Causes of missed MRI diagnosis of radiotherapy-induced temporal lobe injury in nasopharyngeal carcinoma. / MRIæ£€æŸ¥é¼»å’½ç™Œæ”¾å°„æ€§é¢žå¶æŸä¼¤çš„æ¼è¯ŠåŽŸå› .

OBJECTIVES: Radiotherapy is the primary treatment for nasopharyngeal carcinoma, but it frequently leads to radiotherapy-induced temporal lobe injury (RTLI). Magnetic resonance imaging (MRI) is the main diagnostic method for RTLI after radiotherapy for nasopharyngeal carcinoma, but it is prone to missed diagnoses. This study aims to investigate the causes of missed diagnoses of RTLI in nasopharyngeal carcinoma patients undergoing MRI after radiotherapy. METHODS: Clinical and MRI data from nasopharyngeal carcinoma patients diagnosed and treated with radiotherapy at Xiangya Hospital of Central South University, from January 2010 to April 2021, were collected. Two radiologists reviewed all head and neck MRIs (including nasopharyngeal and brain MRIs) before and after radiotherapy of identify cases of late delayed response-type RTLI for the first time. If the original diagnosis of the initial RTLI in nasopharyngeal carcinoma patients did not report temporal lobe lesions, it was defined as a missed diagnosis. The first diagnosis of RTLI cases was divided into a missed diagnosis group and a non-missed diagnosis group. Clinical and imaging data were compared between the 2 groups, and multivariate logistic regression analysis was used to identify independent risk factors for MRI missed diagnoses of initial RTLI. RESULTS: A total of 187 nasopharyngeal carcinoma with post-radiotherapy RTLI were included. The original diagnostic reports missed 120 cases and accurately diagnosed 67 cases, with an initial RTLI diagnosis accuracy rate of 35.8% and a missed diagnosis rate of 64.2%. There were statistically significant differences between the missed diagnosis group and the non-missed diagnosis group in terms of lesion size, location, presence of contralateral temporal lobe lesions, white matter high signal, cystic degeneration, hemorrhage, fluid attenuated inversion recovery (FLAIR), and examination site (all P<0.05). Multivariate logistic regression analysis showed that lesions ≤25 mm, non-enhancing lesions, lesions without cystic degeneration or hemorrhage, lesions located only in the medial temporal lobe, and MRI examination only of the nasopharynx were independent risk factors for missed MRI diagnosis of initial RTLI (all P<0.05). CONCLUSIONS: The missed diagnosis of initial RTLI on MRI is mainly related to lesion size and location, imaging characteristics, and MRI examination site.

[Diagnosis and emergency management of radiological incidents]. / Diagnostic et prise en charge en urgence des incidents radiologiques.

Incidents involving ionizing radiation pose a risk of immediate and long-term clinical consequences for both victims and responders in the event of secondary contamination. Rapid identification of the problem and a coordinated response are crucial. This article summarizes the key challenges related to the emergency management of a single patient or multiple victims, addressing the importance of recognizing such a case, radioprotection measures, decontamination, and available treatments.

Les incidents impliquant des rayonnements ionisants représentent un risque aux conséquences cliniques immédiates et à long terme, tant pour les victimes que pour les intervenants en cas de contamination secondaire. L'identification rapide de la problématique et une réponse coordonnée sont cruciales. Cet article résume les principaux enjeux liés à la prise en charge en urgence d'un patient unique ou de plusieurs victimes, en abordant l'importance de la reconnaissance d'un tel cas, des mesures de radioprotection, de la décontamination et des traitements disponibles.

Radiation Induced Skin Fibrosis (RISF): Opportunity for Angiotensin II-Dependent Intervention.

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. The primary goal is to offer essential insights in order to better care for and improve the quality of life of cancer survivors who face the risk of developing RISF.

Effect of dose to parotid ducts on Sticky Saliva and Xerostomia in radiotherapy of head and neck squamous cell carcinoma.

