title: T4 rectal cancer treated with preoperative chemoradiation to the posterior pelvis followed by multivisceral resection: patterns of failure and limitations of treatment.
abstract: OBJECTIVE
  To analyze the overall pattern of treatment failure and sites of pelvic disease recurrence relative to the radiation fields used in treating patients with clinically staged T4 rectal cancer with preoperative chemoradiation followed by multivisceral resection.
  
  
  METHODS
  Between 1990 and 1998, 45 patients with T4 rectal cancer were treated with preoperative chemoradiation. Clinical staging was according to the system of the American Joint Cancer Committee and was based on endoscopic ultrasonography, chemotherapy (CT), and physical examination. A diagnosis of T4 disease required evidence of invasion of a contiguous structure on CT (n = 31) or endorectal ultrasonography (n = 6), vaginal mucosal involvement on pelvic examination (n = 6), or a combination of these findings (n = 2). Chemoradiation was delivered with 18 MV photons using a 3-field belly-board technique. The median total dose was 45 Gy in all patients (range 45-63). Nine patients received a boost with external beam radiotherapy (EBRT) (n = 5, 1.8-18 Gy), intraoperative RT (n = 3, 10-20 Gy), or interstitial brachytherapy (n = 1, 20 Gy). All patients received concurrent chemotherapy consisting of protracted venous infusion 5-fluorouracil (300 mg/m(2), 5 d/wk). Resection was not performed in 13 (29%) of the 45 patients because of metastases detected before resection or patient refusal. Multivisceral resection and pelvic exenteration was required in 21 (66%) and 11 (34%) of 32 patients, respectively. We compared the location of pelvic disease recurrence with the RT simulation films. The Kaplan-Meier method was used to calculate the 4-year actuarial pelvic and distant recurrent rates and the overall survival rate.
  
  
  RESULTS
  The median length of follow-up was 31.0 months for all patients and 40.0 months for patients alive at last follow-up. When only the resected cases were considered, the local recurrence rate was 20%. Distant metastases occurred in 44% of cases; the overall survival rate was 69%. When all patients were considered, the local recurrence rate was similar (24%), but the rate of distant recurrence (51%) was higher and the overall survival rate lower (50%). Pelvic disease was controlled in all 8 patients whose disease responded well to chemoradiation (either a histologically complete response or microscopic residual disease). Three of 4 patients with close or positive margins had pelvic recurrences despite intraoperative RT and brachytherapy. Nine of the 10 pelvic recurrences occurred in the radiation field. Elective external iliac nodal irradiation was not used, and nodal metastases were not seen in that region. In 1 case, marginal recurrence occurred in a common iliac node at the superior edge of the treatment field.
  
  
  CONCLUSIONS
  Despite aggressive multimodality therapy including multivisceral resection, a high rate of pelvic and distant disease recurrence occurred in patients with clinically staged T4 disease. Regional disease recurred almost exclusively in the radiation field. The intraoperative RT and interstitial brachytherapy doses used did not prevent pelvic disease recurrence in patients with close or positive margins. Novel strategies such as higher preoperative doses of RT with or without altered fractionation or more effective radiosensitizers are needed to improve locoregional control in patients with T4 disease. Future strategies must also include more effective systemic therapy.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Sanfilippo
authors.forename: C H
authors.initials: CH
authors.lastname: Crane
authors.forename: J
authors.initials: J
authors.lastname: Skibber
authors.forename: B
authors.initials: B
authors.lastname: Feig
authors.forename: J L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: S
authors.initials: S
authors.lastname: Curley
authors.forename: J N
authors.initials: JN
authors.lastname: Vauthey
authors.forename: L M
authors.initials: LM
authors.lastname: Ellis
authors.forename: P
authors.initials: P
authors.lastname: Hoff
authors.forename: R A
authors.initials: RA
authors.lastname: Wolff
authors.forename: T D
authors.initials: TD
authors.lastname: Brown
authors.forename: K
authors.initials: K
authors.lastname: Cleary
authors.forename: A
authors.initials: A
authors.lastname: Wong
authors.forename: T
authors.initials: T
authors.lastname: Phan
authors.forename: N A
authors.initials: NA
authors.lastname: Janjan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D011183:Postoperative Complications / Q000209:etiology; D011855:Radiodermatitis / Q000473:pathology; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil