The role of pre- and post-SRS systemic therapy in patients with NSCLC brain metastases
Purpose: We report our experience with stereotactic radiosurgery (SRS) for NSCLC brain metastases. We then assess the prognostic value of pre- and post-SRS systemic therapy (PrSST and PoSST) and evaluate the timing of PoSST.
Methods: In this retrospective study, we analyzed 96 patients with lung cancer and ECOG PS ≤ 3 who underwent SRS during 2007-2013. Recorded factors included SRS treatment parameters, systemic status of disease (SDS) at time of SRS, and the use of PrSST and PoSST. SDS was designated as pulmonary disease or extrapulmonary disease. For analysis, the SRS-PoSST interval (SPI) was divided into ≤30 days and >30 days. Univariate and multivariate analyses were performed.
Results: 85 patients with NSCLC were included in this analysis. 48% received PrSST and 48% received PoSST. 57% of patients had pulmonary disease while 40% had extrapulmonary disease. 46% of patients had synchronous metastases. At a median follow-up of 6 months, the median survival was 6.4 months and the actuarial overall survival at 3, 6, 12, and 36 months was 80%, 52%, 31%, and 6%. Extrapulmonary disease (p = 0.008) negatively predicted for survival while the receipt of any systemic therapy (p = 0.050) or PoSST alone (p = 0.039) positively predicted for survival. In patients receiving PoSST, an SPI >30 days positively predicted for survival (HR 0.28, 95% CI 0.13-0.62, p = 0.002) regardless of SDS.
Conclusion: Our results indicate the prognostic importance of systemic therapy and specifically PoSST. Additionally, delaying the initiation of PoSST to >30 days seems beneficial. This finding was potentially influenced by neurotoxicity after SRS. Further investigation is warranted to define the optimal SPI.
Palmieri D. Central nervous system metastasis, the biological basis and clinical considerations. New York: Springer; 2012.
Davis FG, Dolecek TA, McCarthy BJ, et al. Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 united states cancer incidence data. Neuro Oncol 2012;14:1171-7.
Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: A randomized trial. JAMA 1998; 280:1485-9.
Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322:494-500.
Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase iii results of the rtog 9508 randomised trial. Lancet 2004;363:1665-72.
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;10:1037-44.
Tsao M, Xu W, Sahgal A. A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy, or both for patients presenting with a limited number of brain metastases. Cancer 2012;118:2486-93.
Langer CJ, Mehta MP. Current management of brain metastases, with a focus on systemic options. J Clin Oncol 2005;23:6207-19.
Walbert T, Gilbert MR. The role of chemotherapy in the treatment of patients with brain metastases from solid tumors. Int J Clin Oncol 2009;14:299-306.
Sperduto PW, Wang M, Robins HI, et al. A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus wbrt and srs with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation therapy oncology group 0320. Int J Radiat Oncol Biol Phys 2013;85:1312-18.
Lombardi G, Di Stefano AL, Farina P, et al. Systemic treatments for brain metastases from breast cancer, non-small cell lung cancer, melanoma and renal cell carcinoma: An overview of the literature. Cancer Treat Rev 2014;40(8):951-9.
Zimmermann S, Dziadziuszko R, Peters S. Indications and limitations of chemotherapy and targeted agents in non-small cell lung cancer brain metastases. Cancer Treat Rev 2014;40:716-22.
Dawe DE, Greenspoon JN, Ellis PM. Brain metastases in non-small-cell lung cancer. Clin Lung Cancer 2014;15:249-57.
Fidler IJ. The biology of brain metastasis: Challenges for therapy. Cancer J 2015;21:284-93.
Hu J, Kesari S. Strategies for overcoming the blood-brain barrier for the treatment of brain metastases. CNS Oncol 2013;2:87-98.
Puhalla S, Elmquist W, Freyer D, et al. Unsanctifying the sanctuary: Challenges and opportunities with brain metastases. Neuro Oncol 2015;17:639-51.
Kim YS, Kondziolka D, Flickinger JC, et al. Stereotactic radiosurgery for patients with nonsmall cell lung carcinoma metastatic to the brain. Cancer 1997;80:2075-83.
