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

Wednesday, September 20, 2023

3 Questions on… Breaking Down Clinical Trial Participation Disparities

​With Maria Velez, MD, at the David Geffen School of Medicine at UCLA

By Sarah DiGiulio

Maria Velez.jpgPatients with limited English proficiency are likely to be systematically excluded from clinical trials, which may contribute to the underrepresentation of certain racial and ethnic groups in cancer research. This is given that people with limited English proficiency often form part of historically underrepresented racial and ethnic groups. Individuals from historically under-represented racial and ethnic groups are less likely to join cancer clinical trials than individuals from higher-represented racial and ethnic groups. These individuals also are more likely to have limited English proficiency.

This led researchers at UCLA Jonsson Comprehensive Cancer Center to ask questions. Do costs associated with consent document translation dissuade investigators running non-industry studies from offering patients with limited English proficiency, who require translated consent documents, the opportunity to participate in those studies? They conducted a study to answer this question (Nature 2023; https://doi.org/10.1038/s41586-023-06382-0).

Maria Velez, MD, a fellow in hematology and oncology at the David Geffen School of Medicine at UCLA and the lead author of the study, told Oncology Times that the answers to these questions are a small part of what leads to disparities in cancer clinical trials and cancer care.

“I think we need to address it like we approach all cancer research. We approach cancer research in a very targeted way," she said. “The same goes for researching disparities. It's a huge problem, but there's not going to be one huge solution. I think there's going to be small solutions and, as they add up, they're going to make a big difference over time."

1. Explain your analysis of whether translation costs affect minority participation?

“We decided on a study period that was already set by the cancer center (to avoid a potential source of investigator bias)—the last competing renewal period for our cancer center, which spans from 2013 to 2018. Then we looked at data for all the consent events—when a patient signed a consent form. It doesn't matter if the patient ended up enrolling in the study or screening out of the study; if they signed a consent form, they were included in the study that we ran. We ended up with a total of about 12,000 consent events we were able to include in the study.

“Then we looked at the difference in the proportion of consent events in patients with limited English proficiency in studies that were primarily sponsored and funded by an industry partner versus those that were not. When a study is funded and sponsored by industry, the funds are much less restricted and it's easier for investigators to translate however many consent forms they want because, ultimately, those costs will be completely covered by the industry partner. Whereas in studies with other funding streams, consent form translation costs may or may not be covered. If they're not, investigators often have to find ways of covering those costs via their institution or other grants. That's why we looked at the proportion between those types of studies and the difference in the proportion of consent events, which was significantly different between patients with limited English proficiency in industry versus non-industry studies.

“When patients did sign consent forms in studies not sponsored by industry, we looked if the investigators translated the consent forms. We found that actually they often did not. It was very often that, when patients signed a consent form that was not sponsored by industries, they signed the consent in English. So even if the patient clearly required a translated consent document (because we knew they had limited English proficiency) they were not presented with one."

2. What were the key research findings?

“Patients with limited English proficiencies who likely required a translated consent form were less likely to participate in non-industry sponsored studies compared to industry-sponsored studies. When they did participate in a non-industry-sponsored study, they often signed consent form documents in a language different from their primary language. This is why we think that the cost of translation of consent is a barrier to enrollment.

“Ultimately, the proportion of patients with limited English proficiency is small, but we think it is a barrier to the participation of these patients in clinical studies. While this doesn't address all of the barriers in terms of inclusion of historically underrepresented groups in clinical trials, we do think this addresses one of the barriers to the inclusion."

3. What solutions might help this problem?

“One of the things this data brought about was our cancer center looking at ways it can support investigators, especially [for] non-industry studies in which they can access extra funds for translation of consent form documents. I think one of the important solutions at the institutional level is that cancer centers could support investigators running these types of studies when it comes to helping them access extra funds they otherwise wouldn't have to translate consent forms.

“Another important aspect is that, when there is an industry partner, really make sure that partner is willing and able to cover the cost of translating consent forms. Lastly, when people apply for an NIH or other grant, the cost of translating consent forms should be budgeted.

“Our next research steps are looking at the true cost of enrolling patients with limited English proficiency into studies considering all translation costs. Translation cost is not an easy number for cancer clinical trial investigators to estimate upfront. The cost varies depending on how extensive the consent form is. Less common languages are usually more expensive to translate. And whenever there's a change to the protocol of the study that you have to disclose to patients, you will have to retranslate the consent form. So, it can be really hard for the investigators to know at the beginning of the study how many times they will have to amend the consent form."

