Total Neoadjuvant Therapy Outcomes in Primarily Hispanic Patients with Locally Advanced Rectal Adenocarcinoma

Summary: For locally advanced rectal adenocarcinoma, total neoadjuvant therapy (TNT) is the current standard of care. If a complete clinical response (CCR) is achieved, the goal is to offer watch and wait (WW). In our institution, we serve many underserved communities with limited access to health care presenting with locally advanced disease. The purpose of this study was to report our experience on achieving CCR as well as to evaluate the association between peripheral immune cell counts and outcomes. Patients (n= 39) with rectal adenocarcinoma who received TNT between 2019 to 2023 were evaluated. We collected demographics, clinical staging, treatment, and weekly lab values (WBCs, lymphocytes, neutrophils) during TNT, noting the nadir. Tumor sizes after TNT and nadir cell counts were normalized as a percentage of the baseline values. Wilcoxon rank sum tests evaluated paired samples. Univariable and multivariable linear regressions, or generalized linear models for dichotomous outcomes were used to examine correlation between immune cell counts and clinical variables with clinical outcomes and reported as odds ratios (OR). Cox proportional hazard models with hazard ratios (HR) were used to evaluate overall survival as well as distant metastases free survival. A total of 39 patients were included in the study with the majority being male (77%) and of Hispanic ethnicity (69%) with no insurance or county insurance supplemented by social work (30%). Median age was 54 years (range 32- 74). The majority of patients had T4 disease ( 53%) with T4b (30%) and N2 (61.5%). Median tumor size at diagnosis was 7 cm (interquartile range, IQR, 4.3). The median follow up time was 528 days (IQR 428 days). After completion of TNT, there was statistically significant tumor size reduction between pre- and post-TNT tumor size ( median post size: 3.8 cm; p= 0.003). There were 5 instances of pathologic complete response with no patients achieving WW via CCR. Reduction in immune cells was significant pre- and post- TNT, WBCs (p= 0.001), lymphocytes (p=0.003), and neutrophils (p=0.04). Greater normalized lymphocyte counts were related to greater tumor size downstaging (OR 1.3, CI: 1.01- 1.8, p =0.043). Higher CEA post TNT correlated with less tumor regression (OR 1.02, CI: 1.01- 1.03, p =0.03) as well as metastases ( HR 1.2 95% 1.1-1.3) . In addition to N2 status, greater normalized leukocyte counts during TNT reduced chance of distant metastases (HR 0.94 95% (0.91-0.98, p=0.02) which remained on multivariate analysis. Sequence of TNT had no impact on OS or MFS. In our cohort of patients with low healthcare access as well as larger tumor sizes, and high T and N stages are unlikely to achieve a clinical complete response. Efforts to mitigate hematologic toxicity of radiation and chemotherapy administration can potentially improve clinical outcomes. Sabi Shrestha (she/her/hers), MD (Presenting Author) - UT Health San Antonio; Rahul Khandekar, B.S. (Co-Author) - UT Health San Antonio; Samantha Murphy, MD (Co-Author) - UT Health San Antonio; Bilal Nasim, MD (Co-Author) - UT Health San Antonio; Mio Kitano, MD (Co-Author) - UT Health San Antonio; Alicia Logue, MD (Co-Author) - UT Health San Antonio; Haiser Dao, MD (Co-Author) - UT Health San Antonio; Sukeshi Arora, MD (Co-Author) - UT Health San Antonio; Colin Court, MD (Co-Author) - UT Health San Antonio; Neil B. Newman, MD (Co-Author) - UT Health San Antonio