Chromosomal radiosensitivity in oncological and non-oncological patients with rheumatoid arthritis and connective tissue diseases.

BACKGROUND: The risk of developing late radiotoxicity after radiotherapy in patients with high chromosomal radiosensitivity after radiotherapy could potentially be higher compared to the risk in patients with average radiosensitivity. In case of extremely high radiosensitivity, dose reduction may be appropriate. Some rheumatic diseases (RhD), including connective tissue diseases (CTDs) appear to be associated with higher radiosensitivity. The question arises as to whether patients with rheumatoid arthritis (RA) also generally have a higher radiosensitivity and whether certain parameters could indicate clues to high radiosensitivity in RA patients which would then need to be further assessed before radiotherapy. METHODS: Radiosensitivity was determined in 136 oncological patients with RhD, 44 of whom were RA patients, and additionally in 34 non-oncological RA patients by three-colour fluorescence in situ hybridization (FiSH), in which lymphocyte chromosomes isolated from peripheral blood are analysed for their chromosomal aberrations of an unirradiated and an with 2 Gy irradiated blood sample. The chromosomal radiosensitivity was determined by the average number of breaks per metaphase. In addition, correlations between certain RA- or RhD-relevant disease parameters or clinical features such as the disease activity score 28 and radiosensitivity were assessed. RESULTS: Some oncological patients with RhD, especially those with connective tissue diseases have significantly higher radiosensitivity compared with oncology patients without RhD. In contrast, the mean radiosensitivity of the oncological patients with RA and other RhD and the non-oncological RA did not differ. 14 of the 44 examined oncological RA-patients (31.8%) had a high radiosensitivity which is defined as ≥ 0.5 breaks per metaphase. No correlation of laboratory parameters with radiosensitivity could be established. CONCLUSIONS: It would be recommended to perform radiosensitivity testing in patients with connective tissue diseases in general. We did not find a higher radiosensitivity in RA patients. In the group of RA patients with an oncological disease, a higher percentage of patients showed higher radiosensitivity, although the average radiosensitivity was not high.

Usability of magnetic resonance images acquired at a novel low-field 0.55 T scanner for brain radiotherapy treatment planning.

Background and Purpose: Low-field magnetic resonance imaging (MRI) may offer specific advantages over high-field MRI, e.g. lower susceptibility-dependent distortions and simpler installation. The study aim was to evaluate if a novel 0.55 T MRI scanner provides sufficient image accuracy and quality for radiotherapy (RT) treatment planning. Material and methods: The geometric accuracy of images acquired at a low-field MRI scanner was evaluated in phantom measurements regarding gradient non-linearity-related distortions. Patient-induced B0-susceptibility changes were investigated via B0-field-mapping in ten volunteers. Patients were positioned in RT-setup using a 3D-printed insert for the head/neck-coil that was tested for sufficient signal-to-noise-ratio (SNR). The suitability of the MRI-system for detection of metastases was evaluated in eleven patients. In comparison to diagnostic images, acquired at ≥1.5 T, three physicians evaluated the detectability of metastases by counting them in low- and high-field-images, respectively. Results: The phantom measurements showed a high imaging fidelity after 3D-distortion-correction with (1.2 ± 0.9) mm geometric distortion in 10 cm radius from isocentre. At the edges remaining distortions were greater than at 1.5 T. The mean susceptibility-induced distortions in the head were (0.05 ± 0.05) mm and maximum 0.69 mm. SNR analysis showed that optimised positioning of RT-patients without signal loss in the head/neck-coil was possible with the RT-insert. No significant differences (p = 0.48) in detectability of metastases were found. Conclusion: The 0.55 T MRI system provided sufficiently geometrically accurate and high-resolution images that can be used for RT-planning for brain metastases. Hence, modern low-field MRI may contribute to simply access MRI for RT-planning after further investigations.

Differences and Similarities in the Pattern of Early Metabolic and Morphologic Response after Induction Chemo-Immunotherapy versus Induction Chemotherapy Alone in Locally Advanced Squamous Cell Head and Neck Cancer.

Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a double immune checkpoint blockade (DICB) of tremelimumab and durvalumab to IC on imaging parameters and their significance with regard to tumor cell remission. Methods: Response variables of 53 patients treated with IC+DICB (ICIT) were compared with those of 104 who received IC alone. Three weeks after one cycle, pathologic and, in some cases, clinical and endoscopic primary tumor responses were evaluated and correlated with a change in 18F-FDG PET and CT/MRI-based maximum-standardized uptake values (SUVmax) before (SUVmaxpre), after treatment (SUVmaxpost) and residually (resSUVmax in % of SUVmaxpre), and in maximum tumor diameter (Dmax) before (Dmaxpre) and after treatment (Dmaxpost) and residually (resD). Results: Reduction of SUVmax and Dmax occurred in both groups; values were SUVmaxpre: 14.4, SUVmaxpost: 6.6, Dmaxpre: 30 mm and Dmaxpost: 23 mm for ICIT versus SUVmaxpre: 16.5, SUVmaxpost: 6.4, Dmaxpre: 21 mm, and Dmaxpost: 16 mm for IC alone (all p < 0.05). ResSUVmax was the best predictor of complete response (IC: AUC: 0.77; ICIT: AUC: 0.76). Metabolic responders with resSUVmax ≤ 40% tended to have a higher rate of CR to ICIT (88%; n = 15/17) than to IC (65%; n = 30/46; p = 0.11). Of the metabolic nonresponders (resSUVmax > 80%), 33% (n = 5/15) achieved a clinical CR to ICIT versus 6% (n = 1/15) to IC (p = 0.01). Conclusions: ICIT and IC quickly induce a response and 18F-FDG PET is the more accurate modality for identifying complete remission. The rate of discrepant response, i.e., pCR with metabolic nonresponse after ICIT was >30%.