[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.

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.

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.

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.

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.

Methods for induction and assessment of intestinal permeability in rodent models of radiation injury.

Ionizing radiation (IR) is a significant contributor to the contemporary market of energy production and an important diagnostic and treatment modality. Besides having numerous useful applications, it is also a ubiquitous environmental stressor and a potent genotoxic and epigenotoxic agent, capable of causing substantial damage to organs and tissues of living organisms. The gastrointestinal (GI) tract is highly sensitive to IR. This problem is further compounded by the fact that there is no FDA-approved medication to mitigate acute radiation-induced GI syndrome. Therefore, establishing the animal model for studying IR-induced GI-injury is crucially important to understand the harmful consequences of intestinal radiation damage. Here, we discuss two different animal models of IR-induced acute gastrointestinal syndrome and two separate methods for measuring the magnitude of intestinal radiation damage.

Prognostic assessment of the zone of occurrence of radiation combined injuries within a nuclear blast area.

BACKGROUND: A detonation of nuclear weapon (NW) is considered as one of the most devastating radiological scenarios in the list of modern global threats. An essential proportion of victims in a mass casualty radiation event may require an immediate medical care due to radiation combined injuries (RCI). Surprisingly, there is a lack of clear guidance for quantitative prognosis of the spatial distribution of expected RCI casesin a given nuclear explosion scenario. PURPOSE: This work is aimed at the presentation of a new, improved model, allowing more confident evaluation of the contributions from different NW destructive forces to RCI formation, thus leading to more accurate approximation of the zone around the epicenter for a guided search for RCI cases. MATERIALS AND METHODS: The model is made compatible with a classic approach and provides the estimates of radial distance from the epicenter, at which NW explosion can produce RCI. Mathematical formalism comprises a set of equations for the reciprocal assessment of a distance-effect for radiation dose (separately for neutrons and gamma-rays), thermal wave and blast shock wave depending on the NW type, detonation yield and altitude, environmental conditions (i.e. season) and shielding factors. The model's capabilities were demonstrated using an example of the RCI grade causing a profound operational performance decrement of military personnel in two marginal scenarios: Troops deployed in an open area or a tank crew. RESULTS: A remarkable difference in the expected radial zones of possible RCI occurrence was found between the actions of a 'historical' atomic bomb, thermonuclear weapons, and low-yield neutron munitions, also with a noticeable impact of the season factor (summer/winter). For a tank crew the clinically manageable RCI are possible only in very high yield explosion scenarios, while the damage caused by radiation alone possess much higher risk. CONCLUSIONS: Suggested formalism may provide guidance for a preliminary planning of countermeasures, targeting of radiation reconnaissance, and clarification of triage results in a broad range of radiological scenarios based on NW detonation. Further improvement of the model is possible by considering neutrons' and gamma-rays' relative biological efficacy, possible shielding factors, and a synergetic effect of NW's destructive forces.

The centrally restricted diffusion sign on MRI for assessment of radiation necrosis in metastases treated with stereotactic radiosurgery.

PURPOSE: Differentiation of radiation necrosis from tumor progression in brain metastases treated with stereotactic radiosurgery (SRS) is challenging. For this, we assessed the performance of the centrally restricted diffusion sign. METHODS: Patients with brain metastases treated with SRS who underwent a subsequent intervention (biopsy/resection) for a ring-enhancing lesion on preoperative MRI between 2000 and 2020 were included. Excluded were lesions containing increased susceptibility limiting assessment of DWI. Two neuroradiologists classified the location of the diffusion restriction with respect to the post-contrast T1 images as centrally within the ring-enhancement (the centrally restricted diffusion sign), peripherally correlating to the rim of contrast enhancement, both locations, or none. Measures of diagnostic accuracy and 95% CI were calculated for the centrally restricted diffusion sign. Cohen's kappa was calculated to identify the interobserver agreement. RESULTS: Fifty-nine patients (36 female; mean age 59, range 40 to 80) were included, 36 with tumor progression and 23 with radiation necrosis based on histopathology. Primary tumors included 34 lung, 12 breast, 5 melanoma, 3 colorectal, 2 esophagus, 1 head and neck, 1 endometrium, and 1 thyroid. The centrally restricted diffusion sign was seen in 19/23 radiation necrosis cases (sensitivity 83% (95% CI 63 to 93%), specificity 64% (95% CI 48 to 78%), PPV 59% (95% CI 42 to 74%), NPV 85% (95% CI 68 to 94%)) and 13/36 tumor progression cases (difference p < 0.001). Interobserver agreement was substantial, at 0.61 (95% CI 0.45 to 70.8). CONCLUSION: We found a low probability of radiation necrosis in the absence of the centrally restricted diffusion sign.

