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Prognostic factors and survival after whole-brain radiotherapy for initial brain metastases arising from non-small cell lung cancer

Published online by Cambridge University Press:  06 April 2021

Yukinori Okada Open the ORCID record for Yukinori Okada [Opens in a new window] ,
Mariko Kobayashi ,
Mio Shinozaki ,
Tatsuyuki Abe  and
Naoki Nakamura
Yukinori Okada*
Affiliation:
Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan
Mariko Kobayashi
Affiliation:
Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan
Mio Shinozaki
Affiliation:
Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan
Tatsuyuki Abe
Affiliation:
Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan
Naoki Nakamura
Affiliation:
Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan
*
Author for correspondence: Yukinori Okada, Department of Radiology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan. E-mail: [email protected]
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Abstract

Aim:

To identify prognostic factors and investigate patient survival after whole-brain radiotherapy (WBRT) for initial brain metastases arising from non-small cell lung cancer (NSCLC).

Methods:

Patients diagnosed with NSCLC between 1 January 2010 and 30 September 2019, and who received WBRT upon first developing a brain metastasis, were investigated. Overall survival was determined as related to age, sex, duration between initial examination and brain metastasis detection, stage at the first examination, presence of metastases outside the brain, blood analysis findings, brain metastasis symptoms, radiotherapy dose and completion, imaging findings, therapeutic course of chemotherapy and/or radiation therapy, histological type, and gene mutation status.

Results:

Thirty-one consecutive patients (20 men and 11 women) with a mean age of 63·8 years and median survival of 129 days were included. Multivariate analysis with stepwise testing was performed to investigate differences in survival according to gene mutation status, lactate dehydrogenase (LDH) level, irradiation dose, WBRT completion and Stage status. Of these, a statistically significant difference in survival was observed in patients with gene mutation status (hazard ratio: 0·31, 95% CI: 0·11–0·86, p = 0·025), LDH levels <230 vs. ≥230 IU/L (hazard ratio: 4·08, 95% CI: 1·45–11·5, p < 0·01) received 30 Gy, 30 Gy/10 fractions to 35 Gy/14 fractions, and 37·5 Gy/15 fractions (hazard ratio: 0·26, 95% CI: 0·09–0·71, p < 0·01), and stage IV versus non-stage IV (hazard ratio: 0·13, 95 CI:0·02–0·64, p < 0·01)

Findings:

Gene mutation, LDH, radiation dose and Stage are prognostic factors for patients with initial brain metastases who are treated with WBRT.

