Radiation-induced toxicity, particularly radiation pneumonitis (RP), negatively affects patients’ quality of life (QOL) and survival after definitive thoracic radiation therapy (RT) [1,2]. Baseline...

Functional avoidance radiation therapy (RT) aims at sparing functional lung regions. The purpose of this simulation study was to evaluate the feasibility of functional lung avoidance methodology in RT of lung cancer and to characterize the achievable dosimetry of single photon emission computed tomography (SPECT) guided treatment planning. Fifteen consecutive lung cancer patients were included and planned for definitive RT of 60–66 Gy in 2-Gy fractions. Two plans were optimized: a standard CT-plan, and functional SPECT-plan. The objective was to reduce dose to the highly functional lung subvolumes without compromising tumour coverage, and respecting dose to other organs at risk. For each patient a 3D-conformal, intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy plans were created for standard and functional avoidance. Standard versus functional dose-volume parameters for functional lung (FL) subvolumes, organs at risk and tumour coverage were compared. The largest dose reduction was achieved with IMRT plans. Functional plans resulted in dose reduction from 9.0 Gy to 6.7 Gy (mean reduction of 2.3 Gy or 26%) to the highest functional subvolume FL80% (95%CI 1.1; 3.5). Dose to FL40% was reduced from 13.3 Gy to 11.6 Gy with functional planning. Dose reduction to FL40% was 1.7 Gy (95%CI 0.9; 2.6). Functional volume of lung receiving over 20 Gy improved by 5% (standard 22%, functional 17%). Dose to organs at risk and tumour coverage were not significantly different between plans. SPECT/CT-guided planning resulted in improved dose-volumetric outcomes for functional lung. This methodology may lead to potential reduction in radiation-induced lung toxicity.

Background: Radiation therapy (RT) plays a key role in curative-intent treatment for locally advanced lung cancer. Radiation induced pulmonary toxicity can be significant for some patients and becomes a limiting factor for radiation dose, suitability for treatment, as well as post treatment quality of life and suitability for the newly introduced adjuvant immunotherapy. Modern RT techniques aim to minimise the radiation dose to the lungs, without accounting for regional distribution of lung function. Many lung cancer patients have significant regional differences in pulmonary function due to smoking and chronic lung co-morbidity. Even though reduction of dose to functional lung has shown to be feasible, the method of preferential functional lung avoidance has not been investigated in a randomised clinical trial.Methods: In this study, single photon emission computed tomography (SPECT/CT) imaging technique is used for functional lung definition, in conjunction with advanced radiation dose delivery method in randomised, double-blind trial. The study aims to assess the impact of functional lung avoidance technique on pulmonary toxicity and quality of life in patients receiving chemo-RT for lung cancer. Eligibility criteria are biopsy verified lung cancer, scheduled to receive (chemo)-RT with curative intent. Every patient will undergo a pre-treatment perfusion SPECT/CT to identify functional lung. At radiation dose planning, two plans will be produced for all patients on trial. Standard reference plan, without the use of SPECT imaging data, and functional avoidance plan, will be optimised to reduce the dose to functional lung within the predefined constraints. Both plans will be clinically approved. Patients will then be randomised in a 2:1 ratio to be treated according to either the functional avoidance or the standard plan. This study aims to accrue a total of 200 patients within 3 years. The primary endpoint is symptomatic radiation-induced lung toxicity, measured serially 1–12 months after RT. Secondary endpoints include: a quality of life and patient reported lung symptoms assessment, overall survival, progression-free survival, and loco-regional disease control.Discussion: ASPECT trial will investigate functional avoidance method of radiation delivery in clinical practice, and will establish toxicity outcomes for patients with lung cancer undergoing curative chemo-RT.Trial registration: Clinicaltrials.gov Identifier:NCT04676828. Registered 1 December 2020.

E15238 Background: Little evidence exists on 2nd line therapy for gemcitabine resistant patients. The combination of oxaliplatin (Ox) and 5-FU has shown efficacy in small trials. We wanted to establish a tolerable dose of the combination of irinotecan, cetuximab and everolimus(ICE), and test it vs. the combination of capecitabine (Cap) and Ox in a randomized phase I/II setting. Methods: Patients were initially recruited in a 3+3 dose finding design with an expanded MDT cohort. After establishing MDT; patients were randomized between ICE (at MDT-1) and CapOx (Cap: 1250 mg/m2 BID and Ox: 70 mg/m2 q14d). Patients that progressed could cross-over to the other arm. (NCT01042028) Results: Between January 2010 and November 2012, 40 patients were recruited. Due to DLT toxicity (mainly mucositis) at dose level 1 of the phase I trial, the protocol was amended and patients were treated at dose level -1. Ten patients were safely treated at this dose. The final dose for everolimus was 2.5 mg q1d, for irinotecan 180 mg...