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Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Radiotherapy | Research

Analysis of the efficacy of upfront brain radiotherapy versus deferred radiotherapy for EGFR/ALK-positive non-small cell lung cancer with brain metastases: a retrospective study

Authors: Jing Qian, Zelai He, Ying Wu, Hongwei Li, Qun Zhang, Xianming Li

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

For brain metastases (BMs) from EGFR/ALK-positive non-small cell lung cancer (NSCLC), the best time to administer tyrosine kinase inhibitors (TKIs) and brain radiotherapy (RT) has not been identified. This analysis was an attempt to solve this problem in part.

Methods

A total of 163 patients with EGFR/ALK-positive NSCLC and brain metastasis (BM) who were diagnosed between January 2017 and July 2022 were included in this study. Ninety-one patients underwent upfront RT, and 72 patients received deferred RT. Comparing the clinical efficacy and safety in these two patient cohorts was the main goal of the study.

Results

The average follow-up period was 20.5 months (range 2.0 to 91.9 months). The median overall survival (OS) was 26.5 months, and the median intracranial progression-free survival (iPFS) was 23.6 months. Upfront RT considerably increased the iPFS (26.9 vs. 20.2 months, hazard ratio [HR] = 5.408, P = 0.020) and OS (31.2 vs. 22.3 months, HR = 4.667, P = 0.031) compared to deferred RT. According to multivariate analysis, upfront RT was an independent risk factor for predicting iPFS (HR = 1.670, P = 0.021). Upfront RT (HR = 1.531, P = 0.044), TKI therapy (HR = 0.423, P < 0.001), and oligometastases (HR = 2.052, P = 0.021) were found to be independent risk factors for OS.

Conclusion

This study showed that upfront RT combined with TKI treatment can significantly improve intracranial disease management and prolong survival in patients with EGFR/ALK mutations in BMs from NSCLC.
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Literature
1.
go back to reference Gelatti ACZ, Drilon A, Santini FC. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Lung cancer (Amsterdam Netherlands). 2019;137:113–22.CrossRefPubMed Gelatti ACZ, Drilon A, Santini FC. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Lung cancer (Amsterdam Netherlands). 2019;137:113–22.CrossRefPubMed
2.
go back to reference Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA: a cancer journal for clinicians 2021, 71(1):7–33. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA: a cancer journal for clinicians 2021, 71(1):7–33.
3.
go back to reference Page S, Milner-Watts C, Perna M, Janzic U, Vidal N, Kaudeer N, Ahmed M, McDonald F, Locke I, Minchom A, et al. Systemic treatment of brain metastases in non-small cell lung cancer. Eur J cancer (Oxford England: 1990). 2020;132:187–98.CrossRef Page S, Milner-Watts C, Perna M, Janzic U, Vidal N, Kaudeer N, Ahmed M, McDonald F, Locke I, Minchom A, et al. Systemic treatment of brain metastases in non-small cell lung cancer. Eur J cancer (Oxford England: 1990). 2020;132:187–98.CrossRef
4.
go back to reference Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.CrossRefPubMed Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.CrossRefPubMed
5.
go back to reference Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167–77.CrossRefPubMed Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167–77.CrossRefPubMed
6.
go back to reference Thomas NJ, Myall NJ, Sun F, Patil T, Mushtaq R, Yu C, Sinha S, Pollom EL, Nagpal S, Camidge DR, et al. Brain metastases in EGFR- and ALK-Positive NSCLC: outcomes of central nervous system-penetrant tyrosine kinase inhibitors alone Versus in Combination with Radiation. J Thorac Oncology: Official Publication Int Association Study Lung Cancer. 2022;17(1):116–29.CrossRef Thomas NJ, Myall NJ, Sun F, Patil T, Mushtaq R, Yu C, Sinha S, Pollom EL, Nagpal S, Camidge DR, et al. Brain metastases in EGFR- and ALK-Positive NSCLC: outcomes of central nervous system-penetrant tyrosine kinase inhibitors alone Versus in Combination with Radiation. J Thorac Oncology: Official Publication Int Association Study Lung Cancer. 2022;17(1):116–29.CrossRef
7.
go back to reference Hughes RT, McTyre ER, LeCompte M, Cramer CK, Munley MT, Laxton AW, Tatter SB, Ruiz J, Pasche B, Watabe K, et al. Clinical outcomes of upfront stereotactic radiosurgery alone for patients with 5 to 15 brain metastases. Neurosurgery. 2019;85(2):257–63.CrossRefPubMed Hughes RT, McTyre ER, LeCompte M, Cramer CK, Munley MT, Laxton AW, Tatter SB, Ruiz J, Pasche B, Watabe K, et al. Clinical outcomes of upfront stereotactic radiosurgery alone for patients with 5 to 15 brain metastases. Neurosurgery. 2019;85(2):257–63.CrossRefPubMed
8.
go back to reference Kayama T, Sato S, Sakurada K, Mizusawa J, Nishikawa R, Narita Y, Sumi M, Miyakita Y, Kumabe T, Sonoda Y et al. Effects of surgery with salvage stereotactic radiosurgery versus surgery with whole-brain Radiation Therapy in patients with one to four brain metastases (JCOG0504): a phase III, Noninferiority, Randomized Controlled Trial. J Clin Oncology: Official J Am Soc Clin Oncol 2018:Jco2018786186. Kayama T, Sato S, Sakurada K, Mizusawa J, Nishikawa R, Narita Y, Sumi M, Miyakita Y, Kumabe T, Sonoda Y et al. Effects of surgery with salvage stereotactic radiosurgery versus surgery with whole-brain Radiation Therapy in patients with one to four brain metastases (JCOG0504): a phase III, Noninferiority, Randomized Controlled Trial. J Clin Oncology: Official J Am Soc Clin Oncol 2018:Jco2018786186.
9.
go back to reference Nadler E, Vasudevan A, Wang Y, Ogale S. Real-world patterns of biomarker testing and targeted therapy in de novo metastatic non-small cell lung cancer patients in the US oncology network. Cancer Treat Res Commun. 2022;31:100522.CrossRefPubMed Nadler E, Vasudevan A, Wang Y, Ogale S. Real-world patterns of biomarker testing and targeted therapy in de novo metastatic non-small cell lung cancer patients in the US oncology network. Cancer Treat Res Commun. 2022;31:100522.CrossRefPubMed
10.
go back to reference Wu Y, Verma V, Liang F, Lin Q, Zhou Z, Wang Z, Wang Y, Wang J, Chang JY. Local consolidative therapy Versus systemic therapy alone for metastatic non-small cell Lung Cancer: a systematic review and Meta-analysis. Int J Radiat Oncol Biol Phys. 2022;114(4):635–44.CrossRefPubMed Wu Y, Verma V, Liang F, Lin Q, Zhou Z, Wang Z, Wang Y, Wang J, Chang JY. Local consolidative therapy Versus systemic therapy alone for metastatic non-small cell Lung Cancer: a systematic review and Meta-analysis. Int J Radiat Oncol Biol Phys. 2022;114(4):635–44.CrossRefPubMed
11.
go back to reference Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J cancer Res. 2015;5(9):2892–911.PubMedPubMedCentral Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J cancer Res. 2015;5(9):2892–911.PubMedPubMedCentral
12.
go back to reference Johung KL, Yeh N, Desai NB, Williams TM, Lautenschlaeger T, Arvold ND, Ning MS, Attia A, Lovly CM, Goldberg S, et al. Extended survival and prognostic factors for patients with ALK-Rearranged non-small-cell Lung Cancer and Brain Metastasis. J Clin Oncology: Official J Am Soc Clin Oncol. 2016;34(2):123–9.CrossRef Johung KL, Yeh N, Desai NB, Williams TM, Lautenschlaeger T, Arvold ND, Ning MS, Attia A, Lovly CM, Goldberg S, et al. Extended survival and prognostic factors for patients with ALK-Rearranged non-small-cell Lung Cancer and Brain Metastasis. J Clin Oncology: Official J Am Soc Clin Oncol. 2016;34(2):123–9.CrossRef
13.
go back to reference Rangachari D, Yamaguchi N, VanderLaan PA, Folch E, Mahadevan A, Floyd SR, Uhlmann EJ, Wong ET, Dahlberg SE, Huberman MS, et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung cancer (Amsterdam Netherlands). 2015;88(1):108–11.CrossRefPubMed Rangachari D, Yamaguchi N, VanderLaan PA, Folch E, Mahadevan A, Floyd SR, Uhlmann EJ, Wong ET, Dahlberg SE, Huberman MS, et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung cancer (Amsterdam Netherlands). 2015;88(1):108–11.CrossRefPubMed
14.
go back to reference Noé J, Lovejoy A, Ou SI, Yaung SJ, Bordogna W, Klass DM, Cummings CA, Shaw AT. ALK Mutation Status before and after Alectinib Treatment in locally Advanced or metastatic ALK-Positive NSCLC: pooled analysis of two prospective trials. J Thorac Oncology: Official Publication Int Association Study Lung Cancer. 2020;15(4):601–8.CrossRef Noé J, Lovejoy A, Ou SI, Yaung SJ, Bordogna W, Klass DM, Cummings CA, Shaw AT. ALK Mutation Status before and after Alectinib Treatment in locally Advanced or metastatic ALK-Positive NSCLC: pooled analysis of two prospective trials. J Thorac Oncology: Official Publication Int Association Study Lung Cancer. 2020;15(4):601–8.CrossRef
15.
16.
go back to reference Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, Beal K, Amini A, Patil T, Kavanagh BD, et al. Management of brain metastases in tyrosine kinase Inhibitor-Naïve epidermal growth factor receptor-mutant non-small-cell Lung Cancer: a retrospective multi-institutional analysis. J Clin Oncology: Official J Am Soc Clin Oncol. 2017;35(10):1070–7.CrossRef Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, Beal K, Amini A, Patil T, Kavanagh BD, et al. Management of brain metastases in tyrosine kinase Inhibitor-Naïve epidermal growth factor receptor-mutant non-small-cell Lung Cancer: a retrospective multi-institutional analysis. J Clin Oncology: Official J Am Soc Clin Oncol. 2017;35(10):1070–7.CrossRef
17.
go back to reference Yang S, Xiao J, Liu Q, Zhang Y, Bi N, Huang X, Chen X, Wang K, Ma Y, Deng L, et al. The sequence of intracranial radiotherapy and systemic treatment with tyrosine kinase inhibitors for Gene-Driven Non-small Cell Lung Cancer Brain metastases in the targeted treatment era: a 10-Year single-center experience. Front Oncol. 2021;11:732883.CrossRefPubMedPubMedCentral Yang S, Xiao J, Liu Q, Zhang Y, Bi N, Huang X, Chen X, Wang K, Ma Y, Deng L, et al. The sequence of intracranial radiotherapy and systemic treatment with tyrosine kinase inhibitors for Gene-Driven Non-small Cell Lung Cancer Brain metastases in the targeted treatment era: a 10-Year single-center experience. Front Oncol. 2021;11:732883.CrossRefPubMedPubMedCentral
18.
go back to reference Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, et al. Stereotactic ablative radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: long-term results of the SABR-COMET phase II randomized trial. J Clin Oncology: Official J Am Soc Clin Oncol. 2020;38(25):2830–8.CrossRef Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, et al. Stereotactic ablative radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: long-term results of the SABR-COMET phase II randomized trial. J Clin Oncology: Official J Am Soc Clin Oncol. 2020;38(25):2830–8.CrossRef
