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.
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Date
2017-12-01Author
Reis Ferreira, M
Khan, A
Thomas, K
Truelove, L
McNair, H
Gao, A
Parker, CC
Huddart, R
Bidmead, M
Eeles, R
Khoo, V
van As, NJ
Hansen, VN
Dearnaley, DP
Type
Journal Article
Metadata
Show full item recordAbstract
PURPOSE: To investigate the feasibility of dose escalation and hypofractionation of pelvic lymph node intensity modulated radiation therapy (PLN-IMRT) in prostate cancer (PCa). METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject
Pelvis
Humans
Prostatic Neoplasms
Androgen Antagonists
Kallikreins
Prostate-Specific Antigen
Lymphatic Irradiation
Cohort Studies
Follow-Up Studies
Feasibility Studies
Time Factors
Aged
Middle Aged
Male
Radiotherapy, Intensity-Modulated
Radiation Dose Hypofractionation
Research team
Clinical Academic Radiotherapy (Dearnaley)
Clinical Academic Radiotherapy (Huddart)
Oncogenetics
Stereotactic and Precision Body Radiotherapy
Language
eng
Date accepted
2017-07-26
License start date
2017-12
Citation
International journal of radiation oncology, biology, physics, 2017, 99 (5), pp. 1234 - 1242
Publisher
ELSEVIER SCIENCE INC