1037 - Neoadjuvant Chemoradiotherapy with Modern Bowel-Sparing IMRT for Locally Advanced Rectal Cancer: A Multi-Institutional Phase II Trial

08:10am - 08:15am ET

Room 162

Presenter(s)

Katsuyuki Sakanaka, MD, PhD - Kindai University, Osaka-Sayama, Osaka

K. Sakanaka¹, K. Hida², D. Ito³, Y. Negoro⁴, S. Hamasu⁵, N. Horii⁶, M. Yoshitomi⁷, S. Okumura⁸, R. Mizuno⁹, K. Ueki¹⁰, R. Takahashi¹¹, T. Sakamoto¹², M. Fukuda¹³, T. Takagi¹⁴, K. Ueno¹⁵, H. Iramina¹⁶, H. Inoo¹⁶, K. Obama², and T. Mizowaki¹; ¹Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan, ²Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan, ³Department of Surgery, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan, ⁴Department of Radiation Oncology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan, ⁵Department of Surgery, Japanese Red Cross Otsu Hospital, Otsu, Japan, ⁶Department of Radiation Oncology, Japanese Red Cross Otsu Hospital, Otsu, Japan, ⁷Department of Surgery, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan, ⁸Department of Radiation Oncology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan, ⁹Department of Surgery, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan, ¹⁰Department of Radiation Oncology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan, ¹¹Department of Surgery, Kyoto Katsura Hospital, Kyoto, Japan, ¹²Department of Radiation Oncology, Kyoto Katsura Hospital, Kyoto, Japan, ¹³Department of Surgery, Kitano Hospital, Osaka, Japan, ¹⁴Department of Radiation Oncology, Kitano Hospital, Osaka, Japan, ¹⁵Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan, ¹⁶Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Purpose/Objective(s): In RTOG 0822, neoadjuvant chemoradiotherapy (NeoCRT) using intensity-modulated radiotherapy (IMRT) did not show clear clinical benefits over three-dimensional conformal radiotherapy (3DCRT) in locally advanced rectal cancer (LARC), possibly due to limited bowel sparing and the use of composite gastrointestinal (GI) toxicity as the primary endpoint, despite acute diarrhea being a key patient relevant, dose-dependent toxicity. Contemporary IMRT planning may enable greater bowel sparing compared with earlier-era IMRT planning used in RTOG 0822. We hypothesized that modern bowel-sparing IMRT would significantly reduce grade =2 acute diarrhea, compared with historical 3DCRT-based NeoCRT in this population.

Materials/Methods: This single-arm non-randomized multi-institutional phase II trial enrolled patients with LARC (MRI-positive circumferential resection margin or cT3–4N0/N+, UICC TNM 8th), ECOG PS 0–2, and adequate organ function. Protocol treatment was concurrent capecitabine (CAPE) and IMRT (45 Gy in 25 fractions) for elective nodes, with an optional boost to gross tumor (5.4 Gy in 3 fractions). A pre-enrollment IMRT dummy run was required at each institution to verify compliance with delineation and planning protocols. Small bowel was spared per predefined dose-volume constraints, including volume receiving 15 Gy (V15Gy) < 200 cc. Toxicities were assessed at least once every 2 weeks for 8 weeks after initiation of NeoCRT and graded per CTCAE v5.0; thereafter, assessments were performed at least once until the earliest of day 90 after starting NeoCRT, radical surgery, or initiation of additional chemotherapy, which defined the primary endpoint window for grade =2 acute diarrhea. The primary endpoint, grade =2 acute diarrhea, was tested using a one-sample exact binomial test versus a 26% historical rate (prior CAPE + 3DCRT phase II trials), assuming a true rate =12% with 51 patients required for 80% power (one-sided a = 0.05). Adverse events, pathological complete response (pCR), locoregional progression-free survival (LPFS), and overall survival (OS) constituted the secondary endpoints.

Results: Fifty-five patients were enrolled from October 2022 to February 2024 (cStage II/III: 7/48), with a median tumor distance of 5 cm from the anal verge. A boost was administered to 5 patients, and 98.2% (54/55) completed planned NeoCRT. Median small bowel V15Gy was 85 cc. Grade =2 acute diarrhea occurred in 7.3% (90% CI, 2.5–15.9; p < 0.001). Grade =2 anorectal toxicities occurred in 16.3%, which may support a toxicity-specific reduction in diarrhea. Radical surgery was performed in 50 patients; pCR was 6.0% (3/50). At median follow-up of 14 months, 12-month LPFS and OS were 95.0% and 98.2%, respectively.

Conclusion: Despite the single-arm design without concurrent control, NeoCRT using modern bowel-sparing IMRT may reduce acute diarrhea, maintain favorable short-term locoregional outcomes, and support further follow-up to assess long-term efficacy and toxicity in LARC.