Background: Current segmentation approaches for radiation treatment planning in head and neck cancer patients (HNCP) typically consider the entire mandible as an organ at risk, whereas segmentation of the maxilla remains uncommon. Accurate risk assessment for osteoradionecrosis (ORN) or implant-based dental rehabilitation after radiation therapy may require a nuanced analysis of dose distribution in specific mandibular and maxillary segments. Manual segmentation is time-consuming and inconsistent, and there is no definition of jaw subsections. Materials and methods: The mandible and maxilla were divided into 12 substructures. The model was developed from 82 computed tomography (CT) scans of HNCP and adopts an encoder-decoder three-dimensional (3D) U-Net structure. The efficiency and accuracy of the automated method were compared against manual segmentation on an additional set of 20 independent CT scans. The evaluation metrics used were the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and surface DSC (sDSC). Results: Automated segmentations were performed in a median of 86 s, compared to manual segmentations, which took a median of 53.5 min. The median DSC per substructure ranged from 0.81 to 0.91, and the median HD95 ranged from 1.61 to 4.22. The number of artifacts did not affect these scores. The maxillary substructures showed lower metrics than the mandibular substructures. Conclusions: The jaw substructure segmentation demonstrated high accuracy, time efficiency, and promising results in CT scans with and without metal artifacts. This novel model could provide further investigation into dose relationships with ORN or dental implant failure in normal tissue complication prediction models.
Anal squamous cell carcinoma (ASCC) is associated with immunosuppression and infection with human papillomavirus (HPV). Response to standard chemoradiotherapy (CRT) varies considerably. A comprehensive molecular characterization of CRT resistance is lacking, and little is known about the interplay between tumor immune contexture, host immunity, and immunosuppressive and/or immune activating effects of CRT. Patients with localized ASCC, treated with CRT at three different sites of the German Cancer Consortium (DKTK) were included. Patient cohorts for molecular analysis included baseline formalin fixed paraffin embedded biopsies for immunohistochemistry (n = 130), baseline RNA sequencing (n = 98), peripheral blood immune profiling (n = 47), and serum cytokine measurement (n = 35). Gene set enrichment analysis showed that pathways for IFNγ, IFNα, inflammatory response, TNFα signaling via NF-κB, and EMT were significantly enriched in poor responders (all p < 0.001). Expression of interferon-induced transmembrane protein 1 (IFITM1), both on mRNA and protein levels, was associated with reduced Freedom from locoregional failure (FFLF, p = 0.037) and freedom from distant metastasis (FFDM, p = 0.014). An increase of PD-L1 expression on CD4+ T-cells (p < 0.001) and an increase in HLA-DR expression on T-cells (p < 0.001) was observed in the peripheral blood after CRT. Elevated levels of regulatory T-cells and CXCL2 were associated with reduced FFLF (p = 0.0044 and p = 0.004, respectively). Inflammatory pathways in tissue in line with elevated levels of regulatory T-cells and CXCL2 in peripheral blood are associated with resistance to CRT. To counteract this resistance mechanism, the RADIANCE randomized phase-2 trial currently tests the addition of the immune checkpoint inhibitor durvalumab to standard CRT in locally advanced ASCC.
Purpose Node-positive prostate cancer is a potentially curable disease. Definitive radiotherapy to the prostate and lymphatic drainage is an effective treatment option but prospective long-term outcome data are scarce. Thus, the current study aimed to evaluate the toxicity and efficacy of definitive radiation therapy for men with prostate cancer and nodal metastases using modern irradiation techniques. Methods A total of 40 treatment-naïve men with node-positive prostate cancer were allocated to the trial. All patients received definitive radiation therapy at two German university hospitals between 2009 and 2018. Radiation was delivered as intensity-modulated radiation therapy (IMRT) with 51 Gy to the lymphatic drainage with simultaneous integrated boost (SIB) up to 61.2 Gy to involved nodes and 76.5 Gy to the prostate in 34 fractions. Feasibility and safety, overall and progression-free survival, toxicity, and quality of life measurements were analyzed. Results During a median follow-up of 79 months, median overall survival was 107 months and progression-free survival was 78 months. Based on imaging follow-up, no infield relapse was reported during the first 24 months of follow-up. There were 3 (8%) potentially treatment-related grade 3 toxicities. Common iliac node involvement was associated with a higher risk of progression (HR 15.8; 95% CI 2.1–119.8; p = 0.007). Conclusion Definitive radiation to the lymphatic drainage with SIB to the involved nodes and prostate is a safe and effective treatment approach for patients with treatment-naïve, node-positive prostate cancer with excellent infield tumor control rates and tolerable toxicity. Location rather than number of involved nodes is a major risk factor for progression.
Research in the field of local and locoregional breast cancer radiotherapy aims to maintain excellent oncological outcomes while reducing treatment-related toxicity. Adaptive radiotherapy (ART) considers variations in target and organs at risk (OARs) anatomy occurring during the treatment course and integrates these in re-optimized treatment plans. Exploiting ART routinely in clinic may result in smaller target volumes and better OAR sparing, which may lead to reduction of acute as well as late toxicities. In this review MR-guided and CT-guided ART for breast cancer patients according to different clinical scenarios (neoadjuvant and adjuvant partial breast irradiation, whole breast, chest wall and regional nodal irradiation) are reviewed and their advantages as well as challenging aspects discussed.
This retrospective study aimed at clinical evaluation of autonomous radiotherapy planning for ten prostate cancer cases, including organ-at-risk/target contouring and treatment planning. Five experts scored the clinical acceptability of each step using a 4-level Likert-scale resulting in 78%, 66% and 90% acceptance. For 6/10 patients the entire workflow was considered acceptable.
Abstract BACKGROUND Comprehensive genomic profiling and biomarker-based therapies are increasingly used in clinical trials and in innovative health care systems including the center for personalized medicine network. Systematic assessments of patient-reported outcomes (PRO) are warranted to gain insight into the perspective of patients during biomarker-based therapies. In the present study, we focused on the feasibility of and compliance to an electronic PRO assessment in patients treated at our center. MATERIAL AND METHODS Based on a retrospective evaluation of symptom burden in 265 neurooncology patients in the Molecular Tumor Board (MTB), we developed an app by 14 expert rounds including validated assessments of health-related quality of life (HRQoL), burden of symptoms und psychological stress, and tested it in a pilot study. After informed consent, patients were introduced to the app by study staff and completed subsequently patient-reported outcomes at several time points (weekly, monthly, and quarterly). We conducted a structured interview with health care personnel and the patients as users after 3 months to assess the app’s usability and feasibility. The interview was transcribed and analyzed according to Mayring´s qualitative content analysis regarding handling, feasibility and applicability in daily routine.Furthermore, we assessed compliance and descriptive data of the ePROs. RESULTS So far, 14 patients and caregivers have been enrolled, (9 female, 5 male). Median age was 50 years (range 28 -79), 3 out of 14 patients dropped out due to death. A total of 4 study staff members, 9 patients and one caregiver were interviewed regarding usability /feasibility. Both evaluated as good (study staff members in total n=40 quotes, patients/caregivers n=112 quotes). Main advantages were the possibility to complete questionnaires at home and the easy implementation in daily life. Compliance to questionnaires was high, e.g., 91% of weekly distributed NCCN Distress Thermometer were answered in time (range 65-100%, assessment duration 5-56 weeks, 262 answers), we observed a median Distress score of 4 (range 0-9, n=262, weekly assessed) and a median Global health score of 66.7 (range 16.7-100, n=69, EORTC QLQ-C30, question 29 and 30, monthly assessed, compliance 94%). CONCLUSION This pilot study proved feasibility and acceptance of the app and might enable PRO assessment during biomarker-guided therapies.