19.
go back to reference Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, Bhatt A, Jensen AW, Brown PD, Shih H, 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):655–61.CrossRefPubMed Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, Bhatt A, Jensen AW, Brown PD, Shih H, 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):655–61.CrossRefPubMed
20.
go back to reference Balasubramanian SK, Sharma M, Venur VA, Schmitt P, Kotecha R, Chao ST, Suh JH, Angelov L, Mohammadi AM, Vogelbaum MA, et al. Impact of EGFR mutation and ALK rearrangement on the outcomes of non-small cell lung cancer patients with brain metastasis. Neurooncology. 2020;22(2):267–77. Balasubramanian SK, Sharma M, Venur VA, Schmitt P, Kotecha R, Chao ST, Suh JH, Angelov L, Mohammadi AM, Vogelbaum MA, et al. Impact of EGFR mutation and ALK rearrangement on the outcomes of non-small cell lung cancer patients with brain metastasis. Neurooncology. 2020;22(2):267–77.
21.
go back to reference Bodensohn R, Kaempfel AL, Boulesteix AL, Orzelek AM, Corradini S, Fleischmann DF, Forbrig R, Garny S, Hadi I, Hofmaier J, et al. Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4–10 brain metastases: a nonrandomized controlled trial. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology. 2023;186:109744.CrossRefPubMed Bodensohn R, Kaempfel AL, Boulesteix AL, Orzelek AM, Corradini S, Fleischmann DF, Forbrig R, Garny S, Hadi I, Hofmaier J, et al. Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4–10 brain metastases: a nonrandomized controlled trial. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology. 2023;186:109744.CrossRefPubMed
22.
go back to reference Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, et al. First-line lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020;383(21):2018–29.CrossRefPubMed Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, et al. First-line lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020;383(21):2018–29.CrossRefPubMed
23.
go back to reference Cooper AJ, Sequist LV, Lin JJ. Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management. Nat Reviews Clin Oncol. 2022;19(8):499–514.CrossRef Cooper AJ, Sequist LV, Lin JJ. Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management. Nat Reviews Clin Oncol. 2022;19(8):499–514.CrossRef
24.
go back to reference Tatineni V, O’Shea PJ, Ozair A, Khosla AA, Saxena S, Rauf Y, Jia X, Murphy ES, Chao ST, Suh JH et al. First- versus third-generation EGFR tyrosine kinase inhibitors in EGFR-Mutated Non-small Cell Lung Cancer patients with brain metastases. Cancers 2023, 15(8). Tatineni V, O’Shea PJ, Ozair A, Khosla AA, Saxena S, Rauf Y, Jia X, Murphy ES, Chao ST, Suh JH et al. First- versus third-generation EGFR tyrosine kinase inhibitors in EGFR-Mutated Non-small Cell Lung Cancer patients with brain metastases. Cancers 2023, 15(8).
25.
go back to reference Zhao Y, Li S, Yang X, Chu L, Wang S, Tong T, Chu X, Yu F, Zeng Y, Guo T, et al. Overall survival benefit of osimertinib and clinical value of upfront cranial local therapy in untreated EGFR-mutant nonsmall cell lung cancer with brain metastasis. Int J Cancer. 2022;150(8):1318–28.CrossRefPubMed Zhao Y, Li S, Yang X, Chu L, Wang S, Tong T, Chu X, Yu F, Zeng Y, Guo T, et al. Overall survival benefit of osimertinib and clinical value of upfront cranial local therapy in untreated EGFR-mutant nonsmall cell lung cancer with brain metastasis. Int J Cancer. 2022;150(8):1318–28.CrossRefPubMed
26.
go back to reference Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, et al. Osimertinib in untreated EGFR-Mutated Advanced Non-small-cell Lung Cancer. N Engl J Med. 2018;378(2):113–25.CrossRefPubMed Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, et al. Osimertinib in untreated EGFR-Mutated Advanced Non-small-cell Lung Cancer. N Engl J Med. 2018;378(2):113–25.CrossRefPubMed
Metadata
Title
Analysis of the efficacy of upfront brain radiotherapy versus deferred radiotherapy for EGFR/ALK-positive non-small cell lung cancer with brain metastases: a retrospective study
Authors
Jing Qian
Zelai He
Ying Wu
Hongwei Li
Qun Zhang
Xianming Li
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-11868-9

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