Chang, George J.

1541 Background: Frailty is common in older adults undergoing major cancer surgery. Mounting evidence indicates multimodal interventions to optimize patient functional status by addressing vulnerabilities associated with frailty before surgery result in decreased complications and enhanced functional recovery. This study tested the effectiveness of OPTI-Surg, a surgical prehabilitation toolkit for improving surgical care and outcomes in older patients undergoing major cancer surgery. Here, we report results from the planned futility interim analysis (IA). Methods: Thoracic (T), gastrointestinal (GI), and urologic (GU) oncological surgery practices affiliated with NCI’s Community Oncology Research Program were randomized 1:1:1, stratified by practice type, to usual care (control), OPTI-Surg toolkit, or OPTI-Surg with an implementation coach. The toolkit was implemented at the practice level. It consisted of the 12-item Edmonton Frail Scale and guided recommendations for interventions directed at identified vulnerabilities. Eligible patients were adults ≥70 years old undergoing curative intent surgery for lung, gastrointestinal, or urologic cancers. Primary outcome was 8-week post-operative function (weekly caloric expenditure) derived from the validated Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire. A linear mixed model was used to compare usual care to the 2 OPTI-Surg arms combined, controlling for baseline function. Results: From July 2019 to October 2021, 225 patients, 50% of the total accrual goal, were enrolled from 29 practices, triggering the IA. Study was suspended to new patient accrual March to June 2020 due to the COVID-19 pandemic. There were no differences in demographics by arm (mean age 76.2 years; 46.4% women; 79.6% white; 20.4% lung resection, 69.8% major GI surgery, 9.8% total cystectomy). Of the 225 patients, 140 (47 Usual Care, 93 OPTI-Surg) were evaluable for the IA. There was no significant difference in post-operative function between OPTI-Surg and usual care (mean decrease of 0.59 kCal/week for OPTI-Surg patients and 0.19 kCal/week for usual care patients, p = 0.762, intraclass correlation = 0.033). Based on the futility analysis, the DSMB recommended closure of recruitment on September 16, 2022. Conclusions: Implementation of the OPTI-Surg toolkit did not significantly improve functional outcomes 8 weeks after surgery for patients aged 70 and older undergoing major cancer surgery compared to usual care. Future analysis of implementation and ethnographic data may identify reasons why significant differences between the intervention and usual care arms were not observed, potentially including disruptions due to the COVID-19 pandemic. Clinical trial information: NCT03857620 .

PURPOSE The standard of care for locally advanced rectal cancer in North America is neoadjuvant pelvic chemoradiation with fluorouracil (5FUCRT). Neoadjuvant chemotherapy with fluorouracil and oxaliplatin (FOLFOX) is an alternative that may spare patients the morbidity of radiation. Understanding the relative patient experiences with these options is necessary to inform treatment decisions. METHODS PROSPECT was a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX versus 5FUCRT, which enrolled adults with rectal cancer clinically staged as T2N+, cT3N–, or cT3N+ who were candidates for sphincter-sparing surgery. Neoadjuvant FOLFOX was given in six cycles over 12 weeks, followed by surgery. Neoadjuvant 5FUCRT was delivered in 28 fractions over 5.5 weeks, followed by surgery. Adjuvant chemotherapy was suggested but not mandated in both groups. Enrolled patients were asked to provide patient-reported outcomes (PROs) at baseline, during neoadjuvant treatment, and at 12 months after surgery. PROs included 14 symptoms from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Additional PRO instruments measured bowel, bladder, sexual function, and health-related quality of life (HRQL). RESULTS From June 2012 to December 2018, 1,194 patients were randomly assigned, 1,128 initiated treatment, and 940 contributed PRO-CTCAE data (493 FOLFOX; 447 5FUCRT). During neoadjuvant treatment, patients reported significantly lower rates of diarrhea and better overall bowel function with FOLFOX while anxiety, appetite loss, constipation, depression, dysphagia, dyspnea, edema, fatigue, mucositis, nausea, neuropathy, and vomiting were lower with 5FUCRT (all multiplicity adjusted P < .05). At 12 months after surgery, patients randomly assigned to FOLFOX reported significantly lower rates of fatigue and neuropathy and better sexual function versus 5FUCRT (all multiplicity adjusted P < .05). Neither bladder function nor HRQL differed between groups at any time point. CONCLUSION For patients with locally advanced rectal cancer choosing between neoadjuvant FOLFOX and 5FUCRT, the distinctive PRO profiles inform treatment selection and shared decision making.

