National Trends of Inpatient Radiation Cystitis: 2016-2019.

INTRODUCTION: Radiation cystitis with hematuria (RCH) is a potentially devastating complication after pelvic radiation. The cumulative incidence of RCH is debated, and certain severe manifestations may require hospital admission. We aimed to evaluate demographics and outcomes of patients hospitalized for RCH. METHODS: We performed a retrospective review of hospitalized patients with a primary or secondary diagnosis of RCH from 2016 to 2019 using the National Inpatient Sample. Our unit of analysis was inpatient encounters. Our primary outcome was inpatient mortality. Secondary outcomes included need for inpatient procedures, transfusion, length of stay (LOS), and cost of admission. We then performed multivariate analysis using either a logistic or linear regression to identify predictors of mortality and LOS. Cost was analyzed using a generalized linear model controlling for LOS. RESULTS: We identified 21,320 weighted cases of hospitalized patients with RCH. The average patient age was 75.4 years, with 84.7% male and 69.3% White. The median LOS was 4 days, and the median cost was $8767. The inpatient mortality rate was 1.3%. The only significant predictor for mortality was older age. The only significant predictor of both higher cost and longer LOS was an Elixhauser Comorbidity Score ≥ 3. CONCLUSIONS: RCH represents a significant burden to patients and the health care system, and we observed an increasing number of hospitalized patients over time. Additional research is needed to identify underlying causes of RCH and effective treatments for this sometimes-severe complication of pelvic radiation.

Imaging Assessment of Radiation Therapy-Related Normal Tissue Injury in Children: A PENTEC Visionary Statement.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium has made significant contributions to understanding and mitigating the adverse effects of childhood cancer therapy. This review addresses the role of diagnostic imaging in detecting, screening, and comprehending radiation therapy-related late effects in children, drawing insights from individual organ-specific PENTEC reports. We further explore how the development of imaging biomarkers for key organ systems, alongside technical advancements and translational imaging approaches, may enhance the systematic application of imaging evaluations in childhood cancer survivors. Moreover, the review critically examines knowledge gaps and identifies technical and practical limitations of existing imaging modalities in the pediatric population. Addressing these challenges may expand access to, minimize the risk of, and optimize the real-world application of, new imaging techniques. The PENTEC team envisions this document as a roadmap for the future development of imaging strategies in childhood cancer survivors, with the overarching goal of improving long-term health outcomes and quality of life for this vulnerable population.

[Prevention of radiotherapy-related cardiotoxicity : benefits of a specialized cardio-oncologic assessment and follow-up]. / Prévention de la cardio-toxicité de la radiothérapie : apport de la prise en charge cardio-oncologique.

To accept the toxic side effects of any treatment, whether medical, surgical or radiotherapeutic, cannot be avoided but implies to evaluate them taking into account the severity and prognosis of the disease that is concerned. Screening, preventing and treatment of these side effects are an integral aspect of the treatment of cancers. We will here review the contribution of the cardio-oncology, a recently emerged medical specialty. Cardiac irradiation cannot be avoided when treating several cancers, most frequently left sided breast cancer. As soon as radiotherapy is considered, it is of prime importance to evaluate each patient's risk factors and to handle them. If technical progresses have led to the complete disappearance of acute side effects of radiotherapy, this is not true for the delayed ones that may occur many years after the irradiation. Hence the need for «red flags¼ and for a systematic follow-up. Cardiac complications of left breast irradiation concern all aspects of cardiology: diseases of cardiac rhythm, valvulopathies, heart failure, coronary and pericardial disorders.

Admettre les effets secondaires d'un traitement, qu'il soit médical, chirurgical ou radiothérapique, est inévitable, mais impose de les évaluer en intégrant la gravité de l'affection pour laquelle ils sont prescrits. Leur dépistage, leur prévention et leur prise en charge font partie intégrante du traitement d'un cancer. Dans cette revue, nous ferons la synthèse de l'apport à cette démarche d'une discipline récente, la cardio-oncologie. L'irradiation cardiaque est incontournable lors du traitement de plusieurs cancers au premier rang desquels le cancer du sein gauche. Dès qu'elle est envisagée, il est essentiel d'évaluer les facteurs de risque de chaque patient et d'organiser leur prise en charge éventuelle. En effet, si les progrès techniques ont permis la disparition des complications cardiaques aiguës de la radiothérapie, ce n'est encore pas le cas des complications différées qui peuvent survenir de nombreuses années après l'irradiation. D'où la nécessité de «drapeaux rouges¼ et d'un suivi régulier systématique. Ces complications, rarement isolées, concernent tous les aspects de la cardiologie : troubles du rythme, valvulopathies, insuffisance cardiaque, maladies coronaires et atteintes péricardiques.

Tuning spatially fractionated radiotherapy dose profiles using the moiré effect.

Spatially Fractionated Radiotherapy (SFRT) has demonstrated promising potential in cancer treatment, combining the advantages of reduced post-radiation effects and enhanced local control rates. Within this paradigm, proton minibeam radiotherapy (pMBRT) was suggested as a new treatment modality, possibly producing superior normal tissue sparing to conventional proton therapy, leading to improvements in patient outcomes. However, an effective and convenient beam generation method for pMBRT, capable of implementing various optimum dose profiles, is essential for its real-world application. Our study investigates the potential of utilizing the moiré effect in a dual collimator system (DCS) to generate pMBRT dose profiles with the flexibility to modify the center-to-center distance (CTC) of the dose distribution in a technically simple way.We employ the Geant4 Monte Carlo simulations tool to demonstrate that the angle between the two collimators of a DCS can significantly impact the dose profile. Varying the DCS angle from 10 ∘ to 50 ∘ we could cover CTC ranging from 11.8 mm to 2.4 mm, respectively. Further investigations reveal the substantial influence of the multi-slit collimator's (MSC) physical parameters on the spatially fractionated dose profile, such as period (CTC), throughput, and spacing between MSCs. These findings highlight opportunities for precision dose profile adjustments tailored to specific clinical scenarios.The DCS capacity for rapid angle adjustments during the energy transition stages of a spot scanning system can facilitate dynamic alterations in the irradiation profile, enhancing dose contrast in normal tissues. Furthermore, its unique attribute of spatially fractionated doses in both lateral directions could potentially improve normal tissue sparing by minimizing irradiated volume. Beyond the realm of pMBRT, the dual MSC system exhibits remarkable versatility, showing compatibility with different types of beams (X-rays and electrons) and applicability across various SFRT modalities.Our study illuminates the dual MSC system's potential as an efficient and adaptable tool in the refinement of pMBRT techniques. By enabling meticulous control over irradiation profiles, this system may expedite advancements in clinical and experimental applications, thereby contributing to the evolution of SFRT strategies.

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.

Clinical and biochemical assessment of the effect of glutamine in management of radiation induced oral mucositis in patients with head and neck cancer: Randomized controlled clinical trial.

BACKGROUND: This study aimed to evaluate the effect of oral glutamine suspension on salivary levels of transforming growth factor beta 1 (TGF-ß1), a cytokine involved in inflammation and Tumor progression, and the severity of radiation-induced oral mucositis (RIOM) in head and neck cancer patients. This is the first study to investigate the impact of glutamine on TGF-ß1 levels in head and neck cancer patients with radiation induced oral mucositis (RIOM). METHODS: In this randomized controlled clinical trial, 50 HNC patients were enrolled and received either glutamine oral suspension or maltodextrin as a placebo from the baseline of RIOM to the end of radiotherapy. Salivary TGF-ß1 levels were measured at baseline and after treatment. Also, RIOM was assessed using the World Health Organization (WHO) Oral Toxicity Scale, the Oral Mucositis Assessment Scale (OMAS), the Pain Visual Analog Scale (Pain-VAS), the incidence of opioid use, and body mass index (BMI). RESULTS: Glutamine significantly reduced salivary TGF-ß1 levels and improved RIOM symptoms, such as pain, opioid use, and weight loss. The reduction of TGF-ß1 levels was associated with the improvement of RIOM severity. CONCLUSION: Glutamine may modulate the inflammatory response and enhance wound healing in RIOM by decreasing salivary TGF-ß1 levels. These findings support the use of glutamine as a potential intervention for RIOM and nutritional support for improving radiation sensitivity. TRIAL REGISTRATION: This study was registered on clinicalTrials.gov with identifier no. NCT05856188.

