Background The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods Ninety-nine patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Results After a median follow-up of 11.9 months (range 0.7–29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n = 30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p = 0.02), 89% versus 77% (p = 0.02), 76% versus 53% (p = 0.004) and 80% versus 90% (p = 0.03), respectively. In multivariate analysis, concurrent IT (p = 0.022) and tumor volume < 2.07 cc (p = 0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p = 0.03). Conclusion SRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN.

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Introduction: The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods: 99 patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. IT was used concurrently with SRT in 30 patients. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Variables analyzed included histology, age, gender, diagnosis-specific Graded Prognostic Assessment score, recursive partitioning analysis score, number of BM, presence of extracranial metastases, tumor volume, Karnofsky performance status and the timing of ST. Results: After a median follow-up of 11.9 months (range 0.7-29.7), the 1-year LC, FFDBM and RN rate in group 1 and group 2 were 96% versus 78% (p=0.02), 76% versus 53% (p=0.004) and 80% versus 90% (p=0.03), respectively. In multivariate analysis, concurrent IT (p=0.022) and tumor volume <2.07cc (p=0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p=0.03). Conclusion: SRT delivered concurrently with IT improved LC, FFDBM, OS with a higher RN rate.

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis have revolutionized the treatment of patients with Merkel cell carcinoma (MCC). To date, no biomarker conditions access to these ICIs in MCC. We compared the tumor microenvironment of PD-L1+ and PD-L1− areas in a case series of MCC searching for foci evocative of PD-1/PD-L1 adaptive immune resistance. Among 58 tumors studied on digitalized serial tissue sections, 11 (19%) were concluded as “PD-L1+ tumors” [≥1% positive tumor cells (TCs) using PD-L1 immunohistochemistry in the whole tumor slide]. In addition, among the remaining 47 (81%) “PD-L1− tumors,” we nevertheless also identified “PD-L1+ FOV” (ie, “field of view” of about 3 mm² containing ≥1% positive TCs) in 22 (38%) additional tumors. Comparison between paired “PD-L1+ field of view (FOV)” and “PD-L1− FOV” within tumors, and between “PD-L1+ tumors” and “PD-L1− tumors”, revealed correlations between PD-L1 positivity and the abundance of tumor-infiltrating leukocytes, arguing for areas of PD-1/PD-L1-related adaptive immune resistance at least in some foci of “PD-L1+ tumors” and also in “PD-L1− tumors.” Tumor heterogeneity consists in a challenge searching for biomarkers able to predict the response/nonresponse to ICIs. Progress in digital pathology and multiplex immunolabeling may permit to overcome this challenge by better analyzing the interactions between TCs and immune and nonimmune non-TCs in the same tissue section. This approach of tumor heterogeneity may contribute to elucidate and to predict why some patients respond impressively to ICIs, whereas others do not.

Background: The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods: 99 patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Results: After a median follow-up of 11.9 months (range 0.7-29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n=30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p=0.02), 89% versus 77% (p=0.02), 76% versus 53% (p=0.004) and 80% versus 90% (p=0.03), respectively. In multivariate analysis, concurrent IT (p=0.022) and tumor volume <2.07cc (p=0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p=0.03).Conclusion: SRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN.