio

Some prostate cancers grow slowly and don't need treatment. Others are aggressive, spread quickly, and require timely treatment with surgery, radiation, chemotherapy, or a combination. But other prostate cancers fall in the middle of this scale. They require treatment, but not as aggressive as fast-spreading tumors. And patients with this category of prostate cancer may be candidates for high-intensity focused ultrasound treatment (sometimes referred to as HIFU). It's a minimally invasive, outpatient treatment for localized prostate cancer that uses high-frequency sound waves directed at the cancerous tissue through an ultrasound probe inserted into the rectum. The sound waves direct enough energy to the tumor to cause cell death.

Clinicians use high-resolution images combined with biopsy data and real-time ultrasound imaging to provide urologists with a 3D view of cancerous tissues. Physicians can then draw precise contours around the diseased tissue and ablate only that portion of the affected organ. The procedure minimizes damage to surrounding structures, as well as the risk of urinary incontinence and erectile dysfunction.

David Crawford, MD, a urologic oncologist at University of California San Diego Health and Professor of Urology at UC San Diego School of Medicine, is one of the physicians who does the procedure at UC San Diego. The treatment option is not yet available at all cancer centers. But given its reduced risk of side effects and effectiveness compared with other treatment options, Crawford hopes the procedure becomes more widely available.

1. How does high-intensity focused ultrasound (HIFU) for prostate cancer work?

“With HIFU, you focus the sound waves and energy to heat up the cancer and kill the cancer cells. The technology has graduated from the beginning machine to the ones we use now, which use computers to very safely outline and treat the lesions in the prostate. This and other safety mechanisms built into the machine make sure we don't overheat the rectum or any of the surrounding tissue.

“The patient needs to be very still during the procedure. Usually, we do it with the patient under general anesthesia. The treatment doesn't take that long. The whole thing is usually over in a little over an hour. The side effects are pretty minimal. But it's only appropriate for the right patient."

2. Which patients are the right candidates for this procedure?

“There are some prostate tumors that are so slow-growing they don't need treatment. Some more aggressive cancers may require surgery and radiation, treatment of the whole prostate. But for a subset of men, they have tumors that you don't necessarily just want to watch and wait, but you don't want to treat aggressively. They're sort of in the middle.

“The tumors need to be localized in the prostate, usually only in one or two places that are away from critical areas, like the sphincter that controls urination, the rectum, and other organs. With this procedure you can target the lesions and, with one simple outpatient treatment, can eradicate it. When it comes to treatment for prostate cancer, one size doesn't fit all. Not everyone is eligible for this technique."

3. What is the bottom line oncologists should know about this treatment?

“For men with low-risk prostate cancer that is localized (and the whole prostate does not need to be treated), HIFU may be a really good option. There are other options for localized treatment (like lumpectomy and cryotherapy), but this is a better mouse trap in a way. It's more precise. And the technology has improved since these machines were first introduced.

“It's a step forward. But it should be used in the right person. If you don't, there's the risk of not curing the cancer or overtreating some people that may not need to be treated." 

Wednesday, April 20, 2022

With Wei Yang, PhD, Associate Professor of Surgery & Biomedical Sciences at Cedars-Sinai Cancer

By Sarah DiGiulio​

Researchers have identified a new protein suspected to be involved in prostate cancer metastasis. Their data suggest that the anticancer drug ponatinib, an existing FDA-approved protein inhibitor, reduced prostate cancer growth in mouse models. While there's a lot more research needed before the work can be translated into helping improve outcomes for patients with metastatic prostate cancer, the researchers say the data so far is encouraging.

“Our findings suggest that pharmacological inhibition of RIPK2 is a very promising approach to preventing or delaying prostate cancer metastasis," said study author Wei Yang, PhD, Associate Professor of Surgery and Biomedical Sciences at Cedars-Sinai Cancer. “Targeting RIPK2 will delay the painful symptoms of metastatic prostate cancer and may increase patient survival by years rather than months." The data were published online in Nature Communications (2022; doi.org/10.1038/s41467-022-28340-6). In an interview with Oncology Times, Yang shared more about his work.

