Phase I trial of pelvic nodal dose escalation with hypofractionated IMRT for high-risk prostate cancer

Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):184-90. doi: 10.1016/j.ijrobp.2010.09.018. Epub 2010 Dec 14.

Abstract

Purpose: 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 and materials: 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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / secondary
  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use
  • Dose Fractionation, Radiation
  • Follow-Up Studies
  • Gastrointestinal Hemorrhage / etiology
  • Gastrointestinal Tract / radiation effects
  • Gonadotropin-Releasing Hormone / agonists
  • Humans
  • Lymphatic Irradiation / adverse effects
  • Lymphatic Irradiation / methods*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Pelvis
  • Prospective Studies
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / radiotherapy*
  • Radiotherapy, Image-Guided / adverse effects
  • Radiotherapy, Image-Guided / methods*
  • Radiotherapy, Intensity-Modulated / methods*
  • Rectum / radiation effects
  • Urogenital System / radiation effects

Substances

  • Androgen Antagonists
  • Gonadotropin-Releasing Hormone