Development and evaluation of two open-source nnU-Net models for automatic segmentation of lung tumors on PET and CT images with and without respiratory motion compensation.

OBJECTIVES: In lung cancer, one of the main limitations for the optimal integration of the biological and anatomical information derived from Positron Emission Tomography (PET) and Computed Tomography (CT) is the time and expertise required for the evaluation of the different respiratory phases. In this study, we present two open-source models able to automatically segment lung tumors on PET and CT, with and without motion compensation. MATERIALS AND METHODS: This study involved time-bin gated (4D) and non-gated (3D) PET/CT images from two prospective lung cancer cohorts (Trials 108237 and 108472) and one retrospective. For model construction, the ground truth (GT) was defined by consensus of two experts, and the nnU-Net with 5-fold cross-validation was applied to 560 4D-images for PET and 100 3D-images for CT. The test sets included 270 4D- images and 19 3D-images for PET and 80 4D-images and 27 3D-images for CT, recruited at 10 different centres. RESULTS: In the performance evaluation with the multicentre test sets, the Dice Similarity Coefficients (DSC) obtained for our PET model were DSC(4D-PET) = 0.74 ± 0.06, improving 19% relative to the DSC between experts and DSC(3D-PET) = 0.82 ± 0.11. The performance for CT was DSC(4D-CT) = 0.61 ± 0.28 and DSC(3D-CT) = 0.63 ± 0.34, improving 4% and 15% relative to DSC between experts. CONCLUSIONS: Performance evaluation demonstrated that the automatic segmentation models have the potential to achieve accuracy comparable to manual segmentation and thus hold promise for clinical application. The resulting models can be freely downloaded and employed to support the integration of 3D- or 4D- PET/CT and to facilitate the evaluation of its impact on lung cancer clinical practice. CLINICAL RELEVANCE STATEMENT: We provide two open-source nnU-Net models for the automatic segmentation of lung tumors on PET/CT to facilitate the optimal integration of biological and anatomical information in clinical practice. The models have superior performance compared to the variability observed in manual segmentations by the different experts for images with and without motion compensation, allowing to take advantage in the clinical practice of the more accurate and robust 4D-quantification. KEY POINTS: Lung tumor segmentation on PET/CT imaging is limited by respiratory motion and manual delineation is time consuming and suffer from inter- and intra-variability. Our segmentation models had superior performance compared to the manual segmentations by different experts. Automating PET image segmentation allows for easier clinical implementation of biological information.

Deep inspiration breath-hold radiation therapy in left-sided breast cancer patients: a single-institution retrospective dosimetric analysis of organs at risk doses.

BACKGROUND: Radiotherapy can induce cardiac injury in left-sided breast cancer cases. Cardiac-sparing irradiation using the deep inspiration breath-hold (DIBH) technique can achieve substantial dose reduction to vulnerable cardiac substructures compared with free breathing (FB). This study evaluated the dosimetric differences between both techniques at a single institution. METHODS: From 2017 to 2019, 130 patients with left-sided breast cancer underwent breast-conserving surgery (BCS; n = 121, 93.1%) or mastectomy (ME; n = 9, 6.9%) along with axillary lymph node staging (n = 105, 80.8%), followed by adjuvant irradiation in DIBH technique; adjuvant systemic therapy was included if applicable. 106 (81.5%) patients received conventional and 24 (18.5%) hypofractionated irradiation. Additionally, 12 patients received regional nodal irradiation. Computed tomography (CT) scans in FB and DIBH position were performed for all patients. Intrafractional 3D position monitoring of the patient surface in deep inspiration and breath gating was performed using Sentinel and Catalyst HD 3D surface scanning systems (C-RAD, Catalyst, C­RAD AB, Uppsala, Sweden). Individual coaching and determination of breathing amplitude during the radiation planning CT was performed. Three-dimensional treatment planning was performed using standard tangential treatment portals (6 or 18 MV). The delineation of cardiac structures and both lungs was done in both the FB and the DIBH scan. RESULTS: All dosimetric parameters for cardiac structures were significantly reduced (p < 0.01 for all). The mean heart dose (Dmean) in the DIBH group was 1.3 Gy (range 0.5-3.6) vs. 2.2 Gy (range 0.9-8.8) in the FB group (p < 0.001). The Dmean for the left ventricle (LV) in DIBH was 1.5 Gy (range 0.6-4.5), as compared to 2.8 Gy (1.1-9.5) with FB (p < 0.001). The parameters for LV (V10 Gy, V15 Gy, V20 Gy, V23 Gy, V25 Gy, V30 Gy) were reduced by about 100% (p < 0.001). The LAD Dmean in the DIBH group was 4.1 Gy (range 1.2-33.3) and 14.3 Gy (range 2.4-37.5) in the FB group (p < 0.001). The median values for LAD such as V15 Gy, V20 Gy, V25 Gy, V30 Gy, and V40 Gy decreased by roughly 100% (p < 0.001). An increasing volume of left lung in the DIBH position resulted in dose sparing of cardiac structures. CONCLUSION: For all ascertained dosimetric parameters, a significant dose reduction could be achieved in DIBH technique.

Cost effectiveness and health-related quality of life of chemoradiotherapy versus radiation therapy alone in elderly head and neck cancer patients.

PURPOSE: Radiotherapy (RT) constitutes a mainstay in the treatment of elderly patients with head and neck cancer (HNC), but use of simultaneous chemoradiotherapy (CRT) remains controversial. We have conducted a prospective analysis based on real-world patient data to examine the health-related quality of life (HRQoL) and cost effectiveness (CE) of CRT vs. RT in elderly HNC patients. METHODS: Eligible participants ≥ 65 years treated in a large tertiary cancer center between July 2019 and February 2020 who completed the validated EQ-5D-5L questionnaire (health state index [HI] and visual analog scale [VAS]) before and after RT were included. CE referred to direct medical costs, including diagnosis-related group (DRG)-based billings for inpatients and uniform assessment standard (EBM)-based costs for outpatients. The primary endpoint was cost (euros [€]) per quality-adjusted life year (QALY). The incremental cost-effectiveness ratios (ICERs) were calculated. Costs and QALYs were not discounted for short overall survival (OS). RESULTS: Baseline HRQoL was 0.878 (±0.11) in the CRT group and 0.857 (±0.17) in the RT group. Upon completion of therapy, HRQoL amounted to 0.849 (±0.14) in the CRT and 0.850 (±0.13) in the RT group. The mean treatment-related cost in the CRT cohort was €22,180.17 (±8325.26) vs. €18,027.87 (±26,022.48) in the RT group. The corresponding QALYs amounted to 2.62 in the CRT and 1.91 in the RT groups. The ICER was €5848.31. CONCLUSION: This is the first analysis from the German health care system demonstrating that the addition of chemotherapy to RT for selected elderly HNC patients is cost effective and not associated with a significant HRQoL decline.

Optimization of hippocampus sparing during whole brain radiation therapy with simultaneous integrated boost-tutorial and efficacy of complete directional hippocampal blocking.

PURPOSE: Hippocampus-avoidance whole brain radiotherapy with simultaneous integrated boost (HA-WBRT+SIB) is a complex treatment option for patients with multiple brain metastases, aiming to prevent neurocognitive decline and simultaneously increase tumor control. Achieving efficient hippocampal dose reduction in this context can be challenging. The aim of the current study is to present and analyze the efficacy of complete directional hippocampal blocking in reducing the hippocampal dose during HA-WBRT+SIB. METHODS: A total of 30 patients with multiple metastases having undergone HA-WBRT+SIB were identified. The prescribed dose was 30 Gy in 12 fractions to the whole brain, with 98% of the hippocampus receiving ≤ 9 Gy and 2% ≤ 17 Gy and with SIB to metastases/resection cavities of 36-51 Gy in 12 fractions. Alternative treatment plans were calculated using complete directional hippocampal blocking and compared to conventional plans regarding target coverage, homogeneity, conformity, dose to hippocampi and organs at risk. RESULTS: All alternative plans reached prescription doses. Hippocampal blocking enabled more successful sparing of the hippocampus, with a mean dose of 8.79 ± 0.99 Gy compared to 10.07 ± 0.96 Gy in 12 fractions with the conventional method (p < 0.0001). The mean dose to the whole brain (excluding metastases and hippocampal avoidance region) was 30.52 ± 0.80 Gy with conventional planning and 30.28 ± 0.11 Gy with hippocampal blocking (p = 0.11). Target coverage, conformity and homogeneity indices for whole brain and metastases, as well as doses to organs at risk were similar between planning methods (p > 0.003). CONCLUSION: Complete directional hippocampal blocking is an efficient method for achieving improved hippocampal sparing during HA-WBRT+SIB.

Interleukin-6 as surrogate marker for imaging-based hypoxia dynamics in patients with head-and-neck cancers undergoing definitive chemoradiation-results from a prospective pilot trial.

PURPOSE: Intratumoral hypoxia increases resistance of head-and-neck squamous cell carcinoma (HNSCC) to radiotherapy. [18F]FMISO PET imaging enables noninvasive hypoxia monitoring, though requiring complex logistical efforts. We investigated the role of plasma interleukin-6 (IL-6) as potential surrogate parameter for intratumoral hypoxia in HNSCC using [18F]FMISO PET/CT as reference. METHODS: Within a prospective trial, serial blood samples of 27 HNSCC patients undergoing definitive chemoradiation were collected to analyze plasma IL-6 levels. Intratumoral hypoxia was assessed in treatment weeks 0, 2, and 5 using [18F]FMISO PET/CT imaging. The association between PET-based hypoxia and IL-6 was examined using Pearson's correlation and multiple regression analyses, and the diagnostic power of IL-6 for tumor hypoxia response prediction was determined with receiver-operating characteristic analyses. RESULTS: Mean IL-6 concentrations were 15.1, 19.6, and 31.0 pg/mL at baseline, week 2 and week 5, respectively. Smoking (p=0.050) and reduced performance status (p=0.011) resulted in higher IL-6 levels, whereas tumor (p=0.427) and nodal stages (p=0.334), tumor localization (p=0.439), and HPV status (p=0.294) had no influence. IL-6 levels strongly correlated with the intratumoral hypoxic subvolume during treatment (baseline: r=0.775, p<0.001; week 2: r=0.553, p=0.007; week 5: r=0.734, p<0.001). IL-6 levels in week 2 were higher in patients with absent early tumor hypoxia response (p=0.016) and predicted early hypoxia response (AUC=0.822, p=0.031). Increased IL-6 levels at week 5 resulted in a trend towards reduced progression-free survival (p=0.078) and overall survival (p=0.013). CONCLUSION: Plasma IL-6 is a promising surrogate marker for tumor hypoxia dynamics in HNSCC patients and may facilitate hypoxia-directed personalized radiotherapy concepts. TRIAL REGISTRATION: The prospective trial was registered in the German Clinical Trial Register (DRKS00003830). Registered 20 August 2015.

Incidental irradiation of the regional lymph nodes during deep inspiration breath-hold radiation therapy in left-sided breast cancer patients: a dosimetric analysis.

BACKGROUND: Radiotherapy using the deep inspiration breath-hold (DIBH) technique compared with free breathing (FB) can achieve substantial reduction of heart and lung doses in left-sided breast cancer cases. The anatomical organ movement in deep inspiration also cause unintended exposure of locoregional lymph nodes to the irradiation field. METHODS: From 2017-2020, 148 patients with left-sided breast cancer underwent breast conserving surgery (BCS) or mastectomy (ME) with axillary lymph node staging, followed by adjuvant irradiation in DIBH technique. Neoadjuvant or adjuvant systemic therapy was administered depending on hormone receptor and HER2-status. CT scans in FB and DIBH position with individual coaching and determination of the breathing amplitude during the radiation planning CT were performed for all patients. Intrafractional 3D position monitoring of the patient surface in deep inspiration and gating was performed using Sentinel and Catalyst HD 3D surface scanning systems (C-RAD, Catalyst, C-RAD AB, Uppsala, Sweden). Three-dimensional treatment planning was performed using standard tangential treatment portals (6 or 18 MV). The delineation of ipsilateral locoregional lymph nodes was done on the FB and the DIBH CT-scan according to the RTOG recommendations. RESULTS: The mean doses (Dmean) in axillary lymph node (AL) level I, II and III in DIBH were 32.28 Gy (range 2.87-51.7), 20.1 Gy (range 0.44-53.84) and 3.84 Gy (range 0.25-39.23) vs. 34.93 Gy (range 10.52-50.40), 16.40 Gy (range 0.38-52.40) and 3.06 Gy (range 0.21-40.48) in FB (p < 0.0001). Accordingly, in DIBH the Dmean for AL level I were reduced by 7.59%, whereas for AL level II and III increased by 22.56% and 25.49%, respectively. The Dmean for the supraclavicular lymph nodes (SC) in DIBH was 0.82 Gy (range 0.23-4.11), as compared to 0.84 Gy (range 0.22-10.80) with FB (p = 0.002). This results in a mean dose reduction of 2.38% in DIBH. The Dmean for internal mammary lymph nodes (IM) was 12.77 Gy (range 1.45-39.09) in DIBH vs. 11.17 Gy (range 1.34-44.24) in FB (p = 0.005). This yields a mean dose increase of 14.32% in DIBH. CONCLUSIONS: The DIBH technique may result in changes in the incidental dose exposure of regional lymph node areas.

CT-guided interstitial HDR-brachytherapy for recurrent glioblastoma multiforme: a 20-year single-institute experience.

PURPOSE: To report our results of computed tomography-guided interstitial high-dose-rate (HDR) brachytherapy (BRT) in the treatment of patients with recurrent inoperable glioblastoma multiforme (GBM). PATIENTS AND METHODS: Between 1995 and 2014, 135 patients were treated with interstitial HDR BRT for inoperable recurrent GBM located within previously irradiated volumes. Patient's median age was 57.1 years (14-82 years). All patients were pretreated with surgery, postoperative external beam radiation therapy (EBRT) and systemic chemotherapy (ChT). The median recurrent tumor volume was 42 cm3 (2-207 cm3). The prescribed HDR dose was median 40 Gy (30-50 Gy) delivered in twice-daily fractions of 5.0 Gy over consecutive days. No repeat surgery or ChT was administered in conjunction with BRT. Survival from BRT, progression-free survival (PFS), toxicity as well as the impact of several prognostic factors were evaluated. RESULTS: At a median follow-up of 9.2 months, the median overall survival following BRT and the median PFS were 9.2 and 4.6 months, respectively. Of the prognostic variables evaluated in univariate analysis, extent of surgery at initial diagnosis, tumor volume at recurrence, as well as time from EBRT to BRT reached statistical significance, retained also in multivariate analysis. Eight patients (5.9%) developed treatment-associated complications including intracerebral bleeding in 4 patients (2.9%), symptomatic focal radionecrosis in 3 patients (2.2%), and severe convulsion in 1 patient (0.7%). CONCLUSIONS: For patients with recurrent GBM, interstitial HDR BRT is an effective re-irradiation method for even larger tumors providing palliation without excessive toxicity.

Biological imaging for individualized therapy in radiation oncology: part I physical and technical aspects.

Recently, there has been an increase in the imaging modalities available for radiotherapy planning and radiotherapy prognostic outcome: dual energy computed tomography (CT), dynamic contrast enhanced CT, dynamic contrast enhanced magnetic resonance imaging (MRI), diffusion-weighted MRI, positron emission tomography-CT, dynamic contrast enhanced ultrasound, MR spectroscopy and positron emission tomography-MR. These techniques enable more precise gross tumor volume definition than CT alone and moreover allow subvolumes within the gross tumor volume to be defined which may be given a boost dose or an individual voxelized dose prescription may be derived. With increased plan complexity care must be taken to immobilize the patient in an accurate and reproducible manner. Moreover the physical and technical limitations of the entire treatment planning chain need to be well characterized and understood, interdisciplinary collaboration ameliorated (physicians and physicists within nuclear medicine, radiology and radiotherapy) and image protocols standardized.

Biological imaging for individualized therapy in radiation oncology: part II medical and clinical aspects.

Positron emission tomography and multiparametric MRI provide crucial information concerning tumor extent and normal tissue anatomy. Moreover, they are able to visualize biological characteristics of the tumor, which can be considered in the radiation treatment planning and monitoring. In this review we discuss the impact of biological imaging positron emission tomography and multiparametric MRI for radiation oncology, based on the data of the literature and on the experience of our own institution in this field.

Mathematical Description of Changes in Tumour Oxygenation from Repeated Functional Imaging.

Functional imaging of tumour hypoxia has been suggested as a tool for refining target definition and treatment optimization in radiotherapy. The approach, however, has been slow to be adopted clinically as most of the studies on the topic do not take into account the in-treatment changes of hypoxia. The present study aimed to introduce a function that quantifies the changes of oxygen distributions in repeated PET images taken during treatment. The proposed approach for determining the reoxygenation function was tested for feasibility on patients with head and neck cancer, repeatedly imaged with FMISO PET during radiotherapy. Reoxygenation functions were derived by solving the convolution between functions describing the oxygen distributions of successive images. The method was found to be mathematically feasible. The results indicate that the reoxygenation functions describing the change in oxygenation have distinct shapes prompting the hypothesis that oxygenation changes reflected by them might have predictive power for treatment outcome. Future studies on a larger patient population to search for predictive correlations based on the reoxygenation function are planned.

Simultaneous integrated protection : A new concept for high-precision radiation therapy.

OBJECTIVE: Stereotactic radiotherapy near serial organs at risk (OAR) requires special caution. A novel intensity-modulated radiotherapy (IMRT) prescription concept termed simultaneous integrated protection (SIP) for quantifiable and comparable dose prescription to targets very close to OAR is described. MATERIALS AND METHODS: An intersection volume of a planning risk volume (PRV) with the total planning target volume (PTV) defined the protection volume (PTVSIP). The remainder of the PTV represented the dominant PTV (PTVdom). Planning was performed using IMRT. Dose was prescribed to PTVdom according to ICRU in 3, 5, 8, or 12 fractions. Constraints to OARs were expressed as absolute and as equieffective doses at 2 Gy (EQD2). Dose to the gross risk volume of an OAR was to respect constraints. Violation of constraints to OAR triggered a planning iteration at increased fractionation. Dose to PTVSIP was required to be as high as possible within the constraints to avoid local relapse. RESULTS: SIP was applied in 6 patients with OAR being large airways (n = 2) or bowel (n = 4) in 3, 5, 8, and 12 fractions in 1, 3, 1, and 1 patients, respectively. PTVs were 14.5-84.9 ml and PTVSIP 1.8-3.9 ml (2.9-13.4 % of PTV). Safety of the plans was analyzed from the absolute dose-volume histogram (dose to ml). The steepness of dose fall-off could be determined by comparing the dose constraints to the PRVs with those to the OARs (Wilcoxon test p = 0.001). Constraints were respected for the corresponding OARs. All patients had local control at a median 9 month follow-up and toxicity was low. CONCLUSION: SIP results in a median dose of ≥100 % to PTV, to achieve high local control and low toxicity. Longer follow-up is required to verify results and a prospective clinical trial is currently testing this new approach in chest and abdomen stereotactic body radiotherapy.

Evaluation of RADIANCE Monte Carlo algorithm for treatment planning in electron based Intraoperative Radiotherapy (IOERT).

PURPOSE: To perform experimental as well as independent Monte Carlo (MC) evaluation of the MC algorithm implemented in RADIANCE version 4.0.8, a dedicated treatment planning system (TPS) for 3D electron dose calculations in intraoperative radiation therapy (IOERT). METHODS AND MATERIALS: The MOBETRON 2000 (IntraOp Medical Corporation, Sunnyvale, CA) IOERT accelerator was employed. PDD and profiles for five cylindrical plastic applicators with 50-90 mm diameter and 0°, 30° beveling were measured in a water phantom, at nominal energies of 6, 9 and 12 MeV. Additional PDD measurements were performed for all the energies without applicator. MC modeling of the MOBETRON was performed with the user code BEAMnrc and egs_chamber of the MC simulation toolkit EGSnrc. The generated phase space files of the two 0°-bevel applicators (50 mm, 80 mm) and three energies in both RADIANCE and BEAMnrc, were used to determine PDD and profiles in various set-ups of virtual water phantoms with air and bone inhomogeneities. 3D dose distributions were also calculated in image data sets of an anthropomorphic tissue-equivalent pelvis phantom. Image acquisitions were realized with a CT scanner (Philips Big Bore CT, Netherlands). Gamma analysis was applied to quantify the deviations of the RADIANCE calculations to the measurements and EGSnrc calculations. Gamma criteria normalized to the global maximum were investigated between 2%, 2 mm and 3%, 3 mm. RESULTS: RADIANCE MC calculations satisfied the gamma criteria of 3%, 3 mm with a tolerance limit of 85% passing rate compared to in- water phantom measurements, except for the dose profiles of the 30° beveled applicators. Mismatches lay in surface doses, in umbra regions and in the beveled end of the 30° applicators. A very good agreement to the EGSnrc calculations in heterogeneous media was observed. Deviations were more pronounced for the larger applicator diameter and higher electron energy. In 3D dose comparisons in the anthropomorphic phantom, gamma passing rates were higher than 96 % for both simulated applicators. CONCLUSIONS: RADIANCE MC algorithm agrees within 3%, 3 mm criteria with in-water phantom measurements and EGSnrc MC dose distributions in heterogeneous media for 0°-bevel applicators. The user should be aware of missing scattering components and the 30° beveled applicators should be used with attention.

Predictors of radiation-induced late rectal toxicity in prostate cancer treatment: a volumetric and dosimetric analysis.

Introduction: Prostate cancer (PCa) is a prevalent malignancy in European men, often treated with radiotherapy (RT) for localized disease. While modern RT achieves high success rates, concerns about late gastrointestinal (GI) toxicities persist. This retrospective study aims to identify predictors for late GI toxicities following definitive conventionally fractionated external beam RT (EBRT) for PCa, specifically exploring the dose to the rectal wall. Materials and methods: A cohort of 96 intermediate- to high-risk PCa patients underwent EBRT between 2008 and 2016. Rectum and rectum wall contours were delineated, and 3D dose matrices were extracted. Volumetric and dosimetric indices were computed, and statistical analyses were performed to identify predictors using the Mann-Whitney U-rank test, logistic regression, and recursive feature elimination. Results: In our cohort, 15 out of 96 patients experienced grade II late proctitis. Our analysis reveals distinct optimal predictors for rectum and rectum wall (RW) structures varying with α/ß values (3.0 and 2.3 Gy) across prescribed doses of 68 to 76 Gy. Despite variability, RW predictors demonstrate greater consistency, notably V68Gy[%] to V74Gy[%] for α/ß 3.0 Gy, and V68Gy[%] to V70Gy[%] for α/ß 2.3 Gy. The model with α/ß 2.3 Gy, featuring RW volume receiving 70 Gy (V70Gy[%]), stands out with a BIC value of 62.92, indicating its superior predictive effectiveness. Finally, focusing solely on the rectum structure, the V74Gy[%] emerges the best predictor for α/ß 3.0 Gy, with a BIC value of 66.73. Conclusion: This investigation highlights the critical role of V70Gy[%] in the rectum wall as a robust predictor for grade II late gastrointestinal (GI) toxicity following external beam radiation therapy (EBRT) for prostate cancer (PCa). Furthermore, our findings suggest that focusing on the rectum wall specifically, rather than the entire rectum, may offer improved accuracy in assessing proctitis development. A V70Gy (in EQD2 with α/ß 2.3 Gy) of ≤5% and if possible ≤1% for the rectal wall should be achieved to minimize the risk of late grade II proctitis.

The role of the soft palate dose regarding normal tissue toxicities in older adults with head and neck cancer undergoing definitive radiotherapy.

PURPOSE: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is continuously increasing. Older HNSCC patients may be more vulnerable to radiotherapy-related toxicities, so that extrapolation of available normal tissue complication probability (NTCP) models to this population may not be appropriate. Hence, we aimed to investigate the correlation between organ at risk (OAR) doses and chronic toxicities in older patients with HNSCC undergoing definitive radiotherapy. METHODS: Patients treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between 2009 and 2019 in a large tertiary cancer center were eligible for this analysis. OARs were contoured based on international consensus guidelines, and EQD2 doses using α/ß values of 3 Gy for late effects were calculated based on the radiation treatment plans. Treatment-related toxicities were graded according to Common Terminology Criteria for Adverse Events version 5.0. Logistic regression analyses were carried out, and NTCP models were developed and internally validated using the bootstrapping method. RESULTS: A total of 180 patients with a median age of 73 years fulfilled the inclusion criteria and were analyzed. Seventy-three patients developed chronic moderate xerostomia (grade 2), 34 moderate dysgeusia (grade 2), and 59 moderate-to-severe (grade 2-3) dysphagia after definitive radiotherapy. The soft palate dose was significantly associated with all analyzed toxicities (xerostomia: OR = 1.028, dysgeusia: OR = 1.022, dysphagia: OR = 1.027) in the multivariable regression. The superior pharyngeal constrictor muscle was also significantly related to chronic dysphagia (OR = 1.030). Consecutively developed and internally validated NTCP models were predictive for the analyzed toxicities (optimism-corrected AUCs after bootstrapping: AUCxerostomia=0.64, AUCdysgeusia=0.60, AUCdysphagia=0.64). CONCLUSIONS: Our data suggest that the dose to the soft palate is associated with chronic moderate xerostomia, moderate dysgeusia and moderate-to-severe dysphagia in older HNSCC patients undergoing definitive radiotherapy. If validated in external studies, efforts should be undertaken to reduce the soft palate dose in these patients.

The significance of partial volume effect on the estimation of hypoxic tumour volume with [18F]FMISO PET/CT.

BACKGROUND: The purpose of this study was to evaluate how a retrospective correction of the partial volume effect (PVE) in [18F]fluoromisonidazole (FMISO) PET imaging, affects the hypoxia discoverability within a gross tumour volume (GTV). This method is based on recovery coefficients (RC) and is tailored for low-contrast tracers such as FMISO. The first stage was the generation of the scanner's RC curves, using spheres with diameters from 10 to 37 mm, and the same homogeneous activity concentration, positioned in lower activity concentration background. Six sphere-to-background contrast ratios were used, from 10.0:1, down to 2.0:1, in order to investigate the dependence of RC on both the volume and the contrast ratio. The second stage was to validate the recovery-coefficient correction method in a more complex environment of non-spherical lesions of different volumes and inhomogeneous activity concentration. Finally, we applied the correction method to a clinical dataset derived from a prospective imaging trial (DRKS00003830): forty nine head and neck squamous cell carcinoma (HNSCC) cases who had undergone FMISO PET/CT scanning for the quantification of tumour hypoxia before (W0), 2 weeks (W2) and 5 weeks (W5) after the beginning of radiotherapy. Here, PVE was found to cause an underestimation of the activity in small volumes with high FMISO signal. RESULTS: The application of the proposed correction method resulted in a statistically significant increase of both the hypoxic subvolume (171% at W0, 691% at W2 and 4.60 × 103% at W5 with p < 0.001) and the FMISO standardised uptake value (SUV) (27% at W0, 21% at W2 and by 25% at W5 with p < 0.001) within the primary GTV. CONCLUSIONS: The proposed PVE-correction method resulted in a statistically significant increase of the hypoxic fraction (HF) with p < 0.001 and demonstrated results in better agreement with published HF data for HNSCC. To summarise, the proposed RC-based correction method can be a useful tool for a retrospective compensation against PVE.

Computed tomography-guided interstitial high dose rate brachytherapy for centrally located liver tumours: a single institution study.

OBJECTIVES: To evaluate the clinical outcome of computed tomography (CT)-guided interstitial (IRT) high-dose-rate (HDR) brachytherapy (BRT) in the treatment of unresectable primary and secondary liver malignancies. This report updates and expands our previously described experience with this treatment technique. METHODS: Forty-one patients with 50 tumours adjacent to the liver hilum and bile duct bifurcation were treated in 59 interventions of CT-guided IRT HDR BRT. The tumours were larger than 4 cm with a median volume of 84 cm(3) (38-1,348 cm(3)). The IRT HDR BRT delivered a median total physical dose of 20.0 Gy (7.0-32.0 Gy) in twice daily fractions of median 7.0 Gy (4.0-10.0 Gy) in 19 patients and in once daily fractions of median 8.0 Gy (7.0-14.0 Gy) in 22 patients. RESULTS: With a median follow-up of 12.4 months, the local control for metastatic hepatic tumours was 89 %, 73 % and 63 % at 6, 12 and 18 months respectively. The local control for primary hepatic tumours was 90 %, 81 % and 50 % at 6, 12 and 18 months respectively. Severe side effects occurred in 5.0 % of interventions with no treatment-related deaths. CONCLUSIONS: CT-guided IRT HDR BRT is a promising procedure for the radiation treatment of centrally located liver malignancies. KEY POINTS: • Interstitial high-dose-rate brachytherapy (IRT HDR BRT) is a promising treatment for central liver tumours • CT-guided IRT HDR BRT is safe for treating extensive tumours • CT-guided IRT HDR BRT could play a role in managing unresectable hepatic malignancies.

Determination of the dose rate around a HDR 192Ir brachytherapy source with the microDiamond and the microSilicon detector.

PURPOSE: To employ the microDiamond and the microSilicon detector (mDD and mSD, both PTW-Freiburg, Germany) to determine the dose rate around a HDR 192Ir brachytherapy source (model mHDR-v2r, Elekta AB, Sweden). METHODS: The detectors were calibrated with a 60Co beam at the PTW Calibration Laboratory. Measurements around the 192Ir source were performed inside a PTW MP3 water phantom. The detectors were placed at selected points of measurement at radial distances r, ranging from 0.5 to 10 cm, keeping the polar angle θ = 90°. Additional measurements were performed with the mSD at fixed distances r = 1, 3 and 5 cm, with θ varying from 0 to 150°, 0 to 166°, and 0 to 168°, respectively. The corresponding mDD readings were already available from a previous work (Rossi et al., 2020). The beam quality correction factor of both detectors, as well as a phantom effect correction factor to account for the difference between the experimental geometry and that assumed in the TG-43 formalism, were determined using the Monte Carlo (MC) toolkit EGSnrc. The beam quality correction factor was factorized into energy dependence and volume-averaging correction factors. Using the abovementioned MC-based factors, the dose rate to water at the different points of measurement in TG-43 conditions was obtained from the measured readings, and was compared to the dose rate calculated according to the TG-43 formalism. RESULTS: The beam quality correction factor was considerably closer to unity for the mDD than for the mSD. The energy dependence of the mDD showed a very weak radial dependence, similar to the previous findings showing a weak angular dependence as well (Rossi et al., 2020). Conversely, the energy dependence of the mSD decreased significantly with increasing distances, and also showed a considerably more pronounced angular dependence, especially for the smallest angles. The volume-averaging showed a similar radial dependence for both detectors: the correction had a maximal impact at 0.5 cm and then approached unity for larger distances, as expected. Concerning the angular dependence, the correction for the mSD was also similar to the one previously determined for the mDD (Rossi et al., 2020): a maximal impact was observed at θ = 0°, with values tending to unity for larger angles. In general, the volume-averaging was less pronounced for the mSD due to the smaller sensitive volume radius. After the application of the MC-based factors, differences between mDD dose rate measurements and TG-43 dose rate calculations ranged from -2.6% to +4.3%, with an absolute average difference of 1.0%. For the mSD, the differences ranged from -3.1% to +5.2%, with an absolute average difference of 1.0%. For both detectors, all differences but one were within the combined uncertainty (k = 2). The differences of the mSD from the mDD ranged from -3.9% to +2.6%, with the vast majority of them being within the combined uncertainty (k = 2). For θ ≠ 0°, the mDD was able to provide sufficiently accurate results even without the application of the MC-based beam quality correction factor, with differences to the TG-43 dose rate calculations from -1.9% to +3.4%, always within the combined uncertainty (k = 2). CONCLUSION: The mDD and the mSD showed consistent results and appear to be well suitable for measuring the dose rate around HDR 192Ir brachytherapy sources. MC characterization of the detectors response is needed to determine the beam quality correction factor and to account for energy dependence and/or volume-averaging, especially for the mSD. Our findings support the employment of the mDD and mSD for source QA, TPS verification and TG-43 parameters determination.

Recurrence analysis of glioblastoma cases based on distance and dose information.

BACKGROUND AND PURPOSE: Radiation therapy for glioblastoma (GBM) typically involves large target volumes. The aim of this study was to examine the recurrence pattern of GBM following modern radiochemotherapy according to EORTC guidelines and provide dose and distance information for the choice of optimal target volume margins. MATERIALS AND METHODS: In this study, the recurrences of 97 GBM patients, treated with radiochemotherapy from 2013 to 2017 at the Medical Center- University of Freiburg, Germany were analysed. Dose and distance based metrices were used to derive recurrence patterns. RESULTS: The majority of recurrences (75%) occurred locally within the primary tumor area. Smaller GTVs had a higher rate of distant recurrences. Larger treated volumes did not show a clinical benefit regarding progression free and overall survival. CONCLUSION: The identified recurrence pattern suggests that adjustments or reductions in target volume margins are feasible and could result in similar survival rates, potentially combined with a lower risk of side effects.

Photon-counting computed tomography of coronary and peripheral artery stents: a phantom study.

Accurate small vessel stent visualization using CT remains challenging. Photon-counting CT (PCD-CT) may help to overcome this issue. We systematically investigate PCD-CT impact on small vessel stent assessment compared to energy-integrating-CT (EID). 12 water-contrast agent filled stents (3.0-8 mm) were scanned with patient-equivalent phantom using clinical PCD-CT and EID-CT. Images were reconstructed using dedicated vascular kernels. Subjective image quality was evaluated by 5 radiologists independently (5-point Likert-scale; 5 = excellent). Objective image quality was evaluated by calculating multi-row intensity profiles including edge rise slope (ERS) and coefficient-of-variation (CV). Highest overall reading scores were found for PCD-CT-Bv56 (3.6[3.3-4.3]). In pairwise comparison, differences were significant for PCD-CT-Bv56 vs. EID-CT-Bv40 (p ≤ 0.04), for sharpness and blooming respectively (all p < 0.05). Highest diagnostic confidence was found for PCD-CT-Bv56 (p ≤ 0.2). ANOVA revealed a significant effect of kernel strength on ERS (p < 0.001). CV decreased with stronger PCD-CT kernels, reaching its lowest in PCD-CT-Bv56 and highest in EID-CT reconstruction (p ≤ 0.05). We are the first study to verify, by phantom setup adapted to real patient settings, PCD-CT with a sharp vascular kernel provides the most favorable image quality for small vessel stent imaging. PCD-CT may reduce the number of invasive coronary angiograms, however, more studies needed to apply our results in clinical practice.