Kemeny, Margaret

Abstract Background Reference sets are needed to evaluate performance of multi-cancer detection (MCD) assays. The National Cancer Institute funded the Alliance reference set study to assess MCDs for use in future trials. Methods Individuals with cancer and controls were recruited; blood specimens were collected prior to cancer treatment. A performance evaluation study was designed utilizing reference set samples. Companies (n = 6) were selected to participate based on review of performance data and ability to utilize the blood collection tube. Companies received samples from cancer types their assay was designed to detect (“targeted”), plus additional “non-targeted” and control samples. Companies reported positive/negative calls, risk scores, and tissue-of-origin (TOO) predictions. Sensitivity was computed for early (I-II) and late (III-IV) stage cases, based on positive/negative calls (SEPN) and at fixed 98% specificity (SE98). Specificity and TOO accuracy were computed. Results Five hundred and forty nine cases (encompassing 13 cancer types) and 413 controls from the reference set were included in the study. Companies assessed samples from median 6 (range 5-9) targeted cancer types and median 8 (range: 7-11) overall cancer types. Median (range) specificity was 92.3% (76.5%-98.5%). Median (range) SEPN was 32% (25%-42%) for early stage and 73% (48%-89%) for late stage; while median (range) SE98 was 19% (8%-35%) for early stage and 66% (13%-79%) for late stage. Median sensitivity for non-targeted types was 40% (early stage) and 52% (late stage). Median (range) TOO accuracy (primary predicted site) was 75% (64%-78%). Conclusions Sensitivity and specificity varied widely across assays with early-stage sensitivity substantially lower than late-stage sensitivity. Clinical Trial Registration Number ClinicalTrials.gov identifier NCT05334069.

PURPOSE This study determined whether an electronic version of the geriatric assessment is feasible in a multi-institutional, diverse setting. METHODs Ten sites within the Alliance for Clinical Trials in Oncology participated. Patients who had active cancer or a history of cancer and were 65 years of age or older were eligible. The geriatric assessment was completed with an electronic data capture system that had been loaded onto iPads. Feasibility was defined a priori as completion in at least 70% of patients either with or without help. To enhance racial diversity, the original sample size was later changed and augmented by 50% with the intention of increasing enrollment of older minority patients. RESULTS A total of one hundred fifty-four patients were registered with a median age of 72 years (range, 65-91 years). Forty-three (28%) identified themselves as African American or Black. One hundred forty-one patients (92%) completed the electronic geriatric assessment. Feasibility was observed across all subgroups, regardless of race, education, performance status, comorbidities, and cognition; 124 patients (81%) completed the geriatric assessment without help. Reasons for not completing the geriatric assessment are as follows: clinic visit did not occur (n = 6), no iPad connection to the Internet (n = 3), patient declined (n = 2), prolonged hospitalization (n = 1), and patient died (n = 1). Reasons for needing help, as reported by study personnel, were as follows: the patient preferred that research personnel ask the questions (n = 9), vision problem (n = 3), lack of comfort with the iPad (n = 2), questions were not clear (n = 1), less proficient in English (n = 1), and challenge in pressing the green button to go to the next question (n = 1). CONCLUSION The electronic geriatric assessment is feasible in a multi-institutional setting that includes a notable proportion of African American or Black patients.

Abstract Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and toxicity limits use of these agents. Vitamin D is a potential prevention therapy for both ER+ and ER− disease and is safe with few side effects. This study evaluates the effect of 1-year of vitamin D supplementation on mammographic density (MD), a biomarker of breast cancer risk in a multicenter randomized controlled trial. Premenopausal women with ≥25% MD and no history of cancer were randomly assigned to 2,000 international units (IU) of vitamin D or placebo orally daily for 1 year. Change in percent MD was evaluated using Cumulus software after all participants completed treatment. Three hundred women enrolled between January 2011 and December 2013 with a mean age of 43 and diverse ethnicity [14% Hispanic, 12% African American (AA)]. Supplementation significantly increased vitamin D levels compared with placebo (14.5 ng/mL vs. −1.6 ng/mL; P < 0.0001) with all participants on the vitamin D arm achieving vitamin D sufficiency at 12 months. Vitamin D was safe and well tolerated. After adjustment for baseline MD, the mean between-arm difference (vitamin D vs. placebo) at 1 year was −0.75 (−0.26, 1.76; P = 0.56). A greater effect was seen for women with ≥50% MD and AA women, although neither reached significance. This randomized controlled trial demonstrated significant improvement in vitamin D levels with 2,000 IU for 1 year, with 100% of supplemented women achieving sufficiency. However, a null effect was seen regarding change in MD for premenopausal women (the primary outcome of the study). Prevention Relevance: Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and are underutilized due to toxicity and side effects. Vitamin D is a potential prevention therapy for both ER+ and ER− disease and is safe with few side effects.

Abstract Background There are multiple known individual- and practice-level barriers to enrollment of older patients with cancer to clinical trials, but little is known about how the clinical research workforce feels about potential higher-level strategy changes aimed to promote increased enrollment of older patients. Subjects, Materials, and Methods We invited all 11,351 Alliance for Clinical Trials in Oncology (“Alliance”) members to participate in an anonymous, web-based survey to examine awareness of current accrual patterns for older patients to clinical trials, to ascertain consensus on how to tackle enrollment challenges, and to provide the impetus for high-level changes to improve clinical trial accrual of older patients with cancer. Results During the period from February 28, 2017, to June 16, 2017, 1,146 Alliance members participated (response rate = 10%), including a national diverse sample of physicians, nurses, administrative/clinical research staff, and patient advocates with representation from community, academic, and rural sites. Overall, one third felt that >50% of clinical trial enrollees should be age ≥65, and 64.9% felt the Alliance could improve upon enrollment of older patients. The four most commonly ranked strategies to improve enrollment of older patients were creating more dedicated trials for this population (36.3%), minimizing exclusion criteria focused on comorbidity (35.5%), developing independent strategies for those aged ≥65 and for those aged ≥70 (33.2%), and requiring that most/all Alliance trials have a specific expansion cohort of older patients (30.0%). Conclusion We anticipate that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials. Implications for Practice This survey of the Alliance for Clinical Trials membership sought opinions on potential, large-scale, national strategies to improve accrual of older adults with cancer. Consensus was found around multiple strategies, including creating more dedicated trials for older patients, developing less stringent eligibility criteria, and mandating expansion cohorts of older patients within broader Alliance trials. It is anticipated that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials.