BACKGROUND: Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases. OBJECTIVE: To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS). METHODS: A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis. RESULTS: Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P = .01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P = .005). CONCLUSION: SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.

Department of Neurosurgery Cleveland Clinic Cleveland Ohio

Department of Neurosurgery School of Medicine University of Virginia Charlottesville Virginia

Department of Neurosurgery School of Medicine West Virginia University Morgantown West Virginia

Department of Neurosurgery Taipei Veterans General Hospital Taipei Taiwan

Department of Neurosurgery University of Pittsburgh Medical Center Pittsburgh Pennsylvania

Department of Neurosurgery Yale School of Medicine Yale University New Haven Connecticut

Department of Radiation Oncology Beaumont Health System Royal Oak Michigan

Department of Radiation Oncology School of Medicine West Virginia University Morgantown West Virginia

Department of Radiation Oncology Yale School of Medicine Yale University New Haven Connecticut

Department of Stereotactic and Radiation Neurosurgery Na Homolce Hospital Prague Czech Republic

Division of Neurosurgery Faculté de Médecine et des Sciences de la Santé Université de Sherbrooke Centre de Recherche du CHUS Sherbrooke Canada

Mayfield Clinic Jewish Hospital Cincinnati Ohio

West Virginia Clinical and Translational Science Institute School of Medicine West Virginia University Morgantown West Virginia

See more in PubMed

Nugent JL, Bunn PA, Jr Matthews MJ et al. . CNS metastases in small cell bronchogenic carcinoma: increasing frequency and changing pattern with lengthening survival. Cancer. 1979;44(5):1885-1893. PubMed

Takahashi T, Yamanaka T, Seto T et al. . Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(5):663-671. PubMed

Robin TP, Jones BL, Amini A et al. . Radiosurgery alone is associated with favorable outcomes for brain metastases from small-cell lung cancer. Lung Cancer. 2018;120:88-90. PubMed

Wegner RE, Olson AC, Kondziolka D, Niranjan A, Lundsford LD, Flickinger JC. Stereotactic radiosurgery for patients with brain metastases from small cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;81(3):e21-e27. PubMed

Yomo S, Hayashi M.. Is stereotactic radiosurgery a rational treatment option for brain metastases from small cell lung cancer? A retrospective analysis of 70 consecutive patients. BMC Cancer. 2015;15(1):95-015-1103-6. PubMed PMC

Cordeiro D, Xu Z, Shepard M, Sheehan D, Li C, Sheehan J. Gamma Knife radiosurgery for brain metastases from small-cell lung cancer: Institutional experience over more than a decade and review of the literature. J Radiosurg SBRT. 2019;6(1):35-43. PubMed PMC

Kalbfleisch JD, Prentice RL.. The Statistical Analysis of Failure Time Data. Hoboken, N.J.: J. Wiley; 2002.

Patchell RA, Tibbs PA, Regine WF et al. . Postoperative radiotherapy in the treatment of single metastases to the brain. JAMA. 1998;280(17):1485-1489. PubMed

Sheehan J, Kondziolka D, Flickinger J, Lunsford LD. Radiosurgery for patients with recurrent small cell lung carcinoma metastatic to the brain: outcomes and prognostic factors. J Neurosurg. 2005;102(suppl):247-254. PubMed

Serizawa T, Ono J, Iichi T et al. . Gamma knife radiosurgery for metastatic brain tumors from lung cancer: a comparison between small cell and non-small cell carcinoma. J Neurosurg. 2002;97(5 suppl):484-488. PubMed

Bernhardt D, Hommertgen A, Schmitt D et al. . Whole brain radiation therapy alone versus radiosurgery for patients with 110 brain metastases from small cell lung cancer (ENCEPHALON Trial): study protocol for a randomized controlled trial. Trials. 2018;19(1):388-018-2745-x. PubMed PMC

Wefel JS, Parsons MW, Gondi V, Brown PD. Neurocognitive aspects of brain metastasis. Handb Clin Neurol. 2018;149:155-165. PubMed