Comparative assessment of radiation therapy-induced vasculitis using [18F]FDG-PET/CT in patients with non-small cell lung cancer treated with proton versus photon radiotherapy.

PURPOSE: To assess radiation therapy (RT)-induced vasculitis in patients with non-small cell lung cancer (NSCLC) by examining changes in the uptake of 18F-fluoro-D-deoxyglucose ([18F]FDG) by positron emission tomography/computed tomography (PET/CT) images of the ascending aorta (AA), descending aorta (DA), and aortic arch (AoA) before and after proton and photon RT. METHOD: Thirty-five consecutive locally advanced NSCLC patients were definitively treated with proton (n = 27) or photon (n = 8) RT and concurrent chemotherapy. The patients were prospectively enrolled to undergo [18F]FDG-PET/CT imaging before and 3 months after RT. An adaptive contrast-oriented thresholding algorithm was applied to generate mean standardized uptake values (SUVmean) for regions of interest (ROIs) 3 mm outside and 3 mm inside the outer perimeter of the AA, DA, and AoA. These ROIs were employed to exclusively select the aortic wall and remove the influence of blood pool activity. SUVmeans before and after RT were compared using two-tailed paired t-tests. RESULTS: RT treatments were associated with increased SUVmeans in the AA, DA, and AoA-1.9%, 0.3%, and 1.3% for proton and 15.8%, 9.5%, and 15.5% for photon, respectively. There was a statistically significant difference in the ∆SUVmean (post-RT SUVmean - pre-RT SUVmean) in patients treated with photon RT when compared to ∆SUVmean in patients treated with proton RT in the AA (p = 0.043) and AoA (p = 0.015). There was an average increase in SUVmean that was related to dose for photon patients (across structures), but that was not seen for proton patients, although the increase was not statistically significant. CONCLUSION: Our results suggest that patients treated with photon RT for NSCLC may exhibit significantly more RT-induced inflammation (measured as ∆SUVmean) in the AA and AoA when compared to patients who received proton RT. Knowledge gained from further analyses in larger cohorts could aid in treatment planning and help prevent the significant morbidity and mortality associated with RT-induced vascular complications. TRIAL REGISTRATION: NCT02135679.

Impact of Prostate Cancer-related Genitourinary Radiation Injury on Mental Health Diagnosis and Treatment: Assessment of 55,425 Men.

OBJECTIVE: To investigate the association of low-grade radiation injury (LGRI) and high-grade radiation injury (HGRI) following prostate cancer treatment with mental health diagnoses and therapy. METHODS: A retrospective study of men diagnosed with prostate cancer who were treated with radiotherapy. Men were followed to assess for LGRI or HGRI using IBM MarketScan. Cohorts included: no injury (no-RI), LGRI, HGRI, and controls. Mental health diagnoses and related treatment (medication/therapy) were identified using ICD-10 codes, CPT codes, and national drug codes. A multivariable Cox proportional hazards model from time of radiation to first instance of mental health diagnosis was modeled against injury group, age, and comorbidities. RESULTS: Between 2011 and 2020 we identified 55,425 men who received radiotherapy for prostate cancer. 22,879 (41.3%) experienced a LGRI while 4128 (7.4%) experienced a HGRI. Prior to radiation therapy, mental health diagnoses were equally distributed across cohorts (P > .05). Every marker of mental health showed a step-wise increase in incidence from no-RI to LGRI to HGRI except for alcohol abuse. Use of mental health medications and therapy visits were slightly more likely in the LGRI and HGRI groups prior to radiation, however, this difference was greatly increased postradiation therapy. LGRI (HR 1.38; P < .001) and HGRI (HR 2.1; P < .001) were independently associated with an increased likelihood of mental health diagnoses. CONCLUSION: LGRI and HGRI following prostate cancer radiotherapy are associated with increased risk of mental health diagnosis, medication use, and therapy need compared to men who do not develop injuries. The most common mental health diagnoses were depression and anxiety.

Comprehensive geriatric assessment predicts radiation-induced acute toxicity in prostate cancer patients.

