Discussion
SRS
MINOR, METASTASES
The results of a randomized phase 3 trial comparing two SRS treatment approaches using different platforms, each characterized by specific features, were reported. The main differing characteristics among the two arms are: (i) the use of a rigid frame system in one and a frameless in the other; (ii) the employ of margins from the GTV in one arm only; (iii) the different dose prescriptions. Concerning the use of the frame, although more modern versions of the multi-source gamma rays system allow the frameless treatments, this is not the usual practice applied, while, on the linacs, the use of masks instead of frames is the most employed mode of patient immobilization in clinical practice. The PTV generation, applying margins from GTV, is, once more related to historical procedures, related to the older linacs technologies, in which the mechanical precision was lower than what is currently available. Nevertheless, the study, which started seven years ago, applied the clinical practice at the design time and was not modified. The evolution of the linac-based techniques would allow today the application of smaller or even zero margins. Such practice is ongoing also in our institute for patients treated out of the protocol but was not included for obvious reasons. However, no increasing RN has been observed despite larger volumes being handled in Arm B. Finally, a two-level dose prescription was also foreseen in the linac arm as per the protocol. In practice, the lesion diameter of the larger metastases in the Arm-B was modestly exceeding the threshold except for one lesion in a multiple lesion patient. This was far from any organ at risk. Since in all cases no dose-volume parameters were at risk for those patients if treated at full dose. For this reason, the Arm-B does not include any patient treated with 20 Gy; we acknowledge this as a minor protocol violation. We also acknowledge that most clinical centers exclusively use one device or the other according to availability. Nevertheless, the availability of the two in a single institute allowed this trial although a better data analysis consistency would be in a multi-institutional investigation. About 20% of eligible patients were excluded from the analysis for the patient cohort for various reasons. This strategy is a formal deviation from the trial protocol, which assumed an intention-to-treat analysis. Nevertheless, due to this significant rate and to minimize potential negative biases, we opted for their exclusion, which is also supported by the fact that most patients did not receive any radiosurgery treatment. We acknowledge this as a protocol deviation and a limitation of the study. The study’s primary endpoint was the RN assessment, assuming a superiority of linac-based SRS compared to the gamma-ray platform. Published data, although not randomized but only comparative, showed a comparable local control using the two modalities for SRS, but a higher risk of RN employing gamma-ray platform compared to linac-based SRS, above all when large BMs are treated, has been recorded [