The Clinical Trial Of Preoperative Chemoradiotherapy For Locally Advanced Mid-low Rectal Cancer

Part one: Dosimetric analysis of VMAT technique in preoperative chemoradioth-erapy for locally advanced mid-lowrectal cancerObjective: To evaluate the dosimetric feasibility of volumetric modulated arc therapy with a simultaneous integrated boost (SIB-VMAT58.75Gy) in preoperative chemoradiation for mid-low locally advanced rectal cancer (LARC).Methods: Nine patients with stage Ⅱ～Ⅲ rectal cancerwhich treated with preoperative chemoradiation were collected in this study, and two plans were made for each patient.In the boost group (SIB-VMAT58.75Gy),the prescribed doses were 58.75Gy to the gross tumor (pGTV58.75Gy) and 50 Gy to areas at high risk of harboring microscopic disease(PTV50Gy) in 25 fractions; In the no-boost group (VMAT50Gy), the prescribed dose was 50Gy to PTV50Gy without a boost. The dose distribution in target areas and involved organs was assessed according to the dose-volume histogram (DVH).Results: Two plans all meet prescribed dose requirements for the target area, no statistically significant difference between the two plans conformal index (CI) for PTV(1.0±0.0vs. 1.0±0.0, p>0.05) and the homogeneity index (HI) of SIB group for PTV higher than that of the control group (0.2±0.2 vs. 0.1 ±0.0, p<0.05). There was no statistically significant difference in the dose of V10-V50 between the small intestine,bladder, femoral heads, pelvis bone, but the D2cc of small intestineis higher in SIB group compared with the control group (P=0.038).Conclusions: The SIB group is feasible dosimetrically with respect to dose limitations of target areas and involved organs for mid-low LARC and the clinical research evalutation could be promising.Part two: Preoperative chemoradiotherapy in locally advanced mid-low rectal cancer: preliminary results of a prospective phase II studyObjective: To evaluate the feasibility, safety and efficacy of preoperative SIB-IMRT and capecitabine, followed by a cycle of neoadjuvant capecitabine in patients with mid-low LARC.Methods: Between March 2015 and August 2016, 43 patients with stage Ⅱ or Ⅲrectal cancer received SIB-IMRT delivering 58.75 Gy to the primary tumor and regional lymph nodes while delivering 50Gy to areas at risk for harboring microscopic disease in 25 fractions and synchronize chemotherapy of capecitabine. One cycle of capecitabine (1250 mg/m2, twice daily, dl-14) was given one week after the completion of chemoradiotherapy (CRT), and TME was scheduled 6 to 8 weeks after the end of CRT. The primary endpoint included ypCR. Secondary endpoints included acute toxicity, tumor downstaging, surgical morbidity, R0 resection, postoperative complications, sphincter preservation rate, LR, OS and DFS.Results: 43 patients were successfully completed chemoradiationas as planed and 40 patients received surgical resection, 2 patients refused surgery and clinical symptom relieved and 1 patient delayed surgery due to perianal edema after radiotherapy. 16 patients received ypCR and 30 patients underwent the sphincter preserving surgery and R0 resection rate was 100%. Downstaging of the tumor and lymph nodes was 80% and 93%, respectively. During the period of chemoradiotherapy, most of the adverse reactions were grade 1/2, Grade 3 toxicities were found in 5 cases, and no grade 4 or 5 toxicities were found. Postoperative complications included 1 case of ureteral injury and 1 case of intestinal obstruction, no death in perioperative period.Conclusions: The pattern of preoperative SIB-IMRT58.75 plus concurrent capeciabine,followed by one cycle neoadjuvant capecitabineis a safe, well-tolerated treatment,gained a good pCR and downstage for patients with LARC.