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.

Hypofractionated Postprostatectomy Radiation Therapy for Prostate Cancer to Reduce Toxicity and Improve Patient Convenience: A Phase 1/2 Trial.

PURPOSE: The phase 1 portion of this multicenter, phase 1/2 study of hypofractionated (HypoFx) prostate bed radiation therapy (RT) as salvage or adjuvant therapy aimed to identify the shortest dose-fractionation schedule with acceptable toxicity. The phase 2 portion aimed to assess the health-related quality of life (QoL) of using this HypoFx regimen. METHODS AND MATERIALS: Eligibility included standard adjuvant or salvage prostate bed RT indications. Patients were assigned to receive 1 of 3 daily RT schedules: 56.6 Gy in 20 Fx, 50.4 Gy in 15 Fx, or 42.6 Gy in 10 Fx. Regional nodal irradiation and androgen deprivation therapy were not allowed. Participants were followed for 2 years after treatment with outcome measures based on prostate-specific antigen levels, toxicity assessments (Common Terminology Criteria for Adverse Events, v4.0), QoL measures (the Expanded Prostate Cancer Index Composite [EPIC] and EuroQol EQ-5D instruments), and out-of-pocket costs. RESULTS: There were 32 evaluable participants, and median follow-up was 3.53 years. The shortest dose-fractionation schedule with acceptable toxicity was determined to be 42.6 Gy in 10 Fx, with most patients (23) treated with this schedule. Grade 3 genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 3 patients and 1 patient, respectively. There was 1 grade 4 sepsis event. Higher dose to the hottest 25% of the rectum was associated with increased risk of grade 2+ GI toxicity; no dosimetric factors were found to predict for GU toxicity. There was a significant decrease in the mean bowel, but not bladder, QoL score at 1 year compared with baseline. Prostate-specific antigen failure occurred in 34.3% of participants, using a definition of nadir plus 2 ng/mL. Metastases were more likely to occur in regional lymph nodes (5 of 7) than in bones (2 of 7). The mean out-of-pocket cost for patients during treatment was $223.90. CONCLUSIONS: We identified 42.6 Gy in 10 fractions as the shortest dose-fractionation schedule with acceptable toxicity in this phase 1/2 study. There was a higher than expected rate of grade 2 to 3 GU and GI toxicity and a decreased EPIC bowel QoL domain with this regimen. Future studies are needed to explore alternative adjuvant/salvage HypoFx RT schedules after radical prostatectomy.

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 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.

Cost-effectiveness analysis of voice rehabilitation for patients with laryngeal cancer: a randomized controlled study.

INTRODUCTION: Voice problems are common following radiotherapy for laryngeal cancer. Few studies exist covering the effect of voice rehabilitation, and no previous studies exist regarding the cost of said rehabilitation. This randomized controlled study aimed to analyze the cost-effectiveness of voice rehabilitation after radiotherapy for patients with laryngeal cancer. MATERIAL AND METHODS: A total of 66 patients with laryngeal cancer with follow-up data 12 months post-radiotherapy were included. Patients were randomized into receiving either voice rehabilitation (n = 32) or no voice rehabilitation (n = 34). The patient outcome was measured as quality-adjusted life years (QALYs). The index range between 0 and 1, where 0 equals death and 1 represents perfect health. The QALYs were assessed with the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30 mapped to EuroQoL 5 Dimension values. The cost of rehabilitation and other healthcare visits was derived from hospital systems. The patients reported the total amount of sick leave days during the first 12 months following radiotherapy. The cost-effectiveness of the voice rehabilitation was compared with no rehabilitation intervention based on the incremental cost-effectiveness ratio. RESULTS: The cost per gained QALY with voice rehabilitation compared to no rehabilitation from a societal perspective was - 27,594 € (SEK - 250,852) which indicates that the voice rehabilitation is a cost-saving alternative compared to no rehabilitation due to lower costs and a slightly better health outcome. From a healthcare perspective, the voice rehabilitation indicates a cost 60,800 € (SEK 552,725) per gained QALY. CONCLUSION: From a societal perspective, i.e., including the costs of production loss, voice rehabilitation compared to no voice rehabilitation following radiotherapy for laryngeal cancer seems to be cost-saving. When analyzing only the healthcare costs in relation to health outcomes, voice rehabilitation indicates an incremental cost of 60,800 € per gained QALY, which is just above the threshold of the maximum willingness to pay level.

RETROSPECTIVE ASSESSMENT OF CLINICAL-MORPHOLOGICAL CHANGES OF THE HEPATOBILIARY SYSTEM IN LIVER CIRRHOSIS OF THE CHORNOBYL NPP ACCIDENT CLEAN-UP WORKERS. / RETROSPEKTYVNA OTsINKA KLINIKO-MORFOLOGIChNYKh ZMIN GEPATOBILIARNOÏ SYSTEMY PRY TsYROZI PEChINKY V UChASNYKIV LIKVIDATsIÏ NASLIDKIV ChORNOBYL'S'KOÏ KATASTROFY.

OBJECTIVE: to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident. MATERIALS AND METHODS: Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated. RESULTS: A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %. CONCLUSION: Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment.

Plasma-based biomaterials for the treatment of cutaneous radiation injury.

Cutaneous wounds caused by an exposure to high doses of ionizing radiation remain a therapeutic challenge. While new experimental strategies for treatment are being developed, there are currently no off-the-shelf therapies for the treatment of cutaneous radiation injury that have been proven to promote repair of the damaged tissues. Plasma-based biomaterials are biologically active biomaterials made from platelet enriched plasma, which can be made into both solid and semi-solid forms, are inexpensive, and are available as off-the-shelf, nonrefrigerated products. In this study, the use of plasma-based biomaterials for the mitigation of acute and late toxicity for cutaneous radiation injury was investigated using a mouse model. A 2-cm diameter circle of the dorsal skin was irradiated with a single dose of 35 Gy followed by topical treatment with plasma-based biomaterial or vehicle once daily for 5 weeks postirradiation. Weekly imaging demonstrated more complete wound resolution in the plasma-based biomaterial vs. vehicle group which became statistically significant (p < 0.05) at weeks 12, 13, and 14 postmaximum wound area. Despite more complete wound healing, at 9 and 17 weeks postirradiation, there was no statistically significant difference in collagen deposition or skin thickness between the plasma-based biomaterial and vehicle groups based on Masson trichrome staining nor was there a statistically significant difference in inflammatory or fibrosis-related gene expression between the groups. Although significant improvement was not observed for late toxicity, plasma-based biomaterials were effective at promoting wound closure, thus helping to mitigate acute toxicity.

Assessment and agreement of the CT appearance pattern and its severity grading of radiation-induced lung injury after stereotactic body radiotherapy for lung cancer.

PURPOSE: Radiographic severity of radiation-induced lung injury (RILI) has not been well-studied. The goal of this study was to assess the CT appearance pattern and severity of RILI without consideration of the clinical presentation. MATERIAL AND METHODS: A total of 49 patients, 41 with primary lung cancer and 8 with metastatic lung cancer, were treated by 4-fraction stereotactic body radiotherapy (SBRT). RILI after SBRT was separately assessed by two observers. The early and late CT appearance patterns and CT-based severity grading were explored. RESULTS: The median follow-up period was 39.0 months. In the early CT findings of observers 1 and 2, there was diffuse consolidation in 15 and 8, diffuse ground glass opacity (GGO) in 0 and 0, patchy consolidation and GGO in 17 and 20, patchy GGO in 3 and 3, and no changes in 10 and 14, respectively (kappa = 0.61). In late CT findings of observer 1 and 2, there were modified conventional pattern in 28 and 24, mass-like pattern in 8 and 11, scar-like pattern in 12 and 12, and no changes in 1 and 2, respectively (kappa = 0.63). In the results of the CT-based grading by observers 1 and 2, there were grade 0 in 1 and 2, grade 1 in 10 and 14, grade 2 in 31 and 29, grade 3 in 7 and 4, and none of grade 4 or more, respectively (kappa = 0.66). According to multivariate analyses (MVA), the significant predicting factors of grade 2 or more CT-based RILI were age (p = 0.01), oxygen dependence (p = 0.03) and interstitial shadow (p = 0.03). CONCLUSIONS: The agreement of the CT appearance and CT-based grading between two observers was good. These indicators may be able to provide us with more objective information and a better understanding of RILI.