PURPOSE: The purpose of the present prospective study was to evaluate the significance of geriatric conditions measured by a comprehensive geriatric assessment (GA) for the prediction of the risk of high-grade acute radiation-induced toxicity. METHODS: A total of 314 prostate cancer patients (age ≥ 65 years) undergoing definitive radiotherapy at a tertiary academic center were included. Prior to treatment, patients underwent a GA. High-grade toxicity was defined as acute toxicity grade ≥ 2 according to standard RTOG/EORTC criteria. To analyze the predictive value of the GA, univariable and multivariable logistic regression models were applied. RESULTS: A total of 40 patients (12.7%) developed acute toxicity grade ≥ 2; high grade genitourinary was found in 37 patients (11.8%) and rectal toxicity in 8 patients (2.5%), respectively. Multivariable analysis revealed a significant association of comorbidities with overall toxicity grade ≥ 2 (odds ratio [OR] 2.633, 95% confidence interval [CI] 1.260-5.502; p = 0.010) as well as with high-grade genitourinary and rectal toxicity (OR 2.169, 95%CI1.017-4.625; p = 0.045 and OR 7.220, 95%CI 1.227-42.473; p = 0.029, respectively). Furthermore, the Activities of Daily Living score (OR 0.054, 95%CI 0.004-0.651; p = 0.022), social status (OR 0.159, 95%CI 0.028-0.891; p = 0.036), and polypharmacy (OR 4.618, 95%CI 1.045-20.405; p = 0.044) were identified as independent predictors of rectal toxicity grade ≥ 2. CONCLUSION: Geriatric conditions seem to be predictive of the development of high-grade radiation-induced toxicity in prostate cancer patients treated with definitive radiotherapy.

[Radiation-induced intestinal fibrosis: pathological assessment and pharmacological prevention].

Although radiotherapy can improve the local control rate of tumors and prolong the survival period of patients, it can also lead to long-term adverse effects such as radiation-induced intestinal fibrosis. Radiation-induced intestinal fibrosis has a high incidence and poses significant challenges to treatment, severely impacting the quality of life of patients. Combining findings from domestic and international research, along with experiences of our center, this article mainly discusses the pathological changes of radiation-induced intestinal fibrosis, as well as the current status and challenges of pathological assessment and pharmacological prevention of this condition. At present, there is no definitive method to reverse the fibrotic pathological changes. Thus, the prevention of fibrosis is a crucial issue to be resolved. In the meantime, there is a lack of ideal assessment methods and effective preventive medications in clinical practice. It is necessary to enhance both basic and clinical research, thoroughly investigate the pathogenesis of the disease, and identify effective intervention targets to promote the diagnosis and treatment of radiation-induced intestinal fibrosis.

RISREAC Study: Assessment of Cutaneous Radiation Injury Through Clinical Documentation.

OBJECTIVE: Radiation dermatitis (RD) occurs in 95% of patients receiving radiation therapy (RT) for cancer treatment, affecting 800 million patients annually. We aimed to demonstrate the feasibility of developing a historical RD cohort, Radiation Induced Skin Reactions (RISREAC) cohort. METHODS: This retrospective study evaluated RD-related clinical documentation for 245 breast cancer patients who received RT at the University of Rochester Medical Center, to understand the RD progression, scoring, and management. All statistical analyses were performed at 0.05 level of significance. RESULTS: Clinician-documented RD severity was observed for 169 (69%) patients with a mean severity of 1.57 [1.46, 1.68]. The mean descriptor-based severity score of 2.31 [2.18, 2.45] moderately correlated (r = 0.532, P < 0.0001) with documented RD grade. Most patients (91.8%) received skin care treatment during RT, with 66.7% receiving more than 2 modalities. CONCLUSIONS: The RISREAC cohort is the first retrospective cohort established from clinical documentation of radiation-induced skin changes for the study of RD and cutaneous radiation injury (CRI). RD symptom descriptors were more reliably documented and suitable for all skin types compared to Radiation Therapy Oncology Group (RTOG) or Common Toxicity Criteria for Adverse Events (CTCAE) grades. A new descriptor-based scoring tool would be useful for RD and CRI.