BACKGROUND: Radiotherapy (RT) in head and neck squamous cell cancer (HNSCC) often leads to sticky saliva and xerostomia (SSX). Dose sparing of salivary glands (SG) reduces occurrence of SSX but few studies investigated the relationship between RT dose to SG substructures and SSX. We therefore investigated this hypothesis, focusing on the parotid duct (PD). METHODS: Retrospective data was collected from 99 HNSCC patients treated at our center with (chemo-)radiotherapy (CRT). PD and other organs-at-risk (OAR) were (re-)contoured and DVHs were generated without re-planning. SSX was graded according to CTCAE v.4.03 and evaluated at acute, subacute, and two late timepoints. RESULTS: Most patients presented with loco-regionally advanced disease. In 47% of patients, up-front neck dissection preceded CRT. Weighted mean dose was 28.6 Gy for bilateral parotid glands (PG), and 32.0 Gy for PD. Acute SSX presented as grades 0 (35.3%), I (41.4%), II (21.2%) and III (2.0%). There was no association of OARs and SSX ≥ grade 2 in univariable logistic regression (LR). Multivariable LR showed statistically significant relationship of acute SSX with: PG weighted mean dose (OR 0.84, p = 0.004), contralateral PG mean dose (OR 1.14, p = 0.02) and contralateral PD planning OAR (PD PRV) mean dose (OR 1.84, p = 0.03). CONCLUSIONS: There was an association of acute SSX with dose exposure of PD PRV in multivariable regression, only. Due to statistical uncertainties and the retrospective nature of this analysis, further studies are required to confirm or reject the hypothesis.

Pubic bone osteomyelitis and fistulas after radiation therapy of the pelvic region: patient-reported outcomes and urological management of a rare but serious complication.

PURPOSE: This study investigated late urinary adverse events (UAEs) in patients who underwent pelvic radiation therapy, with a focus on occurrence, diagnostic characteristics and the impact of subsequent extirpative surgery with the need of urinary diversion on quality of life. METHODS: A retrospective analysis of 20 patients after pelvic radiotherapy (2016-2022) was conducted. Data included demographics, perioperative details, oncological parameters, and patient-reported outcomes. Imaging (CT, MRI) was examined for early manifestations of late UAEs. RESULTS: In the study cohort, prostate cancer was the primary malignancy in 85% with a mean radiation dose of 84 Gray over 35 days. Time to diagnosis of late UAEs was 4.0 years post-radiation. Radiological assessment demonstrated a progressive increase in typical CT and MRI features of pubic bone osteomyelitis over time. Surgical interventions, mainly cystectomy, were required with variable outcomes in patient-reported post-surgery quality of life. CONCLUSION: Diagnosing and managing late UAEs after pelvic radiation necessitate an understanding of their occurrence, diagnostic features and appropriate management strategies. Early imaging, particularly MRI, is crucial for timely diagnosis and treatment planning. Variable post-surgery quality of life underscores the importance of a multidisciplinary approach in managing late UAEs. The study contributes to understanding these complications and emphasizes their consideration in post-radiation follow-up care.

Long-term evaluation of the safety of a rectal-prostate spacer, the ProSpace® balloon, in patients treated with radiotherapy for prostate cancer.

