Primary endpoint analysis of the multicentre phase II hypo-FLAME trial for intermediate and high risk prostate cancer

Abstract

Background and purpose: Local recurrences after radiotherapy for prostate cancer (PCa) often originate at the location of the macroscopic tumour(s). Since PCa cells are known to be sensitive to high fraction doses, hypofractionated whole gland stereotactic body radiotherapy (SBRT) in conjunction with a simultaneous ablative microboost to the macroscopic tumour(s) within the prostate could be a way to reduce the risk of local failure. We investigated the safety of this treatment strategy. Materials and methods:Patients with intermediate or high risk PCa were enrolled in a prospective phase II trial, called hypo-FLAME. All patients were treated with extreme hypofractionated doses of 35 Gy in 5 weekly fractions to the whole prostate gland with an integrated boost up to 50 Gy to the multiparametric (mp) MRI-defined tumour(s). Treatment related toxicity was measured using the CTCAE v4.0. The primary endpoint of the trial was treatment related acute toxicity.Results: Between April 2016 and December 2018, 100 men were treated in 4 academic centres. All patients were followed up for a minimum of 6 months. The median mean dose delivered to the visible tumour nodule(s) on mpMRI was 44.7 Gy in this trial. No grade ≥3 acute genitourinary (GU) or gastrointestinal (GI) toxicity was observed. Furthermore, 90 days after start of treatment, the cumulative acute grade 2 GU and GI toxicity rates were 34.0% and 5.0%, respectively. Conclusion:Simultaneous focal boosting to the macroscopic tumour(s) in addition to whole gland prostate SBRT is associated with acceptable acute GU and GI toxicity.

IPEM Topical Report: an international IPEM survey of MRI use for external beam radiotherapy treatment planning

“…% of GDP spent on healthcare data and cost of healthcare per capita in USD cover funding from all finance schemes and are included as a surrogate for RT healthcare costs as this data is not available for every country. hypofractionation, in the primary endpoints analysis of the hypo-FLAME phase 2 trial which demonstrated acceptable acute toxicity including no grade 3 toxicity (Draulans et al 2020). MRI access was reported to be high, with all but 3 responding centres having at least some limited access to MR for EBRT planning.…”

The Role of Multiparametric Magnetic Resonance in Volumetric Modulated Arc Radiation Therapy Planning for Prostate Cancer Recurrence After Radical Prostatectomy: A Pilot Study

“…This means that mpMRI-guided, precise delineation of tumor boundaries may allow the complete eradication of disease through highly-escalated dose delivery, leading to radiation doses of up to 80 Gy on the high-risk GTVs while ensuring lower doses to the low-risk, less aggressive prostate areas, with better OARs dose saving and hence limited treatment-related toxicity. In this regard, the ongoing prospective, phase II trials, hypo-FLAME Trial and DELINEATE Trial, both reached their primary endpoint in terms of acceptable acute toxicity with simultaneous focal boosting to the mpMRI-detected macroscopic tumor(s) in addition to whole gland prostate irradiation ( 31 , 32 ). Thus, in the setting of salvage RT for macroscopic, local recurrence of PC after radical prostatectomy, such findings are likely to improve the efficacy and safety of radiotherapy: firstly, thanks to a dose-escalated boost over the mpMRI-delineated RPC lesions, in addition to the 64 to 70 Gy-standard irradiation of the prostate fossa ( 33 , 34 ); secondly, thanks to the precise segmentation of prostate bed recurrent masses with the help of mpMRI co-registration, enabling stereotactic salvage treatments to be performed in the attempt to provide a better local control than the conventional, normofractionated RT protocols ( 35 ).…”

MR-Guided Hypofractionated Radiotherapy: Current Emerging Data and Promising Perspectives for Localized Prostate Cancer

“…In contrast, the recently published primary endpoint analysis of the multicenter prospective HYPO-FLAME trial reported acceptable acute GI and GU toxicity rates in a population of 100 men with intermediate and high-risk prostate cancer [54]. More mature data now provide further evidence in terms of clinical benefits, including the currently ongoing FLAME phase III trial [55].…”