title: Phase I trial of pelvic nodal dose escalation with hypofractionated IMRT for high-risk prostate cancer.
abstract: OBJECTIVE
  Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5½ weeks.
  
  
  METHODS
  Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months.
  
  
  RESULTS
  The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving ≥30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 ± 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only.
  
  
  CONCLUSIONS
  Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose escalation may be an option in any future exploration of potential benefits of pelvic radiation therapy in high-risk prostate cancer patients.
authors.affiliation: Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Jarrod B
authors.initials: JB
authors.lastname: Adkison
authors.forename: Derek R
authors.initials: DR
authors.lastname: McHaffie
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.forename: Rakesh R
authors.initials: RR
authors.lastname: Patel
authors.forename: Deepak
authors.initials: D
authors.lastname: Khuntia
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Petereit
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Hong
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Tomé
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ritter
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D041981:Gastrointestinal Tract / Q000528:radiation effects; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D015182:Lymphatic Irradiation / Q000009:adverse effects / Q000379:methods*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010388:Pelvis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D061089:Radiotherapy, Image-Guided / Q000009:adverse effects / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012007:Rectum / Q000528:radiation effects; D014566:Urogenital System / Q000528:radiation effects
chemical_list: D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone