Yolande Lievens1, Matthias Guckenberger2, Daniel Gomez3, Morten Hoyer4, Puneeth Iyengar5, Isabelle Kindts6, Alejandra Méndez Romero7, Daan Nevens8, David Palma9, Catherine Park10, Umberto Ricardi11, Marta Scorsetti12, James Yu13, Wendy A Woodward3. 1. Department of Radiation Oncology, Ghent University Hospital, Ghent University, Belgium. Electronic address: yolande.lievens@uzgent.be. 2. Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Switzerland. 3. Department of Radiation Oncology, UT MD Anderson Cancer Center, Houston, USA. 4. Danish Center for Particle Therapy, Aarhus University Hospital, Denmark. 5. Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, USA. 6. Department of Radiotherapy, Cancer Centre, General Hospital Groeninge, Kortrijk, Belgium. 7. Department of Radiation Oncology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. 8. Iridium Kankernetwerk, Radiation Oncology Department, Universiteit Antwerpen, Antwerp, Belgium. 9. London Health Sciences Centre, Canada. 10. Department of Radiation Oncology, UCSF Helen Diller Comprehensive Cancer Center, San Francisco, USA. 11. Department of Oncology, University of Turin, Italy. 12. Radiotherapy and Radiosurgery Dept, Humanitas Clinical and Research Hospital - IRCCS, Rozzano-Milan, Italy. 13. Yale School of Medicine, New Haven, USA.
Abstract
BACKGROUND: Recognizing the rapidly increasing interest and evidence in using metastasis-directed radiotherapy (MDRT) for oligometastatic disease (OMD), ESTRO and ASTRO convened a committee to establish consensus regarding definitions of OMD and define gaps in current evidence. METHODS: A systematic literature review focused on curative intent MDRT was performed in Medline, Embase and Cochrane. Subsequent consensus opinion, using a Delphi process, highlighted the current state of evidence and the limitations in the available literature. RESULTS: Available evidence regarding the use of MDRT for OMD mostly derives from retrospective, single-centre series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. Consensus was reached that OMD is largely independent of primary tumour, metastatic location and the presence or length of a disease-free interval, supporting both synchronous and metachronous OMD. In the absence of clinical data supporting a maximum number of metastases and organs to define OMD, and of validated molecular biomarkers, consensus supported the ability to deliver safe and clinically meaningful radiotherapy with curative intent to all metastatic sites as a minimum requirement for defining OMD in the context of radiotherapy. Systemic therapy induced OMD was identified as a distinct state of OMD. High-resolution imaging to assess and confirm OMD is crucial, including brain imaging when indicated. Minimum common endpoints such as progression-free and overall survival, local control, toxicity and quality-of-life should be reported; uncommon endpoints as deferral of systemic therapy and cost were endorsed. CONCLUSION: While significant heterogeneity exists in the current OMD definitions in the literature, consensus was reached on multiple key questions. Based on available data, OMD can to date be defined as 1-5 metastatic lesions, a controlled primary tumor being optional, but where all metastatic sites must be safely treatable. Consistent definitions and reporting are warranted and encouraged in ongoing trials and reports generating further evidence to optimize patient benefits.
BACKGROUND: Recognizing the rapidly increasing interest and evidence in using metastasis-directed radiotherapy (MDRT) for oligometastatic disease (OMD), ESTRO and ASTRO convened a committee to establish consensus regarding definitions of OMD and define gaps in current evidence. METHODS: A systematic literature review focused on curative intent MDRT was performed in Medline, Embase and Cochrane. Subsequent consensus opinion, using a Delphi process, highlighted the current state of evidence and the limitations in the available literature. RESULTS: Available evidence regarding the use of MDRT for OMD mostly derives from retrospective, single-centre series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. Consensus was reached that OMD is largely independent of primary tumour, metastatic location and the presence or length of a disease-free interval, supporting both synchronous and metachronous OMD. In the absence of clinical data supporting a maximum number of metastases and organs to define OMD, and of validated molecular biomarkers, consensus supported the ability to deliver safe and clinically meaningful radiotherapy with curative intent to all metastatic sites as a minimum requirement for defining OMD in the context of radiotherapy. Systemic therapy induced OMD was identified as a distinct state of OMD. High-resolution imaging to assess and confirm OMD is crucial, including brain imaging when indicated. Minimum common endpoints such as progression-free and overall survival, local control, toxicity and quality-of-life should be reported; uncommon endpoints as deferral of systemic therapy and cost were endorsed. CONCLUSION: While significant heterogeneity exists in the current OMD definitions in the literature, consensus was reached on multiple key questions. Based on available data, OMD can to date be defined as 1-5 metastatic lesions, a controlled primary tumor being optional, but where all metastatic sites must be safely treatable. Consistent definitions and reporting are warranted and encouraged in ongoing trials and reports generating further evidence to optimize patient benefits.
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