A dosiomics model for prediction of radiation-induced acute skin toxicity in breast cancer patients: machine learning-based study for a closed bore linac.

BACKGROUND: Radiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals. METHODS: Dosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 - (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 - and AST 2 + groups and cutoff value calculations. RESULTS: Results showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71-0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models. CONCLUSIONS: This study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.

Radiation-induced lumbosacral plexopathy and pelvic insufficiency fracture: A case report of unique coexistence of complications after radiotherapy for prostate cancer.

Case reports of plexopathy after prostate cancer are usually neoplastic. Radiation-induced lumbosacral plexopathy and insufficiency fractures have clinical significance due to the need to differentiate them from tumoral invasions, metastases, and spinal pathologies. Certain nuances, including clinical presentation and screening methods, help distinguish radiation-induced plexopathy from tumoral plexopathy. This case report highlights the coexistence of these two rare clinical conditions. Herein, we present a 78-year-old male with a history of radiotherapy for prostate cancer who developed right foot drop, severe lower back and right groin pain, difficulty in standing up and walking, and tingling in both legs over the past month during remission. The diagnosis of lumbosacral plexopathy and pelvic insufficiency fracture was made based on magnetic resonance imaging, positron emission tomography, and electroneuromyography. The patient received conservative symptomatic treatment and was discharged with the use of a cane for mobility. Radiation-induced lumbosacral plexopathy following prostate cancer should be kept in mind in patients with neurological disorders of the lower limbs. Pelvic insufficiency fracture should also be considered if the pain does not correspond to the clinical findings of plexopathy. These two pathologies, which can be challenging to diagnose, may require surgical or complex management approaches. However, in this patient, conservative therapies led to an improvement in quality of life and a reduction in the burden of illness.

Analysis of the Parotid Glands on an Energy Spectrum CT Iodine Map to Evaluate Irradiation-Induced Acute Xerostomia in Patients With Nasopharyngeal Carcinoma.

Objective: This prospective study aims to evaluate acute irradiation-induced xerostomia during radiotherapy by utilizing the normalized iodine concentration (NIC) derived from energy spectrum computed tomography (CT) iodine maps. Methods: In this prospective study, we evaluated 28 patients diagnosed with nasopharyngeal carcinoma. At 4 distinct stages of radiotherapy (0, 10, 20, and 30 fractions), each patient underwent CT scans to generate iodine maps. The NIC of both the left and right parotid glands was obtained, with the NIC at the 0-fraction stage serving as the baseline measurement. After statistically comparing the NIC obtained in the arterial phase, early venous phase, late venous phase, and delayed phase, we chose the late venous iodine concentration as the NIC and proceeded to analyze the variations in NIC at each radiotherapy interval. Using the series of NIC values, we conducted hypothesis tests to evaluate the extent of change in NIC within the parotid gland across different stages. Furthermore, we identified the specific time point at which the NIC decay exhibited the most statistically significant results. In addition, we evaluated the xerostomia grades of the patients at these 4 stages, following the radiation therapy oncology group (RTOG) xerostomia evaluation standard, to draw comparisons with the changes observed in NIC. Results: The NIC in the late venous phase exhibited the highest level of statistical significance (P < .001). There was a noticeable attenuation in NIC as the RTOG dry mouth grade increased. Particularly, at the 20 fraction, the NIC experienced the most substantial attenuation (P < .001), a significant negative correlation was observed between the NIC of the left, right, and both parotid glands, and the RTOG evaluation grade of acute irradiation-induced xerostomia (P < .001, r = -0.46; P < .001, r = -0.45; P < .001, r = -0.47). The critical NIC values for the left, right, and both parotid glands when acute xerostomia occurred were 0.175, 0.185, and 0.345 mg/ml, respectively, with AUC = 0.73, AUC = 0.75, and AUC = 0.75. Conclusion: The NIC may be used to evaluate changes in parotid gland function during radiotherapy and acute irradiation-induced xerostomia.