1. What are the key findings from this research and what do they add to what was previously known about prostate cancer metastasis?

“The key findings are that receptor-interacting protein kinase 2 (RIPK2) is a novel drug target in prostate cancer metastasis; RIPK2 functions by activating a previously unknown signaling pathway (RIPK2/MKK7/c-Myc phosphorylation cascade) in prostate cancer cells; and RIPK2 inhibition by the FDA-approved ponatinib reduces prostate cancer metastasis in mice by 92 percent. These findings reveal a previously unknown drug target and molecular mechanism in prostate cancer metastasis.

“Despite advances in prostate cancer treatment, distant metastasis remains a major cause of morbidity and mortality from the disease. Most patients diagnosed with metastatic prostate cancer die within 2-3 years. As the proverb goes: 'An ounce of prevention is worth a pound of cure.'

“Thus, an urgent unmet clinical need is to identify new drug targets whose pharmacological inhibition can prevent the formation of radiographically visible metastases. In this study, we discovered RIPK2 as one such drug target. Although RIPK2 has been well-characterized in inflammatory disorders, little is known about its functions and mechanisms in prostate cancer metastasis."

2. How did you land on RIPK2 as a potential target?

“The first question is: Which druggable proteins are involved in prostate cancer progression and metastasis? To answer this question, we analyzed three publicly accessible clinical omics databases to identify potential drug targets in prostate cancer metastasis. Among the seven candidates, RIPK2 has the greatest change in expression levels as prostate cancer progresses. Therefore, we decided to focus on studying the roles and mechanisms of RIPK2 in prostate cancer metastasis.

“Next, is RIPK2 alteration associated with prostate cancer progression and poor prognosis? Indeed, we found that RIPK2 alteration occurs more frequently along with prostate cancer progression and that high RIPK2 expression levels are associated with poor patient survival. Notably, RIPK2 is overexpressed in about half of lethal prostate cancer tumors, suggesting that targeting RIPK2 may benefit a large population of patients with advanced prostate cancer.

“Is RIPK2 required for prostate cancer metastasis? Through in vitro cell assays, we showed that RIPK2 is required for cell invasion and colony formation—two key biological processes in cancer metastasis. Through in vivo studies, we found that RIPK2 is primarily required for prostate cancer metastasis rather than tumor growth.

“How does RIPK2 function in prostate cancer metastasis? Using multidisciplinary techniques, including multi-level proteomics, we discovered that RIPK2 functions primarily by activating MKK7/c-Myc signaling, a novel pathway distinct from the canonical RIPK2/NF-κB signaling pathway.

“Is it possible to drug the RIPK2/MKK7/c-Myc signaling pathway? Indeed, we found that the signaling pathway can be inhibited by two different RIPK2 inhibitors—ponatinib and GSK583, with the former being more potent than the latter. Importantly, our mouse studies showed that ponatinib can reduce prostate cancer metastasis by up to 92 percent with few side effects."

3. What's the next step of your work and the bottom-line message practicing oncologists should know?

“The next step is to identify molecular biomarkers for selecting right patients for anti-RIPK2 treatment and monitoring drug response. We will also develop small-molecule inhibitors that specifically inhibit the RIPK2/MKK7/c-Myc signaling pathway, minimizing side effects caused by inhibition of other RIPK2 pathways (such as the canonical RIPK2/NF-κB pathway). Our ultimate goal is to translate the findings into clinical trials to substantially improve cancer patients' survival and quality of life.

“The bottom line is that targeting RIPK2, specifically RIPK2/MKK7/c-Myc signaling, is a very promising approach for preventing prostate cancer metastasis and increasing patient survival by years."

Thursday, April 7, 2022

With Richard Wender, MD, Chair & Professor of Family Medicine and Community Health at Penn Medicine

By Sarah DiGiulio​

Disparities in cancer outcomes related to social factors are common, including income, health insurance, social support, and access to high-quality treatment. That's a bottom line Richard Wender, MD, Chair and Professor of Family Medicine and Community Health at Penn Medicine, believes the oncology community needs to know. A growing tome of evidence points to this. He recently wrote an editorial published in the journal Cancer about the findings of one such study (2022; doi: 10.1002/cncr.33890). The new data is a prospective analysis of cancer mortality and eight potential social determinants of health in a cohort of more than 29,000 adults (Cancer 2022; doi: 10.1002/cncr.33894). That new data reported a significant association between cancer mortality and six of those social determinants of health. Wender cites examples of the many other studies that point to the same conclusion in the editorial.

