Loco-regional treatment is the mainstay of cancer cures in non small lung and head and neck cancer. For advanced stage cancer, dose intense multimodality treatment is required yet affected by substantial side effects. Our aim is to improve treatment outcome in locally advanced head and neck and lung cancer patients by:1. Optimizing local control by introducing novel radiation techniques resulting in redistribution of the radiation dose, creating inhomogeneous dose distribution towards the most active part of the tumour instead of conventional homogenous doses. This redistribution can be performed without increase of toxicity. As recently reported radiation accidents in the US demonstrate, QA is of outmost importance for safe radiation delivery in complex treatments. To assure accurate delivery over time, we will monitor both the patient’s geometry as well as the delivered dose using image guided adaptive plan modifications and 3D in-vivo dosimetric verification.2. Maximizing the benefit of combined modality treatmentBoth cisplatin and Cetuximab in combination with radiotherapy have shown to improve local control and survival but both drugs have severe side effects. As these drugs are not active in all patients, there is a large need to select patients which are sensitive to either drug. For this purpose the uptake of Cetuximab will be estimated by imaging tumour uptake with Zr89 labelled Cetuximab, while cisplatin sensitive tumours can be selected by biomarkers. This part was stopped in May 2014.This proposal will:1 optimise efficiency by selecting patients on treatment specific tumour response predictors and tailoring radiation to most active parts of the tumour.2 improve quality of life by withholding ineffective, toxic treatments and redistribution of dose.3 decrease community costs by reserving expensive treatments for those who will benefit.This will be studied in randomized phase II clinical trials in top European institutes, followed by phase III trials outside this proposal.