Outcome of intraoperative brachytherapy as a salvage treatment for locally recurrent rectal cancer.

BACKGROUND: Locally advanced recurrent rectal cancer (RRC) requires a multimodal approach. Intraoperative high-dose-rate brachytherapy (HDR-BT) may reduce the risk of local recurrence. However, the optimal therapeutic regimen remains unclear. The aim of this retrospective monocentric study was to evaluate the toxicity of HDR-BT after resection of RRC. METHODS: Between 2018 and 2022, 17 patients with RRC received resection and HDR-BT. HDR-BT was delivered alone or as an anticipated boost with a median dose of 13 Gy (range 10-13 Gy) using an 192iridium microSelectron HDR remote afterloader (Elekta AB, Stockholm, Sweden). All participants were followed for assessment of acute and late adverse events using the Common Terminology Criteria for Adverse Events version 5.0 and the modified Late Effects in Normal Tissues criteria (subjective, objective, management, and analytic; LENT-SOMA) at 3­ to 6­month intervals. RESULTS: A total of 17 patients were treated by HDR-BT with median dose of 13 Gy (range 10-13 Gy). Most patients (47%) had an RRC tumor stage of cT3­4 N0. At the time of RRC diagnosis, 7 patients (41.2%) had visceral metastases (hepatic, pulmonary, or peritoneal) in the sense of oligometastatic disease. The median interval between primary tumor resection and diagnosis of RRC was 17 months (range 1-65 months). In addition to HDR-BT, 2 patients received long-course chemoradiotherapy (CRT; up to 50.4 Gy in 1.8-Gy fractions) and 2 patients received short-course CRT up to 36 Gy in 2­Gy fractions. For concomitant CRT, all patients received 5­fluorouracil (5-FU) or capecitabine. Median follow-up was 13 months (range 1-54). The most common acute grade 1-2 toxicities were pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and lymphedema in 2 patients (11.8%). Chronic toxicities were similar: grade 1-2 pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and incontinence in 2 patients (11.8%). No patient experienced a grade ≥3 event. CONCLUSION: Reirradiation using HDR-BT is well tolerated with low toxicity. An individualized multimodality approach using HDR-BT in the oligometastatic setting should be evaluated in prospective multi-institutional studies.

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 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.

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.

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.

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.