title: The efficacy and roles of combining temozolomide with whole brain radiotherapy in protection neurocognitive function and improvement quality of life of non-small-cell lung cancer patients with brain metastases.
abstract: Brain metastasis (BM) is a poor prognostic factor for non-small-cell lung cancer (NSCLC). The efficacy and roles of combining temozolomide (TMZ) with whole brain radiotherapy (WBRT) in protection neurocognitive function (NCF) and improvement quality of life (QOL) were investigated and compared with WBRT alone in the treatment of NSCLC patients with BM.
  
  
  
  A total of 238 NSCLC patients with BM were reviewed and categorized into WBRT plus TMZ (RCT) arm and WBRT alone (RT), respectively. The efficacy was evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model. NCF was assessed by using revised Hopkins Verbal Learning Test (HVLT-R), Controlled Oral Word Association (COWA) test and Trail-making Test (TMT). QOL was assessed by the Functional Assessment of Cancer Treatment-Lung (FACT-L) Chinese version 4.0 questionnaire.
  
  
  
  The average intracranial objective response (ORR) and disease control rate (DCR) for all the patients were 26.9 and 95.8%, respectively. The intracranial ORR and DCR for RCT and RT arm were 34.9% vs. 20.2% (p = 0.01) and 98.4% vs. 92.7% (p = 0.03), respectively. The median intracranial progression-free survival (PFS) and overall survival (OS) of NSCLC patients with BM were 5.2 and 7.3 months, respectively. The median PFS of RCT arm was significantly longer than that of RT arm (5.9 vs. 4.9 months, p = 0.002). The median OS of the RCT arm was also slightly longer than that of the RT arm (8.5 vs. 5.9 months), but without statistical significance (p = 0.11). Multivariate analysis indicated that TMZ was a significant factor for PFS. Statistically significant differences on NCF and QOL were observed between CRT and RT arms at 5 months. RCT showed a trend of toxicities increase compared with RT, however, the toxicities were tolerable and manageable.
  
  
  
  Adding TMZ to WBRT in the treatment of NSCLC patients with BM could improve the intracranial ORR, DCR, and median PFS compared with WBRT alone. Although no remarkable difference on median OS was found, adding TMZ could prevent NCF and QOL from worsening. The side effects increased by adding TMZ, but the difference was not statistical significance and toxicities were well tolerated.
authors.affiliation: Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Baochai
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Huafang
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Hanbin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Shaoran
authors.initials: S
authors.lastname: Fei
authors.affiliation: Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Fei
authors.affiliation: Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Lihao
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, 325000, China. jinxc1979@hotmail.com.
authors.forename: Xiance
authors.initials: X
authors.lastname: Jin
authors.affiliation: Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, Wenzhou, 325000, China. wzxiecongying@163.com.|Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, 325000, China. wzxiecongying@163.com.
authors.forename: Cong-Ying
authors.initials: CY
authors.lastname: Xie
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000556:secondary / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D016371:Cranial Irradiation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019965:Neurocognitive Disorders / Q000517:prevention & control*; D011379:Prognosis; D011788:Quality of Life; D012189:Retrospective Studies; D015996:Survival Rate; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Brain metastases; Neurocognitive function; Non-small-cell lung cancer; Quality of life; Temozolomide; Whole brain radiotherapy