BACKGROUND: Due to the close proximity of the prostate and rectum, rectal toxicity remains a major problem in patient treated by radiotherapy for prostate adenocarcinoma. One method of increasing the distance between the prostate and the rectum is to use a spacer implanted into the rectoprostatic space. This report describes the long-term outcomes obtained with a new ballon spacer. METHODS: Patients treated with curative radiotherapy for low- or intermediate-risk prostate adenocarcinoma, who underwent insertion of the ProSpace® (BioProtect Ltd, Tzur Yigal, Israel) rectal-prostate balloon spacer, were included. The main objective was to evaluate the dosimetric benefit of the spacer for OARs. The secondary objectives were to evaluate the feasibility and tolerability of ProSpace® balloon placement and to evaluate its long-term therapeutic efficacy and tolerance. RESULTS: Between October 2013 and March 2015, 16 patients were enrolled in the Pasteur Clinic, Toulouse, France. The median follow-up was 85.5 months. From top to bottom, the space created was a mean of 16.3 mm (range: 11-20.5 mm) at the base of the prostate, 12.1 mm (range: 4-16 mm) at the middle and 8.9 mm at the apex (range: 5-15 mm). On average, rectal volumes receiving a dose of 70 Gy, 60 Gy and 50 Gy were significantly lower after balloon implantation: -4.81 cc (1.5 vs. 6.3; p < 0.0005), -8.08 cc (6.4 vs. 14.5; p = 0.002) and -9.06 cc (16.7 vs. 25.7; p = 0.003), respectively. There were significant differences in coverage after balloon implantation: Median V95% (p < 0.0005), median Dmin (p = 0.01) and median V98% (p < 0.001) were higher after balloon implantation. At 5 years, cumulative gastrointestinal toxicity was grade 1 in 6% (1/16 patients). No toxicity of grade 2 or higher was found. At 5 years, no urinary toxicity grade 3 or 4 toxicity was found. The QoL was not deteriorated. CONCLUSIONS: The use of the ProSpace® balloon seems to be well accepted by patients, allowing a double dosimetric gain: a decrease in doses received by the rectum and an improvement in the coverage of the high-risk PTV. The long-term gastrointestinal toxicity remains low and QoL is preserved in all treated patients.

Prostate radiotherapy may cause fertility issues: a retrospective analysis of testicular dose following modern radiotherapy techniques.

BACKGROUND: Prostate cancer in younger men is rare but not exceptional. Radiotherapy is a cornerstone of prostate cancer treatment and yet, its impact on fertility is scarcely reported in literature. Given the radiosensitivity of testicular tissue, this study aimed to determine the testicular dose using modern radiotherapy techniques for definitive prostate irradiation. METHODS: One hundred radiotherapy plans were reviewed. Testicles were contoured retrospectively without dosimetric optimization on testicles. RESULTS: The median testicular dose was 0.58 Gy: 0.18 Gy in stereotactic plans, 0.62 Gy in Volumetric Modulated Arc Therapy plans and 1.50 Gy in Tomotherapy plans (p < 0.001). Pelvic nodal irradiation increased the median testicular dose to 1.18 Gy versus 0.26 Gy without nodal irradiation (p < 0.001). Weight and BMI were inversely associated with testicular dose (p < 0.005). 65% of patients reached the theoretical dose threshold for transient azoospermia, and 10% received more than 2 Gy, likely causing definitive azoospermia. CONCLUSION: Despite being probably lower than doses from older techniques, the testicular dose delivered with modern prostate radiotherapy is not negligible and is often underestimated because the contribution of daily repositioning imaging is not taken into account and most Treatment Planning Systems underestimate the out of field dose. Radiation oncologists should consider the impact on fertility and gonadal endocrine function, counseling men on sperm preservation if they wish to maintain fertility. TRIAL REGISTRATION: retrospectively registered.

Results of the study of factors predicting the risk of the development of grade III radiation-induced mucositis during radiation or chemoradiation therapy in patients with oral cavity and oropharynx cancer.

