Margriet Kwint

Chapter 2 38 Table 5: Association Cox proportional hazards analysis to test the association for overall survival between the reduction-cohort and patient, tumour, treatment characteristics and toxicity. HR (95% CI) P Relative HR change Reduction 0.63 (0.45, 0.88) 0.007 - + MLD 0.70 (0.50, 0.98) 0.039 11.1% + Heart V 2 0.61 (0.43, 0.86) 0.004 3.2% + Mean heart dose 0.64 (0.45, 0.90) 0.011 1.6% + Oesophagus V 50 0.67 (0.48, 0.94) 0.021 6.3% + Acute toxicity ≥G3 0.67 (0.47, 0.94) 0.019 6.3% + Acute pulmonary toxicity ≥G3 0.68 (0.48, 0.95) 0.024 7.9% + Acute dysphagia ≥G3 0.63 (0.45, 0.89) 0.008 - + Late toxicity ≥G3 0.64 (0.46, 0.90) 0.010 1.6% + Late pulmonary toxicity ≥G3 0.64 (0.46, 0.89) 0.009 1.6% + Late dysphagia ≥G3 0.62 (0.44, 0.87) 0.005 1.6% MLD=mean lung dose; Heart V2=volume of the heart receiving ≥2 Gy; Oesophagus V50 =volume of the oesophagus receiving ≥50 Gy (EQD210); Pulmonary toxicity=cough, dyspnea and radiation pneumonitis. Discussion Previously, we published the results of a differential analysis of local and regional control after chemoradiotherapy, demonstrating that lymph nodes recur less often than the primary tumor due to a lower volume [12]. The current analysis in LA- NSCLC patients compared 70 Gy (EQD2 10 ) versus 60 Gy (EQD2 10 ) to the mediastinal lymph nodes while treating the primary tumour to 70 Gy (EQD2 10 ) using IMRT. Simultaneously, the PTV-margins were reduced following the implementation of daily image guidance with online carina registration replacing a bony anatomy registration. Comparison with a historical cohort, treated with 70 Gy (EQD2 10 ) to both the primary tumour and the lymph nodes, was performed to determine the safety of this new treatment strategy in terms of toxicity and RF. The reduction-cohort demonstrated significantly lower acute toxicity rates, a comparable incidence of LF and RF as well as a significantly improved OS. Since the RTOG-0617, dose-escalation while increasing the overall treatment time in lung cancer, is regarded with restraint. This phase 3-trial reported an increased acute toxicity as well as a worse OS in the conventionally fractionated 74 Gy-arm compared to the 60 Gy-arm of 20.3 vs 28.7 months, respectively, in patients treated with concurrent chemotherapy (weekly Paclitaxel and Carboplatin +/- Cetuximab) [1].