Design and evaluation of a deep learning-based automatic segmentation of maxillary and mandibular substructures using a 3D U-Net.

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.

Inflammatory pathways confer resistance to chemoradiotherapy in anal squamous cell carcinoma.

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.

Prostate cancer and elective nodal radiation therapy for cN0 and pN0-a never ending story? : Recommendations from the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO).

For prostate cancer, the role of elective nodal irradiation (ENI) for cN0 or pN0 patients has been under discussion for years. Considering the recent publications of randomized controlled trials, the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO) aimed to discuss and summarize the current literature. Modern trials have been recently published for both treatment-naïve patients (POP-RT trial) and patients after surgery (SPPORT trial). Although there are more reliable data to date, we identified several limitations currently complicating the definitions of general recommendations. For patients with cN0 (conventional or PSMA-PET staging) undergoing definitive radiotherapy, only men with high-risk factors for nodal involvement (e.g., cT3a, GS ≥ 8, PSA ≥ 20 ng/ml) seem to benefit from ENI. For biochemical relapse in the postoperative situation (pN0) and no PSMA imaging, ENI may be added to patients with risk factors according to the SPPORT trial (e.g., GS ≥ 8; PSA > 0.7 ng/ml). If PSMA-PET/CT is negative, ENI may be offered for selected men with high-risk factors as an individual treatment approach.

Whole-pelvic irradiation with boost to involved nodes and prostate in node-positive prostate cancer-long-term data from the prospective PLATIN-2 trial.

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.

Adaptive radiotherapy for breast cancer.

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.

Estimation of secondary cancer projected risk after partial breast irradiation at the 1.5 T MR-linac.

PURPOSE: For patients treated with partial breast irradiation (PBI), potential long-term treatment-related toxicities are important. The 1.5 T magnetic resonance guided linear accelerator (MRL) offers excellent tumor bed visualization and a daily treatment plan adaption possibility, but MRL-specific electron stream and return effects may cause increased dose deposition at air-tissue interfaces. In this study, we aimed to investigate the projected risk of radiation-induced secondary malignancies (RISM) in patients treated with PBI at the 1.5 T MRL. METHODS: Projected excess absolute risk values (EARs) for the contralateral breast, lungs, thyroid and esophagus were estimated for 11 patients treated with PBI at the MRL and compared to 11 patients treated with PBI and 11 patients treated with whole breast irradiation (WBI) at the conventional linac (CTL). All patients received 40.05 Gy in 15 fractions. For patients treated at the CTL, additional dose due to daily cone beam computed tomography (CBCT) was simulated. The t­test with Bonferroni correction was used for comparison. RESULTS: The highest projected risk for a radiation-induced secondary cancer was found for the ipsilateral lung, without significant differences between the groups. A lower contralateral breast EAR was found for MRL-PBI (EAR = 0.89) compared to CTL-PBI (EAR = 1.41, p = 0.01), whereas a lower thyroid EAR for CTL-PBI (EAR = 0.17) compared to MRL-PBI (EAR = 0.33, p = 0.03) and CTL-WBI (EAR = 0.46, p = 0.002) was observed. Nevertheless, when adding the CBCT dose no difference between thyroid EAR for CTL-PBI compared to MRL-PBI was detected. CONCLUSION: Better breast tissue visualization and the possibility for daily plan adaption make PBI at the 1.5 T MRL particularly attractive. Our simulations suggest that this treatment can be performed without additional projected risk of RISM.

Acceptance of physical activity monitoring in cancer patients during radiotherapy, the GIROfit phase 2 pilot trial.

