# The Impact of Intraoperative Radiotherapy on Margin Positive Locally Advanced Rectal Cancer: A Propensity‐Matched Analysis of The National Cancer Database

## TL;DR

This study finds that adding intraoperative radiotherapy (IORT) to standard treatment does not significantly improve survival in advanced rectal cancer patients with positive surgical margins.

## Contribution

The study is the first nationwide analysis using propensity matching to assess IORT's impact on survival in margin-positive rectal cancer patients.

## Key findings

- IORT was not associated with improved 5-year overall survival compared to neoadjuvant radiotherapy.
- Patients receiving IORT were younger and more likely to be treated at academic centers.
- The observed survival benefit of IORT was not significant after adjusting for confounding factors.

## Abstract

Intraoperative radiotherapy (IORT) is utilized as an adjunctive treatment in advanced rectal cancer, particularly in cases with threatened surgical margins. Although IORT has shown benefits in enhancing local tumor control, its impact on overall survival (OS) remains unclear. This study assesses the effect of IORT on survival outcomes using a large cohort from the National Cancer Database (NCDB) and examines factors influencing its application in clinical practice across the United States.

The National Cancer Database was retrospectively reviewed (2006–2019) to identify patients with pathological T3–T4, M0 rectal cancer who underwent surgery following neoadjuvant chemotherapy. Patients with microscopically residual margin‐positive were included and categorized into two groups: those who received neoadjuvant radiotherapy (RT) and those treated with intraoperative radiotherapy (IORT) combined with adjuvant/neoadjuvant RT. Groups were propensity score–matched (1:4) to balance baseline characteristics. The primary outcome was 5‐year overall survival (OS), assessed using Kaplan–Meier analysis and Cox proportional hazards modeling.

Among 1,788 patients with margin‐positive rectal cancer, IORT was administered to 119 patients (6.7%) while 1,669 patients (93.3%) received neoadjuvant RT. Patients receiving IORT were younger, more likely to have private insurance, more frequently treated at academic/research programs, and more commonly underwent pelvic exenteration and Multiagent chemotherapy. After propensity score matching, 119 IORT patients were compared with 476 neoadjuvant RT patients. IORT was associated with lower mortality in univariate analysis (HR: 0.63; p < 0.001); however, this benefit was attenuated after adjusting for confounders (HR: 0.84; p = 0.07). The 5‐year overall survival rates were 58.4% for IORT versus 54.9% for neoadjuvant RT alone (p = 0.18).

This nationwide analysis suggests that adding IORT to treatment does not significantly improve overall survival in margin‐positive rectal cancer patients. However, due to heterogeneity in patient selection and dosing, further prospective trials are warranted to clarify its clinical role.

This nationwide study analyzed 1,788 patients with margin‐positive locally advanced rectal cancer from the National Cancer Database to evaluate the impact of intraoperative radiotherapy (IORT) on overall survival in patients with pathologic T3–T4, M0 rectal adenocarcinoma and microscopically positive margins (R1). The findings indicate that adding IORT to standard treatment does not significantly improve overall survival in margin‐positive rectal cancer patients, highlighting the heterogeneity in IORT use and emphasizing the need for well‐designed prospective trials to define its clinical utility