title: Development of symptomatic brain metastases after chemoradiotherapy for stage III non-small cell lung cancer: Does the type of chemotherapy regimen matter?
abstract: 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.
  
  
  
  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.
  
  
  
  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)).
  
  
  
  approximately 18% developed symptomatic BM after stage III diagnosis, not dependent on type of chemotherapy regimen used within a CRT treatment.
authors: Dept. of Pulmonary Diseases, GROW ⿿ School for Oncology and Developmental Biology, Maastricht University Medical Center+, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: lizza.hendriks@mumc.nl.
authors: Lizza E L
authors: LEL
authors: Hendriks
authors: Dept. of Pulmonary Diseases, Zuyderland Medical Center location Heerlen, PO Box 5500, 6130 MB Sittard-Geleen, The Netherlands. Electronic address: a.brouns@zuyderland.nl.
authors: -Anita J W M
authors: -JWM
authors: Brouns
authors: Dept. of Pulmonary Diseases, Jeroen Bosch Hospital, PO Box 90153, 5200 ME ⿿s Hertogenbosch, The Netherlands. Electronic address: M.Amini@jbz.nl.
authors: Mohammad
authors: M
authors: Amini
authors: Dept. of Thoracic Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, PO Box 90203, 1006 BE Amsterdam, The Netherlands. Electronic address: W.uyterlinde@nki.nl.
authors: Wilma
authors: W
authors: Uyterlinde
authors: Dept. of Radiation Oncology, Radboud University Hospital, PO Box 9100, 6500 HA Nijmegen, The Netherlands. Electronic address: Robin.Wijsman@radboudumc.nl.
authors: Robin
authors: R
authors: Wijsman
authors: Dept. of Radiation Oncology, Radboud University Hospital, PO Box 9100, 6500 HA Nijmegen, The Netherlands. Electronic address: Jan.Bussink@radboudumc.nl.
authors: Jan
authors: J
authors: Bussink
authors: Dept. of Pulmonary Diseases, Jeroen Bosch Hospital, PO Box 90153, 5200 ME ⿿s Hertogenbosch, The Netherlands. Electronic address: b.biesma@jbz.nl.
authors: Bonne
authors: B
authors: Biesma
authors: Dept. of Radiation Oncology, Institute Verbeeten, PO Box 90120, 5000 LA Tilburg, The Netherlands. Electronic address: oei@bvi.nl.
authors: S Bing
authors: SB
authors: Oei
authors: Dept. of Pulmonary Diseases, Isala Clinics, PO Box 10400, 8000 GK Zwolle, The Netherlands. Electronic address: j.a.stigt@isala.nl.
authors: Jos-A
authors: JA
authors: Stigt
authors: Dept. of Pulmonary Diseases, Zuyderland Medical Center location Heerlen, PO Box 5500, 6130 MB Sittard-Geleen, The Netherlands. Electronic address: g.bootsma@zuyderland.nl.
authors: Gerben P
authors: GP
authors: Bootsma
authors: Dept. of Radiation Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, PO Box 90203, 1006 BE Amsterdam, The Netherlands. Electronic address: j.belderbos@nki.nl.
authors: José S A
authors: JSA
authors: Belderbos
authors: Dept. of Radiation Oncology (MAASTRO Clinic), GROW ⿿ School for Oncology and Developmental Biology, Maastricht University Medical Center+, PO Box 3035, 6202 NA Maastricht, The Netherlands. Electronic address: dirk.deruysscher@maastro.nl.
authors: Dirk K M
authors: DKM
authors: De Ruysscher
authors: Dept. of Thoracic Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, PO Box 90203, 1006 BE Amsterdam, The Netherlands. Electronic address: m.vd.heuvel@nki.nl.
authors: Michel M
authors: MM
authors: Van den Heuvel
authors: Dept. of Pulmonary Diseases, GROW ⿿ School for Oncology and Developmental Biology, Maastricht University Medical Center+, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: a.dingemans@mumc.nl.
authors: Anne-Marie C
authors: AC
authors: Dingemans
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005047:Etoposide; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome; D014747:Vinblastine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; D000077143:Docetaxel; C080625:taxane; D014747:Vinblastine; D005047:Etoposide; D002945:Cisplatin; D000077235:Vinorelbine
keywords: Chemoradiation; Chemotherapy; NSCLC; Stage III; Symptomatic brain metastases