Oncologists' perceptions of tumor genomic profiling and barriers to communicating secondary hereditary risks to African American cancer patients.

BACKGROUND: Tumor genomic profiling (TGP) identifies targets for precision cancer treatments, but also secondary hereditary risks. Oncologists are poorly trained to communicate the results of TGP, especially among patients with lower health literacy, poorer genetics knowledge, and higher mistrust. African American (AA) patients are especially vulnerable to poor understanding due to significant cancer disparities and lower uptake of TGP. The goal of this research is to inform the development of an internet-based brief educational support for oncologists to prepare them to provide better decisional support related to TGP for their AA cancer patients. METHODS: This mixed-methods study used semi-structured interviews of oncologists to inform development of an online survey with a convenience sample of US-based oncologists (n = 50) to assess perceptions of the challenges of TGP and communicating results to AA patients. RESULTS: Most interviewed oncologists felt it was important to consider racial/cultural differences when communicating about hereditary risks. Cost, family dynamics, discrimination concerns, and medical mistrust were identified as particularly salient. Survey respondents' views related to AAs and perceptions of TGP were strongly associated with years since completing training, with recent graduates expressing stronger agreement with statements identifying barriers/disadvantages to TGP for AA patients. CONCLUSIONS: Oncologists who had more recently completed training expressed more negative perceptions of TGP and more perceived challenges in communicating about TGP with their AA patients. Focused training for oncologists that addresses barriers specific to AAs may be helpful in supporting improved communication about TGP and improved decisional support for AA patients with cancer considering TGP to evaluate their tumors.

Colorectal Neoplasia in CDH1 Pathogenic Variant Carriers: A Multicenter Analysis.

INTRODUCTION: Germline variants in CDH1 are associated with elevated risks of diffuse gastric cancer and lobular breast cancer. It is uncertain whether there is an increased risk of colorectal neoplasia. METHODS: This was a retrospective analysis of colonoscopy outcomes in patients with germline CDH1 pathogenic/likely pathogenic variants. RESULTS: Eighty-five patients were included with a mean age of 46.9 years. Initial colonoscopy found adenomatous polyps in 30 patients (35.3%), including advanced adenomas in 9 (10.6%). No colorectal cancers were identified on index or subsequent colonoscopies (when available). DISCUSSION: CDH1 carriers have colorectal neoplasia identified at similar rates as in the general population. Despite potential difficulties after gastrectomy, colorectal cancer screening remains important in this population.

Impact of Baseline Nutrition and Exercise Status on Toxicity and Outcomes in Phase I and II Oncology Clinical Trial Participants.

BACKGROUND: Malnutrition and physical inactivity are common in patients with advanced cancer and are associated with poor outcomes. There are increasing data that altered body composition is related to the pharmacokinetic properties of cancer therapies. These adverse conditions may impact outcomes in early-phase oncology clinical trials. MATERIALS AND METHODS: We aimed to understand the relationships between baseline nutrition and exercise status with important trial endpoints including treatment-related toxicity and survival. Baseline assessments of nutrition and exercise status were conducted in patients prior to initiation of phase I and II oncology clinical trials. Patients were followed prospectively for the onset of adverse events. Tumor response and survival data were also obtained. Fisher's exact test and chi-square analysis were used to determine statistical significance. Kaplan-Meier curves were used to compare patient duration on study and survival. RESULTS: One hundred patients were recruited, of whom 87 were initiating a phase I trial. Sixty percent were initiating trials studying immunotherapeutic agents. Critical malnutrition was found in 39% of patients, and 52% were sedentary. Patients who were malnourished had significantly increased rates of grade ≥ 3 toxicity (p = .001), hospitalizations (p = .001), and inferior disease control rate (p = .019). Six-month overall survival was significantly reduced in malnourished patients versus nonmalnourished patients (47% vs. 84%; p = .0003), as was median duration on study (48 days vs. 105 days; p = .047). Being sedentary at baseline was associated with decreased duration on study (57 days vs. 105 days; p = .019). CONCLUSION: Malnutrition and sedentary lifestyle are highly prevalent in patients enrolling on early-phase oncology clinical trials and are associated with poor outcomes. The quality of data from these studies may be compromised as a result of these pre-existing conditions. IMPLICATIONS FOR PRACTICE: Phase I and II trials are critical steps in the development of effective cancer therapeutics, yet only a small percentage of agents are ultimately approved for human cancer care. Despite increasing awareness of the interactions between malnutrition, sarcopenia, and treatment-related outcomes such as toxicity and response, these factors are not commonly incorporated into therapeutic decision making at the time of clinical trial consideration. Nutritional status and physical performance may be key biomarkers of mechanisms mediating treatment-related toxicity, dose modifications, risk of hospitalizations, and success of novel agents. This study advocates that a baseline nutritional assessment and early nutritional support may improve tolerability and response to experimental therapies.

Understanding perceptions of tumor genomic profile testing in Black/African American cancer patients in a qualitative study: the role of medical mistrust, provider communication, and family support.

Tumor genomic profiling (TGP) examines genes and somatic mutations specific to a patient's tumor to identify targets for cancer treatments but can also uncover secondary hereditary (germline) mutations. Most patients are unprepared to make complex decisions related to this information. Black/African American (AA) cancer patients are especially at risk because of lower health literacy, higher levels of medical mistrust, and lower awareness and knowledge of genetic testing. But little is known about their TGP attitudes or preferences. Five in-person focus groups were conducted with Black/AA cancer patients (N = 33) from an NCI-designated cancer center and an affiliated oncology unit in an urban safety-net hospital located in Philadelphia. Focus groups explored participants' understanding of TGP, cultural beliefs about genetics, medical mistrust, and how these perceptions informed decision-making. Participants were mostly female (81.8%), and one-third had some college education; mean age was 57 with a SD of 11.35. Of patients, 33.3% reported never having heard of TGP, and 48.5% were not aware of having had TGP as part of their cancer treatment. Qualitative analysis was guided by the principles of applied thematic analysis and yielded five themes: (1) mistrust of medical institutions spurring independent health-information seeking; (2) genetic testing results as both empowering and overwhelming; (3) how provider-patient communication can obviate medical mistrust; (4) how unsupportive patient-family communication undermines interest in secondary-hereditary risk communication; and (5) importance of developing centralized patient support systems outside of treatment decisions. Results improve understanding of how Black/AA patients perceive of TGP and how interventions can be developed to assist with making informed decisions about secondary hereditary results.

The Role of Medical Mistrust in Concerns about Tumor Genomic Profiling among Black and African American Cancer Patients.

Tumor genomic profiling (TGP) is used in oncology practice to optimize cancer treatment and improve survival rates. However, TGP is underutilized among Black and African American (AA) patients, creating potential disparities in cancer treatment outcomes. Cost, accuracy, and privacy are barriers to genetic testing, but medical mistrust (MM) may also influence how Black and AA cancer patients perceive TGP. From December 2019 to February 2020, 112 Black and AA adults from two outpatient oncology sites in Philadelphia, PA without a known history of having TGP testing conducted completed a cross-sectional survey. Items queried included sociodemographic characteristics, clinical factors, patient-oncologist relationship quality, medical mistrust, and concerns about TGP. A k-means cluster analysis revealed two distinct psychographic clusters: high (MM-H) versus low (MM-L) medical mistrust. Clusters were not associated with any sociodemographic or clinical factors, except for age (MM-H patients older than MM-L patients, p = 0.006). Eleven TGP concerns were assessed; MM-H patients expressed greater concerns than MM-L patients, including distrust of the government, insurance carriers, and pharmaceutical companies. TGP concerns varied significantly based on level of medical mistrust, irrespective of sociodemographic characteristics. Targeted communications addressing TGP concerns may mitigate disparities in TGP uptake among those with medical mistrust.

Oncologists' Perceptions of Tumor Genomic Profiling and the Communication of Test Results and Risks.

Tumor genomic profiling (TGP) identifies genetic targets for precision cancer treatments. The complexity of TGP can expose gaps in oncologists' skills, complicating test interpretation and patient communication. Research on oncologists' use and perceptions of TGP could inform practice patterns and training needs. To study this, a sample of oncologists was surveyed to assess TGP use, perceptions, and perceived skills in TGP interpretation/communication, especially in communication of hereditary risks. Genomic self-efficacy and TGP knowledge were also assessed. The goal sample (n = 50) was accrued from 12/2019 to 1/2020. Respondents were primarily medical oncologists (78%) with >10 (mean 17.7) years of practice experience. TGP use was moderate/high (median 50 [range 2-398]) tests/year. Most oncologists reported informal/no training in interpretation (72%) or communication (86%) of TGP results and risks. Genomic self-efficacy was high and was associated with higher use of TGP (p = 0.047). Perceptions of the benefits and limitations of TGP were mixed: heterogeneity was seen by years of experience, TGP use, and knowledge. Most participants agreed that additional training in TGP communication was needed, especially in communication of hereditary risks, and that an online training tool would be useful (86%). We conclude that oncologists are frequently using TGP despite having mixed views about its utility and not feeling prepared to communicate risks to patients. Oncologists receive little education in interpreting TGP or communicating its results and risks, and would value training in this area.

