title: Late toxicity after intensity-modulated radiation therapy for localized prostate cancer: an exploration of dose-volume histogram parameters to limit genitourinary and gastrointestinal toxicity.
abstract: OBJECTIVE
  To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity.
  
  
  METHODS
  In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V(70)), 65 Gy (V(65)), and 40 Gy (V(40)). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity.
  
  
  RESULTS
  With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V(70) ≤ 10%, V(65) ≤ 20%, and V(40) ≤ 40%; 92% for men with rectal V(70) ≤ 20%, V(65) ≤ 40%, and V(40) ≤ 80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged ≥70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity.
  
  
  CONCLUSIONS
  IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity.
authors.affiliation: Department of Radiation and Cellular Oncology, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Aaron W
authors.initials: AW
authors.lastname: Pederson
authors.forename: Janine
authors.initials: J
authors.lastname: Fricano
authors.forename: David
authors.initials: D
authors.lastname: Correa
authors.forename: Charles A
authors.initials: CA
authors.lastname: Pelizzari
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Liauw
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use; D041981:Gastrointestinal Tract / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects; D011349:Proctitis / Q000209:etiology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D012007:Rectum / Q000528:radiation effects; D047368:Tumor Burden; D001743:Urinary Bladder / Q000528:radiation effects; D014566:Urogenital System / Q000528:radiation effects*
chemical_list: D000726:Androgen Antagonists