Thursday, September 7, 2023

3 Questions on… Cardiovascular Risks After Head & Neck Cancers

​With Lova Sun, MD, MSCE, Assistant Professor of Medicine at the Hospital of the University of Pennsylvania

By Sarah DiGiulio

Sun Lova.jpgAs cancer treatment and care improve, and fewer patients with cancer are eventually dying from their cancers, it's worthwhile to ask: What causes early mortality among these patients? This was the topic of a recent investigation that was published online ahead of print in JAMA Otolaryngology—Head & Neck Surgery (2023; doi:10.1001/jamaoto.2023.1342). The patients in the study were 35,897 U.S. veterans who had been diagnosed with head and neck squamous cell carcinoma between the start of 2000 and the end of 2020.

“Many patients are living a long time after a diagnosis of head and neck cancer, and it is very important to understand and mitigate long-term toxicities, including cardiovascular events, particularly since many of our cancer treatments have known cardiovascular toxicities," noted Lova Sun, MD, MSCE, the study's lead author and Assistant Professor of Medicine at the Hospital of the University of Pennsylvania.

The data showed following: 1) cardiovascular risk factors were highly prevalent (67% hypertension, 22% diabetes, and 51% hyperlipidemia) and suboptimally controlled at time of cancer diagnosis; 2) 10-year cumulative incidence of stroke and myocardial infarction was 12.5 percent and 8.3 percent, respectively; and 3) incident stroke and myocardial infarction were associated with a 47 percent and 71 percent increased risk of all-cause mortality, respectively. Sun shared the importance of this work with Oncology Times.

1. What's new about this data that wasn't known from previous research on this topic?

“We found that there was a substantial burden of cardiovascular risk factors, including smoking, hypertension, diabetes, and hyperlipidemia, at the time of head and neck squamous cell carcinoma diagnosis. Almost half of patients had suboptimally controlled risk factor(s) with highest rates in Black patients and patients with larynx cancer. At 10 years after diagnosis, 12.5 percent of patients had stroke and 8.3 percent of patients had a myocardial infarction. The occurrence of these events was associated with increased risk of all-cause death.

“Several prior studies have shown that head and neck cancer patients, particularly those treated with radiation to the neck, are at high risk for stroke and cardiovascular disease. Our findings add to the literature by comprehensively profiling not only baseline presence of risk factors like hypertension and diabetes, but also medication treatment and control as measured by laboratory/vital sign parameters.

“Overall, the longitudinal risk of cardiovascular events seen in our study agrees with prior reports, but it is the first to our knowledge to show a direct association between the occurrence of cardiovascular events and all-cause death in patients with head and neck cancer."

2. What are the implications of this data for clinical practice?

“Elevated risk of cardiovascular disease in patients with head and neck cancer is a product of both baseline shared risk factors between cancer and cardiovascular disease (e.g., smoking, age, and inflammation), and further exacerbation by cardiotoxic treatments such as radiation therapy and cytotoxic chemotherapy given during the course of cancer therapy.

“Our findings underscore the importance of being aware of, screening for, and managing cardiovascular risk factors in patients with head and neck cancer, both at diagnosis and during and after cancer treatment. Often, in patients with elevated cardiovascular risk, collaboration with cardio-oncologists and other members of a multidisciplinary team is crucial to optimize outcomes.

“For multiple reasons, patients with head and neck cancer are at high risk for cardiovascular disease and events such as heart attack and stroke. As survival expectancies improve with an increasing prevalence of HPV-positive disease and treatment advancements, optimizing head and neck squamous cell carcinoma patients' overall outcomes should include attention to screening for and mitigating cardiovascular risk factors."

3. What's the next step of this work?

“With the results of this study showing substantial cardiovascular risks in the head and neck cancer population, it would be helpful to develop predictive risk scores and tools to distinguish which patients are most likely to experience adverse cardiovascular health outcomes with different cancer treatments. In addition, interventions to target high-risk patients and lower cardiovascular risk should be studied prospectively."

Monday, August 21, 2023

3 Questions on… Actionable Mutations Found in Prostate Cancer

​With Alexandra Sokolova, MD, Assistant Professor of Medicine at Oregon Health & Science University

By Sarah DiGiulio

Alexandra Sokolova.jpgNearly a quarter of men with metastatic castration-resistant prostate cancer have genomic alterations that map to currently available treatment options that have been found to improve outcomes for patients with those specific actionable targets. The challenges of how to test more men with these types of prostate cancers and how to incorporate the results of those tests into treatment decision-making is the topic of a recent Oncology Grand Rounds paper published in the Journal of Clinical Oncology by Catherine H. Marshall, MD, MPH, Assistant Professor of Oncology at the Johns Hopkins University School of Medicine (2023; doi: 10.1200/JCO.23.00350).

