Improving the modelling of irradiation-induced brain activation for in vivo PET verification of proton therapy.

BACKGROUND AND PURPOSES: A reliable Monte Carlo prediction of proton-induced brain tissue activation used for comparison to particle therapy positron-emission-tomography (PT-PET) measurements is crucial for in vivo treatment verification. Major limitations of current approaches to overcome include the CT-based patient model and the description of activity washout due to tissue perfusion. MATERIAL AND METHODS: Two approaches were studied to improve the activity prediction for brain irradiation: (i) a refined patient model using tissue classification based on MR information and (ii) a PT-PET data-driven refinement of washout model parameters. Improvements of the activity predictions compared to post-treatment PT-PET measurements were assessed in terms of activity profile similarity for six patients treated with a single or two almost parallel fields delivered by active proton beam scanning. RESULTS: The refined patient model yields a generally higher similarity for most of the patients, except in highly pathological areas leading to tissue misclassification. Using washout model parameters deduced from clinical patient data could considerably improve the activity profile similarity for all patients. CONCLUSIONS: Current methods used to predict proton-induced brain tissue activation can be improved with MR-based tissue classification and data-driven washout parameters, thus providing a more reliable basis for PT-PET verification.

Quantitative assessment of radiation dose and fractionation effects on normal tissue by utilizing a novel lung fibrosis index model.

BACKGROUND: Normal lung tissue tolerance constitutes a limiting factor in delivering the required dose of radiotherapy to cure thoracic and chest wall malignancies. Radiation-induced lung fibrosis (RILF) is considered a critical determinant for late normal tissue complications. While RILF mouse models are frequently approached e.g., as a single high dose thoracic irradiation to investigate lung fibrosis and candidate modulators, a systematic radiobiological characterization of RILF mouse model is urgently needed to compare relative biological effectiveness (RBE) of particle irradiation with protons, helium-, carbon and oxygen ions now available at HIT. We aimed to study the dose-response relationship and fractionation effect of photon irradiation in development of pulmonary fibrosis in C57BL/6 mouse. METHODS: Lung fibrosis was evaluated 24 weeks after single and fractionated whole thoracic irradiation by quantitative assessment of lung alterations using CT. The fibrosis index (FI) was determined based on 3D-segmentation of the lungs considering the two key fibrosis parameters affected by ionizing radiation i.e., a dose/fractionation dependent reduction of the total lung volume and increase of the mean lung density. RESULTS: The effective dose required to induce 50% of the maximal possible fibrosis (ED 50 ) was 14.55 ± 0.34Gy and 27.7 ± 1.22Gy, for single and five- fractions irradiation, respectively. Applying a deterministic model an α/ß = 4.49 ± 0.38 Gy for the late lung radiosensitivity was determined. Intriguingly, we found that a linear-quadratic model could be applied to in-vivo log transformed fibrosis (FI) vs. irradiation doses. The LQ model revealed an α/ß for lung radiosensitivity of 4.4879 Gy for single fraction and 3.9474 for 5-fractions. Our FI based data were in good agreement with a meta-analysis of previous lung radiosensitivity data derived from different clinical endpoints and various mouse strains. The effect of fractionation on RILF development was further estimated by the biologically effective dose (BED) model with threshold BED (BED Tr ) = 30.33 Gy and BED ED50  = 61.63 Gy, respectively. CONCLUSION: The systematic radiobiological characterization of RILF in the C57BL/6 mouse reported in this study marks an important step towards precise estimation of dose-response for development of lung fibrosis. These radiobiological parameters combined with a large repertoire of genetically engineered C57BL/6 mouse models, build a solid foundation for further biologically individualized risk assessment of RILF and functional RBE prediction on novel of particle qualities.

Quantitative assessment of image-guided radiotherapy for paraspinal tumors.

PURPOSE: To evaluate stereotactic positioning uncertainties of patients with paraspinal tumors treated with fractionated intensity-modulated radiotherapy; and to determine whether target-point correction via rigid registration is sufficient for daily patient positioning. PATIENTS AND METHODS: Forty-five patients with tumors at the cervical, thoracic, and lumbar spine received regular control computed-tomography (CT) scans using an in-room CT scanner. All patients were immobilized with the combination of Scotch cast torso and head masks. The positioning was evaluated regarding translational and rotational errors by applying a rigid registration algorithm based on mutual information. The registration box was fitted to the target volume for optimal registration in the high-dose area. To evaluate the suitability of the rigid registration result for correcting the target volume position we subsequently registered three small subsections of the upper, middle, and lower target volume. The resulting residual deviations reflect the extent of the elastic deformations, which cannot be covered by the rigid-body registration procedure. RESULTS: A total of 321 control CT scans were evaluated. The rotational errors were negligible. Translational errors were smallest for cervical tumors (-0.1 +/- 1.1, 0.3 +/- 0.8, and 0.1 +/- 0.9 mm along left-right, anterior-posterior, and superior-inferior axes), followed by thoracic (0.8 +/- 1.1, 0.3 +/- 0.8, and 1.1 +/- 1.3 mm) and lumbar tumors (-0.7 +/- 1.3, 0.0 +/- 0.9, and 0.5 +/- 1.6 mm). The residual deviations of the three subsections were <1 mm. CONCLUSIONS: The applied stereotactic patient setup resulted in small rotational errors. However, considerable translational positioning errors may occur; thus, on the basis of these data daily control CT scans are recommended. Rigid transformation is adequate for correcting the target volume position.

Postoperative electron beam radiotherapy for keloids: objective findings and patient satisfaction in self-assessment.

AIM: To evaluate the role of postoperative radiotherapy in the management of keloids. METHODS: Forty-seven patients with a combined total of 60 keloids were treated with 6-MeV electron beam radiotherapy after surgical excision of the keloids. Mean daily fractions of 4 Gy (range, 3-5 Gy) were administered up to a total dose of 16 Gy (range, 12-18 Gy). The median follow-up was 70 months. Patients were asked to complete a questionnaire addressing their satisfaction with the treatment results. This self-assessment was compared with the clinical outcome. RESULTS: Four keloids (7%) relapsed completely, and five recurrences (8%) were classified as limited relapses. All recurrences were observed at sites of high stretch-tension. Keloid-associated symptoms, e.g. itching and pain, were improved in 81%. Hypopigmentation was observed in 29 patients (62%), a mild redness of the scar in eight patients (17%), and grade 1 telangiectasias in two patients (4%). No severe complications or secondary malignancies were observed. Self-assessments did not fully correspond to the clinical examination and recurrence status. Twelve patients were not satisfied with the treatment result, but only two of these relapsed completely. Three relapsed patients described the result of therapy as excellent or good. CONCLUSION: Postoperative electron radiotherapy is well tolerated and very effective in preventing keloid recurrence. To avoid an overestimation of cosmetic outcome, patients should be informed about achievable results before therapy starts.