AbstractObjective To analyze the prognosis and influencing factors of patients with brain metastases from non-small cell lung cancer (NSCLC) treated with different doses of whole brain radiotherapy (WBRT). Methods A total of 244 NSCLC patients with brain metastases who underwent WBRT in the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different doses of WBRT (EQD2Gy), they were divided into the 30-39Gy group (n= 104) and ≥40Gy group (n= 140). The intracranial progression-free survival (iPFS) and overall survival (OS) were compared betweentwo groups. According to the number of brain metastases, GPA score, KPS score, chemotherapy and targeted therapy, the prognosis of different doses of WBRT was further analyzed. Results The median iPFS and OS of all patients were 6.9 months and 11.8 months, respectively. Univariate survival analysis:the 1-year iPFS and 1-year OS between two groups were 22.5% and 25.4%(P=0.430) and 41.1% and 46.4%(P=0.068), respectively. Multivariate survival analysis:different doses of WBRT were not associated with the improvement of iPFS and OS;independent factors influencing iPFS included local boost, gender, number of brain metastases, chemotherapy and targeted therapy;independent factors influencing OS included gender, number of brain metastases, chemotherapy and targeted therapy. Subgroup analysis:in patients with KPS≥90, the 1-year iPFS and OS of patients with WBRT ≥ 40Gy were seemingly better than those of their counterparts with 30-39Gy, but the difference was statistically significant only in OS (P=0.047), the difference was not statistically significant in iPFS (P=0.068);in patients with chemotherapy, the 1-year iPFS and OS of patients with WBRT≥40Gy were better than those of their counterparts with 30-39Gy (P=0.017, P=0.012);in patients with targeted therapy, the 1-year iPFS and OS in the WBRT≥40Gy group were better than those in the 30-39Gy group (P=0.012, P=0.045). Conclusions The 30-39Gy may be the appropriate dose of WBRT for NSCLC patients with brain metastases. WBRT≥40Gy does not bring more benefits. WBRT≥40Gy may benefit NSCLC patients with brain metastases with high KPS score or active systemic therapy.
Shen Dongxing,Liu Zhikun,Li Zhensheng et al. Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with different doses of whole brain radiotherapy[J]. Chinese Journal of Radiation Oncology, 2022, 31(4): 340-346.
Shen Dongxing,Liu Zhikun,Li Zhensheng et al. Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with different doses of whole brain radiotherapy[J]. Chinese Journal of Radiation Oncology, 2022, 31(4): 340-346.
[1] Chen AM, Jahan TM, Jablons DM, et al. Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall-cell lung cancer:clinical implications for the subsequent management of the brain[J]. Cancer, 2007, 109(8):1668-1675. DOI:10.1002/cncr.22565.
[2] Weissman DE. Glucocorticoid treatment for brain metastases and epidural spinal cord compression:a review[J]. J Clin Oncol, 1988, 6(3):543-551. DOI:10.1200/JCO.1988.6.3.543.
[3] Patla A, Walasek T, Jakubowicz J, et al. Methods and results of locoregional treatment of brain metastases in patients with non-small cell lung cancer[J]. Contemp Oncol (Pozn), 2016, 20(5):358-364. DOI:10.5114/wo.2015.51825.
[4] Nabors LB, Portnow J, Ahluwalia M, et al. Central nervous system cancers, version 3.2020, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2020, 18(11):1537-1570. DOI:10.6004/jnccn.2020.0052.
[5] Trifiletti DM, Ballman KV, Brown PD, et al. Optimizing whole brain radiation therapy dose and fractionation:results from a prospective phase 3 trial (NCCTG N107C[Alliance]/CEC.3)[J]. Int J Radiat Oncol Biol Phys, 2020, 106(2):255-260. DOI:10.1016/j.ijrobp.2019.10.024.
[6] 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[J]. Lancet Oncol, 2009, 10(11):1037-1044. DOI:10.1016/S1470-2045(09)70263-3.
[7] Monaco EA 3rd, Faraji AH, Berkowitz O, et al. Leukoencephalopathy after whole-brain radiation therapy plus radiosurgery versus radiosurgery alone for metastatic lung cancer[J]. Cancer, 2013, 119(1):226-232. DOI:10.1002/cncr.27504.
[8] Peters S, Bexelius C, Munk V, et al. The impact of brain metastasis on quality of life, resource utilization and survival in patients with non-small-cell lung cancer[J]. Cancer Treat Rev, 2016, 45:139-162. DOI:10.1016/j.ctrv.2016.03.009.
[9] Tsao MN, Xu W, Wong RK, et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases[J]. Cochrane Database Syst Rev, 2018, 1(1):CD003869. DOI:10.1002/14651858.CD003869.pub4.
[10] Gondi V, Pugh SL, Tome WA, et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933):a phase Ⅱ multi-institutional trial[J]. J Clin Oncol, 2014, 32(34):3810-3816. DOI:10.1200/JCO.2014.57.2909.
[11] Harth S, Abo-Madyan Y, Zheng L, et al. Estimation of intracranial failure risk following hippocampal-sparing whole brain radiotherapy[J]. Radiother Oncol, 2013, 109(1):152-158. DOI:10.1016/j.radonc.2013.09.009.