BACKGROUND: Today, a number of methods and ways of prevention and treatment of radiation- -induced mucositis of the oral cavity and oropharynx have been developed, but the represented approaches are still not effective enough. Therefore, to increase the effectiveness of the prevention and treatment of radiation-induced mucositis, it is necessary to approach this problem comprehensively and individually, and to evaluate the factors affecting the development of mucositis. MATERIALS AND METHODS: In this single-center prospective controlled non-randomized clinical trial, the results of clinical observation of the development of complications of radiation and chemoradiation therapy in 105 patients with a newly diagnosed squamous cell cancer of the oral cavity and oropharynx were analyzed. Factors affecting the risk of the development of grade III radiation-induced mucositis including the age, gender of the patients, their general condition before the treatment according to World Health Organisation scales, type of the treatment and its doses, additional use of immunotherapy with alpha/beta defensins, characteristic signs of the tumor process and all indices of the immune status of the patients before the treatment have been analyzed. RESULTS: The method of construction and analysis of one-factor logistic regression models, where 24 indices were analyzed as factorial features, showed that the reduction of the risk of the development of grade III radiation-induced mucositis is predicted by several factors: immunotherapy, gender, serum concentrations of IgG and IgA. A decrease (P < 0.001) in the risk of the development of grade III radiation-induced mucositis was revealed if immunotherapy with alpha/beta defensins (with a total dose of 40 mg) was included into the treatment scheme (relative odds (RO) 0.05; 95% reference interval (RI) 0.02-0.18), in comparison with patients of the groups where it was not present or this immune agent was used in a total dose of 60 mg (P = 0.001, RO 0.06; 95% RI 0.01-0.30). The next factorial sign was gender, namely the risk of the development of grade III radiation-induced mucositis was lower for men (P = 0.003; RO 0.15; 95% RI 0.04-0.53) compared to women. An increase (P = 0.024) in the risk of the development of grade III radiation-induced mucositis with an increase in the initial level of IgG serum concentration was revealed, (RO 1.08; 95% RI 1.01-1.16) for each 1 mg/mL, as well as an increase (P = 0.044) in the possibility of the appearance of grade III radiation-induced mucositis with an increase in the serum concentration of IgA (RO 1.23; 95% RI 1.01-1.50) for every 1 mg/mL also before the beginning of the treatment. Multifactorial analysis has also confirmed that the risk of the development of grade III radiation-induced mucositis increases (P = 0.008) with a high serum IgG concentration before the treatment or with an increase in this index during therapy (RO 1.13; 95% RI 1.03-1.09) for every 1 mg/mL (when standardized by other risk factors). It was determined that when standardizing according to other factors (gender, IgG level), the risk of the development of grade III radiation-induced mucositis in the use of the immune agent alpha/beta defensins in a total dose of 40 mg per course decreases (P < 0.001; RO 0.08; 95% RI 0.02-0.27) compared to patients with oral cavity and oropharynx cancer who were not treated with immunotherapy. The risk of the development of grade III radiation-induced mucositis also decreases (P = 0.001) in the use of immunotherapy in a higher dose, i.e. 60 mg per course (RO 0.03; 95% RI 0.004-0.24 compared to patients whose treatment did not include immunotherapy (when standardized by other factors). CONCLUSION: As a result of this controlled clinical study, some factors were determined in addition to the radiation as those affecting the risk of the development of grade III radiation-induced mucositis in patients with oral cavity and oropharynx cancer during special treatment. These factors comprise the inclusion of immunotherapy with alpha/beta defensins into the specific treatment; gender, and baseline levels of serum IgG and IgA concentrations suggest a pattern in which the higher the serum IgG and IgA concentrations are before the start of the treatment, the greater is the likelihood of severe radiation-induced mucositis degree during special therapy. The results of the study of humoral state of the immune system in patients with oral cavity and oropharynx cancer before the beginning of chemoradiation therapy can be used as prognostic risk factors for the development of severe gamma-irradiation-induced mucositis of the oropharyngeal area, as well as an indication for the use of immunotherapeutic agents (in particular, alpha/beta defensins) that are able to polarize the immune response towards type 1 T-helpers through their immunomodulatory action.

Intramuscular injections of human placental extract versus conventional symptomatic approaches in radiation-induced oral mucositis, in patients with head and neck cancers, on definitive chemoradiotherapy - A ray of hope?

BACKGROUND: Despite the availability of a wide range of agents, no single treatment exists for the management of radiation-induced oral mucositis, in patients, with head and neck malignancies, on radical chemoradiation; a debilitating and limiting sequela. Human placental extract is one option that has been proposed. AIMS AND OBJECTIVES: This study aimed at evaluating the therapeutic benefits of human placental extract (Placentrex) in the management of radiation-induced oral mucositis in patients on curative intent treatment for head and neck cancers with concurrent chemoradiation, and to compare the observations with other conventional approaches. MATERIAL AND METHODS: Patients presenting to the Department of Radiation Oncology, of a tertiary cancer care center, with biopsy-proven carcinoma of the oral cavity, oropharynx, and hypopharynx, planned for definitive, curative intent chemoradiation, between January 2020 and June 2021, were recruited for this study. The interventional group received a deep intramuscular injection of 2 ml of Placentrex to the deltoid muscle, once-a-day from the 11th fraction of radiation till completion, on treatment and non-treatment days. The control group received supportive, symptomatic, conventional treatments for mucositis. The response was assessed every week during treatment and at the third and sixth months of follow-up and was compared. RESULTS: The study comprised 26 patients, 15 in the interventional group and 11 in the control group. On completion of treatment, 40% in the interventional arm and 81.82% in the control arm had progressed to grade 2 and 3 mucositis (P < 0.05). Treatment interruption was seen in 13% in the interventional arm and 55% in the control arm (P < 0.001). CONCLUSIONS: Results from this study show that human placental extract, injection Placentrex, had a significant effect in decreasing the severity of radiation-induced mucositis and thereby reducing any interruption or delay in treatment when compared to other conventional methods.