Research is ongoing to improve rates of cascade testing (informing and then testing family members of known genetic mutation carriers) for men who may be BRCA1/2 mutation carriers (and, therefore, at higher risk for prostate cancer and its aggressive types)—and then to better understand how to provide screening and potentially early treatment for those with mutations, explained Alexandra Sokolova, MD, Assistant Professor of Medicine in the Division of Hematology/Medical Oncology at the School of Medicine at Oregon Health & Science University. Research is also ongoing to better understand if patients with certain mutations would benefit more than current standard of care from other drug combinations. “There is still a lot to be learned," Sokolova told Oncology Times, who previously collaborated with Marshall on research projects. Here's why she says the arguments in this latest paper are important ones.

1. What stood out to you as important from this paper?
“PARP inhibitors are important tools we now have available for prostate cancer patients. They appear to be very effective, but for the right patient population. I think there is still a lot to be learned: which is the right patient population that can benefit from PARP inhibitors.

“Research has caused some dialogue in the genitourinary oncology field, especially when it comes to patients with HRR-negative mutations. Current data suggest benefit in the HRR-positive patient population, particularly in patients with BRCA mutations. For the HRR-positive cohort, it's important to understand in which scenarios are appropriate to use: PARP monotherapy or PARP inhibitors plus abiraterone.

“I agree with Dr. Marshall that, in BRCA1/2 mutation carriers, good performance status and prior treatment with ADT or ADT plus docetaxel as first line would be a good combination to consider a patient for treatment with abiraterone plus PARP inhibitors. But so far, PARP inhibitors are only approved for patients with BRCA1 or BRCA2 mutations. And that's still where we see the biggest benefit from the PARP inhibitor.

“We don't currently have data about PARP inhibitor and abiraterone combination use in first-line metastatic castration-resistant prostate cancer after progression on an androgen receptor pathway inhibitor (ARPI) in the past. I agree it currently should not be used in this scenario due to the lack of data. However, there is some data suggesting that continuing ARPI pathway inhibitor with chemotherapy after progressing on one— enzalutamide with docetaxel—improved outcomes. It is possible in the future it will be worthwhile to look into the combination (PARP inhibitor + ARPI) after the APRI pathway inhibitor, and I would be curious to see what the data would show. Potentially, there would be a biological role for that in the future. But, currently, this is a data-free zone and I would not use it now clinically outside of clinical trials."

2. The research noted genetic mutation status for patients with prostate cancer can help aid treatment decision-making. What are the barriers to this?
“I think the biggest barrier to incorporating genetic information into decision-making is not having genetic information on time. We need to do more testing, and we need to do it early and in a timely manner to be impactful. I think we're doing much better than we used to. But I think there is still room for improvement.
“Educating patients, educating providers, improving access to both germline and somatic testing, and limiting the financial impact they have on patients are all important.

“The other important point, especially if we talk about germline mutations, is early identification and potentially decreasing risk of metastatic prostate cancer with cascade testing. Whenever we have a patient with a germline mutation, it's very important to initiate cascade testing and test both their female and male family members. This way we would be able to identify those patients before they develop prostate cancer.

“We know that BRCA1/2 is associated with a high chance of breast and ovarian cancer, but it's also associated with a higher risk of developing and more aggressive prostate cancer phenotype. That means that, if we're able to catch those patients before they develop prostate cancer and monitor them closely and treat them at the early signs of prostate cancer development, hopefully we can prevent the development of lethal prostate cancer. I think cascade testing is the best way to do that."

3. Do patients struggle to undergo testing because of cost, lack of providers, lack of getting the right referral, or other factors?
“I think all of the above. Traditional models for germline testing include referrals to genetic counselors, and there is a shortage of genetic counselors nationwide. So the wait time can make it hard to get in. Also, not all insurance covers a genetic counseling visit or germline testing. Some commercial platforms offer patient-initiated germline testing for a generally smaller out-of-pocket fee (perhaps a few hundred dollars) and no insurance is involved. But undergoing that still involves getting to the provider and paying for the test.

“It also involves educating the providers. Medical oncologists are very busy during appointments with our patients, and because patients often come to us with more acute issues, it's not always on the top of our list to talk about genetic testing. So having a workflow where we're reminded to talk about both somatic and germline genetic testing is important."​​

Sarah DiGiulio is a contributing writer. 

