The impact of the temporal sequence of cranial radiotherapy and platin-based chemotherapy on hearing impairment in pediatric and adolescent CNS and head-and-neck cancer patients: A report from the PanCareLIFE consortium.

The impact of the temporal sequence by which cranial radiotherapy (CRT) and platin-based chemotherapy (PCth) are administered on sensorineural hearing loss (SNHL) in pediatric and adolescent central nervous system (CNS) and head-and-neck (HN) cancer patients has not yet been studied in detail. We examined the ototoxic effects of sequentially applied CRT and PCth. This study included children and adolescents with CNS and HN tumors who participated in the multicountry PanCareLIFE (PCL) consortium. Audiological outcomes were compared between patients who received CRT prior to PCth and those who received it afterwards. The incidence, degree and posttreatment progression of SNHL, defined as Muenster classification grade ≥MS2b, were evaluated in 141 patients. One hundred and nineteen patients were included in a time-to-onset analysis. Eighty-eight patients received CRT prior to PCth (Group 1) and 53 patients received PCth before CRT (Group 2). Over a median follow-up time of 1.6 years, 72.7% of patients in Group 1 experienced SNHL ≥ MS2b compared to 33.9% in Group 2 (P < .01). A time-to-onset analysis was performed for 74 patients from Group 1 and 45 patients from Group 2. Median time to hearing loss (HL) ≥ MS2b was 1.2 years in Group 1 and 4.4 years in Group 2 (P < .01). Thus, audiological outcomes were better for patients who received CRT after PCth than before. This finding should be further evaluated and considered within clinical practice in order to minimize hearing loss in children and adolescents with CNS and HN tumors

Risk stratification of pulmonary toxicities in the combination of whole lung irradiation and high-dose chemotherapy for Ewing sarcoma patients with lung metastases: a review

Background!#!Whole lung irradiation (WLI) represents an important part of multimodal therapy in Ewing sarcoma (EwS) patients diagnosed with pulmonary metastases. This review discusses pulmonary toxicity in EwS patients with pulmonary metastases treated with WLI, who received different modes of high-dose chemotheray (HD-Cth).!##!Methods!#!Literature was compiled using the Cochrane Library, PubMed database, and the National Institute of Health (NIH) clinical trials register. Relevant patient information, including nature of HD-Cth, acute and late lung toxicities, and pulmonary function disorders, was selected from the above databases.!##!Results!#!Nine reports with a total of 227 patients, including 57 patients from a single randomized trial were included in this review. No acute or chronic symptomatic pulmonary toxicities were observed in patients that received WLI after HD busulfan-melphalan (HD-Bu/Mel), but 8% of these patients were diagnosed with asymptomatic restrictive lung disease. Grade 1 or 2 acute or chronic lung adverse effects were observed in up to 30% of patients that received WLI after HD treosulfan/Mel (HD-Treo/Mel) or HD etoposide (E)/Mel. Interstitial pneumonitis was present in 9% of patients treated concurrently with E/Mel and total body irradiation (TBI) with 8 Gy. Radiation doses as well as time between HD-Cth and WLI were both identified as significant risk factors for pulmonary function disorders.!##!Conclusion!#!The risk of adverse lung effects after WLI depends on several factors, including cumulative radiation dose and dose per fraction, HD-Cth regimen, and time interval between HD-Cth and WLI. A cumulative radiation dose of up to 15 Gy and a time interval of at least 60 days can potentially lead to a reduced risk of pulmonary toxicities. No evident adverse lung effects were registered in patients that received simultaneous therapy with HD-Cth and TBI. However, pulmonary function testing and lung toxicity reports were lacking for most of these patients

A novel approach to SBRT patient quality assurance using EPID-based real-time transit dosimetry A step to QA with in vivo EPID dosimetry

Purpose Intra- and inter-fraction organ motion is a major concern in stereotactic body radiation therapy (SBRT). It may cause substantial differences between the planned and delivered dose distribution. Such delivery errors may lead to medical harm and reduce life expectancy for patients. The project presented here investigates and improves a rapid method to detect such errors by performing online dose verification through the analysis of electronic portal imaging device (EPID) images. Methods To validate the method, a respiratory phantom with inhomogeneous insert was examined under various scenarios: no-error and error-simulated measurements. Simulation of respiratory motions was practiced for target ranges up to 2 & x202f;cm. Three types of treatment planning technique - 3DCRT (three-dimensional conformal radiation therapy), IMRT (intensity modulated radiation therapy), and VMAT (volumetric modulated arc therapy - were generated for lung SBRT. A total of 54 plans were generated to assess the influence of techniques on the performance of portal dose images. Subsequently, EPID images of 52 SBRT patients were verified. Both for phantom and patient cases, dose distributions were compared using the gamma index method according to analysis protocols in the target volume. Results The comparison of error-introduced EPID-measured images to reference images showed no significant differences with 3%/3 & x202f;mm gamma evaluation, though target coverage was strongly underestimated. Gamma tolerance of 2%/2 & x202f;mm reported noticeable detection in EPID sensitivity for simulated errors in 3DCRT and IMRT techniques. The passing rates for 3DCRT, IMRT, and VMAT with 1%/1 & x202f;mm in open field were 84.86%, 92.91%, and 98.75%, and by considering MLC-CIAO & x202f;+ 1 & x202f;cm (threshold 5%), were 68.25%, 83.19%, and 95.29%, respectively. Conclusion This study demonstrates the feasibility of EPID for detecting the interplay effects. We recommend using thin computed tomography slices and adding sufficient tumor margin in order to limit the dosimetric organ motion in hypofractionated irradiation with preserved plan quality. In the presence of respiratory and gastrointestinal motion, tighter criteria and consequently using local gamma evaluation should be considered, especially for VMAT. This methodology offers a substantial step forward in in vivo dosimetry and the potential to distinguish errors depending on the gamma tolerances. Thus, the approach/prototype provides a fast and easy quality assurance procedure for treatment delivery verification

