Effectiveness and safety of "real" concurrent stereotactic radiotherapy and immunotherapy in metastatic solid tumors: a systematic review.

BACKGROUND: in the setting of metastatic malignancies, the role of concurrent stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) and immune-checkpoint inhibitors (ICI) is increasing. Few data are available about effectiveness and safety of this strategy. METHODS: we used the PRISMA guidelines to perform a systematic review. We selected only articles reporting a "real" concurrent treatment, defined as SRS/SRT performed within 30 days of ICI administration. RESULTS: Despite several limits due to the heterogeneity and retrospective nature of the studies, 1-year local control for brain lesions ranged from 42 to 100% and 1-year regional brain control ranged from 31 to 83%. An interesting rate of local and distant control was reported for concurrent SBRT-ICI on extra-cranial lesions. No relevant signals about toxicity emerged. CONCLUSIONS: Based on published evidence, concurrent SRS/SRT and ICI seems to lead intriguing outcomes, without increasing toxicity. Further investigations are warranted to obtain stronger prospective evidence.

Meeting with triumph and disaster: Osimertinib in T790M-unknown CNS progression in EGFR-mutated non-small cell lung cancer.

INTRODUCTION: Treatment paradigms for EGFR-mutated non-small cell lung cancer (NSCLC) have successfully evolved since the introduction of osimertinib. The detection of EGFR T790M mutation in plasma or tumor samples obtained at disease progression to first-/second-generation EGFR inhibitors is mandatory for osimertinib prescription. Nevertheless, pharmacokinetics properties of osimertinib guarantee its usefulness in central nervous system (CNS) disease even in the case of T790M-negative or unknown status. PATIENTS AND METHODS: In this brief report, we share the clinical histories of two patients with CNS-preeminent progression under first-/second-generation EGFR inhibitors in which it was not possible to document the presence of T790M resistance mutation. RESULTS: Patient outcomes diverged dramatically due to the differential availability of off-label osimertinib. CONCLUSIONS: Waiting for the novel molecule to be approved and licensed in first-line treatment, our report of hope and frustration is intended to stress the opportunity of its administration in the case of CNS failure of first-line EGFR inhibition, even in the absence of T790M proof.