Harris S, Chan MD, Lovato JF et al. . Gamma knife stereotactic radiosurgery as salvage therapy after failure of whole-brain radiotherapy in patients with small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2012;83(1):e53-e59. PubMed PMC

Nakazaki K, Higuchi Y, Nagano O, Serizawa T. Efficacy and limitations of salvage gamma knife radiosurgery for brain metastases of small-cell lung cancer after whole-brain radiotherapy. Acta Neurochir. 2013;155(1):107-114; discussion 113-114. PubMed

Postmus PE, Haaxma-Reiche H, Gregor A et al. . Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study. Radiother Oncol. 1998;46(1):29-32. PubMed

Carmichael J, Crane JM, Bunn PA, Glatstein E, Ihde DC. Results of therapeutic cranial irradiation in small cell lung cancer. Int J Radiat Oncol Biol Phys. 1988;14(3):455-459. PubMed

Bernhardt D, Bozorgmehr F, Adeberg S et al. . Outcome in patients with small cell lung cancer re-irradiated for brain metastases after prior prophylactic cranial irradiation. Lung Cancer. 2016;101:76-81. PubMed

Sperduto PW, Chao ST, Sneed PK et al. . Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010;77(3):655-661. PubMed

Bernhardt D, Adeberg S, Bozorgmehr F et al. . Outcome and prognostic factors in patients with brain metastases from small-cell lung cancer treated with whole brain radiotherapy. J Neurooncol. 2017;134(1):205-212. PubMed

Ward MC, Riaz N, Caudell JJ et al. . Refining patient selection for reirradiation of head and neck squamous carcinoma in the IMRT Era: a multi-institution cohort study by the MIRI collaborative. Int J Radiat Oncol Biol Phys. 2018;100(3):586-594. PubMed PMC

Minniti G, Clarke E, Lanzetta G et al. . Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol. 2011;6(1):48. PubMed PMC

Rae A, Gorovets D, Rava P et al. . Management approach for recurrent brain metastases following upfront radiosurgery may affect risk of subsequent radiation necrosis. Adv Radiat Oncol. 2016;1(4):294-299. PubMed PMC

Sneed PK, Mendez J, Vemer-van den Hoek JG et al. . Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors. J Neurosurg. 2015;123(2):373-386. PubMed

Sharma M, Jia X, Ahluwalia M et al. . First follow-up radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastases. Cancer Med. 2017;6(9):2076-2086. PubMed PMC

Shaw E, Scott C, Souhami L et al. . Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47(2):291-298. PubMed

Nong J, Gong Y, Guan Y et al. . Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer. Nat Commun. 2018;9(1):3114. PubMed PMC

Yang M, Topaloglu U, Petty WJ et al. . Circulating mutational portrait of cancer: manifestation of aggressive clonal events in both early and late stages. J Hematol Oncol. 2017;10(1):100. PubMed PMC

Arriagada R, Le Chevalier T, Borie F et al. . Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst. 1995;87(3):183-190. PubMed

Giuliani M, Sun A, Bezjak A et al. . Utilization of prophylactic cranial irradiation in patients with limited stage small cell lung carcinoma. Cancer. 2010;116(24):5694-5699. PubMed

Guo WL, He ZY, Chen Y et al. . Clinical features of brain metastases in small cell lung cancer: an implication for hippocampal sparing whole brain radiation therapy. Transl Oncol. 2017;10(1):54-58. PubMed PMC

Aoyama H, Shirato H, Tago M et al. . Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295(21):2483-2491. PubMed

Chang EL, Wefel JS, Hess KR et al. . Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037-1044. PubMed

Kocher M, Soffietti R, Abacioglu U et al. . Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952–26001 study. J Clin Oncol. 2011;29(2):134-141. PubMed PMC

Brown PD, Jaeckle K, Ballman KV et al. . Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA. 2016;316(4):401-409. PubMed PMC