The potential for increased tumor control probability in non-small cell lung cancer with a hypofractionated integrated boost to the gross tumor volume.

Treatment outcomes in locally advanced non-small cell lung cancer (NSCLC) to date have been poor, with normal tissue toxicity often limiting the dose that can be delivered to the tumor. Treatment intensification in NSCLC via targeted dose escalation with modern delivery techniques may offer the potential for a significant increase in tumor control probability (TCP) without a clinically significant increase in organ-at-risk (OAR) toxicity. In this planning study, 20 patients were re-planned with a volumetric modulated arc therapy (VMAT) and an inhomogeneous dose distribution with iteratively escalated doses to the gross tumor volume (iGTV) (composite GTV across multiple 4-dimensional computed tomography [4DCT] phases) in a series of 20 fraction regimes. For each plan OAR doses, target coverage and predicted TCPs were collected and compared with homogenous 3-dimensional (3D) and VMAT plans, as well as with each other. In 70% of patients, it was possible to escalate to 75 Gy in 20 fractions within OAR tolerances, opening the possibility of treating these patients to a biological effective dose (BED) of 103.1 Gy. This planning study forms the basis of a clinical trial INTENSE (Inhomogeneous Targeted Dose Escalation in Non-Small CEll Lung Cancer), CTRIAL 15-47.