Background: In radiotherapy the timely identification of patients needing intervention and supportive care due to side effects is an important task especially in the outpatient setting. Activity trackers as an increasingly used lifestyle device may enable physicians to monitor patient's physical activity (PA) and to intervene early during the course of radiotherapy. Objective: The primary aim of this trial was to assess patient acceptance of PA monitoring in an outpatient setting and to correlate changes in PA with toxicity and changes in quality of life. Methods: Patients undergoing radio(chemo-)therapy with a curative intent were eligible to participate in this prospective pilot phase II trial. Patients were instructed to wear a commercially available activity tracker during the course of radiotherapy and four weeks afterwards. Quality of life (QoL) and fatigue was scored using the Functional assessment of Chronic Illness Therapy questionnaire. A linear regression was performed to determine baseline activity and changes in step counts during radiotherapy. Results: We included 23 patients in this trial. Two withdrew consent before the start of treatment, two patients were excluded after prophylactic feeding tube placement and prolonged recovery. Compliance in the remaining 19 patients was high, with availability of step-counts on 92% of the days. Baseline step counts were 6274 for breast cancer patients and 3621 for patients with other entities. Decreasing activity during radiotherapy coincided with the development of side effects and declines in quality of life. Conclusions: Activity trackers as tool to monitor PA during and after radiotherapy were accepted by a majority of the patients included in the current trial. Observed changes in PA correlated with patient reported side effects and QoL in some of the patients.

Evaluation of prognostic factors after primary chemoradiotherapy of anal cancer: A multicenter study of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG).

BACKGROUND AND PURPOSE: Prognosis after chemoradiotherapy (CRT) for anal squamous cell carcinoma (ASCC) shows marked differences among patients according to TNM subgroups, however individualized risk assessment tools to better stratify patients for treatment (de-) escalation or intensified follow-up are lacking in ASCC. MATERIALS AND METHODS: Patients' data from eight sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG), comprising a total of 605 patients with ASCC, treated with standard definitive CRT with 5-FU/Mitomycin C or Capecitabine/Mitomycin C between 2004-2018, were used to evaluate prognostic factors based on Cox regression models for disease-free survival (DFS). Evaluated variables included age, gender, Karnofsky performance score (KPS), HIV-status, T-category, lymph node status and laboratory parameters. Multivariate cox models were separately constructed for the whole cohort and the subset of patients with early-stage (cT1-2 N0M0) tumors. RESULTS: After a median follow-up of 46 months, 3-year DFS for patients with early-stage ASCC was 84.9%, and 67.1% for patients with locally-advanced disease (HR 2.4, p < 0.001). T-category (HR vs. T1: T2 2.02; T3 2.11; T4 3.03), N-category (HR versus N0: 1.8 for N1-3), age (HR 1.02 per year), and KPS (HR 0.8 per step) were significant predictors for DFS in multivariate analysis in the entire cohort. The model performed with a C-index of 0.68. In cT1-2N0 patients, T-category (HR 2.14), HIV status (HR 2.57), age (1.026 per year), KPS (HR 0.7 per step) and elevated platelets (HR 1.3 per 100/nl) were associated with worse DFS (C-index of 0.7). CONCLUSION: Classical clinicopathologic parameters like T-category, N-category, age and KPS remain to be significant prognostic factors for DFS in patients treated with contemporary CRT for ASCC. HIV and platelets were significantly associated with worse DFS in patients with early stage ASCC.

Primary immunosuppressive TNI-based conditioning regimens in pediatric patients treated with haploidentical hematopoietic cell transplantation.

PURPOSE: This retrospective analysis aims to address the toxicity and efficacy of a modified total nodal irradiation (TNI)-based conditioning regimen before haploidentical hematopoietic cell transplantation (HCT) in pediatric patients. MATERIALS AND METHODS: Patient data including long-term follow-up were evaluated of 7 pediatric patients with malignant (n = 2) and non-malignant diseases (n = 5) who were treated by a primary TNI-based conditioning regimen. TNI was performed using anterior/posterior opposing fields. All patients received 7 Gy single-dose TNI combined with systemic agents followed by an infusion of peripheral blood stem cells (n = 7). All children had haploidentical family donors. RESULTS: Engraftment was reached in 6/7 children after a median time of 9.5 days; 1 child had primary graft failure but was successfully reconditioned shortly thereafter. After an average follow-up time of 103.5 months (range 8.8-138.5 months), event-free (EFS) and overall survival (OS) rates were 71.4% and 85.7%, respectively. One child with a non-malignant disease died 8.8 months after transplantation due to a relapse and a multiple organ failure. Follow-up data was available for 5/6 long-term survivors with a median follow-up (FU) of 106.2 months (range 54.5-138.5 months). Hypothyroidism and deficiency of sexual hormones was present in 3/5 patients each. Mean forced expiratory volume in 1 s (FEV1) after TNI was 71%; mean vital capacity (VC) was 78%. Growth failure (< 10th percentile) occurred in 2/5 patients (height) and 1/5 patient (weight). No secondary malignancies were reported. CONCLUSION: In this group of patients, a primary single-dose 7 Gy TNI-based conditioning regimen before HCT in pediatric patients allowed sustained engraftment combined with a tolerable toxicity profile leading to long-term OS/EFS. Late toxicity after a median FU of over 9 years includes growth failure, manageable hormonal deficiencies, and acceptable decrease in lung function.

Integration of radiation oncology teaching in medical studies by German medical faculties due to the new licensing regulations : An overview and recommendations of the consortium academic radiation oncology of the German Society for Radiation Oncology (DEGRO).

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.

Analysis of the electron-stream effect in patients treated with partial breast irradiation using the 1.5 T MR-linear accelerator.

INTRODUCTION: The hybrid magnetic resonance linear accelerator (MRL) has the potential to test novel concepts in breast cancer patients such as daily MR-guided real-time plan adaptation. Before starting clinical trials, preparatory studies for example of the MR-dependent electron stream effect (ESE) are necessary. MATERIAL AND METHODS: To prospectively investigate the ESE, data from 11 patients treated with partial breast irradiation (PBI) at the 1.5 T MRL were evaluated. A bolus was placed on the chin and in vivo dosimetry results were compared with the dose simulated by the treatment planning system (TPS). The same measurements were carried out for three patients treated at a conventional linac. Toxicity and cosmesis were evaluated. RESULTS: Median doses measured and simulated on top/ underneath the bolus were 1.91 / 0.62 Gy and 2.82 / 0.63 Gy, respectively. Median differences between calculations and measurements were 0.8 Gy and 0.1 Gy. At the conventional linac, median measured doses on top/ underneath the bolus were 0.98 and 1.37 Gy. No acute toxicity exceeding grade 2 was recorded. Cosmesis was good or excellent and patient reported outcome measures were mostly scored as none or mild. CONCLUSION: The dose due to the ESE is low, correctly predicted by the TPS and effectively minimized by a bolus.

Marker-less online MR-guided stereotactic body radiotherapy of liver metastases at a 1.5 T MR-Linac - Feasibility, workflow data and patient acceptance.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is an established ablative treatment for liver tumors with excellent local control rates. Magnetic resonance imaging guided radiotherapy (MRgRT) provides superior soft tissue contrast and may therefore facilitate a marker-less liver SBRT workflow. The goal of the present study was to investigate feasibility, workflow parameters, toxicity and patient acceptance of MRgSBRT on a 1.5 T MR-Linac. METHODS: Ten consecutive patients with liver metastases treated on a 1.5 T MR-Linac were included in this prospective trial. Tumor delineation was performed on four-dimensional computed tomography scans and both exhale triggered and free-breathing T2 MRI scans from the MR-Linac. An internal target volume based approach was applied. Organ at risk constraints were based on the UKSABR guidelines (Version 6.1). Patient acceptance regarding device specific aspects was assessed and toxicity was scored according to the common toxicity criteria of adverse events, version 5. RESULTS: Nine of ten tumors were clearly visible on the 1.5 T MR-Linac. No patient had fiducial markers placed for treatment. All patients were treated with three or five fractions. Median dose to 98% of the gross tumor volume was 38.5 Gy. The median time from "patient identity check" until "beam-off" was 31 min. Median beam on time was 9.6 min. Online MRgRT was well accepted in general and no treatment had to be interrupted on patient request. No event of symptomatic radiation induced liver disease was observed after a median follow-up of ten month (range 3-17 months). CONCLUSION: Our early experience suggests that online 1.5 T MRgSBRT of liver metastases represents a promising new non-invasive marker-free treatment modality based on high image quality, clinically reasonable in-room times and high patient acceptance. Further studies are necessary to assess clinical outcome, to validate advanced motion management and to explore the benefit of online response adaptive liver SBRT.

Treatment outcome after radiochemotherapy in anal cancer patients staged with 18F-FDG-PET-CT.

BACKGROUND: Anal cancer (AC) is a malignancy with increasing incidence and commonly treated with radiochemotherapy. Positron-emission tomography-computed tomography (PET/CT) has been shown to improve treatment outcome in various oncological diseases, however, for AC long-term outcome data is sparse. The aim of the present study is therefore to report outcomes in our cohort of PET/CT staged AC patients treated with radiochemotherapy. METHODS: Patients with AC who were treated with radiochemotherapy in curative intent were included in this retrospective study if a PET/CT scan was performed pre-therapeutically. Information from PET/CT was considered for nodal and primary target volume definition. Radiotherapy dose to the primary tumor was 50-66 Gy and concomitant chemotherapy included 5-fluorouracil and mitomycin-C. The uptake of 18F-fluorodeoxyglucose (FDG) was quantified using 50%-isocontour volumes of interests (VOIs) and measuring the standardized uptake value (SUV) and the metabolic tumor volume (MTV).18F-FDG uptake was correlated with baseline clinical parameters and long-term oncological outcome. Survival estimates were determined according to Kaplan-Meier. RESULTS: A total of 60 patients were included in this study. Estimates for three-year overall survival (OS) and disease free survival (DFS) were 94.5% and 80%. Five patients developed local (n = 2) or locoregional and local (n = 3) failure. Baseline PET/CT related parameters correlated with primary tumor stage, nodal stage and tumor grading. DFS was independent of T-stage, N-stage and baseline 18F-FDG-uptake. CONCLUSION: In this cohort of PET/CT staged AC patients, excellent outcomes for DFS were seen. PET-based markers of tumor burden correlate with local stage of AC, however, are not of prognostic relevance for disease-free survival.

68Ga-PSMA-PET/CT-directed IGRT/SBRT for oligometastases of recurrent prostate cancer after initial surgery.

Background: We evaluated efficacy and toxicity of 68Ga-PSMA-Positron Emission Tomography/Computed Tomography (PET/CT)-directed stereotactic body radiotherapy and image-guided radiotherapy (SBRT/IGRT) for oligometastases of prostate cancer recurrences after previous surgery.Methods: Nineteen patients were analyzed within a prospective PET-registry study (064/2013BO1) and retrospectively analyzed (807/2017BO2) fulfilling the following inclusion criteria: biochemical recurrence after radical prostatectomy, ≤five 68Ga-PSMA-PET/CT positive lesions. Biochemical control was evaluated with EORTC (European Organization for Research and Treatment of Cancer)- and Phenix-definitions. Toxicity was scored according to CTCAE-criteria v. 4.03.Results: A total of 38 oligometastases (19 patients, 2 with re-treatment) were treated with SBRT/IGRT from October 2014 to July 2017. 68Ga-PSMA-PET/CT-positive lesions were detected on average 39 months (5-139) after prostatectomy (pT2b-3b pN0-1 cM0). Mean PSA (Prostate-specific antigen)-level at time of imaging reached 2.2 ng/mL (range 0.2-10.1). PET/CT-positive lesions were treated with different fractionation schedules reaching biological equivalent doses (BED) of 116.7-230.0 Gy. Concomitant androgen deprivation therapy (ADT) was given in seven patients. After a median follow-up of 17 months (4-42) all patients were alive. Estimated 1-year PSA- control (n = 19) reached 80.8% (Phenix) and 67.5% (EORTC). A PSA-decline (≥50%) was detected in 16/19 patients after radiotherapy. Higher graded G3+-acute toxicity did not occur. Temporary late G3-proctitis was detected in one patient.Conclusions: Reaching of nadir ≤0.1 or 0.2 ng/mL was associated by improved DMFS (distant metastases free survival) and could serve as a surrogate endpoint for RT of oligometastases after initial prostatectomy. Short term effects of 68Ga-PSMA-PET/CT-based ablative radiotherapy for oligometastases demonstrated an acceptable toxicity profile and favorable biochemical response.

Interference of tumour mutational burden with outcome of patients with head and neck cancer treated with definitive chemoradiation: a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group.

BACKGROUND: Tumour mutational burden (TMB) estimated from whole exome sequencing or comprehensive gene panels has previously been established as predictive factor of response to immune checkpoint inhibitors (ICIs). Its predictive value for the efficacy of concurrent chemoradiation (cCRTX), a potential combination partner of ICI, remains unknown. METHODS: The accuracy of TMB estimation by an in-house 327-gene panel was established in the Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) data set. Interference of TMB with outcome after cCRTX was determined in a multicentre cohort of patients with locally advanced HNSCC uniformly treated with cCRTX. Targeted next-generation sequencing was successfully applied in 101 formalin-fixed, paraffin-embedded pretreatment tumour samples. In a subset of cases (n = 40), tumour RNA was used for immune-related gene expression profiling by the nanoString platform. TMB was correlated with TP53 genotype, human papilloma virus (HPV) status, immune expression signatures and survival parameters. Results were validated in the TCGA HNSCC cohort. RESULTS: A high accuracy of TMB estimation by the 327-gene panel was established. High TMB was significantly associated with an increased prevalence of TP53 mutations and immune gene expression patterns unrelated to T cell-inflamed gene expression profiles. Kaplan-Meier analysis revealed significantly reduced overall survival in the patient group with high TMB (hazard ratio for death: 1.79, 95% confidence interval: 1.02-3.14; P = 0.042) which remained significant after correcting for confounding factors in the multivariate model. The prognostic value of TMB was confirmed in the TCGA HNSCC cohort. CONCLUSION: High TMB identifies HNSCC patients with poor outcome after cCRTX who might preferentially benefit from CRTX-ICI combinations.

Radiation Pneumonitis after Intensity-Modulated Radiotherapy for Esophageal Cancer: Institutional Data and a Systematic Review.

Radiation pneumonitis (RP) is a serious complication that can occur after thoracic radiotherapy. The goal of this study is to investigate the incidence of RP after radiochemotherapy with intensity modulated radiotherapy (IMRT) in patients with esophageal cancer and correlate this with dose volume histogram (DVH) related parameters. For this purpose, the clinical course of 73 patients was evaluated and irradiation doses to the lungs were extracted from radiotherapy treatment plans. Furthermore, a systematic review on this topic was conducted across PubMed. In our institutional cohort, Common Terminology Criteria for Adverse Events (CTCAE) grade II or higher RP occurred in four patients (5.5%). The systematic review identified 493 titles of which 19 studies reporting 874 patients qualified for the final analysis. No grade IV or V RP after radiochemotherapy with IMRT for esophageal cancer was reported in the screened literature. Grade II or higher RP is reported in 6.6% of the patients. A higher incidence can be seen with increasing values for lung V20. In conclusion, our institutional data and the literature consistently show a low incidence of symptomatic RP after radiochemotherapy in patients with esophageal cancer treated with IMRT. However, efforts should be made to keep the lung V20 below 23% and specific caution is warranted in patients with pre-existing lung conditions.

Hyperthermic chest wall re-irradiation in recurrent breast cancer: a prospective observational study.

PURPOSE: To prospectively investigate the role of re-irradiation (re-RT) combined with hyperthermia (HT) in a contemporary cohort of patients affected by recurrent breast cancer (RBC). METHODS: Within the prospective registry HT03, patients with resected RBC and previous irradiation were included. Re-RT was applied to the recurrence region with doses of 50-50.4 Gy, with a boost up to 60-60.4 Gy to the microscopically or macroscopically positive resection margins (R1/R2) region. Concurrent HT was performed at 40-42 ℃. Primary endpoint was LC. Acute and late toxicity, overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) were also evaluated. RESULTS: 20 patients and 21 RBC were analyzed. Median re-RT dose was 50.4 Gy and a median of 11 HT fractions were applied. Re-RT+HT was well tolerated, with three patients who experienced a grade (G) 3 acute skin toxicity and no cases of ≥G3 late toxicity. With a median follow up of 24.7 months, two local relapses occurred. Ten patients experienced regional and/or distant disease progression. Five patients died, four of them from breast cancer. PFS was favorable in patients treated with re-RT+HT for the first recurrence with doses of 60 Gy. A trend towards better CSS was found in patients with negative or close margins and after doses of 60 Gy. CONCLUSION: Full-dose re-RT+HT for RBC is well tolerated, provides good LC, and seems to be more effective when applied at the time of the first relapse and after doses of 60 Gy. The registry will be continued for validation in a larger cohort and with longer follow-up.