Comparison of Acute Toxicities, Overall Treatment Time and Quality of Life in Head and Neck Cancer Patients Treated with IMRT and Helical Tomotherapy.

INTRODUCTION: Technical innovations in radiation therapy treatment planning and delivery over the last two decades have changed the practice of radiation therapy dramatically. The benefit of improved dose homogeneity and better sparing of critical structures in helical tomotherapy compared with conventional linac-based IMRT has been reported. This study was conducted to compare acute toxicities (skin, mucous membrane, salivary gland and hematological) during treatment and overall treatment time in Head and Neck Cancer patients treated with IMRT and Helical Tomotherapy and to assess the quality of life of patients during treatment between two groups. MATERIALS AND METHODS: The study involved thirty patients with histologically proven Squamous cell carcinomas of Head and Neck. They were treated with concurrent chemoradiotherapy, to a dose of 60-70 Gray in 30-35 fractions. The study consists of 2 arms which are standard IMRT and Tomotherapy arm. Fifteen consecutive patients were treated under IMRT and 15 patients were treated under Helical tomotherapy, along with concurrent chemotherapy. After completion of planning, plans were evaluated and dose to the targets, organs at risk were tabulated. Patients were assessed weekly for acute toxicities (skin reactions, mucositis, xerostomia, haematological toxicities) during the course of the treatment as per RTOG criteria. Quality of life of patients were assessed using FACT/ NCCN HNSI questionnaire in local language at day 1, day 21 and at completion of radiotherapy. RESULTS: Grade 2-3 skin reactions, mucositis, anemia, leukopenia and thrombocytopenia were predominant in both arms. Treatment time from start of radiotherapy to completion of radiotherapy varied from 39 days to 68 days. Majority of patients completed radiotherapy within 50-56 days. Mean quality of life score did not show much difference between IMRT and tomotherapy arms. CONCLUSION: The study did not show any statistically significant difference in overall treatment time, acute toxicities- skin reactions, xerostomia, mucositis& hematological toxicities and quality of life of patients during radiotherapy between IMRT and Helical Tomotherapy. Dosimetric benefits of Tomotherapy over IMRT do not translate into clinical benefit in terms of reduced acute toxicities, lesser overall treatment time and better quality of life of patients. KEY WORDS: Head and Neck Carcinoma, IMRT, Tomotherapy, RTOG, toxicity, FACT/ NCCN HNSI, quality of life.

Prospective comparison of acute severe toxicities between smokers and non-smokers during radiotherapy for head and neck cancers.

BACKGROUND AND PURPOSE: The association between smoking and acute radiation toxicities of head and neck cancer (HNC) is currently unproven. The aim of the study was to compare the occurrence of acute severe toxicity between active and non-active smokers treated for HNC by radiotherapy. MATERIALS AND METHODS: A prospective monocentric cohort study included patients treated by (chemo)radiotherapy for HNC from January 2021 to January 2023. Smoking status was recorded. Patients underwent a medical exam weekly during the radiotherapy to report acute toxicities according to the Common Terminology Criteria for Adverse Effects system version 5.0. Primary endpoint was the occurrence of at least one grade ≥ 3 acute toxicity among mucositis, dysphagia and dermatitis. RESULTS: Among the 102 patients included, 27.4 % were active smokers, 58.8 % were former smokers and 13.7 % had never smoked. Regarding toxicity, 23.5 % (n = 24) patients experienced severe mucositis, 37.2 % (n = 38) severe dysphagia, 13.7 % (n = 14) severe dermatitis and 54.9 % (n = 56) experienced at least one of them. Occurrence of severe acute toxicity was not statistically associated with smoking during radiotherapy (64.3 % among active smokers versus 51.3 % among non-active smokers; p = 0.24). On multivariate analysis, concurrent chemotherapy (87.5 % vs 65.2 %; OR = 5.04 [1.64-15.52]; p = 0.004) and 2.12 Gy versus 2 Gy fractionation schedule (64.3 % vs 41.3 %; OR = 2.53 [1.09-5.90]; p = 0.03) were significantly associated with severe acute toxicity. CONCLUSION: This study did not find an association between smoking during radiotherapy for HNC and occurrence of severe acute toxicities.

Dose-Volume Parameters of Spared Magnetic Resonance Imaging-Defined Active Bone Marrow Predict Hematologic Toxicity in Pelvic Malignancies Patients Undergoing Radiotherapy: A Cohort Study.

Background: The objective of this investigation is to evaluate the superiority of dose-volume parameters relying on magnetic resonance imaging (MRI)-defined active bone marrow (ABM) over those based on total bone marrow (TBM) contoured via CT in the prediction of hematologic toxicity (HT) occurrence among patients with pelvic malignancies undergoing radiotherapy. Methods: The clinical data of 116 patients with pelvic malignancies treated with pelvic radiotherapy were analyzed retrospectively. The ABM areas on T1-weighted MRI were contoured. The statistical significance between TBM and ABM dose-volume measures was assessed through the utilization of either Student's t-test or Wilcoxon signed rank test. Logistic and linear regression models were employed to analyze the correlation between dose-volume parameters (V5-V50) and HT occurrence in pelvic ABM and TBM. Receiver operating characteristic (ROC) curves were used to compare predictors of HT2+. Results: There were significant differences in dosimetric parameters between ABM and TBM. Logistic regression analysis showed that ABM V5, ABM V10, ABM V15, ABM V20, and TBM V5 were significantly associated with the occurrence of HT2+ in pelvic malignancies. Linear regression analysis showed that ABM V5, ABM V10, and ABM V15 were significantly associated with white blood cell (WBC), absolute neutrophil count (ANC), hemoglobin (Hb), and lymphocyte (Lym) nadir. ABM V5, ABM V10, ABM V15, and ABM V30 were predictive of HT2+. Conclusions: More accurate prediction of HT in patients receiving pelvic radiotherapy may be achieved by relying on dose-volume parameters of MRI-based ABM. Further prospective studies are needed to confirm this.

Narrow interval dual phase 18F-FDG PET/CT: A practical approach for distinguishing tumor recurrence from radiation necrosis in brain metastasis.

Purpose of our research is to demonstrate efficacy of narrow interval dual phase [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging in distinguishing tumor recurrence (TR) from radiation necrosis (RN) in patients treated for brain metastases. 35 consecutive patients (22 female, 13 male) with various cancer subtypes, lesion size > 1.0 cm3, and suspected recurrence on brain magnetic resonance imaging (MRI) underwent narrow interval dual phase FDG-PET/CT (30 and 90 min after tracer injection). Clinical outcome was determined via sequential MRIs or pathology reports. Maximum standard uptake value (SUVmax) of lesion (L), gray matter (GM), and white matter (WM) was measured on early (1) and delayed (2) imaging. Analyzed variables include % change, late phase, and early phase for L uptake, L/GM uptake, and L/WM uptake. Statistical analysis (P < .01), receiver operator characteristic (ROC) curve and area under curve (AUC) cutoff values were obtained. Change in L/GM ratio of > -2% was 95% sensitive, 91% specific, and 93% accurate (P < .001, AUC = 0.99) in distinguishing TR from RN. Change in SUVmax of lesion alone was the second-best indicator (P < .001, AUC = 0.94) with an ROC cutoff > 30.5% yielding 86% sensitivity, 83% specificity, and 84% accuracy. Other variables (L alone or L/GM ratios in early or late phase, all L/WM ratios) were significantly less accurate. Utilizing narrow interval dual phase FDG-PET/CT in patients with brain metastasis treated with radiation therapy provides a practical approach to distinguish TR from RN. Narrow time interval allows for better patient comfort, greater efficiency of PET/CT scanner, and lower disruption of workflow.

Reporting Standards for Complication Studies of Radiation Therapy for Pediatric Cancer: Lessons From PENTEC.

The major aim of Pediatric Normal Tissue Effects in the Clinic (PENTEC) was to synthesize quantitative published dose/-volume/toxicity data in pediatric radiation therapy. Such systematic reviews are often challenging because of the lack of standardization and difficulty of reporting outcomes, clinical factors, and treatment details in journal articles. This has clinical consequences: optimization of treatment plans must balance between the risks of toxicity and local failure; counseling patients and their parents requires knowledge of the excess risks encountered after a specific treatment. Studies addressing outcomes after pediatric radiation therapy are particularly challenging because: (a) survivors may live for decades after treatment, and the latency time to toxicity can be very long; (b) children's maturation can be affected by radiation, depending on the developmental status of the organs involved at time of treatment; and (c) treatment regimens frequently involve chemotherapies, possibly modifying and adding to the toxicity of radiation. Here we discuss: basic reporting strategies to account for the actuarial nature of the complications; the reporting of modeling of abnormal development; and the need for standardized, comprehensively reported data sets and multivariate models (ie, accounting for the simultaneous effects of radiation dose, age, developmental status at time of treatment, and chemotherapy dose). We encourage the use of tools that facilitate comprehensive reporting, for example, electronic supplements for journal articles. Finally, we stress the need for clinicians to be able to trust artificial intelligence models of outcome of radiation therapy, which requires transparency, rigor, reproducibility, and comprehensive reporting. Adopting the reporting methods discussed here and in the individual PENTEC articles will increase the clinical and scientific usefulness of individual reports and associated pooled analyses.

Treatment Related Acute Toxicities Between Treatment with 3D-CRT and IMRT in Localised Prostate Cancer.

OBJECTIVE:  To compare the acute toxicities of two radiation treatment techniques, intensity modulated radiation therapy (IMRT), and 3-dimensional conformal radiation therapy (3D-CRT) in localised prostate adenocarcinoma. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Oncology, Dr. Ziauddin Hospital, Karachi, Pakistan, from July 2016 to June 2022. METHODOLOGY: Patients with localised prostate adenocarcinoma who underwent treatment using two different advanced radiotherapy techniques i.e., IMRT and 3D-CRT were recruited during the study period. They were followed up for six months for acute gastrointestinal (GI) and genitourinary (GU) adverse events (acute toxicities) related to both treatment modalities according to Modified radiation therapy oncology group (RTOG) criteria. The acute toxicities were assessed at the 2nd, 4th, and 6th week during treatment and at the 3rd and 6th month after treatment. RESULTS:  There were 78 patients, with 39 patients in each group. The mean age was 68 ± 10 years in the 3D-CRT and 68 ± 07 years in the IMRT group. Patients in the IMRT group exhibited markedly lower treatment-related acute GI and GU effects at the end of 4th and 6th weeks for anorectal pain (p = 0.04) and (p = 0.01) and burning micturition (p = 0.003) and (p = 0.01), respectively. Furthermore, at 3 months anorectal pain (p = 0.02), loose stools (p = 0.005), and burning micturition (p = 0.01) were present and at 6 months anorectal pain was (p = 0.01) still present. CONCLUSION: Radiation therapy modalities 3D-CRT and IMRT both showed acceptable toxicity profile in the management of localised prostate cancer, while IMRT group exhibited significantly lower treatment-related acute GI and GU effects. KEY WORDS: 3D-CRT (3-Dimensional Conformal Radiation Therapy), IMRT (Intensity-Modulated Radiation Therapy), Radiation toxicity.

Acupuncture for Chronic Radiation-Induced Xerostomia in Head and Neck Cancer: A Multicenter Randomized Clinical Trial.

Importance: Patients with head and neck cancer who undergo radiotherapy can develop chronic radiation-induced xerostomia. Prior acupuncture studies were single center and rated as having high risk of bias, making it difficult to know the benefits of acupuncture for treating radiation-induced xerostomia. Objective: To compare true acupuncture (TA), sham acupuncture (SA), and standard oral hygiene (SOH) for treating radiation-induced xerostomia. Design, Setting, and Participants: A randomized, blinded, 3-arm, placebo-controlled trial was conducted between July 29, 2013, and June 9, 2021. Data analysis was performed from March 9, 2022, through May 17, 2023. Patients reporting grade 2 or 3 radiation-induced xerostomia 12 months or more postradiotherapy for head and neck cancer were recruited from community-based cancer centers across the US that were part of the Wake Forest National Cancer Institute Community Oncology Research Program Research Base. Participants had received bilateral radiotherapy with no history of xerostomia. Interventions: Participants received SOH and were randomized to TA, SA, or SOH only. Participants in the TA and SA cohorts were treated 2 times per week for 4 weeks. Those experiencing a minor response received another 4 weeks of treatment. Main Outcomes and Measures: Patient-reported outcomes for xerostomia (Xerostomia Questionnaire, primary outcome) and quality of life (Functional Assessment of Cancer Therapy-General) were collected at baseline, 4 (primary time point), 8, 12, and 26 weeks. All analyses were intention to treat. Results: A total of 258 patients (201 men [77.9%]; mean [SD] age, 65.0 [9.16] years), participated from 33 sites across 13 states. Overall, 86 patients were assigned to each study arm. Mean (SD) years from diagnosis was 4.21 (3.74) years, 67.1% (n = 173) had stage IV disease. At week 4, Xerostomia Questionnaire scores revealed significant between-group differences, with lower Xerostomia Questionnaire scores with TA vs SOH (TA: 50.6; SOH: 57.3; difference, -6.67; 95% CI, -11.08 to -2.27; P = .003), and differences between TA and SA (TA: 50.6; SA: 55.0; difference, -4.41; 95% CI, -8.62 to -0.19; P = .04) yet did not reach statistical significance after adjustment for multiple comparisons. There was no significant difference between SA and SOH. Group differences in Functional Assessment of Cancer Therapy-General scores revealed statistically significant group differences at week 4, with higher scores with TA vs SOH (TA: 101.6; SOH: 97.7; difference, 3.91; 95% CI, 1.43-6.38; P = .002) and at week 12, with higher scores with TA vs SA (TA: 102.1; SA: 98.4; difference, 3.64; 95% CI, 1.10-6.18; P = .005) and TA vs SOH (TA: 102.1; SOH: 97.4; difference, 4.61; 95% CI, 1.99-7.23; P = .001). Conclusions and Relevance: The findings of this trial suggest that TA was more effective in treating chronic radiation-induced xerostomia 1 or more years after the end of radiotherapy than SA or SOH. Trial Registration: ClinicalTrials.gov Identifier: NCT02589938.

Effects of bone marrow sparing radiotherapy on acute hematologic toxicity for patients with locoregionally advanced cervical cancer: a prospective phase II randomized controlled study.

OBJECTIVE: To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation. MATERIALS AND METHODS: LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40 < 25% in the BMS group was additionally prescribed. Acute HT was assessed weekly. Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. The trial was registered with Chinese clinical trial registry (ChiCTR2200066485). RESULTS: A total of 242 patients were included in the analysis. Baseline demographic, disease and treatment characteristics were balanced between the two groups. In the intention-to-treat population, BMS was associated with a lower incidence of grade ≥ 2 and grade ≥ 3 acute HT, leukopenia and neutropenia s(72.70% v 90.90%, P < 0.001*; 16.50% vs. 65.30%, P < 0.001*; 66.10% vs. 85.10%, P = 0.001*; 13.20% vs. 54.50%, P < 0.001*; 37.20% vs. 66.10%, P < 0.001*; 10.70% vs. 43.80%, P < 0.001*). BMS also resulted in decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femoral head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥ 3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959-3.815, P < 0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance. CONCLUSIONS: Receiving BMS pelvic irradiation could reduce the incidence of acute HT in LACC patients, and BM V40 < 25% may be a significant factor in reducing the risks of acute HT.

The clinical manifestations and molecular pathogenesis of radiation fibrosis.

Advances in radiation techniques have enabled the precise delivery of higher doses of radiotherapy to tumours, while sparing surrounding healthy tissues. Consequently, the incidence of radiation toxicities has declined, and will likely continue to improve as radiotherapy further evolves. Nonetheless, ionizing radiation elicits tissue-specific toxicities that gradually develop into radiation-induced fibrosis, a common long-term side-effect of radiotherapy. Radiation fibrosis is characterized by an aberrant wound repair process, which promotes the deposition of extensive scar tissue, clinically manifesting as a loss of elasticity, tissue thickening, and organ-specific functional consequences. In addition to improving the existing technologies and guidelines directing the administration of radiotherapy, understanding the pathogenesis underlying radiation fibrosis is essential for the success of cancer treatments. This review integrates the principles for radiotherapy dosimetry to minimize off-target effects, the tissue-specific clinical manifestations, the key cellular and molecular drivers of radiation fibrosis, and emerging therapeutic opportunities for both prevention and treatment.

A deep learning-based method for the prediction of temporal lobe injury in patients with nasopharyngeal carcinoma.

PURPOSE: To establish a deep learning-based model to predict radiotherapy-induced temporal lobe injury (TLI). MATERIALS AND METHODS: Spatial features of dose distribution within the temporal lobe were extracted using both the three-dimensional convolution (C3D) network and the dosiomics method. The Minimal Redundancy-Maximal-Relevance (mRMR) method was employed to rank the extracted features and select the most relevant ones. Four machine learning (ML) classifiers, including logistic regression (LR), k-nearest neighbors (kNN), support vector machines (SVM) and random forest (RF), were used to establish prediction models. Nested sampling and hyperparameter tuning methods were applied to train and validate the prediction models. For comparison, a prediction model base on the conventional D0.5cc of the temporal lobe obtained from dose volume (DV) histogram was established. The area under the receiver operating characteristic (ROC) curve (AUC) was utilized to compare the predictive performance of the different models. RESULTS: A total of 127 nasopharyngeal carcinoma (NPC) patients were included in the study. In the model based on C3D deep learning features, the highest AUC value of 0.843 was achieved with 5 features. For the dosiomics features model, the highest AUC value of 0.715 was attained with 1 feature. Both of these models demonstrated superior performance compared to the prediction model based on DV parameters, which yielded an AUC of 0.695. CONCLUSION: The prediction model utilizing C3D deep learning features outperformed models based on dosiomics features or traditional parameters in predicting the onset of TLI. This approach holds promise for predicting radiation-induced toxicities and guide individualized radiotherapy.

Comparative analysis of bevacizumab and LITT for treating radiation necrosis in previously radiated CNS neoplasms: a systematic review and meta-analysis.

PURPOSE: Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms. METHODS: PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes. RESULTS: Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT). CONCLUSION: Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.

Prognostic analysis of radiation-induced liver damage following carbon-ion radiotherapy for hepatocellular carcinoma.

