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Τετάρτη 2 Αυγούστου 2017

A phase I/II dose escalation study of the use of intensity modulated radiotherapy (IMRT) to treat the prostate and pelvic nodes in patients with prostate cancer

Publication date: Available online 2 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Miguel Reis Ferreira, Atia Khan, Karen Thomas, Lesley Truelove, Helen McNair, Annie Gao, Chris C. Parker, Robert Huddart, Margaret Bidmead, Ros Eeles, Vincent Khoo, Nicholas J. van As, Vibeke N. Hansen, David P. Dearnaley
BackgroundThe role of pelvic lymph node (PLN) radiotherapy in advanced localised prostate cancer (PCa) remains controversial. In order to minimise toxicity, past studies limited the dose delivered to the PLN. We used Intensity Modulated Radiotherapy (IMRT) to investigate the feasibility of dose-escalation and hypofractionation of PLN-IMRT in PCa.MethodsIn a phase I/II study, patients with advanced localised PCa were sequentially treated with 70-74Gy to the prostate and dose-escalating PLN-IMRT at doses of 50Gy (Cohort 1), 55Gy (Cohort 2) and 60Gy (Cohort 3) in 35-37 fractions. Two hypofractionated cohorts received 60Gy to the prostate and 47Gy 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 RTOG toxicity at 2 years post-radiotherapy for all cohorts. Secondary outcomes were acute and late toxicity using other clinician/patient-reported instruments and treatment efficacy.FindingsBetween Aug 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: Cohort 1 - 8.3%/4.2% (95%CI 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 appeared 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.InterpretationThe study shows the safety and tolerability of PLN-IMRT. Ongoing and planned phase III 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.

Teaser

Elective pelvic lymph node (PLN) radiotherapy and hypofractionation for advanced localised prostate cancer remains controversial. We report a single-centre sequential cohort study using IMRT to deliver conventionally-fractionated 50Gy, 55Gy, and 60Gy to the PLN and 70-74Gy (2Gy/fraction) to the prostate. Additionally we studied modest hypofractionation delivering 60Gy (3Gy/fraction) to the prostate with 47Gy to the PLN over 4-5 weeks. Our findings highlight the safety of dose-escalation and hypofractionation in PLN-IMRT.


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