Who Will Benefit from Charged-Particle Therapy?

Charged-particle therapy (CPT) such as proton beam therapy (PBT) and carbon-ion radiotherapy (CIRT) exhibit substantial physical and biological advantages compared to conventional photon radiotherapy. As it can reduce the amount of radiation irradiated in the normal organ, CPT has been mainly applied to pediatric cancer and radioresistent tumors in the eloquent area. Although there is a possibility of greater benefits, high set-up cost and dearth of high level of clinical evidence hinder wide applications of CPT. This review aims to present recent clinical results of PBT and CIRT in selected diseases focusing on possible indications of CPT. We also discussed how clinical studies are conducted to increase the number of patients who can benefit from CPT despite its high cost.

[Compensation of damage in cancerology]. / Réparation du dommage en cancérologie.

In a few situations, the consequences secondary to a carcinological pathology require an assessment of damages for compensatory purposes. This is particularly the case when liable parties have been found to be at cause of the disease: occupational pathologies in the case of inexcusable employer's fault, exposure to a radioactive risk, for example in the context of full compensation for damages suffered by the victims of nuclear experiments performed by France, or lastly, in the after-effects of late diagnosis. This article does not discuss the imputability of cancer pathologies to an event, but it proposes an adaptation of methods for assessing damages, in an attempt to provide full compensation for damages.

Assessment of Toxic Effects Associated With Dose-Fractionated Radiotherapy Among Patients With Cancer and Comorbid Collagen Vascular Disease.

Importance: The adoption of alternative fractionated radiotherapy regimens for the treatment of patients with cancer and comorbid collagen vascular disease (CVD) is controversial among oncologists because of concerns about potentially severe toxic effects; however, the association between fractionated radiotherapy and toxic effects in the modern era has not been well studied. Objective: To compare acute and late toxic effects among patients with cancer and comorbid CVD who received dose-fractionated radiotherapy. Design, Setting, and Participants: This retrospective cohort study examined 197 adult patients with cancer and CVD who received radiotherapy at a single-institution tertiary academic center over a 12-year period (February 1, 2007, to April 30, 2019), with a median follow-up of 23 months (range, 0-108 months). Data were analyzed from February 1 to August 31, 2020. Exposures: Three dose-fractionated radiotherapy regimens: conventional fractionation (CF; ≤2 Gy per fraction), moderate hypofractionation (MH; >2 Gy to <5 Gy per fraction), and ultrahypofractionation (UH; ≥5 Gy per fraction). Main Outcomes and Measures: The main outcomes were the incidence and severity of acute and late radiotherapy-associated toxic effects, which were assessed separately by dose-fractionation regimen. Toxic effects occurring within 90 days after radiotherapy completion were considered acute, and toxic effects occurring after that 90-day period were considered late. Secondary goals were to identify covariates associated with toxic effects and to characterize the incidence of CVD symptom flares (defined as worsening clinical symptoms and/or worsening results [transient or permanent] on associated blood tests compared with baseline, as documented by managing physicians) after radiotherapy. Results: Of 197 patients with cancer and comorbid CVD (mean [SD] age, 69 [12] years; 134 women [68.0%]; and 149 White participants [75.6%]), 80 patients (40.6%) received CF radiotherapy, 55 patients (27.9%) received MH radiotherapy, and 62 patients (31.5%) received UH radiotherapy. The most common CVD diagnoses were rheumatoid arthritis (74 patients [37.6%]), psoriasis (54 patients [27.4%]), systemic lupus erythematosus (34 patients [17.3%]), and scleroderma (8 patients [4.1%]). The most common radiotherapy sites were the breast (48 patients [24.4%]), thorax (25 patients [12.7%]), central nervous system (24 patients [12.2%]), and prostate (23 patients [11.7%]). Data on acute toxic effects were available for 188 patients (95.4%) and missing for 9 patients (4.6%). Data on late toxic effects were available for 142 patients (72.1%) and missing for 55 patients (27.9%). Over 12 years, the unadjusted incidences of severe acute toxic effects associated with CF, MH, and UH radiotherapy were 5.4% (95% CI, 0.3%-10.5%), 7.4% (95% CI, 0.4%-14.4%), and 1.7% (95% CI, 0%-5.0%), respectively. The incidences of severe late toxic effects associated with CF, MH, and UH radiotherapy were 8.3% (95% CI, 1.3%-15.3%), 0%, and 2.2% (95% CI, 0%-6.4%), respectively. No significant associations were found between severe acute or late toxic effects by dose fractionation regimen. In the multivariable analysis, MH radiotherapy was associated with a lower likelihood of developing late toxic effects (odds ratio [OR], 0.21; 95% CI, 0.05-0.83; P = .03) compared with CF radiotherapy. Those who received UH radiotherapy had a lower likelihood of experiencing late toxic effects (OR, 0.22; 95% CI, 0.04-1.21; P = .08). A total of 19 of 80 patients (23.8%), 15 of 55 patients (27.3%), and 10 of 62 patients (16.1%) experienced CVD symptom flares after receiving CF, MH, and UH radiotherapy, respectively (P = .33). Conclusions and Relevance: In this study, the incidences of unadjusted severe toxic effects over 12 years were less than 10% and were not significantly associated with dose fractionation. When clinically indicated, patients with cancer and comorbid CVD may not require immediate exclusion from the receipt of currently used hypofractionated radiotherapy regimens.

