EP1016 - TNT in the Inland Empire, is it dynamite?

Purpose/Background: Among the benefits of total neoadjuvant therapy (TNT) reported in clinical trials are higher treatment completion rates, up to 84% and 92% in the RAPIDO and PRODIGE 23 trials, respectively, compared to about 66% with standard treatment. Despite TNT widespread use over the past years and growing research on biological and clinical predictors of outcomes, there is a lack of information about completion rates in clincal practice. These rates may influence the efficacy and feasibility of TNT, particularly in relation to social determinants of health (SDOH), non-medical factors such as living conditions, education, and income that significantly affect health.

This study aimed to describe TNT completion rates at a tertiary care institution serving a socioeconomically challenged area informally known as the "Inland Empire", a region of Southern California, home to nearly 4.6 million people that covers approximately 27,000 square miles from urban centers to the rural high desert, including San Bernardino County and Riverside County. Additionally, we aimed to explore the potential association between SDOH and treatment completion.

Methods/Interventions: We conducted a retrospective cohort study of patients over 18 years, diagnosed with rectal cancer between 2019 and 2024, who met TNT criteria. Patients lost to follow-up before starting TNT or those who declined treatment were excluded. Publicly available, zip code-linked indices were used to measure SDOH: the Social Vulnerability Index (SVI) from the CDC and the Distressed Communities Index (DCI) from the Economic Study Group. In both systems, higher scores reflect more distressed or vulnerable populations.

TNT completion was defined as finishing 100% of the prescribed regimen. Reasons for non-completion were recorded from medical records or the absence of progress notes. Data distribution was assessed with the Shapiro-Wilk test. Demographic characteristics were compared using chi-square, Mann-Whitney U, and t-tests. Logistic regression was used to calculate odds ratios (OR) and confidence intervals (CI). Analyses were performed with R (version 4.4.3; "Trophy Case").

Results/Outcomes: The overall TNT completion rate was 71%. Increasing age was associated with lower odds of completion, with a 4.75% decrease in probability per year (OR 0.95, CI 0.92-0.97, p = 0.001). Higher DCI and SVI scores showed a trend toward lower completion rates, however, results were not statistically significant (OR 0.99, CI 0.97-1.01, p = 0.46; OR 0.39, CI 0.015-6.25, p = 0.53). The most frequent reason for non-completion was loss to follow-up, which showed no significant association with SVI (p = 0.25).

Conclusion/Discussion: This study highlights a TNT completion rate lower than in clinical trials, aligning more closely with standard treatment outcomes. Because medical records lack detailed SDOH data, population-level indices may be useful when combined with individual-level information. Age correlated with reduced completion, likely reflecting not only biological but also social and economic challenges faced by older patients.

Although statistical significance was not reached, the trend toward lower completion among patients from socioeconomically disadvantaged areas supports the possibility that SDOH influence TNT adherence. Future prospective studies with individual-level SDOH data may help identify key factors and guide targeted policies to improve completion rates.

TNT completion rates by DCI group
a) Y-axis represents the percentage of patients that completed one hundred percent of the prescribed TNT regimen. The X-axis shows groups categorized by DCI scores, from the lowest on the left, to the highest on the right. b) This pie chart displays the percentage of patients included in each DCI category; most patients were classified as "At risk", followed by "Mid-tier".
TNT completion rates by SVI group
a) Y-axis represents the percentage of patients that completed the full TNT regimen. The X-axis shows two groups categorized by SVI scores, the lowest is displayed on the left, and the highest being on the right. b) The pie chart displays the percentage of patients included in each SVI-based category.