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of complications following surgery and radiotherapy. OBJECTIVES: To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site-specific outcomes; and 4. ADVERSE EVENTS: Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site-specific outcomes. We used GRADE to assess certainty of evidence. MAIN RESULTS: Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN). HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I2 = 0%; 3 RCTs, 166 participants; low-certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I2 = 64%; 5 RCTs, 468 participants; low-certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I2 = 70%; 2 RCTs, 264 participants; low-certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) -10.72, 95% CI -18.97 to -2.47; I2 = 40%; 2 RCTs, 157 participants; moderate-certainty evidence). Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high-certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I2 = 0%; 4 RCTs, 357 participants; high-certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I2 = 74%; 2 RCTs, 158 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

Impact of Volumetric Dosimetry on the Projected Cost of Radiation-Related Late Effects Screening After Childhood Cancer: A Real-World Cohort Analysis.

BACKGROUND: Screening guidelines for childhood cancer survivors treated with radiation currently rely on broad anatomic irradiated regions (IR) to determine risk for late effects. However, contemporary radiotherapy techniques use volumetric dosimetry (VD) to define organ-specific exposure, which supports more specific screening recommendations that could be less costly. PATIENTS AND METHODS: This was a cross-sectional study of 132 patients treated with irradiation at Children's Hospital Los Angeles from 2000 to 2016. For 5 key organs (cochlea, breast, heart, lung, and colon), radiation exposure was determined retrospectively using both IR and VD methods. Under each method, Children's Oncology Group Long-Term Follow-Up Guidelines were used to identify organs flagged for screening and recommended screening tests. Projected screening costs incurred under each method were computed through age 65 using insurance claims data. RESULTS: Median age at the end of treatment was 10.6 years (range, 1.4-20.4). Brain tumor was the most common diagnosis (45%) and head/brain the most common irradiated region (61%). For all 5 organs, use of VD rather than IR resulted in fewer recommended screening tests. This led to average cumulative estimated savings of $3769 (P = .099), with significant savings in patients with CNS tumors (P = .012). Among patients with savings, average savings were $9620 per patient (P = .016) and significantly more likely for females than males (P = .027). CONCLUSION: Use of VD to enhance precision of guideline-based screening for radiation-related late effects permits fewer recommended screening tests and generates cost-savings.

Genitourinary Radiation Injury Following Prostate Cancer Treatment: Assessment of Cost and Health Care System Burden.

OBJECTIVE: To evaluate the healthcare resource impact of radiation injury following prostate cancer treatment. METHODS: Using IBM MarketScan, we performed a retrospective study of men with prostate cancer who were treated with radiotherapy and subsequently developed low-grade (LGRI) and high-grade radiation injury (HGRI). Radiation injury diagnoses included bladder neck stenosis, hematuria/cystitis, fistula, ureteral stricture, and incontinence. LGRI and HGRI included injury diagnosis without intervention and with intervention, respectively. Health care visits and costs were measured over 5 time periods including 2 years before radiation, 1 year before radiation, radiation to injury diagnosis, injury diagnosis to first intervention (LGRI), and following first intervention (HGRI). Negative binomial regression modeling was used to assess the effect of radiation injury on average cost adjusting for demographics and comorbidities. RESULTS: Between 2008 and 2017, we identified 121,027 men who received radiotherapy following prostate cancer diagnosis of which 10,057 (8.3%) experienced a HGRI. The frequency of urologic visits and average costs were similar in those without injury and LGRI. However, men with HGRI experienced higher visit frequency and monthly costs. Amongst high-grade injuries, urinary fistula had the highest frequency of visit utilization at 378 visits before first intervention and 245 visits after first intervention. Following radiation injury diagnosis, the average monthly cost was twice as high in those with HGRI ($85.78) compared to LGRI ($38.66). CONCLUSIONS: HGRI was associated with increased urologic health care use and average monthly cost when compared to those who experienced LGRI or no injury. Urinary fistula was associated with the largest resource burden.

Double scattering and pencil beam scanning Monte Carlo workflows for proton therapy retrospective studies on radiation-induced toxicities.