“The cancer care community should be intolerant of disparities in cancer risk and outcomes," he said. “Every cancer treatment center has an obligation to consider and address these factors." That point is underscored in the editorial; the burden of addressing these inequalities falls to those in the oncology community in addition to others.

“Creating integrated systems of care with shared goals of treatment—between oncologists, the entire treatment team, and hospitals—offers our best opportunity to address social needs," Wender noted. “Partnerships between larger cancer treatment centers or academic health centers and smaller hospitals are critical to increasing the likelihood that all patients benefit from advancements in management and care." In an interview, Wender shared the recommendations he makes in the editorial.

1. The editorial proposes several guidelines to help reduce disparities in cancer outcomes related to social determinants of health. Who are the guidelines for and which players will help move the needle in terms of making change?

“The principal target for the first guideline set is cancer treatment centers. This first set outlines steps that every cancer center must incorporate into routine care. Create a more diverse workforce that reflects the community and can confront implicit bias and structural racism. Screen for social needs. Deploying more resources to help people overcome barriers to care should be an expectation.

“I think the toughest recommendation to meet is helping people address financial toxicity. This demands policy change and innovative practice. Hospitals that are themselves in financial distress will have particular trouble addressing financial toxicity."

2. You also make recommendations for reducing the social and economic disparities that lead to disparities in health, and more specifically, cancer outcomes. What is oncology's role in addressing the root causes of these disparities?
“This second set of recommendations is particularly demanding. I actually think the cancer community and cancer treatment facilities are probably better positioned to follow these steps than most or any other disease-related program.

“Cancer care begins with reducing risk factors and cancer screening, and extends all the way to cancer diagnosis, treatment, and supportive care. Partnerships with community are vital to achieving prevention goals. Measuring outcomes at the level of the population, rather than the level of patients, is actually an expectation for National Cancer Institute-designated cancer centers and should become a routine.
“The cancer community can become powerful advocates for policy change that lessens the likelihood that cancer will lead to bankruptcy. So, yes, I think telling this story through the lens of the cancer patient is very important."

3. What further research needs to be done to better address and improve the social determinants of health, as they relate to cancer?

“There are so many research opportunities. Some are:

  • randomized trials of screening for social needs at diagnosis and periodically through disease management;
  • trials of different types of financial support through treatment;
  • development of models of community health scorecards;
  • studies of the effect of workforce diversity and health outcomes;
  • continued studies of how best to deploy social work and navigators for patients in treatment;
  • studies of various policies, such as expansion of Medicaid on cancer outcomes for people who need cancer treatment; and
  • studies of routinely measuring process and outcomes by income, race, and ethnicity."

Tuesday, March 22, 2022

With Georges Mjaess, MD, at University Clinics of Brussels, Erasme Hospital​

By Sarah DiGiulio

In a recent commentary article in the journal Cancer, researchers noted that there is some very preliminary evidence that the bacteria in the gut may affect immune checkpoint inhibitor therapy efficacy in people with melanoma—and furthermore, that fecal microbiota transplant may help improve response to the drugs in people who would otherwise not do well (2022; https://doi.org/10.1002/cncr.33893). The group investigates how it may be time to explore the potential for a similar approach in urological cancers. Georges Mjaess, MD, the paper's lead author and a researcher in the Department of Urology at University Clinics of Brussels, Erasme Hospital in Belgium, shared more on this research with Oncology Times.

1. What promise does fecal transplant hold for urological cancers?

“Immune checkpoint inhibitors are often considered as the last strong weapon in treating cancer until now, and [they] have a better safety profile compared to other systemic treatments, providing a good quality-of-life to our patients. In urological tumors, they are recently proposed in the adjuvant, as well as in the neoadjuvant settings, in urothelial carcinoma and are the backbone of first-line treatment of metastatic renal cell carcinoma. However, in many situations, we find unfortunately that some patients are resistant to immune checkpoint inhibitors, and until now we do not know exactly why.