Assessment of Radiation-Induced Xerostomia: Validation of the Xerostomia Questionnaire in Chinese Patients With Head and Neck Cancer.

BACKGROUND: Xerostomia is a common complication in patients with head and neck cancer (HNC) during and after radiotherapy. The lack of a simply-administered and well-validated self-reported instrument has hampered the assessment and management of xerostomia for research and clinical purposes in China. OBJECTIVE: This study aimed to evaluate the content validity and psychometric properties of the Xerostomia Questionnaire (XQ) in Chinese patients with HNC undergoing radiotherapy. METHODS: This psychometric evaluation study enrolled 80 patients and was conducted in 2 stages: translation and evaluation of content validity and psychometric evaluation. Cognitive interviews (n = 10) were conducted using the Participant Interview Form. The psychometric evaluation (n = 80) included score distribution, homogeneity (interitem and item-total correlations), factor structure (exploratory factor analysis), internal consistency (Cronbach's α), criterion-related validity (person correlation), and test-retest reliability (intraclass correlations). RESULTS: Content validity was supported by cognitive interviews. The factor analysis resulted in a 1-factor solution with strong factor loadings (0.84-0.91) that explained 75.6% of the total variance. The internal consistency was excellent, with a Cronbach's α of .95. The XQ correlated strongly with other measures of xerostomia (0.70-0.80), which supports criterion-related validity. The test-retest reliability was excellent (intraclass correlation coefficient = 0.92). CONCLUSIONS: The result provides evidence for the validity and reliability of the XQ in a sample of Chinese patients with HNC. IMPLICATIONS FOR PRACTICE: The XQ can be used in both clinical practice and research as a valuable tool to screen for problems with xerostomia, monitor the xerostomia level, and evaluate the effects of treatment and interventions among patients with HNC.

Radiation-induced lens opacities: Epidemiological, clinical and experimental evidence, methodological issues, research gaps and strategy.

In 2011, the International Commission on Radiological Protection (ICRP) recommended reducing the occupational equivalent dose limit for the lens of the eye from 150 mSv/year to 20 mSv/year, averaged over five years, with no single year exceeding 50 mSv. With this recommendation, several important assumptions were made, such as lack of dose rate effect, classification of cataracts as a tissue reaction with a dose threshold at 0.5 Gy, and progression of minor opacities into vision-impairing cataracts. However, although new dose thresholds and occupational dose limits have been set for radiation-induced cataract, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological and mechanistic evidence at doses under 2 Gy. Since the release of the 2011 ICRP statement, the Multidisciplinary European Low Dose Initiative (MELODI) supported in April 2019 a scientific workshop that aimed to review epidemiological, clinical and biological evidence for radiation-induced cataracts. The purpose of this article is to present and discuss recent related epidemiological and clinical studies, ophthalmic examination techniques, biological and mechanistic knowledge, and to identify research gaps, towards the implementation of a research strategy for future studies on radiation-induced lens opacities. The authors recommend particularly to study the effect of ionizing radiation on the lens in the context of the wider, systemic effects, including in the retina, brain and other organs, and as such cataract is recommended to be studied as part of larger scale programs focused on multiple radiation health effects.