PURPOSE: Monte Carlo (MC) simulations can be used to accurately simulate dose and linear energy transfers (LET) distributions, thereby allowing for the calculation of the relative biological effectiveness (RBE) of protons. We present hereby the validation and implementation of a workflow for the Monte Carlo modelling of the double scattered and pencil beam scanning proton beamlines at our institution. METHODS: The TOPAS/Geant4 MC model of the clinical nozzle has been comprehensively validated against measurements. The validation also included a comparison between simulated clinical treatment plans for four representative patients and the clinical treatment planning system (TPS). Moreover, an in-house tool implemented in Python was tested to assess the variable RBE-weighted dose in proton plans, which was illustrated for a patient case with a developing radiation-induced toxicity. RESULTS: The simulated range and modulation width closely matches the measurements. Gamma-indexes (3%/3mm 3D), which compare the TPS and MC computations, showed a passing rate superior to 98%. The calculated RBE-weighted dose presented a slight increase at the necrosis location, within the PTV margins. This indicates the need for reporting on the physical and biological effects of irradiation in high dose regions, especially at the healthy tissues and increased LET distributions location. CONCLUSION: The results demonstrate that the Monte Carlo method can be used to independently validate a TPS calculation, and to estimate LET distributions. The features of the in-house tool can be used to correlate LET and RBE-weighted dose distributions with the incidence of radiation-induced toxicities following proton therapy treatments.

Eye-lens dose rate conversion factors due to hot particles and surface contaminations on the cornea.

In 2012, the International Commission on Radiological Protection issued new recommendations, in publication 118, regarding the dose limits to the eye-lens. New analyses of historical exposure data had indicated that radiation-induced cataracts may appear at lower doses than previously assumed. This spurred largescale efforts in a variety of fields including dosimetry, radiation effects simulations, and the review of national regulatory limits. On the simulation side, much work led to the publication of dose rate conversion factors (DRCFs), to calculate the dose to the radiosensitive part of the eye-lens, and to the whole eye-lens as functions of the incident fluence of electron, photon, positron, and neutron radiation. The standard, ISO-15382 (2015Radiological Protection-Procedures for Monitoring the Dose to the Lens of the Eye, the Skin and the Extremities), from the International Organization for Standardization (ISO), stated that the direct contact of a hot radioactive particle on the eye-lens represents a special contamination condition that must be considered. The aim of this work was to produce tabulated data of eye-lens dose rates, per activity (MBq), for a variety of radionuclides. In this work, the dose to the eye-lens from contamination directly in contact with the cornea, expressed in terms of DRCFs for eye-lens, in units of Gy h-1MBq-1, are presented for 102 radionuclides of interest. These radionuclides were selected as they had been considered by the International Atomic Energy Agency of importance for skin dose. The method consisted of two steps. The first was the determination of the DRCFs for mono-energetic electrons and photons for a hot particle in contact with the eye-lens, followed by the folding of these quantities with the emissions of the radionuclides of interest. Contributions from spontaneous fission neutrons were considered separately. Exposure geometries for spherical hot particles of different dimensions, materials and locations on the cornea were considered. In addition, partial surface coverage of the cornea, consistent with an accidental exposure to a contaminated liquid, was also modelled. Resulting radionuclide DRCFs were verified, for a few specific geometries and radionuclides with dedicated Monte Carlo simulations. The final data are presented in several tables included in this paper.

Ultrasound Histogram Assessment of Acute Breast Toxicity After Breast Cancer Radiation Therapy: A Prospective Longitudinal Study.

Accurate assessment of radiation-induced breast toxicity is crucial for the management of breast radiation therapy (RT). Standard assessment of breast toxicity based on clinicians' visual inspection and palpation has considerable inter- and intra-observer variability. To overcome this challenge, we present an ultrasound histogram method that objectively evaluates radiation-induced breast toxicity longitudinally. In a prospective study, patients enrolled (n = 67) received ultrasound scans at four time points: prior to RT, last day of RT, 3-4 wk post-RT and 9-12-wk post-RT. Ultrasound scans were acquired at five locations (tumor bed and 3, 6, 9 and 12 o'clock) on both breasts. Two hundred sixty-four ultrasound scans and 2640 B-mode images were analyzed. The histogram differences between irradiated and contralateral breasts were calculated to evaluate radiation-induced breast changes. On the basis of the B-mode images, the severity of breast toxicity was graded as absent, mild, moderate or severe. The performance of the histogram method was assessed with the receiver operating characteristic (ROC) curve. The areas under the ROC curve ranged from 0.78 to 0.9 (sensitivity: 0.88-0.96, specificity: 0.53-0.83) at the lower quadrant for differentiating absent/mild from moderate/severe toxicity at various time points. This study provides preliminary evidence that ultrasound histogram differences can serve as an imaging biomarker to longitudinally assess radiation-induced acute toxicity.