The Role of Neuroaxis Irradiation in the Treatment of Intraspinal Ewing Sarcoma: A Review and Meta-Analysis

The role of cranio-spinal irradiation (CSI) for primary extraosseous intraspinal Ewing sarcoma (EwS) remains unclear. Here, we evaluate clinical and survival outcomes in patients with primary intraspinal EwS treated with CSI as part of multimodal primary therapy regimens. We abstracted patient information, including details on treatment application, efficacy, and tolerance from the literature and our hospital database for a cohort of 24 primary intraspinal EwS patients treated with CSI. Median age was 25.5 years, median CSI dose was 36 Gy and mean boost dose was 12.8 Gy. Sixteen patients (66.7%) achieved complete radiological remission, another 5 patients demonstrated partial response and 1 patient showed no response to treatment. Compared to a cohort of patients treated with focal radiotherapy, CSI patients were more likely to have multifocal disease at time of diagnosis (p = 0.001) and intradural tumor location (p p = 0.58). While CSI shows promising results in the treatment of primary intraspinal EwS, treatment should be considered individually based on tumor and patient characteristics in the absence of prospective trials

Definition of an Normal Tissue Complication Probability Model for the Inner Ear in Definitive Radiochemotherapy of Nasopharynx Carcinoma

Background: Definitive radiochemotherapy is the treatment of choice for locally advanced nasopharyngeal carcinoma. Due to the vicinity of the nasopharynx to the inner ear and the use of ototoxic platinum-based chemotherapy, there is a risk for irreversible damage to the auditory system. To avoid or minimize these critical side effects, radiation exposure to each inner ear must be balanced between target volume coverage and toxicity. However, normal tissue complication probability (NTCP) models of the inner ear validated by clinical data are rare. Patients and Methods: This retrospective study investigates the inner ear toxicity of 46 patients who received radio(chemo-)therapy for nasopharyngeal carcinoma at our institution from 2004 to 2021 according to CTCAE 5.0 criteria. For each inner ear, the mean (Dmean) and maximum (Dmax) dose in Gray (Gy) was evaluated and correlated with clinical toxicity data. Based on the data, an NTCP model and a cutoff dose logistic regression model (CDLR) were created. Results: In 11 patients (23.9%) hearing impairment and/or tinnitus was observed as a possible therapy-associated toxicity. Dmean was between 15&ndash;60 Gy, whereas Dmax was between 30&ndash;75 Gy. There was a dose-dependent, sigmoidal relation between inner ear dose and toxicity. A Dmean of 44 Gy and 65 Gy was associated with inner ear damage in 25% and 50% of patients, respectively. The maximum curve slope (m) was found at 50% and is m=0.013. The Dmax values showed a 25% and 50% complication probability at 58 Gy and 69 Gy, respectively, and a maximum slope of the sigmoid curve at 50% with m=0.025. Conclusion: There is a sigmoidal relation between radiation dose and incidence of inner ear toxicities. Dose constraints for the inner ear of &lt;44 Gy (Dmean) or &lt;58 Gy (Dmax) are suggested to limit the probability of inner ear toxicity &lt;25%

Toxicity Reduction after Craniospinal Irradiation via Helical Tomotherapy in Patients with Medulloblastoma: A Unicentric Retrospective Analysis

Objectives: Recent trials with craniospinal irradiation (CSI) via helical Tomotherapy (HT) demonstrated encouraging medulloblastoma results. In this study, we assess the toxicity profile of different radiation techniques and estimate survival rates. Materials and Methods: We reviewed the records of 46 patients who underwent irradiation for medulloblastoma between 1999 and 2019 (27 conventional radiotherapy technique (CRT) and 19 HT). Patient, tumor, and treatment characteristics, as well as treatment outcomes—local control rate (LCR), event-free survival (EFS), and overall survival (OS)—were reviewed. Acute and late adverse events (AEs) were evaluated according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Results: In total, 43 courses of CSI and three local RT were administered to the 46 patients: 30 were male, the median age was 7 years (range 1–56). A median total RT dose of 55 Gy (range 44–68) and a median CSI dose of 35 Gy (range, 23.4–40) was delivered. During follow-up (median, 99 months), six patients (13%) developed recurrence. The EFS rate after 5 years was 84%. The overall OS rates after 5 and 10 years were 95% and 88%, respectively. There were no treatment-related deaths. Following HT, a trend towards lower grade 2/3 acute upper gastrointestinal (p = 0.07) and subacute CNS (p = 0.05) toxicity rates was detected compared to CRT-group. The risk of late CNS toxicities, mainly grade 2/3, was significantly lower following HT technique (p = 0.003). Conclusion: CSI via HT is an efficacious treatment modality in medulloblastoma patients. In all, we detected a reduced rate of several acute, subacute, and chronic toxicities following HT compared to CRT

Diagnostic efficiency of hybrid imaging using PSMA ligands, PET/CT, PET/MRI and MRI in identifying malignant prostate lesions

Objective!#!The objective of this study was to assess the accuracy of !##!Materials and methods!#!35 patients with organ-confined prostate cancer who were assigned to definitive radiotherapy (RT) were divided into three groups based on imaging techniques: !##!Results!#!Diagnostic performance was significantly superior both for manual and automatic IPLs contouring using !##!Conclusion!#!IPL localization was significantly improved when using PSMA-imaging procedures compared to mpMRI. No significant difference for delineating IPLs was found between hybrid method PSMA-PET/MRI and PSMA-PET/CT. PSMA-based imaging technique should be considered for the diagnostics of IPLs and focal treatment modality