Introduction: Testing healthcare delivery interventions in rigorous clinical trials is a critical step in improving patient care, but conducting multisite randomized clinical trials to test the effect of care delivery interventions has unique challenges and requires foresight and planning. Methods: We conducted the first care delivery trial (A191402CD) in the Alliance for Clinical Trials in Oncology, a National Cancer Institute Community Oncology Research Program research base, which tested the effectiveness of two different decision aids for supporting shared decision-making about prostate cancer treatment. Our experience illustrates the kind of challenges that confront care delivery researchers as they seek to test interventions to improve the experiences of patients. Results: Lessons learned include the following: cluster-randomized designs introduce complexity; workflow disruption can discourage site participation; evidence-based methods may not always be sufficient. Conclusion: We conclude with the following recommendations: assessing feasibility requires special rigor; relationships and interpersonal dynamics must be leveraged. Our experiences may inform future care delivery research.

256 Background: Current staging for colon cancer utilizing the American Joint Committee on Cancer TNM framework stratifies disease into groups according to how advanced the disease is and provides important standardized, individual prognostic information. Ideally, staging systems should exhibit hierarchical logic, with increasing stage reflecting worse prognosis. We sought to evaluate hierarchy within the 8th edition AJCC staging system for colon cancer. Methods: All patients with primary colon (including rectosigmoid) cancer diagnosed 2010-2017 were identified from the National Cancer Database (NCDB). Patients were only included if they carried a histologic diagnosis of invasive primary (non-recurrent) cancer, underwent radical surgery, and had complete pathologic staging data (T, N, M category data). Patients with missing follow-up data were excluded. Kaplan-Meier curves were used to assess overall survival by AJCC 8th edition pathologic summary stage group to determine whether staging was hierarchical for colon cancer. Multivariable modeling and log likelihood ratio test was then used to identify relative contributions of T and N variables to overall survival. Results: Among 270,584 colon cancer patients, pathologic staging was noted to be hierarchical by T category alone and by N category alone. However, summary staging was non-hierarchical in both instances. Multivariable modeling confirmed the AJCC non-hierarchy issue (colon HRs: 1, 1.54, 2.62, 2.60, 1.02, 2.15, and 4.38 for stage 1 as reference, 2a, 2b, 2c, 3a, 3b, 3c respectively). Multivariable modeling demonstrated that high T category (T4a, T4b) conferred the greatest risk of mortality based on hazard ratio (T4a HR 2.76, T4b HR 3.04), while high T category as well as high N category (N2a, N2b) contributed substantially to the survival model based on z-score. Further modeling assessing the predictive power of T and N category with respect to overall survival demonstrated that T category more strongly predicted overall survival than N category in colon cancer (likelihood chi-square test statistic pT:7009 vs pN:3586). Conclusions: Hierarchy in survival based on AJCC summary stage was not observed for patients with stage II-III colon cancer resulting in a paradoxical better observed survival with some stage III cancer subgroups compared to stage II cancer subgroups. High T category appears to more significantly impact survival than N category for patients with N0-N1 disease, while high N category appears more important for patients with T1-3 disease. Future revisions of the AJCC staging system should account for the differential impact of T and N category identified herein to more accurately confer prognostic information.

