Phase 1/2 Dose-Escalation Study of the Use of Intensity Modulated Radiation Therapy to Treat the Prostate and Pelvic Nodes in Patients With Prostate Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 99; no. 5; pp. 1234 - 1242
• Main Authors: Reis Ferreira, Miguel, Khan, Atia, Thomas, Karen, Truelove, Lesley, McNair, Helen, Gao, Annie, Parker, Chris C., Huddart, Robert, Bidmead, Margaret, Eeles, Ros, Khoo, Vincent, van As, Nicholas J., Hansen, Vibeke N., Dearnaley, David P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2017; Elsevier Science Inc
• Subjects: Aged; Androgen Antagonists - therapeutic use; Cohort Studies; Feasibility Studies; Follow-Up Studies; FRACTIONATED IRRADIATION; Humans; Kallikreins - blood; LYMPH NODES; Lymphatic Irradiation - methods; Male; Middle Aged; NEOPLASMS; PATIENTS; Pelvis; PROSTATE; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; Radiation Dose Hypofractionation; RADIATION DOSES; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy, Intensity-Modulated - methods; Time Factors
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2017.07.041

To investigate the feasibility of dose escalation and hypofractionation of pelvic lymph node intensity modulated radiation therapy (PLN-IMRT) in prostate cancer (PCa). In a phase 1/2 study, patients with advanced localized PCa were sequentially treated with 70 to 74 Gy to the prostate and dose-escalating PLN-IMRT at doses of 50 Gy (cohort 1), 55 Gy (cohort 2), and 60 Gy (cohort 3) in 35 to 37 fractions. Two hypofractionated cohorts received 60 Gy to the prostate and 47 Gy to PLN in 20 fractions over 4 weeks (cohort 4) and 5 weeks (cohort 5). All patients received long-course androgen deprivation therapy. Primary outcome was late Radiation Therapy Oncology Group toxicity at 2 years after radiation therapy for all cohorts. Secondary outcomes were acute and late toxicity using other clinician/patient-reported instruments and treatment efficacy. Between August 9, 2000, and June 9, 2010, 447 patients were enrolled. Median follow-up was 90 months. The 2-year rates of grade 2+ bowel/bladder toxicity were as follows: cohort 1, 8.3%/4.2% (95% confidence interval 2.2%-29.4%/0.6%-26.1%); cohort 2, 8.9%/5.9% (4.1%-18.7%/2.3%-15.0%); cohort 3, 13.2%/2.9% (8.6%-20.2%/1.1%-7.7%); cohort 4, 16.4%/4.8% (9.2%-28.4%/1.6%-14.3%); cohort 5, 12.2%/7.3% (7.6%-19.5%/3.9%-13.6%). Prevalence of bowel and bladder toxicity seemed to be stable over time. Other scales mirrored these results. The biochemical/clinical failure–free rate was 71% (66%-75%) at 5 years for the whole group, with pelvic lymph node control in 94% of patients. This study shows the safety and tolerability of PLN-IMRT. Ongoing and planned phase 3 studies will need to demonstrate an increase in efficacy using PLN-IMRT to offset the small increase in bowel side effects compared with prostate-only IMRT.