Abstract:Brain metastasis has become a major failure pattern with the prolonged survival of patients with non-small cell lung cancer (NSCLC). Prophylactic cranial irradiation (PCI) has been proven to play a significant role in small cell lung cancer, whereas its value in NSCLC is still controversial. Therefore, this article reviewed the role of PCI in NSCLC, high-risk factors of brain metastasis, timing, dose fraction and toxicity of PCI, etc.
Zhang Yang,Li Hongwei,Liu Jianhui et al. Research progress on prophylactic cranial irradiation in non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2020, 29(6): 486-490.
[1] Gore EM, Bae K, Wong SJ, et al. Phase Ⅲ comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small-cell lung cancer:primary analysis of radiation therapy oncology group study RTOG 0214[J]. J Clin Oncol, 2011, 29(3):272-278. DOI:10.1200/JCO.2010.29.1609. [2] Stuschke M, Eberhardt W, Pottgen C, et al. Prophylactic cranial irradiation in locally advanced non-small-cell lung cancer after multimodality treatment:long-term follow-up and investigations of late neuropsychologic effects[J]. J Clin Oncol, 1999, 17(9):2700-2709. DOI:10.1200/JCO.1999.17.9.2700. [3] 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. [4] Gaspar L, Scott C, Rotman M, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials[J]. Int J Radiat Oncol Biol Phys, 1997, 37(4):745-751. DOI:10.1016/S0360-3016(96)00619-0. [5] Russell AH, Pajak TE, Selim HM, et al. Prophylactic cranial irradiation for lung cancer patients at high risk for development of cerebral metastasis:results of a prospective randomized trial conducted by the Radiation Therapy Oncology Group[J]. Int J Radiat Oncol Biol Phys, 1991, 21(3):637-643. DOI:10.1016/0360-3016(91)90681-S. [6] Cox JD, Stanley K, petrovich Z, et al. Cranial irradiation in cancer of the lung of all cell types[J]. JAMA, 1981, 245(5):469-472. DOI:10.1001/jama.245.5.469. [7] Sun CH, Gore E, Wong S, et al. 10-year updated analysis of NRG ONCOLOGY/RTOG0214:a phase Ⅲ comparison of PCI vs. observation in patients with LA-NSCLC[C]. 19th World Conference on Lung Cancer. Toronto, 2018. [8] De Ruysscher D, Dingemans AC, Praag J, et al. Prophylactic cranial irradiation versus observation in radically treated stage Ⅲ non-small-cell lung cancer:a randomized phase Ⅲ NVALT-11/DLCRG-02 study[J]. J Clin Oncol, 2018, 36(23):2366-2377. DOI:10.1200/JCO.2017.77.5817. [9] Li N, Zeng ZF, Wang SY, et al. Randomized phase Ⅲ trial of prophylactic cranial irradiation versus observation in patients with fully resected stage ⅢA-N2 non-small-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy[J]. Ann Oncol, 2015, 26(3):504-509. DOI:10.1093/annonc/mdu567. [10] Arrieta O, Ramirez-tirado L, Barron F, et al. Prophylactic cranial irradiation reduces the risk of brain metastasis in high-risk lung cancer patients:EGFR and ALK mutations[C]. 19th World Conference on Lung Cancer. Toronto, 2018. [11] Ji Z, Bi N, Wang J, et al. Risk factors for brain metastases in locally advanced non-small cell lung cancer with definitive chest radiation[J]. Int J Radiat Oncol Biol Phys, 2014, 89(2):330-337. DOI:10.1016/j.ijrobp.2014.02.025. [12] Ding X, Dai H, Hui Z, et al. Risk factors of brain metastases in completely resected pathological stage ⅢA-N2 non-small cell lung cancer[J]. Radiat Oncol, 2012, 7:119. DOI:10.1186/1748-717X-7-119. [13] Sun DS, Hu LK, Cai Y, et al. A systematic review of risk factors for brain metastases and value of prophylactic cranial irradiation in non-small cell lung cancer[J]. Asian Pac J Cancer Prev, 2014, 15(3):1233-1239. DOI:10.7314/APJCP.2014.15.3.1233. [14] Zhang F, Zheng W, Ying L, et al. A nomogram to predict brain metastases of resected non-small cell lung cancer patients[J]. Ann Surg Oncol, 2016, 23(9):3033-3039. DOI:10.1245/s10434-016-5206-3. [15] Won YW, Joo J, Yun T, et al. A nomogram to predict brain metastasis as the first relapse in curatively resected non-small cell lung cancer patients[J]. Lung Cancer, 2015, 88(2):201-207. DOI:10.1016/j.lungcan.2015.02.006. [16] Arrieta O, Saavedra-Perez D, Kuri R, et al. Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA) level in advanced non-small cell lung cancer:a prospective analysis[J]. BMC Cancer, 2009, 9:119. DOI:10.1186/1471-2407-9-119. [17] Bajard A, Westeel V, Dubiez A, et al. Multivariate analysis of factors predictive of brain metastases in localised non-small cell lung carcinoma[J]. Lung Cancer, 2004, 45(3):317-323. DOI:10.1016/j.lungcan.2004.01.025. [18] Mujoomdar A, Austin JH, Malhotra R, et al. Clinical predictors of metastatic disease to the brain from non-small cell lung carcinoma:primary tumor size, cell type, and lymph node metastases[J]. Radiology, 2007, 242(3):882-888. DOI:10.1148/radiol.2423051707. [19] Robnett TJ, Machtay M, Stevenson JP, et al. Factors affecting the risk of brain metastases after definitive chemoradiation for locally advanced non-small-cell lung carcinoma[J]. J Clin Oncol, 2001, 19(5):1344-1349. DOI:10.1200/JCO.2001.19.5.1344. [20] Gaspar LE, Chansky K, Albain KS, et al. Time from treatment to subsequent diagnosis of brain metastases in stage Ⅲ non-small-cell lung cancer:a retrospective review by the Southwest Oncology Group[J]. J Clin Oncol, 2005, 23(13):2955-2961. DOI:10.1200/JCO.2005.08.026. [21] Hsiao SH, Chung CL, Chou YT, et al. Identification of subgroup patients with stage ⅢB/Ⅳ non-small cell lung cancer at higher risk for brain metastases[J]. Lung Cancer, 2013, 82(2):319-323. DOI:10.1016/j.lungcan.2013.08.004. [22] Ceresoli GL, Reni M, Chiesa G, et al. Brain metastases in locally advanced nonsmall cell lung carcinoma after multimodality treatment:risk factors analysis[J]. Cancer, 2002, 95(3):605-612. DOI:10.1002/cncr.10687. [23] Dimitropoulos C, Hillas G, Nikolakopoulou S, et al. Prophylactic cranial irradiation in non-small cell lung cancer patients:who might be the candidates?[J]. Cancer Manag Res, 2011, 3:287-294. DOI:10.2147/CMR. S22717. [24] 陈燕,彭伟,黄艳芳,等. 治疗前血清神经元特异性烯醇化酶水平在预测晚期非小细胞肺癌脑转移及预后中的意义[J]. 中华肿瘤杂志,2015,37(7):508-511. DOI:10.3760/cma.j.issn.0253-3766.2015.07.006. Chen Y, Peng W, Huang YF, et al. Significance of serum neuron-specific enolase before treatment in predicting brain metastases and prognosis of advanced non-small cell lung cancer[J]. Chin J Oncol. 2015, 37(7):508-511. DOI:10.3760/cma.j.issn.0253-3766.2015.07.006. [25] Bhatt VR, D′Souza SP, Smith LM, et al. Epidermal growth factor receptor mutational status and brain metastases in non-small-cell lung cancer[J]. J Glob Oncol, 2017, 3(3):208-217. DOI:10.1200/JGO.2016.003392. [26] Ma X, Zhu H, Guo H, et al. Risk factors of brain metastasis during the course of EGFR-TKIs therapy for patients with EGFR-mutated advanced lung adenocarcinoma[J]. Oncotarget, 2016, 7(49):81906-81917. DOI:10.18632/oncotarget.11918. [27] Chen Y, Li J, Zhang Y, et al. Early versus late prophylactic cranial irradiation in patients with extensive small cell lung cancer[J]. Strahlenther Onkol, 2018, 194(10):876-885. DOI:10.1007/s00066-018-1307-1. [28] Goss G, Tsai CM, Shepherd FA, et al. CNS response to osimertinib in patients with T790M-positive advanced NSCLC:pooled data from two phase Ⅱ trials[J]. Ann Oncol, 2018, 29(3):687-693. DOI:10.1093/annonc/mdx820. [29] Reungwetwattana T, Nakagawa K, Cho BC, et al. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated egfr-mutated advanced non-small-cell lung cancer[J]. J Clin Oncol, 2018:JCO2018783118. DOI:10.1200/JCO.2018.78.3118. [30] Cho BC, Chewaskulyong B, Lee KH, et al. Osimertinib versus standard of care egfr tki as first-line treatment in patients with EGFRm advanced NSCLC:FLAURA Asian subset[J]. J Thorac Oncol, 2019, 14(1):99-106. DOI:10.1016/j.jtho.2018.09.004. [31] Le pechoux C, Dunant A, Senan S, et al. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01):a randomised clinical trial[J]. Lancet Oncol, 2009, 10(5):467-474. DOI:10.1016/S1470-2045(09)70101-9. [32] Wolfson AH, Bae K, Komakl R, et al. Primary analysis of a phase Ⅱ randomized trial Radiation Therapy Oncology Group (RTOG) 0212:impact of different total doses and schedules of prophylactic cranial irradiation on chronic neurotoxicity and quality of life for patients with limited-disease small-cell lung cancer[J]. Int J Radiat Oncol Biol Phys, 2011, 81(1):77-84. DOI:10.1016/j.ijrobp.2010.05.013. [33] Van Vulpen M, Kal HB, Taphoorn MJ, et al. Changes in blood-brain barrier permeability induced by radiotherapy:implications for timing of chemotherapy?(Review)[J]. Oncol Rep, 2002, 9(4):683-688. DOI:10.3892/or.9.4.683. [34] Sun A, Bae K, Gore EM, et al. Phase Ⅲ trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer:neurocognitive and quality-of-life analysis[J]. J Clin Oncol, 2011, 29(3):279-286. DOI:10.1200/JCO.2010.29.6053. [35] Ghia A, Tome WA, Thomas S, et al. Distribution of brain metastases in relation to the hippocampus:implications for neurocognitive functional preservation[J]. Int J Radiat Oncol Biol Phys, 2007, 68(4):971-977. DOI:10.1016/j.ijrobp.2007.02.016. [36] Marsh JC, Herskovic AM, Gielda BT, et al. Intracranial metastatic disease spares the limbic circuit:a review of 697 metastatic lesions in 107 patients[J]. Int J Radiat Oncol Biol Phys, 2010, 76(2):504-512. DOI:10.1016/j.ijrobp.2009.02.038. [37] Wan JF, Zhang SJ, Wang L, et al. Implications for preserving neural stem cells in whole brain radiotherapy and prophylactic cranial irradiation:a review of 2270 metastases in 488 patients[J]. J Radiat Res, 2013, 54(2):285-291. DOI:10.1093/jrr/rrs085. [38] Redmond KJ, Mahone EM, Terezakis S, et al. Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children:a prospective study[J]. Neuro Oncol, 2013, 15(3):360-369. DOI:10.1093/neuonc/nos303. [39] Gondi V, Tome WA, Mehta MP. Why avoid the hippocampus? A comprehensive review[J]. Radiother Oncol, 2010, 97(3):370-376. DOI:10.1016/j.radonc.2010.09.013. [40] Gondi V, Hermann BP, Mehta MP, et al. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors[J]. Int J Radiat Oncol Biol Phys, 2013, 85(2):348-354. DOI:10.1016/j.ijrobp.2012.11.031. [41] Paber J, Rola R, Lefevour A, et al. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis[J]. Radiat Res, 2004, 162(1):39-47. DOI:10.1667/rr3206. [42] Rola R, Raber J, Rizk A, et al. Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice[J]. Exp Neurol, 2004, 188(2):316-330. DOI:10.1016/j.expneurol.2004.05.005. [43] Oehlke O, Wucherpfenning D, Fels F, et al. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases:Local tumour control and survival[J]. Strahlenther Onkol, 2015, 191(6):461-469. DOI:10.1007/s00066-014-0808-9. [44] Lin SY, Yang CC, Wu YM, et al. Evaluating the impact of hippocampal sparing during whole brain radiotherapy on neurocognitive functions:A preliminary report of a prospective phase Ⅱ study[J]. Biomed J, 2015, 38(5):439-449. DOI:10.4103/2319-4170.157440. [45] 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. [46] 董昕, 周宗玫, 刘璇, 等. 小细胞肺癌全脑预防照射海马回区保护的Ⅱ期临床研究[J]. 中华放射肿瘤学杂志, 2018, 27(7):638-642. DOI:10.3760/cma.j.issn.1004-4221.2018.07.003. Dong X, Zhou ZM, Liu X, et al. Phase Ⅱ clinical trial of hippocampal-sparing prophylactic cranial irradiation in patients with small cell lung cancer[J]. Chin J Radiat Oncol, 2018, 27(7):638-642. DOI:10.3760/cma.j.issn.1004-4221.2018.07.003.