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Metastatic disease is the leading cause of cancer-related mortality. However, the oligometastatic hypothesis proposes that metastases may vary their aggressiveness according to their presence in one, few or many systemic sites. In this scenario, combined therapies play a crucial role in the management of these disease presentation. We evaluated local control and toxicity in patients receiving radiation therapy concomitant with immune checkpoints inhibitors and we analyzed which oligometastatic disease setting benefits the most from local ablation in terms of advantage in overall survival. 

We retrospectively identified 60 oligoprogressive patients affected by non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), metastatic melanoma, and nasopharyngeal squamous cell carcinoma  treated according to the standard treatment with a PD-1 inhibitor associated with stereotactic radiotherapy regimens or hypofractionated radiotherapy regimens on the site of progression (119 lesions). Regarding timing between systemic and local treatments, we considered only those patients on active therapy with drugs that inhibit immune check-points while receiving radiation without interrupting medical therapy.

After a median follow-up for all patients of 11.7 months (range 1-39), nineteen of 59 irradiated brain metastasis had complete response (CR), twenty-eight/59 partial response (RP). Among extracranial metastases, a complete morphological response was observed in seventeen/60 lesions, a partial response in twenty-three/6. Among the 9 radionecrotic events, 4 (44.5%) occurred on lesions previously irradiated with the 9 Gy x 3 stereotactic technique and who received panencephalic therapy that followed the failure of intracranial over-time control. Three patients reported acute G2 dysphagia. One patient (6.66%) experienced severe treatment-related pneumonia. One patient experienced severe diarrhea Twenty-nine patients (24%) reported Grade 2 fatigue and asthenia during radiation treatment. The number of radiologically evident metastatic sites in patients who received concomitant PD-1 inhibitors and radiotherapy showed a significant increase of survival (respectively, 73% after 12 months and 47% after 24 months ) in patients with 0-3 metastases compared to patients with more than 3 organ sites involved (p <0.0001). A substantial stability of the disease was observed in the 31 patients within 6 months following the radiation treatment. This feature has been shown to indicate a significant increase in both OS and PFS.  These patients had a 82% OS after 12 months and a 69% OS after 19 months. (p=0.001).

Our study confirms the efficacy and overall safety of radiotherapy associated with PD-1 inhibitors. The subgroup analysis suggests that to identify those patients eligible for the intensification of local treatments should include an amount of metastatic sites less or equal to 3 and a controlled disease of at least 6 months after RT .