title: Can increasing the dose of radiation by HDR brachytherapy boost following pre operative chemoradiotherapy for advanced rectal cancer improve surgical outcomes?
abstract: OBJECTIVE
  Preoperative radiotherapy has been shown to improve local control in advanced rectal carcinoma compared with surgery alone. Several large randomized trials have confirmed that chemoradiotherapy (CRT) is better than radiotherapy alone. This pilot study was designed to increase the radiation dose using high-dose rate (HDR) brachytherapy boost following preoperative CRT to evaluate whether this strategy improves the outcome of surgery without increase in toxicity.
  
  
  METHODS
  Since October 2004, we have used the new rectal HDR applicator for brachytherapy boost in 68 patients following CRT. The patients had CT and MRI Scans as part of staging. All had locally advanced disease either bulky low T2 or T3 with threatened circumferential resection margin and multiple suspicious lymph nodes. They were offered preoperative CRT either by 5-FU infusion 1 g/m(2) day 1-4 (week 1 + 5) or by oral capecitabine 825 mg/m(2) Monday-Friday for 5 weeks together with CT planned external beam RT 45Gy in 25 fractions over 5 weeks (CRT). Those downstage on repeat MRI scan were offered additional HDR Boost 10Gy directly to the tumour followed by surgery 6-8 weeks later [group A]. Four patients proceeded directly to surgery but because of involved resection margin had a HDR brachytherapy boost as postoperative treatment [group B]. Thirty patients were not planned for immediate surgery after CRT and brachytherapy boost, as they were either elderly or considered high risk for anaesthesia [group C].
  
  
  RESULTS
  There were 34 patients (median age 67 (range 39-81) years in group A, including 24 men). The PS was 0-1. The clinical stage at presentation was cT2 in five, cT3 in 23 and T4 in six patients and cN0 in 2, cN1 in 21 and N2 in 11. Thirty-three patients had CRT, and one had radiotherapy alone. All patients completed treatment without interruption. Twenty-nine patients had surgery following CRT and brachytherapy boost including anterior resection in 10 patients, Abdominoperineal excision (APR) in 18 and Hartmann's resection in one. Five patients did not have the intended surgery. Twenty-four (83%) patients had an RO resection compared with 63% having conventional preoperative CRT using bolus 5FU regimes. Pathological complete remission (pCR) was achieved in 9 (31%) compared with 12% patients having conventional CRT. There was no increase in G 3-4 toxicity from RT and no delay in wound healing or increase in anastomotic leakage. One of the four patients in group B developed local recurrence. The thirty patients in group C who had modified radical CRT followed by brachytherapy boost as a definitive treatment will be reported in a further communication.
  
  
  CONCLUSIONS
  Increasing the dose of radiation by HDR brachytherapy boost appears to improve the RO resection and pCR rates compared with conventional CRT. The follow up is too short to judge its effect on disease-free survival. This study will be extended to compare this strategy in a randomized phase III trial with conventional CRT in patients who are not fit for more intensive CRT (HERCULES).
authors.affiliation: Brachytherapy Unit, Clatterbridge Centre for Oncology, Bebington, Wirral, UK. sun.myint@ccotrust.nhs.uk
authors.forename: A
authors.initials: A
authors.lastname: Sun Myint
authors.forename: T
authors.initials: T
authors.lastname: Mukhopadhyay
authors.forename: V S
authors.initials: VS
authors.lastname: Ramani
authors.forename: K
authors.initials: K
authors.lastname: Perkins
authors.forename: A J
authors.initials: AJ
authors.lastname: Snee
authors.forename: F
authors.initials: F
authors.lastname: Jelley
authors.forename: H
authors.initials: H
authors.lastname: Wong
authors.forename: C D
authors.initials: CD
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000379:methods*; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009367:Neoplasm Staging; D010865:Pilot Projects; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis