title: Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: investigating dose-volume relationships and role for inverse planning.
abstract: OBJECTIVE
  The relationship between volume of irradiated small bowel (VSB) and acute toxicity in rectal cancer radiotherapy is poorly quantified, particularly in patients receiving concurrent preoperative chemoradiotherapy. Using treatment planning data, we studied a series of such patients.
  
  
  METHODS
  Details of 41 patients with locally advanced rectal cancer were reviewed. All received 45 Gy in 25 fractions over 5 weeks, 3-4 fields three-dimensional conformal radiotherapy with daily 5-fluorouracil and folinic acid during Weeks 1 and 5. Toxicity was assessed prospectively in a weekly clinic. Using computed tomography planning software, the VSB was determined at 5 Gy dose intervals (V5, V10, etc.). Eight patients with maximal VSB had dosimetry and radiobiological modeling outcomes compared between inverse and conformal three-dimensional planning.
  
  
  RESULTS
  VSB correlated strongly with diarrheal severity at every dose level (p<0.03), with strongest correlation at lowest doses. Median VSB differed significantly between patients experiencing Grade 0-1 and Grade 2-4 diarrhea (p<or=0.05). No correlation was found with anorexia, nausea, vomiting, abdominal cramps, age, body mass index, sex, tumor position, or number of fields. Analysis of 8 patients showed that inverse planning reduced median dose to small bowel by 5.1 Gy (p=0.008) and calculated late normal tissue complication probability (NTCP) by 67% (p=0.016). We constructed a model using mathematical analysis to predict for acute diarrhea occurring at V5 and V15.
  
  
  CONCLUSIONS
  A strong dose-volume relationship exists between VSB and acute diarrhea at all dose levels during preoperative chemoradiotherapy. Our constructed model may be useful in predicting toxicity, and this has been derived without the confounding influence of surgical excision on bowel function. Inverse planning can reduce calculated dose to small bowel and late NTCP, and its clinical role warrants further investigation.
authors.affiliation: Colorectal Cancer Team, Beatson Oncology Centre, Western Infirmary, University of Glasgow, United Kingdom. l.tho@beatson.gla.ac.uk
authors.forename: Lye Mun
authors.initials: LM
authors.lastname: Tho
authors.forename: Martin
authors.initials: M
authors.lastname: Glegg
authors.forename: Jennifer
authors.initials: J
authors.lastname: Paterson
authors.forename: Christina
authors.initials: C
authors.lastname: Yap
authors.forename: Alice
authors.initials: A
authors.lastname: MacLeod
authors.forename: Marie
authors.initials: M
authors.lastname: McCabe
authors.forename: Alexander C
authors.initials: AC
authors.lastname: McDonald
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D003967:Diarrhea / Q000209:etiology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011300:Preoperative Care; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D001743:Urinary Bladder / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil