Stereotactic body radiation therapy of lung tumours : clinical and dosimetric aspects

Abstract: The general aim of this thesis was to increase the knowledge regarding some clinical and methodological aspects, relevant in view of toxicity as well as tumour control, in stereotactic body radiation therapy (SBRT) of lung tumours. In the first two studies, reirradiation and radiation-induced atelectasis were studied. In the following two studies, estimations of doses delivered to the tumour, considering geometrical uncertainties, were performed. Considering the very high biological tumour doses delivered in SBRT, knowledge of the risk of high grade toxicity is of utmost importance for its clinical use. In the first study, reirradiation with SBRT of lung tumours after previous SBRT in the same region was retrospectively evaluated in 29 patients with 32 tumours with regard to toxicity, local control and survival. Larger tumour volumes and central location were correlated to more severe toxicity, and larger tumour volumes were also correlated to worse local control. Three of the patients with centrally located lung tumours died due to bleeding, while no grade-5 toxicity was observed for patients with peripherally located tumours. The one- and three-year survival from time of reirradiation was estimated to 59% and 23%, respectively. It was concluded that reirradiation with SBRT in a location previously treated with SBRT was feasible with low rates of toxicity for patient with peripheral lung tumours, while caution should be taken for patients with central lung tumours due to the risk of increased severe toxicity. In the second study a possible dose-response relationship for radiation-induced atelectasis and bronchial doses after SBRT close to the main, lobar or segmental bronchi was evaluated. Out of the 74 patients, 18 (24%) developed radiation-induced atelectasis at a median time of 8 month after radiotherapy. A significant dose-response relationship was found between the high-dose bronchial volume and the incidence of atelectasis. The median of the minimum dose to 0.1 cm3 of the bronchi receiving the highest dose (D0.1cm3) was 210 Gy3 (EQD2, using α/β=3 Gy) for patients with atelectasis, and 105 Gy3 for patients without. The estimated incidence of atelectasis at 1, 2 and 3 years was 3%, 8% and 13%, respectively, at a bronchial D0.1cm3 of 100 Gy3, 10%, 21% and 31% at 150 Gy3, and 25%, 42% and 53%, respectively, at a dose of 200 Gy3. Of decisive importance for the clinical use of SBRT is the balance between the risk of toxicity and the gain expected by control of the treated tumour. As a surrogate, to quantitatively foresee the latter, dose to the tumour is used. As planned and delivered dose may differ more in SBRT as compared to conventional radiotherapy, knowledge of delivered dose is highly important for SBRT. Study three and four were focused on the issue of delivered tumour dose in SBRT. Study three aimed to evaluate the accuracy of a dose-shift approximation used for estimating delivered clinical target volume (CTV) doses, given the geometrical uncertainties pertinent to SBRT. For a set of 10 representative patients with lung tumours, the static dose matrix was shifted according to clinically representative setup errors and a breathing trace scaled with different breathing amplitudes. The dose-shift approximation was compared to the more accurate beam-shift method with recalculation of dose at every geometrical position. Averaged over the patients, the disagreement between the methods for minimum CTV dose (D98%) was approximately 4% (root-mean-square) for setup shifts up to 10 mm, and for setup shifts up to 5 mm the disagreement was approximately 2%. It was concluded that for estimation of delivered dose for a particular patient it is advisable to use the beam-shift method for increased accuracy, while averaged over a group of patients the dose-shift approximation has an acceptable error. In study four, the delivered CTV dose was estimated for a cohort of patients treated with SBRT, taking clinical data of breathing motions and setup errors into account. Two different volumetric soft-tissue image-guidance techniques were compared; pre-treatment verification computed tomography (CT) (IG1) and online verification with cone-beam CT (CBCT) (IG2). Treatment plans for 50 consecutively treated patients, with 69 lung tumours, were retrospectively simulated. The dose-shift approximation was used with the static dose distribution shifted according to a breathing trace scaled with patient-specific amplitudes. Applied were also systematic and random setup errors (for IG1) and matching errors (for IG2), sampled from normal distributions. Each simulation was repeated 500 times for each tumour. For each tumour, 500 different dose-volume histograms were obtained, and from those a tumour-specific dose coverage histogram was calculated. For all tumours, a population-averaged dose coverage histogram was calculated as the mean of the tumourspecific dose coverage histograms. The result showed that prescribed dose, to the periphery of the planning target volume, was delivered to 98% of the CTV with a population coverage probability within 86-96% (range between worst and best case setup assumptions, realistic assumptions: 90%) using IG1, and 97-99% (realistic assumptions: 99%) using IG2. Looking at 90% of the simulations with highest dose to 98% of the CTV (tumour coverage probability), at least the prescribed dose was delivered to 67% of the tumours with IG1 using realistic assumptions of setup errors, and to 99% of the tumours with IG2. In conclusion, the minimum dose delivered to the CTV increased with the use of online CBCT image-guidance, compared to the pre-treatment verification CT.