Margriet Kwint

Chapter 2 26 Background and purpose (Chemo)Radiotherapy for locally advanced non-small lung cancer (LA-NSCLC) causes severe dysphagia due to the radiation dose to the mediastinal lymphadenopathy. Reducing the dose to the mediastinum and the margins to the planning target volume (PTV) might reduce severe toxicity rates. The results of both adaptations in LA-NSCLC patients receiving (chemo) radiotherapy were analysed. Materials and methods Three hundred and eight LA-NSCLC patients were included in an observational study. Both cohorts received hypofractionated RT (24x2.75 Gy) of 70 Gy (EQD2 10 ) to the primary tumour. The reference-cohort (N=170) received the same dose of 70 Gy (EQD2 10 ) to the involved lymph nodes, while the reduction-cohort (N=138) received 24x2.42 Gy, biologically equivalent to 60 Gy (EQD2 10 ). Furthermore, the patient-specific PTV-margins for both the primary tumour and lymph nodes were reduced by 2-3mm in the reduction-cohort after implementing a carina based correction strategy. The effects on toxicity, regional failure and overall survival (OS) were assessed. Results The acute grade 3 (G3) dysphagia and G3 pulmonary toxicity decreased significantly from 12.9% to 3.6% and 4.1% versus 0%, respectively. The regional failures were comparable: 5.9% versus 4.3% (p=0.546). The median OS was significantly different: 26 months (reference-cohort) versus 35 months (reduction-cohort). After correction for confounders, the association between the reduction-cohort and OS remained significant (HR 0.63 versus HR 0.70). Conclusion A reduction in PTV-margins and dose from 70 Gy to 60 Gy to the involved lymph nodes in LA-NSCLC patients receiving (chemo) radiotherapy did not result in an increase in regional failures. Moreover, significantly lower acute toxicities and an improved OS were observed in the reduction-cohort.