Psychological distress in patients with metastatic cancer enrolling on phase I clinical trials.

PURPOSE: Psychological distress is common in patients with cancer and is associated with lower quality-of-life (QOL). Although distress among oncology outpatients undergoing standard therapy has been widely studied, few studies have evaluated distress among patients enrolling on Phase I therapeutic clinical trials. Thus, we aimed to characterize levels of distress and types of stressors in patients enrolling on Phase I clinical trials. METHODS: Participants completed the National Comprehensive Cancer Network Distress Thermometer (NCCN DT) and Problem list and measures of anxiety and depression at the time of Phase I clinical trial initiation. RESULTS: We enrolled 87 patients (95% with metastatic/incurable disease) who were initiating a Phase I clinical trial. Analyses revealed a high prevalence of distress (51%) and anxiety (28%). There were significant correlations between overall distress and practical problems (r = 0.31, p = 0.016), family problems (r = 0.35, p = 0.006), and emotional problems (r = 0.64, p < 0.001), but not physical problems (r = 0.17, p = 0.206). CONCLUSIONS: Patients may be better prepared to manage physical stressors but not practical, emotional, or family stressors at the time of Phase I trial enrollment. IMPLICATIONS FOR CANCER SURVIVORS: Phase I trial patients experience high levels of distress which may be due to the rigors of previous therapies therapy and related emotional and social stressors related to the poor prognosis of their advanced cancer diagnosis. Distress may go unidentified without screening which is not standard practice at the time of Phase I trial consideration. Future studies should evaluate strategies to routinely identify and intervene upon addressable stressors in patients participating in Phase I clinical trials.

A Multi-Institutional Cohort of Therapy-Associated Polyposis in Childhood and Young Adulthood Cancer Survivors.

Prior small reports have postulated a link between gastrointestinal polyposis and childhood and young adulthood cancer (CYAC) treatment (therapy-associated polyposis; TAP), but this remains a poorly understood phenomenon. The aim of this study was to describe the phenotypic spectrum of TAP in a multi-institutional cohort. TAP cases were identified from eight high-risk cancer centers. Cases were defined as patients with ≥10 gastrointestinal polyps without known causative germline alteration or hereditary colorectal cancer predisposition syndrome who had a history of prior treatment with chemotherapy and/or radiotherapy for CYAC. A total of 34 TAP cases were included (original CYAC: 27 Hodgkin lymphoma, three neuroblastoma, one acute myeloid leukemia, one medulloblastoma, one nephroblastoma, and one non-Hodgkin lymphoma). Gastrointestinal polyposis was first detected at a median of 27 years (interquartile range, 20-33) after CYAC treatment. A total of 12 of 34 (35%) TAP cases had ≥50 colorectal polyps. A total of 32 of 34 (94%) had >1 histologic polyp type. A total of 25 of 34 (74%) had clinical features suggestive of ≥1 colorectal cancer predisposition syndrome [e.g., attenuated familial adenomatous polyposis (FAP), serrated polyposis syndrome, extracolonic manifestations of FAP, mismatch repair-deficient colorectal cancer, or hamartomatous polyposis] including 8 of 34 (24%) with features of multiple such syndromes. TAP is an apparently acquired phenomenon that should be considered in patients who develop significant polyposis without known causative germline alteration but who have had prior treatment for a CYAC. Patients with TAP have features that may mimic various hereditary colorectal cancer syndromes, suggesting multiple concurrent biologic mechanisms, and recognition of this diagnosis may have implications for cancer risk and screening.

Randomized Controlled Trials in Hereditary Cancer Syndromes.

Conducting randomized controlled trials (RCTs) in patients with germline mutations in genes that predispose to adult-onset cancer is hampered by the rarity of these mutations, barriers to their identification, and challenges inherent to randomizing high-risk individuals as part of a clinical trial. Most of the clinically relevant RCTs have been conducted in 3 syndromes in only some of the high-risk genes for which clinical testing is currently available. This article reviews the surgical, screening, and chemoprevention RCTs in each of the syndromes in clinically relevant studies conducted in the past 10 years.