[12] Han YM, Cai G, Chai WM, et al. Radiological distribution of brain metastases and its implication for the hippocampus avoidance in whole brain radiotherapy approach[J]. Br J Radiol, 2017, 90(1079):20170099. DOI:10.1259/bjr.20170099.
[13] Tallet AV,Azria D, Barlesi F, et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases:actual assessment[J]. Radiat Oncol, 2012,7(1):77. DOI:10.1186/1748-717X-7-77.
[14] Ryan G, Ball D, Smith J. Treatment of brain metastases from primary lung cancer[J]. Int J Radiat Oncol Biol Phys,1995,1(31):273-278. DOI:10.1016/0360-3016(93) E0073-F.
[15] Nieder C, Nestle U, Walter K, et al. Dose/effect relationships for brain metastases[J]. J Cancer Res Clin Oncol, 1998, 124(6):346-350. DOI:10.1007/s004320050181.
[16] Chung SY, Chang JH, Kim HR, et al. Optimal dose and volume for postoperative radiotherapy in brain oligometastases from lung cancer:a retrospective study[J]. Radiat Oncol J, 2017, 35(2):153-162. DOI:10.3857/roj.2017.00094.
[17] Lu F, Hou Y, Xia Y, et al. Survival and intracranial control outcomes of whole-brain radiotherapy (WBRT) alone versus WBRT plus a radiotherapy boost in non-small-cell lung cancer with brain metastases:a single-institution retrospective analysis[J]. Cancer Manag Res, 2019, 11:4255-4272. DOI:10.2147/CMAR.S203461.
[18] Li Z, Shen D, Zhang J, et al. Relationship between WBRT total dose, intracranial tumor control, and overall survival in NSCLC patients with brain metastases-a single-center retrospective analysis[J]. BMC Cancer, 2019, 19(1):1104. DOI:10.1186/s12885-019-6307-8.
[19] Liu H, Xu X, Wang J, et al. Clinical study on different doses and fractionated radiotherapies for multiple brain metastases of non-EGFR mutant lung adenocarcinoma[J]. Ann Palliat Med, 2020, 9(4):2003-2012. DOI:10.21037/apm-20-1203.
[20] 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[J]. Lancet, 2004, 363(9422):1665-1672. DOI:10.1016/S0140-6736(04)16250-8.
[21] Dobi Á, Fodor E, Maráz A, et al. Boost irradiation integrated to whole brain radiotherapy in the management of brain metastases[J]. Pathol Oncol Res, 2020, 26(1):149-157. DOI:10.1007/s12253-018-0383-y.
[22] Xiang Z, Chen J, Zhang H, et al. Whole brain radiotherapy-based combined modality treatment of brain metastases from non-small cell lung cancer:a retrospective analysis of prognostic factors[J]. Oncol Res Treat, 2015, 38(1-2):35-40. DOI:10.1159/000371501.
[23] Rades D, Schild SE, Lohynska R, et al. Two radiation regimens and prognostic factors for brain metastases in nonsmall cell lung cancer patients[J]. Cancer, 2007, 110(5):1077-1082. DOI:10.1002/cncr.22877.
[24] Goncalves PH, Peterson SL, Vigneau F D, et al. Risk of brain metastases in patients with nonmetastatic lung cancer:analysis of the metropolitan detroit surveillance, epidemiology, and end results (SEER) data[J]. Cancer, 2016,122(12):1921-1927. DOI:10.1002/cncr.30000.
[25] Sperduto PW, Berkey B, Gaspar LE, et al. A new prognostic index and comparison to three other indices for patients with brain metastases:an analysis of 1,960 patients in the RTOG database[J]. Int J Radiat Oncol Biol Phys, 2008, 70(2):510-514. DOI:10.1016/j.ijrobp.2007.06.074.
[26] 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[J]. Int J Radiat Oncol Biol Phys, 2010, 77(3):655-661. DOI:10.1016/j.ijrobp.2009.08.025.
[27] Sperduto PW, Yang TJ, Beal K, et al. The effect of gene alterations and tyrosine kinase inhibition on survival and cause of death in patients with adenocarcinoma of the lung and brain metastases[J]. Int J Radiat Oncol Biol Phys, 2016, 96(2):406-413. DOI:10.1016/j.ijrobp.2016.06.006.
[28] 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.
[29] Sanghavi SN, Miranpuri SS, Chappell R, et al. Radiosurgery for patients with brain metastases:a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method[J]. Int J Radiat Oncol Biol Phys, 2001, 51(2):426-434. DOI:10.1016/s0360-3016(01)01622-4.
[30] Mehta MP, Paleologos NA, Mikkelsen T, et al. The role of chemotherapy in the management of newly diagnosed brain metastases:a systematic review and evidence-based clinical practice guideline[J]. J Neurooncol, 2010, 96(1):71-83. DOI:10.1007/s11060-009-0062-7.
[31] Videtic GM, Reddy CA, Chaoi ST, et al. Do gender and race influence survival in patients with non-small cell lung cance brain metastases? An outcomes study utilizing the RTOG RPA classs tratification[J]. J Clin Oncol, 2006,18(24):402. DOI:10.1245/s10434-009-0903-9.