“An important goal to reach is to try to understand why some patients are non-responders, and to overcome this resistance in a way that helps patients benefit from this type of treatment that has a good safety profile, provides a good quality-of-life, and prolongs survival.

“In the last decade, there is a boom in discoveries and research about the human microbiota, and it has been demonstrated that it plays an important role in immunological, metabolic, and structural landscapes of the human body. Cancer is not an exception, and it has been proven to be in one way or another related to certain patterns of microbiota. More precisely, as the tumor development is dependent on the immune system, and given that immunity is modulated by the gut microbiota, any disruption in this microbiota could result in tumor progression. In the same way, the gut microbiota has been proven to be a potential modulator of response to immune checkpoint inhibitors.

“Regarding urological tumors, the human microbiome was shown to be linked to bladder cancer, prostate cancer, and renal cell carcinoma, both in the progression and treatment response of these malignancies. Moreover, antibiotics, which are a key modulator of the gut microbiome, were linked to worse oncological outcomes in urological tumors.

“Fecal microbiota transplantation is also an important modulator of human microbiome, commonly used in the treatment of refractory C. difficile infection, inflammatory bowel diseases, metabolic disorders, and liver cirrhosis. As the fecal transplant concept is to 'refresh' the status of the gut microbiota, it was interesting in the last years [to test] fecal transplant from responders to non-responders to immune checkpoint inhibitors to see if this can reverse the non-response to the drugs, and this was confirmed in two studies on melanoma. Since immune checkpoint inhibitors are a vital treatment in urological tumors, fecal transplant could be also applied in the field of genitourinary cancers."

2. What research most aptly demonstrates the potential of this approach?

“The most important studies that were recently published are two proof-of-concept studies published on melanoma by Davar, et al (Science 2021; doi: 10.1126/science.abf3363) and Baruch, et al (Science 2021; doi: 10.1126/science.abb5920). In the study by Davar, et al, fecal microbiota transplant was demonstrated to overcome resistance to anti-PD1 immunotherapy, offering a clinical benefit in six out of the 15 included patients (40%) with a median overall survival and progression-free survival of 14 months. In the Baruch, et al, study, three patients out of 10 (30%) have shown clinical responses, including one complete and two partial responses. Fecal microbiota transplant was demonstrated, therefore, to indeed 'reset the dial' in patients whose melanoma is not responding to immune checkpoint inhibitors.

“Until now, there is no published clinical trials on urological tumors and publications are restraint to melanoma patients. However, there are numerous trials ongoing in urological tumors, such as the TACITO trial, a randomized controlled trial assessing fecal microbiota transplant in advanced renal cell carcinoma patients, and the PERFORM trial whose aim is to evaluate the safety of a combination of immune checkpoint inhibitors and fecal microbiota transplant in intermediate/poor risk advanced renal cell carcinoma. On the other hand, fecal microbiota transplant still holds limitations that need to be considered, such as the gut microbiota's large heterogeneity among donors and/or receivers, high cost, and low evidence of the studies published until now. For these reasons, fecal transplant cannot be considered until now in the treatment of immunotherapy-resistant urological tumors."

3. What should cancer care providers know about your work?

“Microbiota modulating strategies, such as fecal transplant for gut microbiota, and the encouraging results recently published with anti-PD1 immunotherapy in melanoma, promote more trials and investigations aiming to test these strategies in urological tumors.

“A clear message from our work is that we cannot nowadays deny the prominent role of the human microbiota in cancer. Polymorphic microbiomes—including gut, skin, vaginal, lung, and oral microbiomes, but also tumoral, and recently urinary microbiota—constitute distinct promoting characteristics that enable the acquisition of hallmark capabilities and modulation of tumor phenotypes.

“We have seen the emergence of targeted therapy whose aim is to target many hallmarks of cancer development. We think that we should now focus more on targeting the human microbiota in cancer treatment, since it is now well-known to be an essential hallmark of cancer, and fecal transplant is a promising modulating strategy that could be one of the new standards in the next decade."