The Dutch Bone Metastasis Study is a pivotal study from the 1990s that validated the use of single fraction (8 Gy) conventional palliative radiation for painful nonspine bone metastases. Compared to conventional multifraction regimen (24 Gy in 6 fractions), pain relief was similar although retreatment rate was ~3x higher for single fraction. However, the higher retreatment rate may be in part due to physician bias, given higher likelihood/lower threshold to retreat after a single fraction than multifraction.   

This study by Spencer et al used longitudinal questionnaires from the Dutch Bone Metastasis Study to evaluate net pain relief (NPR: proportion of remaining life spent with pain response) of the two regimens. Given there has been increasing interest in using SBRT for theoretically more rapid/durable/better pain relief, further evaluation of external beam irradiation is necessary to compare the two techniques head to head. Spencer et al show that in the ~70% of patients who experienced at least partial pain relief, NPR was ~56%. There was no difference between the two regimens unless excluding response after re-treatment (then NPR was 49 vs 57% in single vs multifraction). The clinical significance of this difference is not clear given a re-irradiation event may not directly correlate with pain severity (see physician caveat above).  

This study proposed NPR as a tool for quantifying pain relief (useful for objectively comparing different fractionation regimens and techniques in future studies), and further validates use of single fraction regimen given similarity in net pain relief to multifraction (in context of caveats stated above) with greater cost-effectiveness and patient convenience.  

(Open Access)

Reference (PubMed Link): Spencer K, Velikova G, Henry A, et al. Net pain relief after palliative radiation therapy for painful bone metastases: A useful measure to reflect response duration? A further analysis of the dutch bone metastasis study. Int J Radiat Oncol Biol Phys 2019;105:559-566.

Key Institution: Leeds Institute of Medical Research/University of Leeds, Leeds, UK
Keywords: Bone metastases, 3D conformal, conventional palliative radiation, durability of pain relief

The question of how aggressively to treat oligometastatic disease, and whether or not there is a benefit to doing so, is an evolving paradigm in multiple disease sites. This is of particular importance in primary histologies with a long natural history, such as breast and prostate cancer, where patients may live for years with a diagnosis of metastatic disease. These authors report on the results of a Phase II, multi-center study in which patients with asymptomatic patients with prostate cancer and fewer than 4 extracranial metastases were randomized to either surveillance or metastasis-directed therapy (MDT) at all detected lesions (using either surgery or stereotactic body radiotherapy). The primary endoint was androgen-deprivation free survival, and ADT was started at symptomatic progression, progression to more than 3 metastases, or local progression of known metastases. This study enrolled 62 patients, with 31 patients in each arm. The median ADT-free survival time was 13 months for patients in the surveillance arm and 21 months in the MDT arm (HR 0.60, 80% CI 0.40 –0.90). There were no symptomatic or local progression events observed in the MDT group, whereas 3 and 6 events occurred in the surveillance arm, respectively. The authors conclude that MDT is safe and effective compared to surveillance.
This is an important study that provides support of metastasis-directed therapy for oligometastatic disease. Metastasis-directed therapy has become more common in recent years, particularly as SBRT becomes more widely used and available. 

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Journal & Date: Journal of Clinical Oncology 36, no. 5 (February 2018) 446-453.
Key Institution: Ghent University Hospital, Ghent, Belgium
Keywords: Oligometastatic disease, prostate cancer, metastasis-directed therapy