Precision of T2 TSE MRI-CT-image fusions based on gold fiducials and repetitive T2 TSE MRI-MRI-fusions for adaptive IGRT of prostate cancer by using phantom and patient data.

INTRODUCTION: To increase precision of radiation treatment (RT) delivery in prostate cancer, MRI-based RT as well as the use of fiducials like gold markers (GMs) have shown promising results. Their combined use is currently under investigation in clinical trials. Here, we aimed to evaluate a workflow of image registration based on GMs between CT and MRI as well as weekly MRI-MRI adaption based on T2 TSE sequence. MATERIAL AND METHODS: A gel-phantom with two inserted GMs was scanned with CT and three different MR-scanners of 1.5 and 3 T (T2 TSE and T1 VIBE-Dixon, isotropic, voxel size 2 × 2 × 2 mm). After image fusion, deviations for fiducial and gel match were measured and artifacts were evaluated. Additionally, CT-MRI-match deviations and MRI-MRI-match deviations of 10 Patients from the M-basePro study using GMs were assessed. RESULTS: GMs were visible in all imaging modalities. The outer gel contours were matched with <1 mm deviation, contour volumes varied between 0 and 1%. The deviations of the GMs were less than 2 mm in any direction of MRI/CT. Shifts of peripherally or centrally located GMs were randomly distributed. The average MRI-CT-match precision of 10 patients with GMs was 1.9 mm (range 1.1-3.1 mm). CONCLUSIONS: Match inaccuracies for GMs between reference CT and voxel-isotropic T2-TSE sequences are small. Spatial deviations of CT- and MR-contoured fiducials were less than 2 mm, i.e., below SLT of the applied modalities. In patients, the average CT-MRI-match precision for GMs was 1.9 mm supporting their use in MR-guided high precision RT.

Unilateral cochlea sparing in locoregionally advanced head and neck cancer: a planning study.

BACKGROUND: Cochlea sparing can reduce late ototoxicity in head and neck cancer patients treated with cisplatin-based radiochemotherapy. In this situation, a mean cochlear dose (MCD) constraint of 10 Gy has been suggested by others based on the dose-effect relationship of clinical data. We aimed to investigate whether this is feasible for primary and postoperative radiochemotherapy in locoregionally advanced tumors without compromising target coverage. PATIENTS AND METHODS: Ten patients treated with definitive and ten patients treated with adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy were investigated. The cochleae and a planning risk volume (PRV) with a 3 mm margin were newly delineated, whereas target volumes and other organs at risk were not changed. The initial plan was recalculated with a constraint of 10 Gy (MCD) on the low-risk side. The quality of the resulting plan was evaluated using the difference in the equivalent uniform dose (EUD). RESULTS: A unilateral MCD of below 10 Gy could be achieved in every patient. The mean MCD was 6.8 Gy in the adjuvant cohort and 7.6 Gy in the definitive cohort, while the non-spared side showed a mean MCD of 18.7 and 30.3 Gy, respectively. The mean PRV doses were 7.8 and 8.4 Gy for the spared side and 18.5 and 29.8 Gy for the non-spared side, respectively. The mean EUD values of the initial and recalculated plans were identical. Target volume was not compromised. CONCLUSION: Unilateral cochlea sparing with an MCD of less than 10 Gy is feasible without compromising the target volume or dose coverage in locoregionally advanced head and neck cancer patients treated with IMRT. A prospective evaluation of the clinical benefit of this approach as well as further investigation of the dose-response relationship for future treatment modification appears promising.