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J Neurosurg. 2019 Feb 15:1-6. doi: 10.3171/2018.10.JNS181371. [Epub ahead of print]

Local tumor response and survival outcomes after combined stereotactic radiosurgery and immunotherapy in non-small cell lung cancer with brain metastases.

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1Department of Neurosurgery, Yale New Haven Hospital, New Haven, Connecticut.
2Memorial Sloan Kettering Cancer Center, New York, New York; and.
3Department of Radiation Oncology, Yale New Haven Hospital, New Haven, Connecticut.


OBJECTIVEConcurrent use of anti-PD-1 therapies with stereotactic radiosurgery (SRS) have been shown to be beneficial for survival and local lesional control in melanoma patients with brain metastases. It is not known, however, if immunotherapy (IT) confers the same outcome advantage in lung cancer patients with brain metastases treated with SRS.METHODSThe authors retrospectively reviewed 85 non-small cell lung cancer (NSCLC) patients with brain metastases who were treated with SRS between January 2006 and December 2016. Thirty-nine PD-L1 antibody-positive patients received anti-PD-1 therapy with SRS (IT group) and 46 patients received chemotherapy (CT) with SRS (CT group). Results were obtained using chi-square, Kaplan-Meier, and Mann-Whitney U tests and Cox regression analyses.RESULTSMedian survival following first radiosurgical treatment in the whole study group was 11.6 months (95% CI 8-15.5 months). Median survival times in the IT group and CT group were 10 months (95% CI 8.3-13.2 months) and 11.6 months (95% CI 7.7-15.6 months), respectively (p = 0.23). A Karnofsky Performance Status (KPS) score < 80 (p = 0.001) and lung-specific molecular marker Graded Prognostic Assessment (lungmol GPA) score < 1.5 (p = 0.02) were found to be predictive of worse survival.Maximal percent lesional shrinkage and time to maximal shrinkage were not significantly different between the CT and IT groups. Of the lesions for which a complete response occurred, 94.8% had pre-SRS volumes < 500 mm3. The amount of lesion shrinkage and time to maximal shrinkage were not different between the IT and CT groups for lesions with volumes < 500 mm3. However, in lesions with volume > 500 mm3, 90% of lesions shrank after radiosurgery in the IT group compared with 47.8% in the CT group (p = 0.001). Median times to initial response and times to maximal shrinkage were faster in the IT group than in the CT group: initial response 49 days (95% CI 33.7-64.3 days) versus 84 days (95% CI 28.1-140 days), p = 0.001; maximal response 105 days (95% CI 59-150 days) versus 182 days (95% CI 119.6-244 days), p = 0.12.CONCLUSIONSUnlike patients with melanoma, patients with NSCLC with brain metastases undergoing SRS showed no significant benefit-either in terms of survival or total amount of lesional response-when anti-PD-1 therapies were used. However, in lesions with volume > 500 mm3, combining SRS with IT may result in a faster and better volumetric response which may be particularly beneficial in lesions causing mass effect or located in neurologically critical locations.


BrMets = brain metastases; CR = complete response; GK = Gamma Knife; GPA = Graded Prognostic Assessment; IT = immunotherapy; KPS = Karnofsky Performance Status; NSCLC; NSCLC = non–small cell lung cancer; PD = progressive disease; PR = partial response; RANO-BM = Response Assessment in Neuro-Oncology Brain Metastases; SD = stable disease; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy; brain metastases; immunotherapy; lungmol GPA = lung-specific molecular marker GPA; non–small cell lung cancer; oncology; stereotactic radiosurgery


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