Toward adaptive radiotherapy

Intensity Modulated Radiotherapy (IMRT) and proton therapy are the state-of-art external radiotherapy modalities. To make the most of such precise delivery, accurate knowledge of the patient anatomy and biology during treatment is necessary, as unaccounted variations can compromise the outcome of the treatment. Treatment modification to account for deviations from the planning stage is a framework known as adaptive radiotherapy (ART). To fully utilise the information extracted from different modalities and/or at different time-points it is required to accurately align the imaging data. In this work the feasibility of cone-beam computed tomography (CBCT) and deformable image registration (DIR) for ART was evaluated in the context of head and neck (HN) and lung malignancies, and for IMRT and proton therapy applications. This included the geometric validation of deformations for multiple DIR algorithms, estimating the uncertainty in dose recalculation of a CBCT-based deformed CT (dCT), and the uncertainty in dose summation resulting from the properties of the underlying deformations. The dCT method was shown to be a good interim solution to repeat CT and a superior alternative to simpler direct usage of CBCT for dose calculation; proton therapy treatments were more sensitive to registration errors than IMRT. The ability to co-register multimodal and multitemporal data of the HN was also explored; the results found were promising and the limitations of current algorithms and data acquisition protocols were identified. The use of novel artificial cancer masses as a novel platform for the study of imaging during radiotherapy was explored in this study. The artificial cancer mass model was extended to generate magnetic resonance imaging (MRI)-friendly samples. The tumoroids were imageable in standard T1 and T2 MRI acquisitions, and the relaxometric properties were measured. The main limitation of the current tumour model was the poor reproducibility and controllability of the properties of the samples

Investigation of the evolution of radiation-induced lung damage using serial CT imaging and pulmonary function tests

Background and purpose: Radiation-induced lung damage (RILD) is a common consequence of lung cancer radiotherapy (RT) with unclear evolution over time. We quantify radiological RILD longitudinally and correlate it with dosimetry and respiratory morbidity. Materials and methods: CTs were available pre-RT and at 3, 6, 12 and 24-months post-RT for forty-five subjects enrolled in a phase 1/2 clinical trial of isotoxic, dose-escalated chemoradiotherapy for locally advanced non-small cell lung cancer. Fifteen CT-based measures of parenchymal, pleural and lung volume change, and anatomical distortions, were calculated. Respiratory morbidity was assessed with the Medical Research Council (MRC) dyspnoea score and spirometric pulmonary function tests (PFTs): FVC, FEV1, FEV1/FVC and DLCO. Results: FEV1, FEV1/FVC and MRC scores progressively declined post-RT; FVC decreased by 6-months before partially recovering. Radiologically, an early phase (3–6 months) of acute inflammation was characterised by reversible parenchymal change and non-progressive anatomical distortion. A phase of chronic scarring followed (6–24 months) with irreversible parenchymal change, progressive volume loss and anatomical distortion. Post-RT increase in contralateral lung volume was common. Normal lung volume shrinkage correlated longitudinally with mean lung dose (r = 0.30–0.40, p = 0.01–0.04). Radiological findings allowed separation of patients with predominant acute versus chronic RILD; subjects with predominantly chronic RILD had poorer pre-RT lung function. Conclusions: CT-based measures enable detailed quantification of the longitudinal evolution of RILD. The majority of patients developed progressive lung damage, even when the early phase was absent or mild. Pre-RT lung function and RT dosimetry may allow to identify subjects at increased risk of RILD