Abstract Background Guidelines for follow-up after locoregional breast cancer treatment recommend imaging for distant metastases only in the presence of patient signs and/or symptoms. However, guidelines have not been updated to reflect advances in imaging, systemic therapy, or the understanding of biological subtype. We assessed the association between mode of distant recurrence detection and survival. Methods In this observational study, a stage-stratified random sample of women with stage II-III breast cancer in 2006-2007 and followed through 2016 was selected, including up to 10 women from each of 1217 Commission on Cancer facilities (n = 10 076). The explanatory variable was mode of recurrence detection (asymptomatic imaging vs signs and/or symptoms). The outcome was time from initial cancer diagnosis to death. Registrars abstracted scan type, intent (cancer-related vs not, asymptomatic surveillance vs not), and recurrence. Data were merged with each patient’s National Cancer Database record. Results Surveillance imaging detected 23.3% (284 of 1220) of distant recurrences (76.7%, 936 of 1220 by signs and/or symptoms). Based on propensity-weighted multivariable Cox proportional hazards models, patients with asymptomatic imaging compared with sign and/or symptom detected recurrences had a lower risk of death if estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative (triple negative; hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.54 to 0.99), or HER2 positive (HR = 0.51, 95% CI = 0.33 to 0.80). No association was observed for ER- or PR-positive, HER2-negative (HR = 1.14, 95% CI = 0.91 to 1.44) cancers. Conclusions Recurrence detection by asymptomatic imaging compared with signs and/or symptoms was associated with lower risk of death for triple-negative and HER2-positive, but not ER- or PR-positive, HER2-negative cancers. A randomized trial is warranted to evaluate imaging surveillance for metastases results in these subgroups.

BackgroundDecision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within‐visit and previsit DAs for localized prostate cancer, and minority men were oversampled.MethodsThe interventions were delivered in urology practices affiliated with the NCI Community Oncology Research Program Alliance Research Base. The primary outcome was prostate cancer knowledge (percent correct on a 12‐item measure) assessed immediately after a urology consultation.ResultsFour sites administered the previsit DA (39 patients), 4 sites administered the within‐visit DA (44 patients), 3 sites administered both previsit and within‐visit DAs (25 patients), and 4 sites provided usual care (50 patients). The median percent correct in prostate cancer knowledge, based on the postvisit knowledge assessment after the intervention delivery, was as follows: 75% for the pre+within‐visit DA study arm, 67% for the previsit DA only arm, 58% for the within‐visit DA only arm, and 58% for the usual‐care arm. Neither the previsit DA nor the within‐visit DA had a significant impact on patient knowledge of prostate cancer treatments at the prespecified 2.5% significance level (P = .132 and P = .977, respectively).ConclusionsDAs for localized prostate cancer treatment provided at 2 different points in the care continuum in a trial that oversampled minority men did not confer measurable gains in prostate cancer knowledge.

BackgroundThe objective of this study was to evaluate the association between self‐identified race and overall survival (OS), progression‐free survival (PFS), and response to therapy among patients enrolled in the randomized Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial.MethodsPatients with advanced or metastatic colorectal cancer who were enrolled in the CALGB/SWOG 80405 trial were identified by race. On the basis of covariates (treatment arm, KRAS status, sex, age, and body mass index), each Black patient was exact matched with a White patient. The association between race and OS and PFS was examined using a marginal Cox proportional hazard model for matched pairs. The interaction between KRAS status and race was tested in the model. The association between race and response to therapy and adverse events were examined using a marginal logistic regression model.ResultsIn total, 392 patients were matched and included in the final data set. No difference in OS (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.73‐1.16), PFS (HR, 0.97; 95% CI, 0.78‐1.20), or response to therapy (odds ratio [OR], 1.00; 95% CI, 0.65‐1.52) was observed between Black and White patients. Patients with KRAS mutant status (HR, 1.31; 95% CI, 1.02‐1.67), a performance statusscore of 1 (reference, a performance status of 0; HR, 1.49; 95% CI, 1.18‐1.88), or ≥3 metastatic sites (reference, 1 metastatic site; HR, 1.67; 95% CI, 1.22‐2.28) experienced worse OS. Black patients experienced lower rates and risk of grade ≥3 fatigue (6.6% vs 13.3%; OR, 0.46; 95% CI, 0.24‐0.91) but were equally likely to be treated with a dose reduction (OR, 1.09; 95% CI, 0.72‐1.65).ConclusionsNo difference in OS, PFS, or response to therapy was observed between Black patients and White patients in an equal treatment setting of the CALGB/SWOG 80405 randomized controlled trial.Lay Summary Despite improvements in screening and treatment, studies have demonstrated worse outcomes in Black patients with colorectal cancer. The purpose of this study was to determine whether there was a difference in cancer‐specific outcomes among Black and White patients receiving equivalent treatment on the CALGB/SWOG 80405 randomized clinical trial. In this study, there was no difference in overall survival, progression‐free survival, or response to therapy between Black and White patients treated on a clinical trial. These findings suggest that access to care and differences in treatment may be responsible for racial disparities in colorectal cancer.

