The impact of whole brain radiation therapy on overall survival in patients with extensive stage small cell lung cancer with brain metastases
Ma Jintao, Jia Huijun, Meng Chunliu, Ren Kai, Yu Hao, Xu Liming, Liu Ningbo, Wang Ping, Zhao Lujun
Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
Abstract:Objective To evaluate whether whole brain radiation therapy(WBRT) could benefit small cell lung cancer (SCLC) patients with brain metastases. Methods Clinical data of 245 patients who were diagnosed with extensive stage SCLC with brain metastases admitted to our hospital from 2010 to 2020 were retrospectively analyzed. Among them, 168 patients received WRBT (WBRT group, radiation dose: 30Gy in 10 fractions), and 77 patients did not receive WBRT (non‐WBRT group). All patients received 4‐6 cycles of chemotherapy, and the chemotherapy regimen included cisplatin (or carboplatin) plus etoposide. One hundred and fifteen patients received thoracic radiotherapy. The endpoint was overall survival after brain metastases(BM‐OS). Chi-square test was used to compare categorical data, and stabilized inverse probability of treatment weighting(sIPTW) was used to match the factors between WBRT and no‐WBRT groups. Survival analysis was estimated by Kaplan‐Meier method, and the log‐rank test was used to compare survival curves between two groups. Results The median BM‐OS for the whole group of patients was 9.1 months, and 10.6 months and 6.7 months in the WBRT and non‐WBRT groups, respectively(P=0.003). After balanced influencing factors with stabilized sIPTW, significant difference still existed in BM‐OS between two groups(P=0.02). In 118 patients with synchronous brain metastases, the median BM‐OS in two groups were 13.0 months and 9.6 months(P=0.007); and in 127 patients with metachronous brain metastases, the median BM‐OS were 8.0 months and 4.1 months(P=0.003). In 50 patients without extracranial metastases, the median BM‐OS were 13.3 months and 10.9 months(P=0.259)in two groups; while in 195 patients with extracranial metastases, the median BM‐OS were 9.5 months and 5.9 months(P=0.009)in two groups. Conclusions WBRT could prolong the OS in extensive stage SCLC patients with brain metastases.
Ma Jintao,Jia Huijun,Meng Chunliu et al. The impact of whole brain radiation therapy on overall survival in patients with extensive stage small cell lung cancer with brain metastases[J]. Chinese Journal of Radiation Oncology, 2022, 31(10): 891-896.
[1] Kalemkerian GP, Loo BW, Akerley W, et al. NCCN guidelines insights: small cell lung cancer, version 2.2018 [J]. J Natl Compr Canc Netw, 2018, 16(10):1171‐1182. DOI: 10.6004/jnccn. 2018.0079. [2] Nugent JL, Bunn PA, Matthews MJ, et al.CNS metastases in small cell bronchogenic carcinoma: increasing frequency and changing pattern with lengthening survival[J]. Cancer, 1979,44(5):1885-1893. DOI: 10.1002/1097-0142(197911)44:5<1885::aid-cncr2820440550>3.0.co;2-f. [3] Hirsch FR, Paulson OB, Hansen HH, et al.Intracranial metastases in small cell carcinoma of the lung. prognostic aspects[J]. Cancer, 1983,51(3):529-533. DOI:10.1002/1097-0142 (19830201)51:3<529::aid-cncr2820510327>3.0.co;2-0. [4] Carmichael J, Crane JM, Bunn PA, et al.Results of therapeutic cranial irradiation in small cell lung cancer[J]. Int J Radiat Oncol Biol Phys, 1988,14(3):455-459. DOI: 10.1016/0360-3016(88)90260-x. [5] 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[J]. Radiother Oncol, 1998,46(1):29-32. DOI: 10.1016/s0167-8140(97)00149-7. [6] Seute T, Leffers P, ten Velde GP, et al. Neurologic disorders in 432 consecutive patients with small cell lung carcinoma[J]. Cancer, 2004,100(4):801-806. DOI: 10.1002/cncr.20043. [7] Bernhardt D, Adeberg S, Bozorgmehr F, et al.Outcome and prognostic factors in single brain metastases from small-cell lung cancer[J]. Strahlenther Onkol, 2018,194(2):98-106. DOI: 10.1007/s00066-017-1228-4. [8] Mulvenna P, Nankivell M, Barton R, et al.Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial[J]. Lancet, 2016,388(10055):2004-2014. DOI: 10.1016/S0140-6736(16)30825-X. [9] Jiang W, Haque W, Verma V, et al.Stereotactic radiosurgery for brain metastases from newly diagnosed small cell lung cancer: practice patterns and outcomes[J]. Acta Oncol, 2019,58(4):491-498. DOI: 10.1080/0284186X.2018.1562207. [10] Rusthoven CG, Yamamoto M, Bernhardt D, et al. Evaluation of first‐line radiosurgery vs whole‐brain radiotherapy for small cell lung cancer brain metastases: the FIRE‐SCLC cohort study [J]. JAMA Oncol, 2020, 6(7): 1028‐1037.DOI: 10.1001/jamaoncol. 2020.1271. [11] Gjyshi O, Lin SH, Pezzi TA, et al.Care patterns for stereotactic radiosurgery in small cell lung cancer brain metastases[J]. Clin Lung Cancer, 2022,23(2):185-190. DOI: 10.1016/j.cllc.2021.07.003. [12] Viani GA, Gouveia AG, Louie AV, et al.Stereotactic radiosurgery for brain metastases from small cell lung cancer without prior whole-brain radiotherapy: a meta-analysis[J]. Radiother Oncol, 2021,162:45-51. DOI: 10.1016/j.radonc.2021.06.026. [13] Sun H, Xu L, Wang Y, et al.Additional radiation boost to whole brain radiation therapy may improve the survival of patients with brain metastases in small cell lung cancer[J]. Radiat Oncol, 2018,13(1):250. DOI: 10.1186/s13014-018-1198-4. [14] Ni M, Jiang A, Liu W, et al.Whole brain radiation therapy plus focal boost may be a suitable strategy for brain metastases in SCLC patients: a multi-center study[J]. Radiat Oncol, 2020,15(1):70. DOI: 10.1186/s13014-020-01509-3. [15] Chen LK, Huang H, Liao H, et al.Chemotherapy with concurrent brain and thoracic radiotherapy in brain-only metastases of treatment naive small-cell lung cancer: a phase II study[J]. Med Oncol, 2012,29(3):1687-1692. DOI: 10.1007/s12032-011-0040-8. [16] Kochhar R, Frytak S, Shaw EG.Survival of patients with extensive small-cell lung cancer who have only brain metastases at initial diagnosis[J]. Am J Clin Oncol, 1997,20(2):125-127. DOI: 10.1097/00000421-199704000-00003. [17] Grossi F, Scolaro T, Tixi L, et al.The role of systemic chemotherapy in the treatment of brain metastases from small-cell lung cancer[J]. Crit Rev Oncol Hematol, 2001,37(1):61-67. DOI: 10.1016/s1040-8428(00)00098-6. [18] Seute T, Leffers P, Wilmink JT, et al.Response of asymptomatic brain metastases from small-cell lung cancer to systemic first-line chemotherapy[J]. J Clin Oncol, 2006,24(13):2079-2083. DOI: 10.1200/JCO.2005.03.2946. [19] Postmus PE, Haaxma-Reiche H, Smit EF, et al.Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European organization for the research and treatment of cancer lung cancer cooperative group[J]. J Clin Oncol, 2000,18(19):3400-3408. DOI: 10.1200/JCO.2000.18. 19.3400. [20] Neuhaus T, Ko Y, Muller RP, et al.A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer[J]. Br J Cancer, 2009,100(2):291-297. DOI: 10.1038/sj.bjc.6604835. [21] Martin AM, Cagney DN, Catalano PJ, et al. Immunotherapy and symptomatic radiation necrosis in patients with brain metastases treated with stereotactic radiation [J]. JAMA Oncol, 2018, 4(8):1123‐1124. DOI: 10.1001/jamaoncol. 2017.3993. [22] Kiess AP, Wolchok JD, Barker CA, et al.Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment[J]. Int J Radiat Oncol Biol Phys, 2015,92(2):368-375. DOI: 10.1016/j.ijrobp.2015.01.004. [23] Liu SV, Reck M, Mansfield AS, et al.Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133)[J]. J Clin Oncol, 2021,39(6):619-630. DOI: 10.1200/JCO.20.01055. [24] Renz P, Hasan S, Wegner RE.Survival outcomes after whole brain radiotherapy for brain metastases in older adults with newly diagnosed metastatic small cell carcinoma: a national cancer database (NCDB) analysis[J]. J Geriatr Oncol, 2019,10(4):560-566. DOI: 10.1016/j.jgo.2019.01.017.