A Phase 2 Study of 2 Weeks of Adjuvant Whole Breast/Chest Wall and/or Regional Nodal Radiation Therapy for Patients With Breast Cancer.

PURPOSE: To report the results in terms of feasibility and early toxicity of hypofractionated adjuvant whole breast/chest wall and/or regional nodal radiation therapy for patients with breast cancer. METHODS AND MATERIALS: From June 2013 to October 2014, 50 patients with breast cancer after mastectomy or after breast conservation surgery (BCS) were prospectively included. The institutional ethics committee approved the study, which was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier no. NCT02460744). Treatment planning was performed using a simulator with 2 tangential fields to the breast/chest wall and an incident field to the supraclavicular fossa. The radiation dose delivered was 34 Gy in 10 fractions within 2 weeks, followed by a boost of 10 Gy in 5 fractions within 1 week for patients who underwent BCS. Acute skin toxicities were recorded during and after treatment according to the Radiation Therapy Oncology Group acute radiation toxicity scoring criteria. The primary objective was to obtain estimates of the acute toxicity rates and cosmetic outcomes that could be used to design a subsequent phase III comparative study. Acute skin and late toxicities were recorded during and after treatment. Cosmetic outcomes were assessed before and after treatment and during the regular follow-up period. A cost/benefit analysis was also performed and compared with that for standard treatment of 35 Gy in 15 fractions within 3 weeks. RESULTS: The median follow-up was 39 months (range 14-48). The mean age was 51 years (range 26-75). A left-sided tumor was present in 25 patients (50%). Total mastectomy with axillary clearance was performed in 40 (80%) and BCS in 10 (20%) patients. Acute grade 2 and 3 skin toxicity was seen in 16 (32%) and 1 (2%) patient, respectively. In the BCS patients, grade 2 skin and subcutaneous toxicity was seen in 2 (20%) and 1 (10%) patient, respectively. Grade 2 edema was seen in 1 patient (10%). The cosmesis was excellent or good in 8 (80%) and fair or poor in 2 (20%) patients. The cost/benefit analysis revealed significantly less financial burden on the patients with 2 weeks of treatment. Disease-free and overall survival at 3 years was 94% and 96%, respectively. CONCLUSIONS: Hypofractionated radiation therapy within 2 weeks appears to be feasible for patients with breast cancer and was associated with acute and late skin toxicity profiles similar to those observed with 3 weeks of treatment. The financial burden on the patient and family could be reduced with 2 weeks of treatment. Long-term follow-up data and a prospective comparative study are needed to strengthen these results. Hypofractionation might help radiation centers worldwide to meet the increasing need for radiation for breast cancer, especially in developing countries where resources are limited and patients must travel long distances for treatment.

Normal Tissue Complication Probability Modeling of Pulmonary Toxicity After Stereotactic and Hypofractionated Radiation Therapy for Central Lung Tumors.

PURPOSE: To evaluate clinical pulmonary and radiographic bronchial toxicity after stereotactic ablative radiation therapy and hypofractionated radiation therapy for central lung tumors, and perform normal tissue complication probability modeling and multivariable analyses to identify predictors for toxicity. METHODS AND MATERIALS: A pooled analysis was performed of patients with a central lung tumor treated using ≤12 fractions at 2 centers between 2006 and 2015. Airways were manually contoured on planning computed tomography scans, and doses were recalculated to an equivalent dose of 2 Gy per fraction with an α/ß ratio of 3. Grade ≥3 (≥G3) clinical pulmonary toxicity was evaluated by 2 or more physicians. Radiographic toxicity was defined as a stenosis or an occlusion with or without atelectasis using follow-up computed tomography scans. Logistic regression analyses were used for statistical analyses. RESULTS: A total of 585 bronchial structures were studied in 195 patients who were mainly treated using 5 or 8 fractions (60%). Median patient survival was 27.9 months (95% confidence interval 22.3-33.6 months). Clinical ≥G3 toxicity was observed in 24 patients (12%) and radiographic bronchial toxicity in 55 patients (28%), both mainly manifesting ≤12 months after treatment. All analyzed dosimetric parameters correlated with clinical and lobar bronchial radiographic toxicity, with V130Gy,EQD having the highest odds ratio. Normal tissue complication probability modeling showed a volume dependency for the development of both clinical and radiographic toxicity. On multivariate analyses, significant predictors for ≥G3 toxicity were a planning target volume overlapping the trachea or main stem bronchus (P = .005), chronic obstructive pulmonary disease (P = .034), and the total V130Gy,EQD (P = .012). Radiographic bronchial toxicity did not significantly correlate with clinical toxicity (P = .663). CONCLUSIONS: We identified patient and dosimetric factors associated with clinical and radiographic toxicity after high-dose radiation therapy for central lung tumors. Additional data from prospective studies are needed to validate these findings.