Prediction of auditory brain stem responses damage in patients with head-and-neck cancers receiving radiotherapy using the functional assays of normal tissue complication probability models.

AIM: The purpose of this study was to set four NTCP models on clinical data and develop a model that calculates the possibility of hearing damage due to irradiation of healthy and at-risk brainstem tissue. MATERIALS AND METHODS: ABR tests were performed on 50 head-and-neck cancer patients three years after radiotherapy for evaluation of lesions in a part of the auditory nerve or the auditory pathway in the brainstem. RESULTS: It indicated a significant difference in the latency of the waves assessed by the ABR test between the two groups. The paired sample t-test indicated the latency time of waves I, III, V, I-III, and I-V (P < 0.001) in the right ear, and in the left ear latency time of waves III, V, I-III, I-V, and III-V (P < 0.001) were significantly higher in the case group's ear than those in the control group. The confidence interval of the fitted parameters was 95% for NTCP models. ABR test's binary outcome with differential dose-volume histograms (dDVHs) was calculated and imported as input to the NTCP modeling. The values of the parameters n = 2.3-2.9 and the value s = 1 were obtained, which indicated that the brainstem organ is seriality. CONCLUSION: The best model ranked for the prediction of brainstem hearing damage was the logit model, which had the lowest Akaike value. The nervousness of the auditory organ of the brainstem (VIII nerve) can be declared as one of the reasons for being independent of the received dose.

Pulmonary fibrosis prevalence after adjuvant radiotherapy of Iranian patients with breast cancer: A single-center cross-sectional study.

AIMS: This study aims to investigate the incidence rate of pulmonary fibrosis as a late radiotherapy complication and identify the associated dosimetric and demographic factors using radiological findings between Iranian patients with breast cancer. METHODS AND MATERIAL: Breast cancer patients treated at the education hospital of Shohada-e Tajrish Hospital, Tehran, Iran, from 2017 to 2021 were considered. Patients have included for whom a secondary chest CT scan was available at least six months after radiotherapy. Dose-volume histogram (DVH) parameters of three-dimensional conformal radiotherapy (3D-CRT) treatment plans were exported. Demographic features and data on underlying lung diseases, diabetes, and smoking history were extracted. RESULTS: A total of 250 patients were included in the study with a mean age of 46.1 ± 7.5 yrs and a mean body mass index (BMI) of 24.5 ± 4.2 kg/m2. Pulmonary fibrosis was detected for sixty-two cases. A significant relationship was obtained between the ipsilateral lung DVH parameters of patients with pulmonary fibrosis (P value < 0.05). The V5Gy, V10Gy, V13Gy, V20Gy, V30Gy, MLD, and DMax for individuals with pulmonary fibrosis were significantly higher than those without this injury. CONCLUSIONS: Pulmonary fibrosis was distinguished for 25% of the breast cancer cases at least six months after adjuvant radiotherapy. A significant relationship between the DVH parameters, underlying lung disease, diabetes, radiotherapy fields (i.e., Breast + LN + SC or Breast/Chest-wall only), age, and BMI with the frequency of the ipsilateral pulmonary fibrosis was obtained. V13Gy and V30Gy of the ipsilateral lung may be the most predictor of pulmonary fibrosis incidence.

Deformation-based morphometry: a sensitive imaging approach to detect radiation-induced brain injury?

