title: Dosimetric and clinical predictors of toxicity following combined chemotherapy and moderately hypofractionated rotational radiotherapy of locally advanced pancreatic adenocarcinoma.
abstract: OBJECTIVE
  Hypofractionated radiotherapy (RT) of pancreatic adenocarcinoma is limited by the tolerance of adjacent normal tissues. A better understanding of the influence of dosimetric variables on the rate of toxicity after RT must be considered an important goal.
  
  
  METHODS
  Sixty-one patients with histologically proven locally advanced disease (LAPD) were analyzed. The therapeutic strategy consisted of induction chemotherapy (ChT) followed by concurrent chemoradiotherapy (CRT). In 39 out of 61 patients the target volume was based on a four-dimensional CT (4D-CT) procedure. Delivered dose was 44.25Gy in 15 fractions to PTV2, which consisted of pancreatic tumor and regional lymph nodes considered radiologically involved; 23 out of 61 patients received a simultaneous integrated boost (SIB) to a tumor sub-volume infiltrating the great abdominal vessels (PTV1) with dose in the range of 48-58Gy. RT was delivered with Helical Tomotherapy. Dose-volume histograms (DVHs) of target volumes and organs at risk (OARs) were collected for analysis. The predictive value of clinical/dosimetric parameters was tested by univariate/multivariate analyses.
  
  
  RESULTS
  The crude incidence of acute gastrointestinal (GI) grade 2 toxicity was 33%. The 12-month actuarial rate of "anatomical" (gastro-duodenal mucosa damage) toxicity was 13% (95% CI: 4-22%). On univariate analysis, several stomach and duodenum DVH endpoints are predictive of toxicity after moderately hypofractionated radiotherapy. Multivariate analysis confirmed that baseline performance status and the stomach V20[%] were strong independent predictors of acute GI grade ⩾2 toxicity. The high-dose region of duodenum DVH (V45[%]; V40[%]) was strongly correlated with grade ⩾2 "anatomical" toxicity; the best V40[%] and V45[%] cut-off values were 16% and 2.6% respectively.
  
  
  CONCLUSIONS
  Regarding dosimetric indices, stomach V20[%] correlates with a higher rate of acute toxicity; more severe acute and late anatomical toxicities are related to the high dose region of duodenum DVH.
authors.affiliation: Medical Physics Department, San Raffaele Scientific Institute, Milan, Italy. cattaneo.mauro@hsr.it
authors.forename: Giovanni M
authors.initials: GM
authors.lastname: Cattaneo
authors.forename: Paolo
authors.initials: P
authors.lastname: Passoni
authors.forename: Barbara
authors.initials: B
authors.lastname: Longobardi
authors.forename: Najla
authors.initials: N
authors.lastname: Slim
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.forename: Stefano
authors.initials: S
authors.lastname: Cereda
authors.forename: Nadia
authors.initials: N
authors.lastname: di Muzio
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calandrino
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000368:Aged; D059248:Chemoradiotherapy / Q000009:adverse effects; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects; D008297:Male; D010190:Pancreatic Neoplasms / Q000628:therapy*; D011879:Radiotherapy Dosage
keywords: Dosimetric predictors; Pancreatic cancer; Radiotherapy; Tomotherapy; Toxicity; Unresectable disease