BACKGROUND: Radiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT. METHODS: We retrospectively analyzed 108 patients with HCC treated with CIRT at the Osaka Heavy Ion Therapy Center between December 2018 and December 2022. RILD was defined as a worsening of two or more points in the Child-Pugh score within 12 months following CIRT. The median age of the patients was 76 years (range 47-95 years), and the median tumor diameter was 41 mm (range 5-160 mm). Based on the pretreatment liver function, 98 and 10 patients were categorized as Child-Pugh class A and B, respectively. We analyzed patients who received a radiation dose of 60 Gy (relative biological effectiveness [RBE]) in four fractions. The median follow-up period was 9.7 months (range 2.3-41.1 months), and RILD was observed in 11 patients (10.1%). RESULTS: Multivariate analysis showed that pretreatment Child-Pugh score B (p = 0.003, hazard ratio [HR] = 6.90) and normal liver volume spared from < 30 Gy RBE (VS30 < 739 cm3) (p = 0.009, HR = 5.22) were significant risk factors for RILD. The one-year cumulative incidences of RILD stratified by Child-Pugh class A or B and VS30 < 739 cm3 or ≥ 739 cm3 were 10.3% or 51.8% and 39.6% or 9.2%, respectively. CONCLUSION: In conclusion, the pretreatment Child-Pugh score and VS30 of the liver are significant risk factors for RILD following CIRT for HCC.

Influence of Post-radiation Ocular Surface Disorder on Ocular Surgery: A Case Report and Review of the Literature.

BACKGROUND: Ocular surface disorder after ocular radiation therapy, even though commonly reported, is often overlooked. Any delay in diagnosis may lead to complications that threaten vision. The presented case highlights the clinical outcome of a severe post-radiation disorder of the ocular surface, the importance of intensive therapy, and the limitations of further surgical interventions. CASE PRESENTATION: A 34-year-old woman was referred for a second opinion due to a years-long history of pain and redness in her right eye (OD) after proton beam therapy for recurrent iris melanoma. The patient then developed post-radiation retinopathy with macula edema, secondary glaucoma, cataract, as well as a severe ocular surface disorder with corneal decompensation and band keratopathy. Several surgical treatments have been attempted, including phacoemulsification with IOL implantation and trabeculectomy with mitomycin C. Due to refractory glaucoma, Baerveldt glaucoma drainage was then necessary. Given the worsening clinical presentation of post-radiation ocular surface disorder with progressing band keratopathy, the possibility of penetrating keratoplasty (PKP) was discussed. CONCLUSION: The continuous worsening of clinical symptoms of the disorder of the ocular surface after proton beam radiotherapy can be the result of a post-radiation syndrome. Gradual expansion of ischemia, vasculitis, and inflammatory mediators compresses the retinal tissue, leading to recurrent macular edema as well as to secondary glaucoma and corneal decompensation. Band keratopathy is occasionally noted and seems to result from severe post-radiation disorder of the ocular surface. However, PKP would typically be indicated in cases of corneal perforation, uncontrolled infectious keratitis, or for improving vision in the presence of corneal opacification, none of which applied to our patient. Furthermore, post-radiation keratopathy implies compromised corneal stromal lymphogenesis and angiogenesis, both of which are now considered essential conditions for allograft rejection. Moreover, a previously performed Baerveldt glaucoma drainage surgery can affect the survival rate of the endothelial cells of the recipient cornea. Therefore, a penetrating or endothelial keratoplasty should be viewed as a high-risk procedure. In this instance, the rigorous treatment of the severe ocular surface disorder was crucial. We managed our patient's complex situation by following the latest guidelines set by the Tear Film & Ocular Surface Society and aimed to alleviate the symptoms as effectively as possible. In conclusion, careful decision-making regarding surgical treatment options should be considered, taking into account the complexities and potential risks involved.

A no-fault risk compensation approach for radiation risks incurred in space travel.

In this paper we recommend an appropriate compensation approach should be established for fatality and disabilities that may occur due to space radiation exposures of government or industry workers. A brief review of compensation approaches for nuclear energy and nuclear weapons development workers in the United States and other countries is described. We then summarize issues in the application of probability of causation calculation and provide examples of probability of causation (PC) calculations for missions to the International Space Station and Earth's moon or for Mars exploration. The main focus of this paper follows with a recommendation of a no-fault approach to compensation with the creation of appropriate insurance policies funded by employers to cover all disabilities or fatality, without requiring proof of causation or restriction to conditions that imply causation. Importantly we propose that the compensation described should be managed by recourse to private insurers.