BACKGROUND: Radiotherapy is a major therapeutic approach in patients with brain tumors. However, it leads to cognitive impairments. To improve the management of radiation-induced brain sequalae, deformation-based morphometry (DBM) could be relevant. Here, we analyzed the significance of DBM using Jacobian determinants (JD) obtained by non-linear registration of MRI images to detect local vulnerability of healthy cerebral tissue in an animal model of brain irradiation. METHODS: Rats were exposed to fractionated whole-brain irradiation (WBI, 30 Gy). A multiparametric MRI (anatomical, diffusion and vascular) study was conducted longitudinally from 1 month up to 6 months after WBI. From the registration of MRI images, macroscopic changes were analyzed by DBM and microscopic changes at the cellular and vascular levels were evaluated by quantification of cerebral blood volume (CBV) and diffusion metrics including mean diffusivity (MD). Voxel-wise comparisons were performed on the entire brain and in specific brain areas identified by DBM. Immunohistology analyses were undertaken to visualize the vessels and astrocytes. RESULTS: DBM analysis evidenced time-course of local macrostructural changes; some of which were transient and some were long lasting after WBI. DBM revealed two vulnerable brain areas, namely the corpus callosum and the cortex. DBM changes were spatially associated to microstructural alterations as revealed by both diffusion metrics and CBV changes, and confirmed by immunohistology analyses. Finally, matrix correlations demonstrated correlations between JD/MD in the early phase after WBI and JD/CBV in the late phase both in the corpus callosum and the cortex. CONCLUSIONS: Brain irradiation induces local macrostructural changes detected by DBM which could be relevant to identify brain structures prone to radiation-induced tissue changes. The translation of these data in patients could represent an added value in imaging studies on brain radiotoxicity.

Deciphering the molecular landscape of ionising radiation-induced eye damage with the help of genomic data mining.

Even at low levels, exposure to ionising radiation can lead to eye damage. However, the underlying molecular mechanisms are not yet fully understood. We aimed to address this gap with a comprehensive in silico approach to the issue. For this purpose we relied on the Comparative Toxicogenomics Database (CTD), ToppGene Suite, Cytoscape, GeneMANIA, and Metascape to identify six key regulator genes associated with radiation-induced eye damage (ATM, CRYAB, SIRT1, TGFB1, TREX1, and YAP1), all of which have physical interactions. Some of the identified molecular functions revolve around DNA repair mechanisms, while others are involved in protein binding, enzymatic activities, metabolic processes, and post-translational protein modifications. The biological processes are mostly centred on response to DNA damage, the p53 signalling pathway in particular. We identified a significant role of several miRNAs, such as hsa-miR-183 and hsamiR-589, in the mechanisms behind ionising radiation-induced eye injuries. Our study offers a valuable method for gaining deeper insights into the adverse effects of radiation exposure.

An Overview of Radiation Countermeasure Development in Radiation Research from 1954 to 2024.

Preparation for medical responses to major radiation accidents, further driven by increases in the threat of nuclear warfare, has led to a pressing need to understand the underlying mechanisms of radiation injury (RI) alone or in combination with other trauma (combined injury, CI). The identification of these mechanisms suggests molecules and signaling pathways that can be targeted to develop radiation medical countermeasures. Thus far, the United States Food and Drug Administration (U.S. FDA) has approved seven countermeasures to mitigate hematopoietic acute radiation syndrome (H-ARS), but no drugs are available for prophylaxis and no agents have been approved to combat the other sub-syndromes of ARS, let alone delayed effects of acute radiation exposure or the effects of combined injury. From its inception, Radiation Research has significantly contributed to the understanding of the underlying mechanisms of radiation injury and combined injury, and to the development of radiation medical countermeasures for these indications through the publication of peer-reviewed research and review articles.

Intestinal microbiota composition is predictive of radiotherapy-induced acute gastrointestinal toxicity in prostate cancer patients.

