title: Concomitant boost IMRT-based neoadjuvant chemoradiotherapy for clinical stage II/III rectal adenocarcinoma: results of a phase II study.
abstract: OBJECTIVE
  This study was designed to evaluate the efficacy and toxicities of concomitant boost intensity-modulated radiation therapy (IMRT) along with capecitabine and oxaliplatin, followed by a cycle of Xelox, in neoadjuvant course for locally advanced rectal cancer.
  
  
  METHODS
  Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received IMRT to the pelvis of 50 Gy and a concomitant boost of 5 Gy to the primary tumor in 25 fractions, and concurrent with oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 bid d1-5 weekly). One cycle of Xelox (oxaliplatin 130 mg/m2 on d1 and capecitabine 1000 mg/m2 twice daily d1-14) was given two weeks after the completion of chemoradiation, and radical surgery was scheduled eight weeks after chemoradiation. Tumor response was evaluated by tumor regression grade (TRG) system and acute toxicities were evaluated by NCI-CTC 3.0 criteria. Survival curves were estimated using the Kaplan-Meier method and compared with Log-rank test.
  
  
  RESULTS
  A total of 78 patients were included between March 2009 and May 2011 (median age 54 years; 62 male). Seventy-six patients underwent surgical resection. Twenty-eight patients underwent sphincter-sparing lower anterior resection and 18 patients (23.7%) were evaluated as pathological complete response (pCR). The incidences of grade 3 hematologic toxicity, diarrhea, and radiation dermatitis were 3.8%, 10.3%, and 17.9%, respectively. The three-year LR (local recurrence), DFS (disease-free survival) and OS (overall survival) rates were 14.6%, 63.8% and 77.4%, respectively. Initial clinical T stage and tumor regression were independent prognostic factors to DFS.
  
  
  CONCLUSIONS
  An intensified regimen of concomitant boost radiotherapy plus concurrent capecitabine and oxaliplatin, followed by one cycle of Xelox, can be safely administered in patients with locally advanced rectal cancer, and produces a high rate of pCR. A prognostic score model is helpful to distinguish different long-term prognosis groups in early stage.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.forename: Fangqi
authors.initials: F
authors.lastname: Liu
authors.forename: Weilie
authors.initials: W
authors.lastname: Gu
authors.forename: Peng
authors.initials: P
authors.lastname: Lian
authors.forename: Weiqi
authors.initials: W
authors.lastname: Sheng
authors.forename: Junyan
authors.initials: J
authors.lastname: Xu
authors.forename: Gang
authors.initials: G
authors.lastname: Cai
authors.forename: Debing
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, No, 270, Dong'An Road, Shanghai 200032, China. caisanjun@csco.org.cn.
authors.forename: Sanjun
authors.initials: S
authors.lastname: Cai
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000009:adverse effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010071:Oxaloacetates; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D010071:Oxaloacetates; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil