1036 - A Prospective Study of Adaptive MRI-Guided Dose-Escalated Radiation Therapy for Locally Advanced Rectal Cancer

08:05am - 08:10am ET

Room 162

Presenter(s)

Russell Palm, MD - The Ohio State University James Cancer Hospital, Columbus, OH

R. F. Palm¹, J. J. Lee², S. Hoffe³, J. Costello⁴, H. Vadvala⁴, I. Imanirad⁵, T. Biachi de Castria⁶, R. Kim⁶, A. Stefanou⁶, S. Dessureault⁶, J. Sanchez⁶, K. Latifi³, S. Felder⁶, and J. M. Frakes³; ¹The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, Columbus, OH, ²University of South Florida Morsani College of Medicine, Tampa, FL, ³H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, ⁴H. Lee Moffitt Cancer Center and Research Institute, Department of Radiology, Tampa, FL, ⁵H. Lee Moffitt Cancer Center, Department of Gastrointestinal Oncology, Tampa, FL, ⁶H. Lee Moffitt Cancer Center and Research Institute, Department of GI Oncology, Tampa, FL

Purpose/Objective(s):

Evaluate feasibility of online adaptive MR-guided radiation therapy to deliver dose escalation for locally advanced rectal cancer.

Materials/Methods:

Patients motivated for “watch-and-wait” (W/W) with pMMR locally advanced rectal adenocarcinoma (stage II – III) eligible for total neoadjuvant therapy (TNT) starting with chemoradiation (CRT) were enrolled on a single institution prospective study (NCT05108428). Patients were treated to 45 Gy in 25 fractions with a 3-fraction boost to 50.4 Gy with capecitabine followed by consolidative FOLFOX for 8 cycles. After 15 fractions (27 Gy) a mid-CRT MRI was obtained, and patients received an additional 5 fraction sequential boost using MRgRT to 59.4 Gy in 33 fractions if the primary tumor demonstrated a =30% volumetric decrease in size from initial staging. The primary endpoint was feasibility of delivery of MRgRT. Secondary endpoints included OS, DFS, clinical complete (cCR)/near complete (nCR)/incomplete (iCR) response rate, total mesorectal excision (TME) free-survival, and toxicity. Survival outcomes were estimated using the Kaplan-Meier method.

Results:

From 2021 – 2023, 20 patients were enrolled. Patient characteristics are reported in Table 1. Most patients (90%) met the mid-CRT volumetric size criteria for dose escalation to 59.4 Gy. One patient with a cCR after CRT declined consolidative FOLFOX. After completion of TNT, 85% of the cohort proceeded with W/W (55% cCR, 30% nCR). Three patients had persistent disease after TNT (15% iCR) and underwent TME (N=2 LAR, N=1 APR). For 17 patients on W/W, 2 local regrowths (12%) occurred with one patient requiring TME at 31 months after TNT and the other patient salvaged with transanal local excision 10 months after TNT. At a median follow-up of 28.8 months from TNT, 2-year OS was 100% and the 2-year DFS was 94% with a single patient developing metastasis 12 months after APR. The 2-year TME-free-survival rate was 83% (95% CI 67-100%). The overall =G3 acute toxicity during TNT was 25% (15% radiation proctitis, 5% vomiting, 5% diarrhea). There was a single late =G3 toxicity after TNT of radiation proctitis successfully treated with steroid enema and endoscopic argon plasma coagulation.

Conclusion:

Dose-escalated online adaptive MRgRT with a “cone down” sequential boost to gross disease as delineated by mid-CRT diagnostic MRI is feasible and affords an isotoxic intensification strategy for patients motivated for non-operative management with favorable outcomes primarily driven by lower rates of local regrowth on W/W.

N = 20 (%)

Age, Median (Range)

55.5 (30-86)

Gender

Male

Female

14 (70%)

6 (30%)

Stage at Diagnosis

T2N+

T3N-

T3N+

T4aN+

2 (10%)

6 (30%)

11 (55%)

1 (5%)

MRF Status

Clear

Involved/Threatened

12 (60%)

8 (40%)

Tumor Volume (cc), Median (Range)

Initial Tumor Volume

Tumor Volume at 27 Gy

25.2 (8.6 - 66.8)

4.5 (0.8 - 35)

XRT Dose

59.4 (BED₁₀ 70.1 Gy)

50.4 (BED₁₀ 59.5 Gy)

18 (90%)

2 (10%)