Clinical outcomes of patients who underwent total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC): A single center experience.
Authors: Velayati Arash , Kalmuk James , Roubal Kiera , Wolf Bethany , Misniakiewicz Jagoda , Donahue Colleen , George Virgilio , Lupak Oleksandra 
Published: June 2023

e15630

Background: Total neoadjuvant therapy (TNT) has been mainstay of treatment for locally advanced rectal cancer (LARC), with a primary purpose of eradicating minimal residual disease, preserving the rectum, and achieving pathological complete response (pCR). Currently, there lacks consensus on chemotherapy regimen, sequencing, and modality of radiation therapy. The objective of this real-world retrospective analysis is to describe various TNT strategies employed and report patient centered outcomes. Developing a standard protocol based on available evidence and institutional retrospective data is crucial to reduce care variations. Methods: From January 2019 to January 2023, 61 patients with locally advanced rectal cancer were initiated on TNT. Patients were included regardless of whether they received treatment at our academic center or private practice. Retrospective chart review was performed to collect demographic data, chemotherapy regimens, toxicities, dose interruption, dose reduction, timeline of treatment, response rate as well as surgical intervention. Data cutoff was set to 3 years after TNT completion. Combined MRI and flexible sigmoidoscopy were used to evaluate final response. Results: Average age at diagnosis was 59 years old. Majority of patients were stage IIIB (52%), had low rectal disease (51%), received chemotherapy followed by long-course concurrent chemoradiation (80%) and had chemotherapy in an academic center (65%). Complete clinical response (cCR) rate was 36% in the overall cohort. Four out of 22 patients with cCR underwent surgery and the rest were initiated on watch and wait strategy, among these, only one patient had local recurrence requiring surgery. Among all the patients who had surgery, pCR rate was 15.6%. No difference existed in cCR between CAPOX and FOLFOX groups (34.5% vs 33%), however, grade 3/4 toxicities (27% vs 14%), dose reduction (17% vs 7%), dose interruption (11% vs 6%) and hospitalization (6% vs 0%) rates were higher in patients who received CAPOX. Of note, 7 patients received FOLFIRINOX. In this group, disease stage ranged from 2A to oligometastatic stage IV; however, over 50% obtained a cCR with comparable or better toxicity profile. Conclusions: Despite wide range of variations observed in treatment approaches to TNT across the organization and local institutions, organ preservation and complete clinical response rates were observed at the same rate of 1 out of 3 patients. In those patients who pursued surgical intervention, the pCR was lower than expected from trials. Patients who received FOLFOX tolerated treatment better with the same clinical response rate as CAPOX. Greater numbers will be required to determine response rate and superiority of FOLFIRINOX compared to doublet therapy. Further process standardization would likely improve patient outcomes with LARC receiving TNT.