Snyder, Rebecca A.

Although structured reporting of adverse events related to medical therapies is a critical aspect of clinical trials, the current practice fails to capture postoperative complications accurately or systematically, which precludes our ability to fully assess the impact of the risks of surgical interventions on oncologic outcomes. The incorporation of standardized, procedure‐specific definitions and severity classifications for postoperative complications into adverse event reporting in trials conducted through the National Clinical Trials Network is proposed.

PURPOSE Adherence to operative standards and thorough documentation of surgical technique are critical, particularly in multidisciplinary clinical trials. We sought to evaluate variability in the performance and documentation of oncologically relevant aspects of technical surgery among patients enrolled in Alliance A021501, a phase 2 National Clinical Trials Network randomized clinical trial of neoadjuvant therapy for borderline resectable pancreatic adenocarcinoma. METHODS We reviewed the primary operative and pathology reports of all enrolled patients who underwent complete pancreatic resection. Operative techniques and pathologic end points with potential to influence recurrence and survival were evaluated. RESULTS Fifty-one of 126 study participants (40.5%) underwent complete pancreatectomy. The extent of lymphadenectomy was documented in 36 (70.6%) operative reports, and 5 (9.8%) reports outlined the specific lymph node stations removed. Periadventitial dissection of the superior mesenteric artery was described in 25 of 50 (50.0%) operative reports. Immediate histopathologic analysis of the hepatic duct and pancreatic parenchyma margins was documented in 29 of 50 (58.0%) and 32 of 49 (65.3%) reports, respectively, and presence or absence of residual disease following resection was documented in 9 of 51 (17.6%) reports. Specimen orientation was documented in 19 of 51 (37.3%) pathology reports, and 30 of 49 (61.2%) pathology reports stated the distance between the tumor and final SMA margin. CONCLUSION Even in this rigorously controlled, multicenter, randomized pancreatic cancer clinical trial, performance of key elements of technical surgery was inconsistent, and documentation was incomplete. Standardization of technique and documentation in clinical trials and within clinical practice should be addressed to improve quality assurance and trial interpretability.

PURPOSE Social determinants of health (SDOH) shape cancer treatment access, adherence, and outcomes, yet their collection and use within National Clinical Trials Network (NCTN) studies remain poorly defined. This study examined how demographic and SDOH-related variables were historically collected and published to identify gaps that constrain the study of social context within NCTN trials. METHODS Participant-level data from completed phase III trials for gastrointestinal (GI) cancers conducted by the Alliance for Clinical Trials in Oncology (Alliance) or its legacy groups from 1999 to 2018 were pooled. Thirteen measures were assessed: four demographic and nine SDOH-related. The proportion of individual participants with data collected for each measure was evaluated. Data utilization was evaluated for all primary articles and via targeted review of related publications using the number either reporting subgroups or publishing analyses for each measure. RESULTS A total of 12,701 participants across 11 trials were included. All trials collected demographic measures (<2% of patients missing), insurance status (1% missing), and ZIP code (3% missing). Education level was collected in two trials (28% missing) with marital and employment status collected in one trial (41% missing for both). No trials collected data on other SDOH-related measures. Education level was the only SDOH-related measure reported in primary articles, and none reported analysis of SDOH-related measures. Of the 149 related publications, <2% reported or analyzed any SDOH-related measure. CONCLUSION Across Alliance and NCTN legacy group phase III trials for GI cancers, demographic variables have been consistently collected and frequently reported or analyzed, whereas SDOH-related measures are inconsistently collected and rarely published in the literature. These findings demonstrate a historical absence of routine SDOH data capture and utilization within NCTN trials.