Williams J, Enger C, Wharam M, et al. Stereotactic radiosurgery for brain metastases: Comparison of lung carcinoma vs. Non-lung tumors. J Neurooncol 1998;37:79-85.
Li B, Yu J, Suntharalingam M, et al. Comparison of three treatment options for single brain metastasis from lung cancer. Int J Cancer 2000;90:37-45.
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;97:484-88.
Zabel A, Milker-Zabel S, Thilmann C, et al. Treatment of brain metastases in patients with non-small cell lung cancer (nsclc) by stereotactic linac-based radiosurgery: Prognostic factors. Lung Cancer 2002;37:87-94.
Noel G, Medioni J, Valery CA, et al. Three irradiation treatment options including radiosurgery for brain metastases from primary lung cancer. Lung Cancer 2003;41:333-43.
Kress MA, Oermann E, Ewend MG, et al. Stereotactic radiosurgery for single brain metastases from non-small cell lung cancer: Progression of extracranial disease correlates with distant intracranial failure. Radiat Oncol 2013;8:64.
Jezierska D, Adamska K, Liebert W. Evaluation of results of linac-based radiosurgery for brain metastases from primary lung cancer. Rep Pract Oncol Radiother 2014;19:19-29.
Smith TR, Lall RR, Lall RR, et al. Survival after surgery and stereotactic radiosurgery for patients with multiple intracranial metastases: Results of a single-center retrospective study. J Neurosurg 2014:1-7.
Likhacheva A, Pinnix CC, Parikh NR, et al. Predictors of survival in contemporary practice after initial radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 2013;85:656-61.
DiLuna ML, King JT, Jr., Knisely JP, et al. Prognostic factors for survival after stereotactic radiosurgery vary with the number of cerebral metastases. Cancer 2007;109:135-45.
Yomo S, Hayashi M. Upfront stereotactic radiosurgery in patients with brain metastases from small cell lung cancer: Retrospective analysis of 41 patients. Radiat Oncol 2014;9:152.
Davey P. Brain metastases: Treatment options to improve outcomes. CNS Drugs 2002;16:325-38.
Bernardo G, Cuzzoni Q, Strada MR, et al. First-line chemotherapy with vinorelbine, gemcitabine, and carboplatin in the treatment of brain metastases from non-small-cell lung cancer: A phase ii study. Cancer Invest 2002;20:293-302.
Cortes J, Rodriguez J, Aramendia JM, et al. Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. Oncology 2003;64:28-35.
Lippitz B, Lindquist C, Paddick I, et al. Stereotactic radiosurgery in the treatment of brain metastases: The current evidence. Cancer Treat Rev 2014;40:48-59.
Luo D, Ye X, Hu Z, et al. Egfr mutation status and its impact on survival of chinese non-small cell lung cancer patients with brain metastases. Tumour Biol 2014;35:2437-44.
Jamal-Hanjani M, Spicer J. Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of epidermal growth factor receptor-mutant non-small cell lung cancer metastatic to the brain. Clin Cancer Res 2012;18:938-44.
Arrieta O, Villarreal-Garza C, Zamora J, et al. Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation. Radiat Oncol 2011;6:166.
Funai K, Suzuki K, Sekihara K, et al. Five-year tumor-free survival after aggressive trimodality therapy for t3n0m1b non-small cell lung cancer with synchronous solitary brain metastasis. Gen Thorac Cardiovasc Surg 2012;60:370-2.
Gray PJ, Mak RH, Yeap BY, et al. Aggressive therapy for patients with non-small cell lung carcinoma and synchronous brain-only oligometastatic disease is associated with long-term survival. Lung Cancer 2014;85:239-44.
Griffioen GH, Toguri D, Dahele M, et al. Radical treatment of synchronous oligometastatic non-small cell lung carcinoma (nsclc): Patient outcomes and prognostic factors. Lung Cancer 2013;82:95-102.
This work is licensed under a Creative Commons Attribution 3.0 License.
International Journal of Cancer Therapy and Oncology (ISSN 2330-4049)
© International Journal of Cancer Therapy and Oncology (IJCTO)
To make sure that you can receive messages from us, please add the 'ijcto.org' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.