The evolving boundary between palliative and curative radiotherapy in routine irradiation of metastatic patients

Clemens Grassberger, PhD
Harvard Medical School & Massachusetts General Hospital, Boston

Over the last years there has been an accumulation of evidence that Radiotherapy (RT) can improve survival in patients with metastatic disease across a range of indications. Historically these patients were not assumed to be “curable” and treatment was considered palliative. Recent advances in drug development that can be summarized as “targeted therapy”, be it drugs targeting specific oncogene drivers (1) or immunotherapeutic approaches (2-5), have impacted what is considered curative and what it means to be palliative. Even though the term “oligometastatic”, describing a tumor state intermediate between purely localized and widely metastatic, has already been proposed in the 1990’s (6), the advent of these new therapies has definitely increased the portion of patients that fall in this category.

Palma et al. recently reported their results of a randomized phase II trial comparing stereotactic ablative radiotherapy (SABR) versus standard-of-care palliative therapy in 99 patients with various oligometastatic cancers (7). They report a doubling of progression-free survival and superior survival, similar to results of two smaller phase II studies (8, 9). If these observations are confirmed in larger phase III studies, it could have a significant impact on the practice of medical physics and radiation oncology in general, and raise a number of important questions:

  • Dose & fractionation: the objective and underlying purpose of RT might evolve for these patients from eradication of all tumor cells, our traditional goal, to more complex endpoints such as delaying development of resistance (10, 11) or synergizing with immunotherapeutic agents (12, 13). Therefore lower doses or different fractionation regimen might be indicated, especially for immunotherapy-RT combinations (14-16).
  • Planning & QA: This shifts to lower doses, away from cell kill as primary objective, but multiple targets per patient (SABR-COMET allowed RT to up to 5 mets) could impact currently established planning and QA procedures.
  • Patient volume: almost three times the number of patients are diagnosed in stage IV compared to stage III lung cancer (17), indicating that patient numbers for some sites could increase dramatically.

The emergence of this new treatment paradigm, i.e. routine irradiation of metastatic patients, could transform the way a large portion of cancer patients are treated, and presents an opportunity to establish RT as an important pillar of multi-modality treatment strategies in this growing population.


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