BACKGROUND: Significant disparities persist in timely, guideline-concordant breast cancer treatment across the US, impacting cancer outcomes. The influence of both patient-level and facility-level socioeconomic status (SES) on adherence to Commission on Cancer quality measures remains incompletely understood. STUDY DESIGN: We conducted a retrospective cohort study using the National Cancer Database to assess associations between patient and facility SES and concordance with timeliness of 3 Commission on Cancer breast cancer quality measures: surgery, multiagent chemotherapy, and radiotherapy, among patients diagnosed from 2018 to 2022. Multivariable logistic regression models were used to evaluate predictors of concordant care, including a composite measure of facility-level social risk. RESULTS: The analytic cohorts included 471,425 patients for surgery, 82,734 for chemotherapy, and 311,523 for radiotherapy. Black race, uninsured status, and lower educational attainment were each independently associated with lower odds of receiving guideline-concordant care across all measures. Patients treated at low-SES facilities had higher odds of receiving timely surgery (adjusted odds ratio [OR] 1.27, 95% CI 1.24 to 1.31) but lower odds of receiving timely chemotherapy (OR 0.85, 95% CI 0.79 to 0.91) and radiotherapy (OR 0.95, 95% CI 0.92 to 0.97) compared with those at other institutions. Facility type, fragmented care, and comorbidities also contributed to variation in concordance. CONCLUSIONS: Significant disparities in guideline-concordant breast cancer care persist by race, insurance, education, and facility-level social risk, highlighting intervention opportunities to improve outcomes for these already vulnerable populations. These findings highlight the importance of policy and institutional strategies that address both patient- and facility-level barriers to ensure equitable access to high-quality multidisciplinary treatment.

Importance Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined. Objective To develop consensus best practices for delivering NT to patients with localized PDAC. Design, Setting, and Participants This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature and expert opinion. An interdisciplinary panel was formed including 47 North American experts from surgical, medical, and radiation oncology, radiology, pathology, gastroenterology, integrative oncology, anesthesia, pharmacy, nursing, cancer care delivery research, and nutrition as well as patient and caregiver stakeholders. Main Outcome and Measures Statements that reached 75% agreement or greater were included in final consensus statements. Results Of the 47 participating panel members, 27 (57.64%) were male, and the mean (SD) age was 47.6 (8.2) years. Physicians reported completing training a mean (SD) 14.6 (8.6) years prior and seeing a mean (SD) 110.6 (38.4) patients with PDAC annually; 35 (77.7%) were in academic practice. Final consensus was reached on 82 best practices for delivering NT. Of these, 38 statements focused on pre-NT practices, including diagnosis and staging (n = 15), evaluation and optimization (n = 20), and decision-making (n = 3); 29 statements defined best practices during NT, including initiation (n = 3), delivery of therapy (n = 8), restaging practices (n = 12), and management of complications during NT (n = 6); and 15 best practices were identified to guide treatment post-NT, focusing on surgery (n = 7), pathology (n = 4), and follow-up (n = 3). Conclusions Using a modified Delphi consensus technique, best practice guidelines were developed focusing on the optimal standards for delivering NT to patients with localized PDAC. Given the prognostic importance of completing multimodality therapy, efforts to standardize and optimize the delivery of NT represent an immediate opportunity to decrease care variation and improve outcomes for patients with PDAC. Future research should focus on validating and implementing best practice standards into clinical practice.

664 Background: Postoperative complications in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. Further, the impact of preoperative hypofractionated radiotherapy on postoperative outcomes is largely unknown. We sought to quantify perioperative morbidity among patients with pancreatic cancer who received neoadjuvant modified FOLFIRINOX chemotherapy with or without hypofractionated radiotherapy on a multicenter clinical trial. Methods: The A021501 phase 2 trial randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX then hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (Dec 31, 2016-Jan 1, 2019). Patients underwent resection according to defined operative standards at enrolling centers without specific requirements for either surgeon or hospital volume. Surgical complications and adverse events were assessed and captured at a single time point of 90 days after surgery and compared between treatment arms. Results: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n=32, Arm 1; n=19, Arm 2) at 28 institutions. Vascular resection was performed in 19 patients (37%). One patient in Arm 2 died within 90 days after surgery. Rates of any surgical complication were 19% (n=6) in Arm 1 and 42% (n=8) in Arm 2 (p=0.07). Median length of stay was 7 days (range 5-38 days). Five (10%) patients required reoperation within 90 days. Readmission rates were higher in Arm 2 than Arm 1 (16% vs. 42%, p=0.04) but there were no differences in rates of reoperation, pancreatic fistula or abscess requiring drainage, or wound infection between study arms. 54% of patients (n=26/48) experienced a grade 3 or higher adverse event, with no difference between treatment arms (47% versus 67%, p=0.7). Rates of initiation of adjuvant therapy did not differ between treatment arms (66% vs. 68%, p=0.4). Pancreatic fistula and abscess were associated with adjuvant therapy (p<0.01). No difference in overall survival was observed based on occurrence of surgical complications (HR 1.1; 95% CI 0.5-2.6). Conclusions: In this national cooperative group study of patients with borderline resectable pancreatic cancer,postoperative complications following neoadjuvant chemotherapy, radiation, and surgical resection were consistent with rates previously reported by high-volume institutions and using large datasets. Multimodality trials of preoperative therapy for locoregionally advanced pancreatic cancer may be safely performed in the cooperative group setting. Clinical trial information: NCT02839343 .