Friday, August 4, 2023

3 Questions on… Where Addressing Climate Vulnerability & Cancer Disparities Overlap

​With Kilan C. Ashad-Bishop, PhD, of the Sylvester Comprehensive Cancer Center at the University of Miami Health System

By Sarah DiGiulio

Kilan Ashad-Bishop.jpegIn a recent Commentary article in the journal Cancer, Kilan C. Ashad-Bishop, PhD, a postdoctoral fellow at University of Miami's Sylvester Comprehensive Cancer Center in the Cancer Disparities and Equity T32 training program, and coauthors discuss how climate injustice overlaps with cancer inequities and affect similar groups (2023; https://doi.org/10.1002/cncr.34817). The main argument: social and structural barriers to health drive cancer disparities in the U.S., and these social and structural barriers also systematically increase vulnerability and decrease adaptive capacity to cope with climate change ills. Ashad-Bishop told Oncology Times that her learned expertise in molecular cancer biology and personal experience of being involved in environmental justice advocacy led her to get involved in this work.

“When I pitched the idea of this work, it was because in the literature I saw many discussions of populations that experience cancer disparities and environmental injustice separately, but not so much of them being considered together, and I wanted to create a framework through which we could consider those intersections," Ashad-Bishop said. She shared her thoughts on the barriers to addressing these large-scale societal challenges, as well as the opportunities.

1. How would you say cancer disparities overlap with climate vulnerability?

“There are a multitude of ways. We pulled from an Intergovernmental Panel on Climate Change framework that defined vulnerability as a function of exposure, sensitivity, and adaptive capacity to hazards, and also introduced a cancer lens to identify several mechanisms by which climate change can create and/or exacerbate cancer disparities. These include increased risk of exposure to carcinogenic hazards among certain populations, paired with neighborhood-level increases in sensitivity to those hazards and lower adaptive capacity to cope with those hazards at the individual level.

“The same populations, including but not limited to Black people, Latinx people, Indigenous people, and low-income people, that have been historically marginalized and systemically separated from health care are also at the greatest risk to suffer the consequences of anthropogenic climate change. In epidemiology, we call them populations that experience cancer disparities. In climate work, we call them environmental justice or frontline populations. They are largely one and the same: populations that American society has systemically and unapologetically rendered vulnerable to a myriad of risks."

2. What are the biggest opportunities when considering these societal issues and challenges together?

“The opportunity here is to consider and study how, by advancing environmental justice, we also have a crucial opportunity to advance cancer control efforts. For example, as we see an increased number of climate-related disasters, how do we get ahead of disparities in exposure to wildfire smoke or disparities in interrupted access to cancer care in the aftermath of a hurricane? By thinking ahead, we can serve the populations at greatest risk before they are in acute crisis.

“A great example, in light of the [recent] poor air quality in the Northeast, is clearly communicating what we know about the health risks of wildfire smoke inhalation and ensuring that the information is distributed in ways that reach the populations that are at the greatest risk of exposure to that smoke: folks who walk and take public transit, for example.

“There are several scientific collaborations (such as the Thread collaborative) and multisectoral groups (the Urban Heat Research Group) that are working collaboratively to study and address disparities in extreme heat exposure and create equitable awareness campaigns and interventions. I am a part of a new study that aims to investigate how medically vulnerable populations, specifically, are experiencing extreme heat, so that's going to be an exciting addition to the literature."​

3. What are the biggest barriers to getting these types of changes enacted in ways to help address the problems?

“Despite consensus in the scientific community, not everyone 'believes' in anthropogenic climate change and climate action. Among those in power, not everyone believes that the legacy of structural racism in this country needs to be rectified. Not everyone believes that access to quality health care should be a fundamental right. The first barrier is to reach the point where those in power reach a consensus that something must be done to address the disparities that we as a society have created in climate vulnerability and disease risk.

“Further, we need more actionable, transdisciplinary work to understand the behavioral and biological mechanisms by which climate-related events operate to affect cancer disparities and open, bidirectional lines of communication between the affected communities, the scientific community, and responsive elected and appointed officials at all levels of government.

“A bottom-line takeaway anyone in oncology should know is [that] context matters. As a result of anthropogenic (human-caused) climate change, we are seeing an increased frequency and severity of climate-related threats, such as hurricanes, wildfires, and periods of extreme heat. For some of us, dealing with these threats is as simple as evacuating an area or blasting our central AC; for others, these are life-threatening events. When we think about barriers to getting screened for cancer, adhering to treatment for cancer, and surviving cancer, we have to consider the context of our changing world (i.e., climate change) if we want to meaningfully advance cancer health equity."​

Sarah DiGiulio is a contributing writer. 

