Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial (original) (raw)
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Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016
Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). A total of 1,092 men were protocol eligible and had follow-up information; 542 patients wer...
The Lancet. Oncology, 2015
Patient-reported outcomes (PROs) might detect more toxic effects of radiotherapy than do clinician-reported outcomes. We did a quality of life (QoL) substudy to assess PROs up to 24 months after conventionally fractionated or hypofractionated radiotherapy in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial. The CHHiP trial is a randomised, non-inferiority phase 3 trial done in 71 centres, of which 57 UK hospitals took part in the QoL substudy. Men with localised prostate cancer who were undergoing radiotherapy were eligible for trial entry if they had histologically confirmed T1b-T3aN0M0 prostate cancer, an estimated risk of seminal vesicle involvement less than 30%, prostate-specific antigen concentration less than 30 ng/mL, and a WHO performance status of 0 or 1. Participants were randomly assigned (1:1:1) to receive a standard fractionation schedule of 74 Gy in 37 fractions or one of two hypofractionated schedules: 6...
International Journal of Radiation Oncology*Biology*Physics, 2012
Purpose: There are reports of a high sensitivity of prostate cancer to radiotherapy dose fractionation, and this has prompted several trials of hypofractionation schedules. It remains unclear whether hypofractionation will provide a significant therapeutic benefit in the treatment of prostate cancer, and whether there are different fractionation sensitivities for different stages of disease. In order to address this, multiple primary datasets have been collected for analysis. Methods and Materials: Seven datasets were assembled from institutions worldwide. A total of 5969 patients were treated using external beams with or without androgen deprivation (AD). Standard fractionation (1.8-2.0 Gy per fraction) was used for 40% of the patients, and hypofractionation (2.5-6.7 Gy per fraction) for the remainder. The overall treatment time ranged from 1 to 8 weeks. Low-risk patients comprised 23% of the total, intermediate-risk 44%, and high-risk 33%. Direct analysis of the primary data for tumor control at 5 years was undertaken, using the Phoenix criterion of biochemical relapse-free survival, in order to calculate values in the linear-quadratic equation of k (natural log of the effective target cell number), a (dose-response slope using very low doses per fraction), and the ratio a/b that characterizes dose-fractionation sensitivity. Results: There was no significant difference between the a/b value for the three risk groups, and the value of a/b for the pooled data was 1.4 (95% CI = 0.9-2.2) Gy. Androgen deprivation improved the bNED outcome index by about 5% for all risk groups, but did not affect the a/b value. Conclusions: The overall a/b value was consistently low, unaffected by AD deprivation, and lower than the appropriate values for late normal-tissue morbidity. Hence the fractionation sensitivity differential (tumor/normal tissue) favors the use of hypofractionated radiotherapy schedules for all risk groups, which is also very beneficial logistically in limited-resource settings. Ó 2011 Elsevier Inc.
Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznań and Polish Society of Radiation Oncology, 2014
To assess acute and late toxicity of hypofractionated radiotherapy, its efficacy and impact on quality of life in patients with low-risk prostate cancer. Since August 2006 to October 2007, 15 prostate cancer patients with favorable clinical features, aged 54-74 years (mean 67 years) entered the study. Tumor stage in the majority (73%) of patients was T2a, the mean pretreatment PSA value was 7.2 ng/ml (range 5-10.9 ng/ml). The study group was treated 3 times a week with 4 Gy per fraction to the total dose of 60 Gy within 5 weeks. 3D conformal treatment planning was used with no fiducial markers. Acute and late toxicity was evaluated using modified EORTC/RTOG/LENT scoring systems. Patients regularly filled the EORTC QLQ-PR25 questionnaires. All patients completed radiotherapy according to the plan. During radiotherapy, 26% of patients had grade 1-2 rectal symptoms. The incidence of acute urinary toxicity score was 26%, 60%, and 14% for grade 0-1, 2 and 3, respectively. One year after ...
Prostate cancer, 2012
Purpose. To evaluate toxicity associated with the addition of elective nodal irradiation (ENI) to a hypofractionated regimen for the treatment of prostate cancer. Methods and Materials. Fifty-seven patients received pelvic image-guided IMRT to 50.4 Gy in 28 fractions with a hypofractionated simultaneous boost to the prostate to 70 Gy. Thirty-one patients received prostate-only treatment to 70 Gy in 28 fractions. Results. Median followup was 41.1 months. Early grade ≥2 urinary toxicity rates were 49% (28 of 57) for patients receiving ENI and 58% (18 of 31) for those not (P = 0.61). Early grade ≥2 rectal toxicity rates were 40% (23 of 57) and 23% (7 of 31), respectively (P = 0.09). The addition of ENI resulted in a 21% actuarial rate of late grade ≥2 rectal toxicity at 4 years, compared to 0% for patients treated to the prostate only (P = 0.02). Retrospective daily dosimetry of patients experiencing late rectal toxicity revealed an average increase of 2.67% of the rectal volume receiv...
