title: Phase II trial of first-line chemoradiotherapy with intensity-modulated radiation therapy followed by chemotherapy for synchronous unresectable distant metastases rectal adenocarcinoma.
abstract: OBJECTIVE
  Based on the hypothesis that first-line chemoradiation followed by chemotherapy was superior for primary tumor and non-inferior for distant lesions compared to chemotherapy alone in synchronous unresectable distant metastases rectal adenocarcinoma, this study was designed to assess the efficacy and safety of this strategy.
  
  
  METHODS
  Thirty two eligible patients received intensity modulated radiation therapy (45 Gy to the pelvis and a concomitant 10 Gy boost to the gross tumor), along with concurrent weekly capecitabine and oxaliplatin. Patients underwent radical surgery if all lesions were visually evaluated as resectable and received chemotherapy for a total of 6 months, whether pre- or post-operatively (definitive therapy group). The remaining patients received 6 months of consolidation chemotherapy followed by maintenance chemotherapy (non-definitive therapy group).
  
  
  RESULTS
  The toxicities were acceptable, with radiation-induced dermatitis around the anal verge being the most common (18.8%). Fourteen patients underwent surgical resection of the rectal tumor, with 5 (35.7%) experiencing a pathological complete response. Nine out of 14 received definitive treatment, defined as R0 resections of all visible tumors. At a median follow-up of 12 months (range, 4-23 months), 2 cases were evaluated as local failure, and the median overall survival (OS) and progression free survival (PFS) for all 32 patients were 17.5 and 12 months, respectively. OS differed significantly in the definitive and non-definitive therapy groups (p=0.045), and PFS tended to differ (p=0.274).
  
  
  CONCLUSIONS
  It was demonstrated that the strategy of first-line chemoradiation followed by chemotherapy was effective and tolerable, especially for local control. OS and PFS were superior in patients who did than did not undergo curative therapy.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.forename: Peng
authors.initials: P
authors.lastname: Lian
authors.forename: Fangqi
authors.initials: F
authors.lastname: Liu
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Junyan
authors.initials: J
authors.lastname: Xu
authors.forename: Zuqing
authors.initials: Z
authors.lastname: Guan
authors.forename: Liping
authors.initials: L
authors.lastname: Liang
authors.forename: Minghe
authors.initials: M
authors.lastname: Wang
authors.forename: Sanjun
authors.initials: S
authors.lastname: Cai
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000379:methods*; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil