The Effect of Epidermal Growth Factor Receptor Mutation on Intracranial Progression-Free Survival of Non-Small Cell Lung Cancer Patients with Brain Metastasis Underwent Gamma Knife Radiosurgery

Overview

Journal Brain Tumor Res Treat

Date 2020 Oct 29

PMID 33118342

Citations 1

Authors

Seung Hyeon Yang

Hae Yu Kim

Sun Il Lee

Seong Jin Jin

Affiliations

Soon will be listed here.

Abstract

Background: The aim of this study was to survey prognostic factors, particularly those focusing on epidermal growth factor receptor (EGFR) mutations, of patients with non-small cell lung cancer (NSCLC) after Gamma Knife Radiosurgery (GKRS) for metastatic brain tumors.

Methods: We retrospectively reviewed the medical records of 98 patients with NSCLC who underwent GKRS for brain metastases from August 2010 to July 2017. The primary endpoint was progression-free survival (PFS) of the intracranial disease. We analyzed variables such as age, sex, Karnofsky Performance Status, recursive partitioning analysis (RPA) class, smoking status, primary cancer pathology, EGFR mutations, and time to brain metastases as prognostic factors.

Results: The median overall survival (OS) of the patients was 16 months [95% confidence interval (CI), 13-21 months]. Median systemic PFS and intracranial PFS were 9 months (95% CI, 8-11 months) and 11 months (95% CI, 7-14 months), respectively. Kaplan-Meier survival analysis revealed that the patients with EGFR mutations had longer intracranial PFS than those without EGFR mutation (median intracranial PFS: 19 vs. 10 months with =0.01) while they had no benefits in OS and systemic PFS. Furthermore, the patients harboring adenocarcinoma had longer OS (<0.01) and intracranial PFS (<0.01) and the patients with lower RPA class had longer OS (=0.02) and intracranial PFS (=0.03).

Conclusion: EGFR mutations, primary cancer pathology, and RPA class may be proposed as prognostic factors for intracranial PFS in NSCLC patients after GKRS for brain metastasis in this study.

Citing Articles

Whole-Brain Radiotherapy vs. Localized Radiotherapy after Resection of Brain Metastases in the Era of Targeted Therapy: A Retrospective Study.

Koo J, Roh T, Lee S, Heo J, Oh Y, Kim S Cancers (Basel). 2021; 13(18).

PMID: 34572938 PMC: 8472558. DOI: 10.3390/cancers13184711.

References

Porta R, Sanchez-Torres J, Paz-Ares L, Massuti B, Reguart N, Mayo C . Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J. 2010; 37(3):624-31. DOI: 10.1183/09031936.00195609. View

Byeon S, Ham J, Sun J, Lee S, Ahn J, Park K . Analysis of the benefit of sequential cranial radiotherapy in patients with EGFR mutant non-small cell lung cancer and brain metastasis. Med Oncol. 2016; 33(8):97. PMC: 4958121. DOI: 10.1007/s12032-016-0811-3. View

Tini P, Nardone V, Pastina P, Battaglia G, Vinciguerra C, Carfagno T . Perilesional edema in brain metastasis from non-small cell lung cancer (NSCLC) as predictor of response to radiosurgery (SRS). Neurol Sci. 2017; 38(6):975-982. DOI: 10.1007/s10072-017-2876-y. View

Heon S, Yeap B, Britt G, Costa D, Rabin M, Jackman D . Development of central nervous system metastases in patients with advanced non-small cell lung cancer and somatic EGFR mutations treated with gefitinib or erlotinib. Clin Cancer Res. 2010; 16(23):5873-82. PMC: 2999638. DOI: 10.1158/1078-0432.CCR-10-1588. View

Cox J, Scott C, Byhardt R, Emami B, Russell A, Fu K . Addition of chemotherapy to radiation therapy alters failure patterns by cell type within non-small cell carcinoma of lung (NSCCL): analysis of radiation therapy oncology group (RTOG) trials. Int J Radiat Oncol Biol Phys. 1999; 43(3):505-9. DOI: 10.1016/s0360-3016(98)00429-5. View

