Preoperative Chemoradiotherapy Utilizing Intensity Modulated Radiation Therapy (IMRT) Compared With 3D Conformal Radiotherapy (3DCRT) for Patients With Locally Advanced Rectal Cancer: Prospective Phase II Study.

Abstract

PURPOSE/OBJECTIVE(S)\nPreoperative chemoradiotherapy is standard of care treatment for locally advanced rectal cancer, with scarce prospective data on efficacy and safety of Intensity Modulated Radiation Therapy (IMRT). We aim to explore the characteristics and outcomes of this treatment modality and whether IMRT can decrease acute gastrointestinal (GI) toxicity.\n\n\nMATERIALS/METHODS\nA single center prospective phase 2 study enrolling patients with locally advanced rectal cancer who were planned for preoperative chemoradiotherapy. Two radiation plans were prepared for each patient; IMRT and 3D conformal radiotherapy (3DCRT). Dose volume histograms (DVH) for both treatment plans were compared, and plans were evaluated pretreatment for target coverage and organs at risk (OAR) exposure, including small bowel, urinary bladder, femoral heads and perianal skin. Treatment plan was selected accordingly, specifically preferring lower dose to small bowel. All patients received a total dose of 45 Gy in 25 fractions to rectum and draining lymph nodes, followed by a 5.4 Gy boost to the tumor, given concurrently with capecitabine. Weekly follow up visits were performed to assess acute toxicity. Pathological response was assessed.\n\n\nRESULTS\nA total of 72 patients with stage II-III rectal adenocarcinoma were enrolled. IMRT was given to 69 patients, whereas 3 patients received 3DCRT. Dosimetric comparison of plans demonstrated significant superiority of IMRT plans parameters including coverage of planning target volume (PTV) of lymph nodes (95% of dose to 1395 cc vs. 1380 cc, P\u202f=\u202f0.002), dose to small bowel (45 Gy to 42 vs 22 cc, P < 0.0001), mean dose to bladder (30 vs 26, P < 0.0001), and perianal skin (8 vs 6, P < 0.0001). Pathological complete response (pCR) and partial response (PR) ware achieved in 21% and 57% of patients, respectively. Acute grade 2 diarrhea was reported among 25% during IMRT. Acute grade 3-4 toxicity during IMRT were as follows: diarrhea 4%, proctitis 1%, and none had grade 3-4 cystitis and perianal skin erythema.\n\n\nCONCLUSION\nIMRT is feasible in the preoperative treatment of rectal cancer with superior dosimetry, lower dose to small bowel and minimal grade 3-4 toxicity, with good pathological response.