Quantitative Assessment and Comparative Analysis of Longitudinal Lung CT Scans of Chest-Irradiated Nonhuman Primates.

Computed tomography (CT) imaging has been used to diagnose radiation-induced lung injury for decades. However, histogram-based quantitative tools have rarely been applied to assess lung abnormality due to radiation-induced lung injury (RILI). Here, we used first-order summary statistics to derive and assess threshold measures extracted from whole lung histograms of CT radiodensity in rhesus macaques. For the present study, CT scans of animals exposed to 10 Gy of whole thorax irradiation were utilized from a previous study spanning 2-9 months postirradiation. These animals were grouped into survivors and non-survivors based on their clinical and experimental endpoints. We quantified the change in lung attenuation after irradiation relative to baseline using three density parameters; average lung density (ALD), percent change in hyper-dense lung volume (PCHV), hyperdense volume as a percent of total volume (PCHV/TV) at 2-month intervals and compared each parameter between the two irradiated groups (non-survivors and survivors). We also correlated our results with histological findings. All the three indices (ALD, PCHV, PCHV/TV) obtained from density histograms showed a significant increase in lung injury in non-survivors relative to survivors, with PCHV relatively more sensitive to detect early RILI changes. We observed a significant positive correlation between histologic pneumonitis scores and each of the three CT measurements, indicating that CT density is useful as a surrogate for histologic disease severity in RILI. CT-based three density parameters, ALD, PCHV, PCHV/TV, may serve as surrogates for likely histopathology patterns in future studies of RILI disease progression.

The Role of Hyperbaric Oxygen Therapy for the Treatment of Wounds.

Hyperbaric oxygen (HBO) is a Medicare-approved treatment for a variety of diagnoses including chronic nonhealing wounds and radiation necrosis. Hyperbaric oxygen therapy (HBOT) uses high pressures to saturate hemoglobin and dissolve oxygen into blood plasma to create a hyperoxemic environment to nourish and reverse local tissue injury caused by ischemia and hypoxemia. HBOT is expensive and not without risk; therefore, the underlying etiology for the presenting diagnosis must be adequately treated before starting HBO as an adjunct therapy to get maximum benefit.

The association of frailty and outcomes of geriatric assessment with acute radiation-induced toxicity in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Geriatric impairments and frailty are highly prevalent in patients with head and neck cancer (HNC). This study investigated the association of frailty and outcomes of geriatric assessment (GA) with radiation-induced toxicity (RIT) in patients undergoing (chemo)radiotherapy ((C)RT) for HNC. MATERIALS AND METHODS: Between October 2014 and April 2016, patients with HNC were prospectively included in OncoLifeS, an institutional data-biobank. Before treatment initiation, patients underwent GA and frailty screening (Groningen Frailty Indicator and Geriatric 8). The main outcome of this study was RIT (weight loss, mucositis, salivary gland inflammation, oral pain, sore throat, hoarseness, dry mouth, dysgeusia, dysphagia and general pain) according to the common terminology criteria of adverse events (CTCAE) version 4.0. Linear mixed models were performed, to analyse factors associated with increasing mean RIT over time during the treatment period. RESULTS: 160 patients were included. 114 (71.3%) were male and the mean age was 66.1 years. Age ≥ 65 (ß = 0.03(95 %CI = 0.01;0.05), p = 0.01), regional RT (ß = 0.05(95 %CI = 0.02;0.09), p = 0.004), and concurrent chemotherapy (ß = 0.04(95 %CI = 0.02;0.07), p = 0.001), were independent factors associated with increasing toxicity during the 7-week treatment period, adjusted for relevant covariates. None of the single items of GA, as well as the frailty screening instruments, were associated with increasing RIT. CONCLUSION: In this study, frailty and GA were not associated with additional RIT during treatment. These results suggest that (C)RT is equally tolerated in frail and non-frail patients, with respect to acute RIT. RT could be a suitable alternative to surgery in selected frail patients.