Search

Abstract Background Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0–4; 4–8; 8–12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3–4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8–12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial registration Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Abstract Background Vulnerable persons are individuals whose life situations create or exacerbate vulnerabilities, such as low income, housing insecurity and social isolation. Vulnerable people often receive a patchwork of health and social care services that does not appropriately address their needs. The cost of health and social care services escalate when these individuals live without appropriate supports. Compassionate Communities apply a population health theory of practice wherein citizens are mobilized along with health and social care supports to holistically address the needs of persons experiencing vulnerabilities. Aim The purpose of this study was to evaluate the implementation of a compassionate community intervention for vulnerable persons in Windsor Ontario, Canada. Methods This applied qualitative study was informed by the Consolidated Framework for Implementation Research. We collected and analyzed focus group and interview data from 16 program stakeholders: eight program clients, three program coordinators, two case managers from the regional health authority, one administrator from a partnering community program, and two nursing student volunteers in March through June 2018. An iterative analytic process was applied to understand what aspects of the program work where and why. Results The findings suggest that the program acts as a safety net that supports people who are falling through the cracks of the formal care system. The ‘little things’ often had the biggest impact on client well-being and care delivery. The big and little things were achieved through three key processes: taking time, advocating for services and resources, and empowering clients to set personal health goals and make authentic community connections. Conclusion Compassionate Communities can address the holistic, personalized, and client-centred needs of people experiencing homelessness and/or low income and social isolation. Volunteers are often untapped health and social care capital that can be mobilized to promote the health of vulnerable persons. Student volunteers may benefit from experiencing and responding to the needs of a community’s most vulnerable members.