Development of symptomatic brain metastases after chemoradiotherapy for stage III non-small cell lung cancer: Does the type of chemotherapy regimen matter?

Lung Cancer. 2016 Nov:101:68-75. doi: 10.1016/j.lungcan.2016.09.008. Epub 2016 Sep 9.

Abstract

Objectives: Symptomatic brain metastases (BM) occur frequently after chemoradiotherapy (CRT) for stage III NSCLC. Aim of the current study was to determine whether the specific chemotherapy used in a CRT regimen influences BM development.

Materials and methods: Retrospective multicenter study including all consecutive stage III NSCLC who completed CRT. Primary endpoints: symptomatic BM development, whether this was the only site of first relapse. Differences between regimens were assessed with a logistic regression model including known BM risk factors and the specific chemotherapy: concurrent versus sequential (cCRT/sCRT), within cCRT: daily low dose cisplatin (LDC)-cyclic dose polychemotherapy; LDC-(non-)taxane cyclic dose; LDC-polychemotherapy subgroups of ≥50 patients.

Results: Between January 2006 and June 2014, 838 patients were eligible (737 cCRT, 101 sCRT). 18.2% developed symptomatic BM, 8.0% had BM as only site of first relapse. BM patients were significantly younger, female, had more advanced N-stage and had adenocarcinoma histology. In both cCRT and sCRT BM were found in 18% (p=0.904). In cyclic dose cCRT (N=346) and LDC (N=391) BM were found in 18.8% and 17.9%, respectively (p=0.757). In 7.2% and 8.7%, respectively, BM were the only site of first relapse (p=0.463). The chemotherapy used (cCRT versus sCRT) had no influence on BM development, not for all brain relapses nor as only site of first relapse (OR 0.88 (p=0.669), OR 0.93 (p=0.855), respectively). LDC versus cyclic dose cCRT was not significantly different: neither for all brain relapses nor as only site of first relapse (OR 0.96 (p=0.819), OR 1.21 (p=0.498), respectively). Comparable results were found for LDC versus cyclic dose non-taxane (N=277) and cyclic dose taxane regimens (N=69) and for cCRT regimens with ≥50 patients (LDC versus cisplatin/etoposide (N=188), cisplatin/vinorelbin (N=65), weekly cisplatin/docetaxel (N=60)).

Conclusion: approximately 18% developed symptomatic BM after stage III diagnosis, not dependent on type of chemotherapy regimen used within a CRT treatment.

Keywords: Chemoradiation; Chemotherapy; NSCLC; Stage III; Symptomatic brain metastases.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Brain / pathology
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / secondary*
  • Bridged-Ring Compounds / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / complications
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Chemoradiotherapy / methods*
  • Cisplatin
  • Combined Modality Therapy
  • Docetaxel
  • Etoposide
  • Female
  • Humans
  • Lung Neoplasms / complications
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Retrospective Studies
  • Risk Factors
  • Survival Analysis
  • Taxoids / therapeutic use
  • Treatment Outcome
  • Vinblastine / analogs & derivatives
  • Vinblastine / therapeutic use
  • Vinorelbine

Substances

  • Antineoplastic Agents
  • Bridged-Ring Compounds
  • Taxoids
  • Docetaxel
  • taxane
  • Vinblastine
  • Etoposide
  • Cisplatin
  • Vinorelbine

Supplementary concepts

  • VP-P protocol