Mature results of a phase II trial on individualised accelerated radiotherapy based on normal tissue constraints in concurrent chemo-radiation for stage III non-small cell lung cancer

Angela van Baardwijk*, Bart Reymen, Stofferinus Wanders, Jacques Borger, Michel Ollers, Anne-Marie C. Dingemans, Gerben Bootsma, Wiel Geraedts, Cordula Pitz, Ragnar Lunde, Frank Peters, Philippe Lambin, Dirk De Ruysscher

*Corresponding author for this work

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Abstract

Background: Sequential chemotherapy and individualised accelerated radiotherapy (INDAR) has been shown to be effective in non-small cell lung cancer (NSCLC), allowing delivering of high biological doses. We therefore performed a phase II trial (clinicaltrials. gov; NCT00572325) investigating the same strategy in concurrent chemo-radiation in stage III NSCLC. Methods: 137 stage III patients fit for concurrent chemo-radiation (PS 0-2; FEV1 and DLCO >= 30%) were included from April 2006 till December 2009. An individualised prescribed dose based on normal tissue dose constraints was applied: mean lung dose (MLD) 19 Gy, spinal cord 54 Gy, brachial plexus 66 Gy, central structures 74 Gy. A total dose between 51 and 69 Gy was delivered in 1.5 Gy BID up to 45 Gy, followed by 2 Gy QD. Radiotherapy was started at the 2nd or 3rd course of chemotherapy. Primary end-point was overall survival (OS) and secondary end-point toxicity common terminology criteria for adverse events v3.0 (CTCAEv3.0). Findings: The median tumour volume was 76.4 +/- 94.1 cc; 49.6% of patients had N2 and 32.1% N3 disease. The median dose was 65.0 +/- 6.0 Gy delivered in 35 +/- 5.7 days. Six patients (4.4%) did not complete radiotherapy. With a median follow-up of 30.9 months, the median OS was 25.0 months (2-year OS 52.4%). Severe acute toxicity (>= G3, 35.8%) consisted mainly of G3 dysphagia during radiotherapy (25.5%). Severe late toxicity (>= G3) was observed in 10 patients (7.3%). Interpretation: INDAR in concurrent chemo-radiation based on normal tissue constraints is feasible, even in patients with large tumour volumes and multi-level N2-3 disease, with acceptable severe late toxicity and promising 2-year survival.
Original languageEnglish
Pages (from-to)2339-2346
JournalEuropean Journal of Cancer
Volume48
Issue number15
DOIs
Publication statusPublished - Oct 2012

Keywords

  • Non-small cell lung cancer
  • Concurrent chemo-radiation
  • Normal tissue constraints
  • Individualised
  • Combined modality

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