Shin S, Cooper B, Chachoua A, Butler J, Donahue B, Silverman J . Survival but not brain metastasis response relates to lung cancer mutation status after radiosurgery. J Neurooncol. 2015; 126(3):483-91. DOI: 10.1007/s11060-015-1986-8. View

Aiko N, Shimokawa T, Miyazaki K, Misumi Y, Agemi Y, Ishii M . Comparison of the efficacies of first-generation epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in patients with advanced non-small-cell lung cancer harboring EGFR mutations. BMC Cancer. 2018; 18(1):1012. PMC: 6196437. DOI: 10.1186/s12885-018-4911-7. View

Gounant V, Wislez M, Poulot V, Khalil A, Lavole A, Cadranel J . Subsequent brain metastasis responses to epidermal growth factor receptor tyrosine kinase inhibitors in a patient with non-small-cell lung cancer. Lung Cancer. 2007; 58(3):425-8. DOI: 10.1016/j.lungcan.2007.07.010. View

Zhang J, Yu J, Sun X, Meng X . Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of central nerve system metastases from non-small cell lung cancer. Cancer Lett. 2014; 351(1):6-12. DOI: 10.1016/j.canlet.2014.04.019. View

10.

Fekrazad M, Ravindranathan M, Jones Jr D . Response of intracranial metastases to erlotinib therapy. J Clin Oncol. 2007; 25(31):5024-6. DOI: 10.1200/JCO.2007.13.3751. View

11.

Suh J . Stereotactic radiosurgery for the management of brain metastases. N Engl J Med. 2010; 362(12):1119-27. DOI: 10.1056/NEJMct0806951. View

12.

Heimberger A, Learn C, Archer G, McLendon R, Chewning T, Tuck F . Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa). Clin Cancer Res. 2002; 8(11):3496-502. View

13.

Gerber N, Yamada Y, Rimner A, Shi W, Riely G, Beal K . Erlotinib versus radiation therapy for brain metastases in patients with EGFR-mutant lung adenocarcinoma. Int J Radiat Oncol Biol Phys. 2014; 89(2):322-9. PMC: 5691362. DOI: 10.1016/j.ijrobp.2014.02.022. View

14.

Cho K, Lee M, Kong D, Seol H, Nam D, Sun J . Outcome of gamma knife radiosurgery for metastatic brain tumors derived from non-small cell lung cancer. J Neurooncol. 2015; 125(2):331-8. DOI: 10.1007/s11060-015-1915-x. View

15.

Economopoulou P, Mountzios G . Non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases: role of tyrosine kinase inhibitors (TKIs) and evidence in favor or against their use with concurrent cranial radiotherapy. Transl Lung Cancer Res. 2017; 5(6):588-598. PMC: 5233883. DOI: 10.21037/tlcr.2016.12.06. View

16.

Eichler A, Chung E, Kodack D, Loeffler J, Fukumura D, Jain R . The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol. 2011; 8(6):344-56. PMC: 3259742. DOI: 10.1038/nrclinonc.2011.58. View

17.

Qu J, Wang Y, Xu P, Xiang D, Yang R, Wei W . Clinical efficacy of icotinib in lung cancer patients with different EGFR mutation status: a meta-analysis. Oncotarget. 2017; 8(20):33961-33971. PMC: 5464926. DOI: 10.18632/oncotarget.15475. View

18.

Nathoo N, Chahlavi A, Barnett G, Toms S . Pathobiology of brain metastases. J Clin Pathol. 2005; 58(3):237-42. PMC: 1770599. DOI: 10.1136/jcp.2003.013623. View

19.

Buonerba C, Iaccarino S, Dolce P, Pagliuca M, Izzo M, Scafuri L . Predictors of Outcomes in Patients with EGFR-Mutated Non-Small Cell Lung Cancer Receiving EGFR Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis. Cancers (Basel). 2019; 11(9). PMC: 6770537. DOI: 10.3390/cancers11091259. View

20.

Langer C, Mehta M . Current management of brain metastases, with a focus on systemic options. J Clin Oncol. 2005; 23(25):6207-19. DOI: 10.1200/JCO.2005.03.145. View