USE OF ANTHROPOMORPHIC HETEROGENEOUS PHYSICAL PHANTOMS FOR VALIDATION OF COMPUTATIONAL DOSIMETRY OF MEDICAL PERSONNEL AND PATIENTS. / VYKORYSTANNIa ANTROPOMORFNYKh GETEROGENNYKh FIZYChNYKh FANTOMIV DLIa VALIDATsIÏ ROZRAKhUNKOVOÏ DOZYMETRIÏ PERSONALU TA PATsIIeNTIV.

In the dosimetry of ionizing radiation, the phantoms of the human body, which are used as a replacement for thehuman body in physical measurements and calculations, play an important, but sometimes underestimated, role.There are physical phantoms used directly for measurements, and mathematical phantoms for computationaldosimetry. Their complexity varies from simple geometry applied for calibration purposes up to very complex, whichsimulates in detail the shapes of organs and tissues of the human body. The use of physical anthropomorphic phantoms makes it possible to effectively optimize radiation doses by adjusting the parameters of CT-scanning (computed tomography) in accordance with the characteristics of the patient without compromising image quality. The useof phantoms is an indispensable approach to estimate the actual doses to the organs or to determine the effectivedose of workers - values that are regulated, but cannot be directly measured.The article contains an overview of types, designs and the fields of application of anthropomorphic heterogeneousphysical phantoms of a human with special emphasis on their use for validation of models and methods of computational dosimetry.

THE ASSESSMENT OF COMORBID PATHOLOGY IN CLEAN-UP WORKERS OF THE ACCIDENT CONSEQUENCES AT THE CHORNOBYL NPP HAVING CARDIOVASCULAR DISEASES. / OTsINKA KOMORBIDNOÏ PATOLOGIÏ V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChORNOBYL'S'KII AES Z ZAKhVORIuVANNIaMY SERTsEVO-SUDYNNOÏ SYSTEMY.

OBJECTIVE: Analysis of comorbid pathology based on the use of methods for its quantitative assessment in personswho were exposed to radiation because of the Chornobyl accident. MATERIALS AND METHODS: Comorbid pathology was studied in 608 men, including 420 clean-up workers (CW) of theaccident consequences at the Chornobyl NPP (main group) and 188 non-irradiated persons (control group - CG). Allpatients had cardiovascular diseases as their main pathology and were examined in the cardiology department ofthe NRCRM hospital during 2011-2019. The groups did not differ by age, either at the beginning of the accident orat the time of their last examination. Patients of both groups before the accident were practically healthy peopleand were not registered at the dispensary. The Cumulative Illness Rating Scale (CIRS) was used to quantify comorbid pathology. RESULTS: Comorbid pathology was detected in 418 CW (99.5 %) and 183 patients of CG (99.3 %). The total score inCW (10.3 ± 2.9) units significantly (р = 0.000) exceeded the same index in non-irradiated patients (8.8 ± 3.0) units,as well as the mean number of CIRS categories, whose level severity was 1 point (3.3 ± 1.7 vs. 2.6 ± 1.5, р = 0.000),2 points (1.8 ± 1.0 vs. 1.6 ± 1.0, p = 0.032) and 3-4 points (1.2 ± 0.8 vs. 1.0 ± 0.9, р = 0.062). In contrast, the meanvalue of the categories with zero score, i.e. without diseases, was more common in CG (7.8 ± 1.8 vs. 8.8 ± 1.7,р = 0.000). The most common pathology in CW and CG were heart (98.3 % vs. 94.7 %, р < 0.05) and vascular diseases(92.9 % vs. 87.8 %, р > 0.05), followed by diseases of nervous system (79.0 % vs. 57.4 %, р <0.001), musculoskeletal system and skin (69.8 % vs. 56.9 %, р < 0.01), endocrine (56.0 % vs. 49,5 %, р > 0.05) and the respiratory system (53.8 % vs. 53.7 %, р > 0.05) and liver (51.2 % vs. 36.2 %, р < 0.001), which were detected more than in halfpatients of the main group. Diseases of the kidneys (3.3 % vs. 4.8 %, р > 0.05) and lower gastrointestinal tract(3.3 % vs. 0.5 %, р < 0.01) were quite rare. The incidence of the other four CIRS categories was 18.6-34 %. The totalscore in subgroups with different ages varied in descending order of mean values as follows: CW > 65 years (10.5 ± 2.9)units, CW < 65 years (9.9 ± 2.8) units, CG > 65 years (9.5 ± 2.8) units and CG < 65 years (7.8 ± 2.9) units with significant differences both between age subgroups in each of the groups and between CW and CG older subgroups. CONCLUSIONS: Quantitative assessment of comorbidity by CIRS showed that in persons irradiated during their emergency work due to the Chornobyl accident, the incidence of combined pathology of such organ systems as cardiovascular, nervous, endocrine, hematopoietic, urogenital, musculoskeletal, gastrointestinal, liver and kidneys wassignificantly higher than in non-irradiated patients. In irradiated patients, the course of comorbid pathology wasmore severe for each system and in general, reflecting higher values of the total CIRS score. Both among CW andnon-irradiated controls, higher values of the total comorbidity score were observed in patients 65 years and older,compared with younger individuals. In both age subgroups of CW the total score was higher than in patients of thecontrol group.

