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Clinical Trial
. 2021 Jan 1;7(1):e205865.
doi: 10.1001/jamaoncol.2020.5865. Epub 2021 Jan 21.

Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial

Jules Lansu  1 , Judith V M G Bovée  2 , Pètra Braam  3 , Hester van Boven  4 , Uta Flucke  5 , Johannes J Bonenkamp  6 , Aisha B Miah  7   8 , Shane H Zaidi  7   8 , Khin Thway  8   9 , Øyvind S Bruland  10   11 , Elizabeth H Baldini  12 , Nina L Jebsen  13   14 , Astrid N Scholten  1 , Piet L A van den Ende  15 , Augustinus D G Krol  16 , Jan F Ubbels  17 , Jos A van der Hage  18 , Erik van Werkhoven  19 , Houke M Klomp  20 , Winette T A van der Graaf  21 , Frits van Coevorden  20 , Yvonne Schrage  20 , Winan J van Houdt  20 , Rick L Haas  1   16
Affiliations
Clinical Trial

Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial

Jules Lansu et al. JAMA Oncol. .

Abstract

Importance: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity.

Objective: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity.

Design, setting, and participants: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020.

Interventions: The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks.

Main outcomes and measures: As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects.

Results: Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%.

Conclusions and relevance: The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers.

Trial registration: ClinicalTrials.gov Identifier: NCT02106312.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Miah reported receiving grants from National Health Service (NHS) funding to the National Institute for Health Research (NIHR) Biomedical Research Centre for Cancer at The Royal Marsden Hospital and The Institute of Cancer Research during the conduct of the study. Dr van Houdt reported receiving personal fees from Amgen outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Study Flowchart
RT indicates radiotherapy.
Figure 2.
Figure 2.. Kaplan-Meier Survival Analysis of the Intention-to-Treat Population
DSS indicates disease-specific survival; OS, overall survival; PFS, progression-free survival.
See this image and copyright information in PMC

References

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