8031 Background: New orally administered anticancer treatments have launched in recent years, promising gains in survival and quality of life, but with high prices.Financial difficulties encountered over the course of cancer diagnosis and treatment is a growing concern. These difficulties include inability to pay for basic necessities, presence of medical debt, and high out of pocket burdens relative to income. The primary objective of this study was to estimate the proportion of patients with multiple myeloma (MM) who experience financial difficulties in the past 12 months.Methods: Data collection entailed a comprehensive, theoretically grounded telephone survey and companion medical chart abstraction. Subjects included individuals with a current diagnosis of MM whose current or recent treatment included pharmaceutical-based care and who were not enrolled in a treatment-based trial. Practices eligible to recruit respondents included 44 NCORP affiliates of the Alliance. 14 geographically diverse NCORP affiliates participated between 11/2019 and 6/2020. The primary endpoint of the study was the proportion of subjects who reported financial difficulty in the past 12 months, as measured by the EORTC QLQ-C30 item #28. This proportion and 95% Wilson score confidence interval were estimated for all MM patients who responded to the financial difficulty question ((# reported financial difficulty)/(total # in that category who answered the question)). NCI Central IRB approved this study. Results: 393 subjects were recruited. 304 subjects completed the survey (77.4% response rate). Mean age was 67.5 years (SD 9.8), 143 (46.4%) were female, 24 (7.8%) self-reported race as ‘Black or African American’, 82 (26.6%) reported insured by government insurance Medicare only, 116 (38.2%) reported highest education as high school or below, and 94 (30.5%) reported high income. Mean time from diagnosis to survey enrollment was 3.6 years (SD 4.5). 292 (95.1%) were currently receiving treatment and 192 (62.5%) reported currently receiving a pre-defined ‘expensive’ oral pharmaceutical-based cancer treatment. 20.2% (95% CI:16.1%, 25.0%) reported financial difficulties. Conclusions: This is the first national study to systematically assess the prevalence of financial difficulties and its correlates among MM patients. Approximately 1 in 5 surveyed patients reported financial difficulties. Results of this study aim to inform efforts to improve financial navigation and resources for cancer patients.

AbstractThe WHO Classification of Tumours provides the international standards for the classification and diagnosis of tumours. It enables direct comparisons to be made between different countries. In the new fifth edition, the series has gone digital with the launch of a website as well as a series of books, known widely as the WHO Blue Books. The first volume to be produced is on the classification of Digestive System tumours, replacing the successful 2010 version. It has been rewritten and updated accordingly. This article summarises the major diagnostic innovations that have occurred over the last decade and that have now been incorporated in the classification. As an example, it incorporates the recently proposed classification of neuroendocrine tumours, based on the recognition that neuroendocrine tumours and carcinomas differ substantially in the genetic abnormalities that drive their growth, findings relevant to treatment selection and outcome prediction. Several themes have emerged during the production process. One is the importance of the progression from hyperplasia to dysplasia to carcinoma in the evolution of the malignant process. Advances in imaging techniques and endoscopy have resulted in enhanced access to precancerous lesions in the gastrointestinal and biliary tract, necessitating both changes in classification schema and clinical practice. Diagnosis of tumours is no longer the sole purview of pathologists, and some patients now receive treatment before tissue is obtained, based on clinical, radiological and liquid biopsy results. This makes the classification relevant to many disciplines involved in the care of patients with tumours of the digestive system.