Assessment of acute toxicities and early local recurrences in post mastectomy breast cancer patients by accelerated hypofractionated radiotherapy; a single arm clinical trial.

PURPOSE: Hypofractionated post mastectomy radiotherapy (PMRT) is commonly given using conventional radiotherapy technique. Volumetric modulated arc therapy (VMAT) and Intensity modulated radiation therapy (IMRT) are better sparing heart and lungs. This study was conducted to assess the toxicity profile and dosimetry outcomes of patients receiving PMRT using IMRT or VMAT. METHODS: 67 biopsy-proven patients with carcinoma of the breast who had undergone modified radical mastectomy (MRM) were included in the study. They were treated using VMAT or IMRT to a dose of 42.56 Gy in 16 fractions. Acute and late toxicities were graded using RTOG toxicity grading scale. Toxicities and recurrences were summarized as proportions with 95% confidence intervals. Spearman's correlation was used to find association between the dose received by the organs at risk (OARs) and the grade of toxicities. RESULTS: The mean age of the study population was 48±9.5 years. The incidence of acute grade 2 and above radiation dermatitis and pneumonitis were 11.9% and 7.5 % respectively. The incidence of acute esophagitis was 46.3%. With a median follow up of 9 months there were no significant late toxicities. There was only one local recurrence and three progressed to distant metastases but without local recurrence. Twenty-four patients were treated by IMRT, 43 patients were treated by VMAT. Dosimetrically VMAT and IMRT were comparable in planning target volume (PTV) coverage and OAR doses, but VMAT had less number of monitor units and shorter treatment time.

Monte Carlo 90Y PET/CT dosimetry of unexpected focal radiation-induced lung damage after hepatic radioembolisation.