BACKGROUND: The search for factors beyond the radiotherapy dose that could identify patients more at risk of developing radio-induced toxicity is essential to establish personalised treatment protocols for improving the quality-of-life of survivors. To investigate the role of the intestinal microbiota in the development of radiotherapy-induced gastrointestinal toxicity, the MicroLearner observational cohort study characterised the intestinal microbiota of 136 (discovery) and 79 (validation) consecutive prostate cancer patients at baseline radiotherapy. METHODS: Gastrointestinal toxicity was assessed weekly during RT using CTCAE. An average grade >1.3 over time points was used to identify patients suffering from persistent acute toxicity (endpoint). The microbiota of patients was quantified from the baseline faecal samples using 16S rRNA gene sequencing technology and the Ion Reporter metagenomic pipeline. Statistical techniques and computational and machine learning tools were used to extract, functionally characterise, and predict core features of the bacterial communities of patients who developed acute gastrointestinal toxicity. FINDINGS: Analysis of the core bacterial composition in the discovery cohort revealed a cluster of patients significantly enriched for toxicity, displaying a toxicity rate of 60%. Based on selected high-risk microbiota compositional features, we developed a clinical decision tree that could effectively predict the risk of toxicity based on the relative abundance of genera Faecalibacterium, Bacteroides, Parabacteroides, Alistipes, Prevotella and Phascolarctobacterium both in internal and external validation cohorts. INTERPRETATION: We provide evidence showing that intestinal bacteria profiling from baseline faecal samples can be effectively used in the clinic to improve the pre-radiotherapy assessment of gastrointestinal toxicity risk in prostate cancer patients. FUNDING: Italian Ministry of Health (Promotion of Institutional Research INT-year 2016, 5 × 1000, Ricerca Corrente funds). Fondazione Regionale per la Ricerca Biomedica (ID 2721017). AIRC (IG 21479).

Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life. Therefore, there is an urgent need for an approach to predicting normal mucosal responses in patients prior to treatment. We here describe an assay to detect irradiation responses in healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated and cultured for three days. Seven samples were irradiated with X-ray, and three additional samples were irradiated with both X-ray and protons. Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample using standardized automated image analysis. Furthermore, increased levels of inflammation-inducing factors-major drivers of mucositis development-could be detected after irradiation. This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Exploring Memory Systems After Pediatric Posterior Fossa Tumor: From Memory Profile Comparisons in Nonirradiated Versus Irradiated Patients to Episodic Memory Tests Capable of Detecting Radiation-induced Hippocampal Damage.

AIMS: Pediatric posterior fossa tumor (PFT) survivors experience long-term cognitive sequelae, including memory disorders, for which irradiation is one of the main risk factors. The aims of the present study were to (1) explore the profile of impairment in episodic, semantic, working and procedural memory systems in irradiated versus nonirradiated PFT survivors, and (2) test whether an autobiographical questionnaire and a two-phase ecological test (Epireal) assessing episodic memory are more sensitive to radiation-induced hippocampal damage than commonly used tests. MATERIALS AND METHODS: A total of 60 participants (22 irradiated PFT survivors, 17 nonirradiated PFT survivors, and 21 controls) were included in the prospective IMPALA study. They all underwent a broad battery of tests assessing the different memory systems in two 2-day sessions 3 weeks apart. We performed between-groups comparisons and analyzed impairment profiles, using -1.65 SDs as a cut-off. For irradiated patients, correlations were calculated between mean radiation doses to key brain structures involved in memory (hippocampus, cerebellum, and striatum) and corresponding memory scores. RESULTS: PBT survivors performed significantly more poorly than controls (p < 0.001) on conventional tests of episodic, semantic and working memory: 64% of irradiated patients and 35% of nonirradiated patients had a deficit in at least two memory systems, with episodic memory impairment being more specific to the irradiated group. Epireal had a larger effect size than the other episodic memory tests, allowing us to detect deficits in a further 18% of irradiated patients. These deficits were correlated with the mean radiation dose to the left hippocampus. CONCLUSION: Memory impairment is a frequent long-term cognitive sequela in PFT survivors, especially after radiation therapy. New ecological tests of episodic memory that are more sensitive to radiation-induced deficits than conventional tests could yield specific markers of the toxicity of medial temporal lobe irradiation.