PMID- 23510803
OWN - NLM
STAT- MEDLINE
DCOM- 20140409
LR  - 20181202
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 49
IP  - 9
DP  - 2013 Jun
TI  - Accelerated hyperfractionated radiotherapy within trimodality therapy concepts 
      for stage IIIA/B non-small cell lung cancer: Markedly higher rate of pathologic 
      complete remissions than with conventional fractionation.
PG  - 2107-15
LID - S0959-8049(13)00162-7 [pii]
LID - 10.1016/j.ejca.2013.02.030 [doi]
AB  - BACKGROUND: Radiation dose escalation within definitive radiochemotherapy 
      (RTx/CTx) was not successful for stage III non-small cell lung cancer (NSCLC) 
      using conventional fractionation (CF). Accelerated-hyperfractionation (AHF) 
      counteracts tumour cell repopulation. In this observational study, the effects of 
      neoadjuvant RTx/CTx using AHF or CF were studied by histopathology and using the 
      survival end-point. METHODS: Data from all consecutive lung cancer patients 
      treated with neoadjuvant RTx/CTx and thoracotomy between 08/2000 and 06/2012 were 
      analysed. Patients received induction chemotherapy (cisplatin-doublets) followed 
      by concurrent RTx/CTx using AHF (45 Gy/1.5 Gy bid) or CF-RTx (46 Gy/2 Gy qd). For 
      estimating the AHF versus CF treatment effects, multivariate analysis (MA), 
      propensity score weighting (PS), and instrumental variable analysis (IV) were 
      used. FINDINGS: 239 patients were treated, median age 58 (34-78)years, stage 
      II/IIIA/B: 19/88/132, squamous cell/adenocarcinomas/other: 98/107/34; AHF/CF-RTx 
      112/127 patients. No significant differences between both groups, in tumour 
      related factors (age, gender, Charlson comorbiditiy score, lactate dehydrogenase 
      (LDH), haemoglobin, stage, histopathology and grading), existed. Crude rates of 
      pathologic complete responses (pCR) in AHF and CF groups were 37% and 24% 
      respectively. The dose fractionation effect on pCR was significant (p ⩽ 0.006, PS 
      and IV analyses). There was a significant dependence of pCR on biologically 
      effective dose. pCR also depended on treatment time (MA, p = 0.04; PS, p = 
      0.0004). Median treatment time was 22 d or 31 d using AHF or CF (p<0.0001), 
      respectively. Adenocarcinomas had lower pCR rates in comparison to other 
      histologies. Five-year survival of patients with pCR was 65%, independent of the 
      fractionation. INTERPRETATION: This large monoinstitutional analysis demonstrates 
      an increased effect of AHF on pCR of lung cancer which modifies overall survival.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Pottgen, C
AU  - Pottgen C
AD  - Department of Radiotherapy, West German Tumour Centre, University of 
      Duisburg-Essen, Essen, Germany. Electronic address: 
      christoph.poettgen@uk-essen.de.
FAU - Eberhardt, W
AU  - Eberhardt W
AD  - Department of Internal Medicine (Cancer Research), West German Tumour Centre, 
      University of Duisburg-Essen, Essen, Germany.
FAU - Graupner, B
AU  - Graupner B
AD  - Department of Radiotherapy, West German Tumour Centre, University of 
      Duisburg-Essen, Essen, Germany.
FAU - Theegarten, D
AU  - Theegarten D
AD  - Institute of Pathology and Neuropathology, West German Tumour Centre, University 
      of Duisburg-Essen, Essen, Germany.
FAU - Gauler, T
AU  - Gauler T
AD  - Department of Internal Medicine (Cancer Research), West German Tumour Centre, 
      University of Duisburg-Essen, Essen, Germany.
FAU - Freitag, L
AU  - Freitag L
AD  - Department of Interventional Pulmonology, Ruhrlandklinik, West German Tumour 
      Centre, Essen, Germany.
FAU - Abu Jawad, J
AU  - Abu Jawad J
AD  - Department of Radiotherapy, West German Tumour Centre, University of 
      Duisburg-Essen, Essen, Germany.
FAU - Wohlschlaeger, J
AU  - Wohlschlaeger J
AD  - Institute of Pathology and Neuropathology, West German Tumour Centre, University 
      of Duisburg-Essen, Essen, Germany.
FAU - Welter, S
AU  - Welter S
AD  - Department of Thoracic Surgery, Ruhrlandklinik, West German Tumour Centre, Essen, 
      Germany.
FAU - Stamatis, G
AU  - Stamatis G
AD  - Department of Thoracic Surgery, Ruhrlandklinik, West German Tumour Centre, Essen, 
      Germany.
FAU - Stuschke, M
AU  - Stuschke M
AD  - Department of Radiotherapy, West German Tumour Centre, University of 
      Duisburg-Essen, Essen, Germany.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Observational Study
DEP - 20130316
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/mortality/*therapy
MH  - Chemoradiotherapy, Adjuvant/*methods/mortality
MH  - Cisplatin/administration & dosage
MH  - Combined Modality Therapy
MH  - Dose Fractionation, Radiation
MH  - Etoposide/administration & dosage
MH  - Female
MH  - Humans
MH  - Induction Chemotherapy/methods
MH  - Lung Neoplasms/mortality/*therapy
MH  - Male
MH  - Middle Aged
MH  - Propensity Score
MH  - Treatment Outcome
EDAT- 2013/03/21 06:00
MHDA- 2014/04/10 06:00
CRDT- 2013/03/21 06:00
PHST- 2012/11/26 00:00 [received]
PHST- 2013/02/01 00:00 [revised]
PHST- 2013/02/24 00:00 [accepted]
PHST- 2013/03/21 06:00 [entrez]
PHST- 2013/03/21 06:00 [pubmed]
PHST- 2014/04/10 06:00 [medline]
AID - S0959-8049(13)00162-7 [pii]
AID - 10.1016/j.ejca.2013.02.030 [doi]
PST - ppublish
SO  - Eur J Cancer. 2013 Jun;49(9):2107-15. doi: 10.1016/j.ejca.2013.02.030. Epub 2013 
      Mar 16.