Transarterial radioembolization (TARE) with 90Y-loaded microspheres is an established therapeutic option for inoperable hepatic tumors. Increasing knowledge regarding TARE hepatic dose-response and dose-toxicity correlation is available but few studies have investigated dose-toxicity correlation in extra-hepatic tissues. We investigated absorbed dose levels for the appearance of focal lung damage in a case of off-target deposition of 90Y microspheres and compared them with the corresponding thresholds recommended to avoiding radiation induced lung injury following TARE. A 64-year-old male patient received 1.6 GBq of 90Y-labelled glass microspheres for an inoperable left lobe hepatocellular carcinoma. A focal off-target accumulation of radiolabeled microspheres was detected in the left lung upper lobe at the post-treatment 90Y-PET/CT, corresponding to a radiation-induced inflammatory lung lesion at the 3-months 18F-FDG PET/CT follow-up. 90Y-PET/CT data were used as input for Monte-Carlo based absorbed dose estimations. Dose-volume-histograms were computed to characterize the heterogeneity of absorbed dose distribution. The dose level associated with the appearance of lung tissue damage was estimated as the median absorbed dose measured at the edge of the inflammatory nodule. To account for respiratory movements and possible inaccuracy of image co-registration, three different methods were evaluated to define the irradiated off-target volume. Monte Carlo-derived absorbed dose distribution showed a highly heterogeneous absorbed dose pattern at the site of incidental microsphere deposition (volume = 2.13 ml) with a maximum dose of 630 Gy. Absorbed dose levels ranging from 119 Gy to 133 Gy, were estimated at the edge of the inflammatory nodule, depending on the procedure used to define the target volume. This report describes an original Monte Carlo based patient-specific dosimetry methodology for the study of the radiation-induced damage in a focal lung lesion after TARE. In our patient, radiation-induced focal lung damage occurred at significantly higher absorbed doses than those considered for single administration or cumulative lung dose delivered during TARE.

Toxicity after adjuvant therapy for stage III uterine cancer.

OBJECTIVE: The optimal adjuvant therapy for stage III endometrial cancer is unknown. Studies have suggested that combination therapy with chemotherapy and radiation is associated with improved survival. We examined early and late-term toxicities associated with chemotherapy (CT), external beam radiotherapy (RT), or combination chemoradiotherapy for stage III uterine cancer. METHODS: The SEER-Medicare database was used to identify women age ≥ 65 years with stage III uterine cancer who received adjuvant CT, RT, or chemoradiotherapy from 2000 to 2015. The associations between therapy and early and late-term toxicities identified with billing claims, hospitalizations and emergency department visits were examined using multivariable regression models. RESULTS: A total of 2185 patients were identified including 574 (26.3%) who received CT, 636 (29.1%) who received RT, and 975 (44.6%) who received chemoradiotherapy. The proportion of patients receiving chemoradiotherapy or CT increased over time. During the first 6 and 12 months of adjuvant therapy, RT was associated with a lower risk of early-term toxicity compared to chemoradiotherapy (aRR = 0.59, 95%CI 0.49-0.70 and aRR = 0.76, 95%CI 0.67-0.86, respectively) while CT shared a similar risk of early toxicities as chemoradiotherapy. CT and RT shared a similar risk of late-term toxicities compared to chemoradiotherapy. CT and RT alone were associated with a higher hazard for overall mortality than chemoradiotherapy (aHR = 1.27, 95% CI 1.10-1.47 and aHR = 1.25, 95% CI 1.08-1.44, respectively). CONCLUSION: Chemoradiotherapy is associated with lower mortality compared to single modality therapy and has a similar risk of early and late term toxicities compared to CT, though higher risk of early toxicities compared to RT.

Assessment of toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy.

BACKGROUND: Hypofractionation is now becoming the standard of care in breast irradiation. The aim of this study was to assess the toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy (HFRT). METHODS: Patients with localized breast cancer who received adjuvant HFRT between 2013 and 2015 with a minimum follow-up of 6 months following radiation were included in this prospective study. Late toxicities were assessed using CTCAE v 4 and included chest/breast pain, limb pain, limb edema, skin pigmentation, skin fibrosis, and shoulder movement restriction. Outcomes assessed included locoregional control, disease-free survival, and overall survival. Statistical analysis was done using Microsoft Excel and SPSS v22. RESULTS: A total of 81 patients fulfilled the inclusion criteria, of which 19 patients had died during follow-up. Regional nodal irradiation was done in 63 (77.8%) patients using the same hypofractionated schedule of 40 Gy in 15 fractions. Late toxicities were assessed for 62 patients. The median follow-up following the course of hypofractionated radiation was 45 months (range 14 - 65 months). Late toxicities were assessed for 62 patients. Grade 1/2 chest/breast pain, limb pain, limb edema, skin pigmentation, skin fibrosis, and shoulder movement restriction were seen in 11%, 12%, 7%, 6%, 8%, and 11% of cases, respectively. Distant recurrences were seen in 8% of cases, and there were no locoregional recurrences. Five-year overall survival was 76.5%. CONCLUSION: HFRT to whole breast or chest wall and the regional nodal areas was well-tolerated with acceptable rates of late toxicities on follow-up.