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. The Oncologist 2020;25:161-169 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.

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 (<i>n</i> = 50) was accrued from 12/2019 to 1/2020. Respondents were primarily medical oncologists (78%) with &#x3e;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 (<i>p</i> = 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.

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.

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.

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