Objective: To characterize the current state of mental health within the surgical workforce in the United States. Background: Mental illness and suicide is a growing concern in the medical community; however, the current state is largely unknown. Methods: Cross-sectional survey of the academic surgery community assessing mental health, medical error, and suicidal ideation. The odds of suicidal ideation adjusting for sex, prior mental health diagnosis, and validated scales screening for depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol use disorder were assessed. Results: Of 622 participating medical students, trainees, and surgeons (estimated response rate=11.4%–14.0%), 26.1% (141/539) reported a previous mental health diagnosis. In all, 15.9% (83/523) of respondents screened positive for current depression, 18.4% (98/533) for anxiety, 11.0% (56/510) for alcohol use disorder, and 17.3% (36/208) for PTSD. Medical error was associated with depression (30.7% vs. 13.3%, P<0.001), anxiety (31.6% vs. 16.2%, P=0.001), PTSD (12.8% vs. 5.6%, P=0.018), and hazardous alcohol consumption (18.7% vs. 9.7%, P=0.022). Overall, 13.2% (73/551) of respondents reported suicidal ideation in the past year and 9.6% (51/533) in the past 2 weeks. On adjusted analysis, a previous history of a mental health disorder (aOR: 1.97, 95% CI: 1.04–3.65, P=0.033) and screening positive for depression (aOR: 4.30, 95% CI: 2.21–8.29, P<0.001) or PTSD (aOR: 3.93, 95% CI: 1.61–9.44, P=0.002) were associated with increased odds of suicidal ideation over the past 12 months. Conclusions: Nearly 1 in 7 respondents reported suicidal ideation in the past year. Mental illness and suicidal ideation are significant problems among the surgical workforce in the United States.

Objective: We sought to evaluate symptomatic adverse event (AE) rates among patients with pancreatic cancer receiving neoadjuvant therapy on clinical trial (A021501) using the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). Background: To date, pancreatic cancer clinical trials have measured AEs using standard physician reporting [Common Terminology Criteria for Adverse Events (CTCAE)]. Patient-reported symptomatic AEs have been incompletely characterized. Methods: A021501 (December 31, 2016–January 1, 2019) randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX+hypofractionated radiotherapy (Arm 2), followed by pancreatectomy and adjuvant FOLFOX6. Patients completed PRO-CTCAE assessments at baseline, on day 1 of each chemotherapy cycle, and daily during radiotherapy. Results: Of 126 patients, 96 (76%) initiated treatment and completed a baseline plus at least 1 postbaseline PRO-CTCAE assessment. Diarrhea and fatigue were the only symptomatic grade 3 or higher AEs identified in at least 10% of patients using CTCAE. At least 10% of all patients reported an adjusted PRO-CTCAE composite grade 3 AE during neoadjuvant treatment for 10 of 15 items: anxiety (10%), bloating of abdomen (16%), decreased appetite (18%), diarrhea (13%), dry mouth (21%), fatigue (36%), nausea (18%), generalized pain (16%), abdominal pain (21%), and problems tasting (32%). Decreased appetite was higher in Arm 2 than in Arm 1 (P=0.0497); no other differences between study arms were observed. Conclusion: Symptomatic AEs during neoadjuvant therapy were common and were reported more frequently by patients using PRO-CTCAE than were recorded by clinicians using standard CTCAE.

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.