International Journal of Radiation Oncology*Biology*Physics
Context: Whether hypofractionated radiation therapy (RT) compared with conventionally fractionated RT provides comparable or possibly improved cancer control without increased toxicity in localized prostate cancer (PC) remains unknown. Objective: Realizing from the CHHiP trial that outcomes are highly sensitive to the dose fractionation schedule and number of treatments, we conducted a systematic review and meta-analysis selecting only the randomized noninferiority trials, because the randomized arms closely approximated one another in terms of the dose fractionation schedule, and compared cancer control and toxicity of hypofractionated RT with conventionally fractionated RT for localized PC. Evidence acquisition: Randomized noninferiority trials evaluating hypofractionated (2.4-4 Gy daily fractions for 15-30 treatments) versus conventionally fractionated RT (1.8-2 Gy daily fractions for 40-45 treatments) in men with localized PC were selected. Studies that were not noninferiority trials, used extreme hypofractionation, or treated metastatic disease were excluded. Three studies were retained for analysis. Data were pooled using a random-effects model to determine hazard ratio (HR) and risk ratio (RR). Heterogeneity was assessed via chisquare test, I 2 statistics, and metaregression. The primary outcome was disease-free survival (DFS), defined as death from any cause or biochemical, local, regional, or distant progression. Evidence synthesis: Of the 5484 men, 3553 (64.8%) had intermediate-risk PC. Hypofractionated RT as compared with conventionally fractionated RT was associated with significantly improved DFS (HR 0.869; 95% confidence interval [CI], 0.757, 0.998; p = 0.047), whereas overall survival was not (HR 0.84; 95% CI, 0.66, 1.07; p = 0.16). Acute grade 2 or higher gastrointestinal toxicity was significantly increased with hypofractionation (RR 1.42; 95% CI 1.15, 1.77; p = 0.002); however, this did not translate into late grade 2 or higher gastrointestinal toxicity. An increase in late grade 2 or higher genitourinary complications was observed (RR 1.18; 95% CI 0.98, 1.43; p = 0.08). Conclusions: Hypofractionated RT as compared with conventionally fractionated RT could improve DFS in men with intermediate-risk PC and, therefore, would be reasonable to consider in men who do not have risk factors for late genitourinary complications. Patient summary: Treatment with a shorter course of radiation, using higher doses per treatment over fewer days, may be the preferred approach in appropriately selected patients with localized prostate cancer.
European Journal of Cancer, 2004
Late toxicity and other serious adverse events (SAE) were analysed in the European Organisation for Research and Treatment of Cancer (EORTC) trial 22863. The study evaluated the value of adjuvant endocrine treatment for locally advanced prostate cancer treated with radiotherapy. From 1987 to 1995, 415 patients were randomised. There was long-term toxicity information for 377 patients (91%). Median age was 70 years (range 50-80 years). Median follow-up for late toxicity was 42 months (range 3-136 months). Toxicity was graded according to a modified Radiotherapy and Oncology Group (RTOG) scale. Other late SAE, that was not classified as severe treatment toxicity, but were still life-threatening, were also assessed. There were 72 patients with grade 2, 10 patients with grade 3 and 4 patients with grade 4 toxicity. There were 20 patients with other late SAE, who were grouped according to their relationship to treatment; likely related ðn ¼ 1Þ, unrelated ðn ¼ 7Þ and not assessableðn ¼ 12Þ. Although four treatmentrelated deaths (1%) occurred, grade 3 or 4 late complications were less than 5%.
Early toxicity of hypofractionated radiotherapy for prostate cancer
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia, 2016
Hypofractionated accelerated radiotherapy (HART) is now a feasible option for prostate cancer treatment apropos toxicity, biochemical control and shortening of treatment. The aim of this study was to investigate hypofractionated schedules in the treatment of patients with localized prostate cancer. Between 2011-2014, 158 patients were treated using the RapidArc technique with IGRT. The target volume for low risk patients was the prostate alone with a prescribed dose of 20x3.0 Gy (EQD2=77 Gy). Targets volumes for intermediate and high risk patients were prostate and two thirds of the seminal vesicles with a prescribed dose 21-22x3.0/2.1 Gy (EQD2=81/45.4-84.9/47.5). Based on radiobiological modelling of early toxicity, we used four fractions per week in the low risk group and four fractions in odd weeks and three fractions in even weeks in intermediate and high risk groups. The RTOG/EORTC toxicity scale was used. Early genitourinary (GU) toxicity was observed for grades 0, 1, 2, 3 and...
Scandinavian journal of urology, 2023
Problem: A low α/β ratio for prostate cancer (PCa) compared to surrounding normal tissue theoretically implies therapeutical advantages with hypofractionated treatment. Data from large randomised control trials (RCTs) comparing moderate hypofractionated (MHRT, 2.4-3.4 Gray/fraction (Gy/fx)) and ultra-hypofractionated (UHRT, >5 Gy/fx) with conventionally fractionated radiation therapy (CFRT, 1.8-2 Gy/fx) and the possible clinical implications have been reviewed. Materials and method: We searched PubMed, Cochrane and Scopus for RCT comparing MHRT/UHRT with CFRT treatment of locally and/or locally advanced (N0M0) PCa. We found six RCTs, which compared different radiation therapy regimes. Tumour control and acute and late toxicities are reported. Results: MHRT was non-inferior to CFRT for intermediate-risk PCa, non-inferior for low-risk PCa and not superior in terms of tumour control for high-risk PCa. Acute toxicity rates were increased compared to CFRT, especially an increase in acute gastrointestinal adverse effects was seen. Late toxicity related to MHRT seems to be comparable. UHRT was non-inferior in terms of tumour control in one RCT, with increased acute toxicity, but with comparable late toxicity. One trial, however, indicated increased late toxicity rates with UHRT. Discussion and conclusion: MHRT delivers similar therapeutic outcomes compared to CFRT in terms of tumour control and late toxicity for intermediate-risk PCa patients. Slightly more acute transient toxicity could be tolerated in favour of a shorter treatment course. UHRT should be regarded as an optional treatment for patients with low-and intermediate-risk disease applied at experienced centres in concordance with international and national guidelines.