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

Abstract

PurposeTo investigate the feasibility of dose escalation and hypofractionation of pelvic lymph node intensity modulated radiation therapy (PLN-IMRT) in prostate cancer (PCa).Methods and MaterialsIn 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.ResultsBetween 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.ConclusionsThis 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.

Early Toxicity of a Phase 2 Trial of Combined Salvage Radiation Therapy and Hormone Therapy in Oligometastatic Pelvic Node Relapses of Prostate Cancer (OLIGOPELVIS GETUG P07)

“…Global tolerance of the BLINDED protocol was satisfactory, in line with retrospective data for high-dose salvage WPRT in the literature [12]- [14], even in patients with a past history of prostatic irradiation.…”

Microbiota- and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy

“…The first (termed "early cohort") assessed the development of early radiation enteropathy in a group of patients recruited before undergoing high-dose intensity-modulated radiotherapy to the prostate and pelvic lymph nodes (PLN-IMRT) and followed longitudinally up to a year thereafter. Patients undergoing PLN-IMRT were chosen because they are at increased risk of radiation enteropathy when compared with prostate-only radiotherapy (7). Clinical assessment and sampling was performed at baseline (preradiotherapy), at 2/3 weeks, 4/5 weeks, 12 weeks, 6 months, and 12 months post-radiotherapy initiation (Supplementary Fig.…”

“…The second (termed "late cohort") explored late radiation enteropathy and included patients with !2 years of follow-up after PLN-IMRT who were evaluated cross-sectionally. Patients in this cohort were recruited from the population of a previously reported dose-escalation trial of PLN-IMRT (7). Their radiotherapy followed an identical protocol to the longitudinal cohort.…”

“…To not lose data, the CRObased symptom classification was substituted for 13 patients (41%) where PRO data were missing at either of these timepoints, which were chosen as representative of maximal acute enteropathy (4/5 weeks) and early late enteropathy (6 months; ref. 7). This strategy enables identification of patients experiencing…”

“…A total of 134 men were enrolled between March 18, 2014 and February 01, 2016 (Table 1): 32 in the early cohort, 87 in the late cohort, and 15 in the colonoscopy cohort (9 cases/6 controls). All patients in the early and late cohorts underwent prostate and pelvic radiotherapy following a previously published protocol (7). In the colonoscopy cohort, 6 cases had undergone radiotherapy to the prostate and seminal vesicles, 1 had undergone radiotherapy to the prostate, seminal vesicles, and pelvic lymph nodes, and 2 had undergone postprostatectomy radiotherapy to the prostate bed and pelvic lymph nodes.…”