Treatment-related changes in glioblastoma: a review on the controversies in response assessment criteria and the concepts of true progression, pseudoprogression, pseudoresponse and radionecrosis.

The assessment of response to therapy in glioblastoma remains a challenge, because the surrogate measures of survival are subject to radiographic misinterpretation. A solid and reliable definition of progression is needed for both clinical decision-making and for evaluating response within the clinical trials. Historically, assessment criteria have used radiologic and clinical features aimed to correctly classify patients into progressive or non-progressive disease. The widely used RANO criteria are a valuable tool in disease evaluation, both in the clinical setting and in the clinical trials. However, assessment criteria have certain limitations that emerging image techniques have tried to overcome. Differentiating true progression from treatment-related changes (like pseudoprogression or pseudoresponse) is crucial in order not to prematurely discontinue adjuvant chemotherapy or redirect the patient to second-line options. This fact underscores the need for advanced radiologic techniques, like specific diffusion and perfusion MRI sequences, MR spectroscopy and PET, which seem to play a role in distinguishing these phenomena.

Information and statistical support for retrospective study of mortality among people exposed in childhood as a result of the Chornobyl accident and living in contaminated areas of Ukraine: assessment of feasibility. / INFORMATsIY̆NO STATYSTYChNE ZABEZPEChENNIa RETROSPEKTYVNOGO DOSLIDZhENNIa SMERTNOSTI OSIB, OPROMINENYKh U DYTIaChOMU VITsI VNASLIDOK AVARIÏ NA ChORNOBYL'S'KIY̆ AES TA PROZhYVAIuChYKh NA RADIOAKTYVNO ZABRUDNENYKh TERYTORIIaKh UKRAÏNY: OTsINKA PRAKTYChNOÏ MOZhLYVOSTI.

OBJECTIVE: Analysis of information from various sources for its use in epidemiological study on mortality of people (born in 1968-1986) who were children and adolescents at the time of the Chornobyl accident. OBJECT OF STUDY: Information and statistical sources for 1986-2011 on mortality among people who were children and adolescents at the time of the Chornobyl accident and lived on the most radioactive contaminated territories (RCT) of Ukraine (Ivankiv and Polisske regions of Kyiv oblast, Narodychi and Ovruch regions of Zhytomyr oblast). RESEARCH METHODS: theoretical, general scientific, documentary analysis, demographic. RESULTS AND CONCLUSIONS: The study is to determine the suitability of available information and statistical support for measuring and assessing mortality of people exposed in childhood as a result of the Chornobyl accident and liv ing in contaminated areas of Ukraine. A combination of information and statistical data provided by SRU, Ministry of Justice of Ukraine, State Statistics Service (SSS) of Ukraine and NNCRM makes it possible to successfully conduct retrospective cohort studies in any area and for any period.

[PET scan and NMR spectroscopy for the differential diagnosis between brain radiation necrosis and tumour recurrence after stereotactic irradiation of brain metastases: Place in the decision tree]. / TEP/tomodensitométrie et imagerie spectroscopique par résonance magnétique tridmensionnelle pour le diagnostic différentiel entre radionécrose cérébrale et rechute tumorale après irradiation en conditions stéréotaxiques de métastases cérébrales : place dans l'arbre décisionnel.