Monday, July 24, 2023

3 Questions on… Strategies for Finding Cancers in Women With Dense Breasts

​With Wendie Berg, MD, PhD, FACR, at the University of Pittsburgh School of Medicine and Magee-Womens Hospital of UPMC

By Sarah DiGiulio

Wendie Berg.jpgWomen with dense breasts are at increased risk for developing breast cancer, as well as for that cancer to be missed by standard screening methods. Wendie Berg, MD, PhD, FACR, Professor of Radiology and The Dr. Bernard F. Fisher Chair for Breast Cancer Clinical Science at the University of Pittsburgh School of Medicine and Magee-Womens Hospital of UPMC, and colleagues conducted a study to determine if annual technologist-performed screening ultrasounds improve breast cancer detection when performed after digital breast tomosynthesis for women ages 40-75 with dense breasts. The results were published in the Journal of Clinical Oncology (2023; doi: 10.1200/JCO.22.01445).

For the study, 6,179 women underwent three rounds of annual screening, interpreted by two radiologist observers, and had appropriate follow-up. The data showed that adding ultrasound did indeed improve breast cancer detection over digital breast tomosynthesis alone, though with modest benefit. Overall sensitivity of digital breast tomosynthesis was 69 percent, whereas adding ultrasound increased sensitivity to 84 percent. “Overall added cancer detection rate of ultrasound screening after digital breast tomosynthesis was modest," the researchers noted in the paper, “but potentially overcomes substantial increases in false-positive recalls and benign biopsies." In an interview with Oncology Times, Berg discussed the findings.

1. Why did you and your colleagues decide to pursue this research now?

“There is increasing public awareness about the risks of dense breasts—both the increased risk of developing cancer and, more problematic, the risk of cancer being hidden by dense tissue on a mammogram. About 40 percent of women having mammograms have dense breasts (heterogeneously dense or extremely dense). About 30-40 percent of cancers are hidden in dense breasts.

“Currently, 37 states plus DC require some density information with the mammogram results letters (https://tinyurl.com/5dz4an2a). Florida had legislation requiring this, but it expired on the last day of June 2023. As of September 2024, the FDA will require nationally standardized mammogram results letters that inform women their breasts are either dense or not dense, that dense tissue makes it harder to find cancer on a mammogram, and it also raises the risk of developing breast cancer. In women with dense breasts, the letter must also state that 'other imaging tests in addition to a mammogram may help find cancers.'

“We have strong evidence of the benefit of screening MRI in women at high risk or with extremely dense breasts, but there are no clear guidelines for women with heterogeneously dense breasts, and not all women who qualify for an MRI can access or tolerate it. Ultrasound is an alternative to MRI, but there were very few published studies evaluating ultrasound after tomosynthesis (3D mammography), especially incidence screening."

2. What were the key findings from this study?

“Consistent with a large body of work in the United States and Europe, our study showed that mammography alone, even using tomosynthesis, missed over 30 percent of cancers in dense breasts, and adding ultrasound each year improved cancer detection. The cancers found by screening ultrasound were mostly invasive (84%) and node-negative (81%)—the types of cancers that need treatment. We observed a very low interval cancer rate (cancers found because of symptoms). Adding ultrasound also produced additional testing for findings that were not found to be cancer in about 4 percent of women each year."

3. What are the implications of the research?

“The USPSTF just issued draft guidelines for breast cancer screening that fail to adequately address the limitations of mammography in women with dense breasts or the overlapping large group of women at higher-than-average risk. Our work adds to a large body of evidence showing improved detection of invasive cancers by adding ultrasound to mammography in women with dense breasts. MRI finds many more cancers than ultrasound, but not all women qualify for or can tolerate MRI. Many women with dense breasts and a family history or personal history of breast cancer or other risk factors meet 'high-risk' criteria and there are other national guidelines (including NCCN, ACR, ACS) that recommend adding MRI each year, or ultrasound if MRI is not possible. But many women and their doctors are not aware of these guidelines .

“The most important takeaway is that, separate and distinct from the increased risk of developing breast cancer, in women with dense breasts at least 30 percent of cancers are hidden on mammography. Women and their health care providers should be comfortable discussing supplemental screening options such as ultrasound or MRI—and efforts to standardize insurance coverage are equally important. Currently, 21 states plus DC have laws requiring coverage of at least some additional breast screening beyond mammographic (19 MRI or ultrasound and two ultrasound). The Find It Early Act has been introduced in Congress by Reps. Rosa DeLauro (D-CT) and Brian Fitzpatrick (R-PA) requiring a national standard so that all women can afford access to early detection of breast cancer (www.FindItEarlyAct.org)."​