Keywords

brain metastasislactate dehydrogenasenon-small cell lung cancerwhole-brain radiotherapy
Type
Original Article
Information
Journal of Radiotherapy in Practice , Volume 21 , Issue 3 , September 2022 , pp. 360 - 365
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Byers, L A, Rudin, C M. Small cell lung cancer: where do we go from here. Cancer 2015; 121: 664–672.CrossRefGoogle Scholar
Nichols, L, Saunders, R, Knollmann, F D. Causes of death of patients with lung cancer. Arch Pathol Lab Med 2012; 136: 1552–1557.CrossRefGoogle ScholarPubMed
Aoyama, H, Tago, M, Kato, N et al. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys 2007; 68: 1388–1395.CrossRefGoogle ScholarPubMed
Sahgal, A, Aoyama, H, Kocher, M et al. Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol Phys 2015; 91: 710–717.CrossRefGoogle ScholarPubMed
Gondi, V, Pugh, S L, Tome, W A 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 Clin Oncol 2014; 32: 3810–3816.CrossRefGoogle ScholarPubMed
Ma, T M, Grimm, J, McIntyre, R et al. A prospective evaluation of hippocampal radiation dose volume effects and memory deficits following cranial irradiation. Radiother Oncol 2017; 125: 234–240.CrossRefGoogle ScholarPubMed
Miyazawa, K, Shikama, M, Okazaki, S, Koyama, T, Takahashi, T, Kato, S. Predicting prognosis of short survival time after palliative whole-brain radiotherapy. J Radiat Res 2018; 59: 43–49.CrossRefGoogle ScholarPubMed
Nieder, C, Norum, J, Dalhaung, A, Aandahl, G, Pawinski, A. Radiotherapy versus best supportive care in patients with brain metastases and adverse prognostic factors. Clin Exp Met 2013; 30: 723–729.CrossRefGoogle ScholarPubMed
Nieder, C, Norum, J, Dalhaug, A, Aandahl, G, Engljähringer, K. Best supportive care in patients with brain metastases and adverse prognostic factors: development of improved decision aids. Support Care Cancer 2013; 21: 2671–2678.CrossRefGoogle ScholarPubMed
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. BMC Cancer 2019; 19: 1104.CrossRefGoogle ScholarPubMed
Harada, H, Asakura, H, Ogawa, H et al. Prognostic factors in patients with brain metastasis from non-small cell lung cancer treated with whole-brain radiotherapy. J Cancer Res Ther 2016; 12: 267–270.CrossRefGoogle ScholarPubMed
Li, B, Li, C, Guo, M et al. Predictive value of LDH kinetics in bevacizumab treatment and survival of patients with advanced NSCLC. Onco Targets Ther 2018; 11: 6287–6294.CrossRefGoogle ScholarPubMed
Deng, L, Zhang, Z, Meng, Yu, Zhou, Y, Li, W. Higher pretreatment lactate dehydrogenase concentration predicts worse overall survival in patients with lung cancer. Medicine 2018; 97: e12524.CrossRefGoogle ScholarPubMed
Lee, D S, Park, K R, Kim, S J et al. Serum lactate dehydrogenase levels at presentation in stage IV non-small cell lung cancer: predictive value of metastases and relation to survival outcomes. Tumour Biol 2016; 37: 619–625.CrossRefGoogle ScholarPubMed
Zhang, Z, Li, Y, Yan, X et al. Pretreatment lactate dehydrogenase may predict outcome of advanced non small-cell lung cancer patients treated with immune checkpoint inhibitors: a meta-analysis. Cancer Med 2019; 8: 1467–1473.CrossRefGoogle ScholarPubMed
Koukourakis, M I, Giatromanolaki, A, Sivridis, E et al. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer 2003; 89: 877–885.CrossRefGoogle ScholarPubMed
Iwasaki, A, Shirakusa, T, Yoshinaga, Y, Enatsu, S, Yamamoto, M. Evaluation of the treatment of non-small cell lung cancer with brain metastasis and the role of risk score as a survival predictor. Eur J Cardiothorac Surg 2004; 26: 488–493.CrossRefGoogle ScholarPubMed
Doi, H, Nakamatsu, K, Anami, S et al. Neutrophil-to-lymphocyte ratio predicts survival after whole-brain radiotherapy in non-small cell lung cancer. In Vivo 2019; 33: 195–201.CrossRefGoogle ScholarPubMed
Li, Hu, Wang, W, Yang, X et al. The clinical prognostic value of the neutrophil-to-lymphocyte ratio in brain metastases from non-small cell lung cancer-harboring EGFR Mutations. Cancer Manag Res 2020; 12: 5659–5665.CrossRefGoogle ScholarPubMed
Anami, S, Doi, H, Nakamatsu, K et al. Serum lactate dehydrogenase predicts survival in small-cell lung cancer patients with brain metastases that were treated with whole-brain radiotherapy. J Radiat Res 2019; 60: 257–263.CrossRefGoogle ScholarPubMed
Okada, Y, Kobayashi, M, Shinozaki, M, Abe, T, Nakamura, N. Prognostic factors of primary brain metastasis from SCLC treated by whole-brain radiotherapy. J Radiother Pract 2020; DOI: 10.1017/S1460396920000710.Google Scholar
Okada, Y, Kobayashi, M, Shinozaki, M et al. Survival time and prognostic factors after whole-brain radiotherapy of brain metastases from of breast cancer. Acta Radiol Open 2020; 9: 2058460120938744.Google ScholarPubMed
Huang, Z, Hu, C, Tong, Y, Fan, Z, Zhao, C. Construction of a nomogram to predict the prognosis of non-small-cell lung cancer with brain metastases. Medicine (Baltimore) 2020; 99: e21339.CrossRefGoogle ScholarPubMed
Wang, T J C, Saad, S, Qureshi, Y H et al. Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation? Neuro Oncol 2015; 17: 1022–1028.CrossRefGoogle Scholar
Magnuson, W J, Lester-Coll, N H, Wu, A J 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 Oncol 2017; 35: 1070–1077.CrossRefGoogle ScholarPubMed
Mak, K S, Gainor, J F, Niemierko, A et al. Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases. Neuro Oncol 2015; 17: 296–302.CrossRefGoogle ScholarPubMed
Fleschutz, K, Walter, L, Leistne, R et al. ALK Inhibitors Do Not Increase Sensitivity to Radiation in EML4-ALK Non-small Cell Lung Cancer. Anticancer Res 2020; 40: 4937–4946.CrossRefGoogle Scholar
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. Int J Radiat Oncol Biol Phys 1997; 37: 745–751.CrossRefGoogle ScholarPubMed
Sperduto, P W, Yang, T J, Beal, K et al. Estimating survival in patients with lung cancer and brain metastases: an update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA). JAMA Oncol 2017; 3: 827–831.CrossRefGoogle Scholar
Yang, K, Li, J, Bai, C, Sun, Z, Zhao, L. Efficacy of immune checkpoint inhibitors in non-small-cell lung cancer patients with different metastatic sites: a systematic review and meta-analysis. Front Oncol 2020; 10: 1098.CrossRefGoogle ScholarPubMed