PURPOSE: After stereotactic radiation therapy for brain metastases, one of the complications is radionecrosis. Differential diagnosis with tumour recurrence can be helped by different methods of imaging, although histology remains the gold standard. According to the treatment centres, practice diverges. The objective of this single-centre retrospective study was to define the power of MRI, PET scan and NMR spectroscopy to establish a decision tree. MATERIAL AND METHODS: This study included patients who underwent stereotactic radiation therapy for brain metastases, and required, during follow-up, both a PET scan and NMR spectroscopy in order to differentiate a radiation necrosis and tumour recurrence. From 2010 to 2015, 25 patients were consistent with these criteria. RESULTS: Conventional MRI technique, with the T1/T2 mismatch criterion, had a specificity of 75% and a sensitivity of only 44%. A lesion quotient greater than 0.3 diagnosed a recurrence with a sensitivity of 92%. PET scan combined the best sensitivity and specificity, respectively of 92% and 69%. Whatever the thresholds used in NMR spectroscopy for choline/N-acetylaspartate and choline/creatin ratios, the power of this imaging modality did not exceed that of PET scan. CONCLUSION: The criteria described in conventional MRI cannot by themselves establish the differential diagnosis. In first intention in case of doubt, PET scan should be done, combining the best sensitivity and specificity, whereas NMR spectroscopy used in combination does not improve these factors.

An integrative review of skin assessment tools used to evaluate skin injury related to external beam radiation therapy.

AIMS AND OBJECTIVES: To review literature associated with external beam radiotherapy and skin damage. A focus of the literature search is to highlight and discuss the myriad of skin assessment tools that are available to the clinician when assessing skin injury in patients receiving external beam radiation therapy. BACKGROUND: It is apparent that despite considerable work being progressed in the development of individualised skin assessment tools, uptake and use is poor. These tools are designed to assist the clinician in the evaluation of damaged skin and predict the radiation wound development pathway. DESIGN: An integrated review can be used to address a mature or new and emerging topic through a systematic methodology, which is either theoretical or empirical, gained from research, practice or policy initiatives (Whittemore & Knafl, Journal of Advanced Nursing, 52, 2005, 546). This review is particularly concerned with the employment of skin assessment tools by clinicians in patients with radiation damaged skin. Using the search terms synonyms for radiation, skin and epidermal damage, PubMed/MEDLINE, Medical Complete and Web of Science databases were searched. Consulting professional peers was employed as part of the inclusion and exclusion process. CONCLUSION: There is a high level of unpredictability about which patient will have an uncomplicated course of external beam radiotherapy. Variables may include, but are not limited to, an acute reaction, a delayed reaction resulting in actual skin damage or no visible skin disturbance. The skin assessment tools that are readily available are not regularly referenced in clinical practice when attempting to manage the many side effects of radiation therapy. Skin assessment tools require ongoing clinical validation, so they can be used to guide practitioners to undertake further assessment of skin integrity. RELEVANCE TO CLINICAL PRACTICE: The current body of knowledge suggests clinicians caring for patients receiving therapeutic radiotherapy should consider integrating a recognised patient assessment skin framework into their daily routine. Such validated tools may add value to postradiotherapy patient care by providing a consistency of management and accordingly refining best practice.

In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells.

Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitro colony formation; (3) markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, of what appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone. Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.

Principles of a risk evaluation and mitigation strategy (REMS) for breast cancer patients receiving potentially cardiotoxic adjuvant treatments.

INTRODUCTION: The number of breast cancer long survivors has increased in the last few years. However, this increase in survival may be affected by the side effects of adjuvant breast cancer therapies. In this context cardiovascular toxicity is considered one of the most clinically important toxicities. AREAS COVERED: In this work we review the published clinical trials of adjuvant treatment on breast cancer, focusing on the trials which accurately mentioned the cardiotoxicity of the adjuvant treatments and those which underwent long term follow up of cardiac function. This article tries to summarize and evaluate the risk of cardiac toxicities associated with different adjuvant treatments for breast cancer (chemotherapy, radiotherapy, endocrine therapy and trastuzumab). EXPERT OPINION: In our opinion, each individual breast cancer patient should be meticulously evaluated before starting adjuvant treatment in order to basically asses cardiac function and to manage any predisposing risk factor which may increase the probability of treatment induced cardiotoxicity. Rigorous and frequent reassessment of cardiac function along with providing different mitigation strategies that can prevent or decrease the risk of such cardiovascular toxicities are inevitable methods to protect the patient from cardiac events which can mask the survival benefit associated with different adjuvant treatments.

Radiation Therapy Alone in cT1-3N0 Non-small Cell Lung Cancer Patients Who Are Unfit for Surgical Resection or Stereotactic Radiation Therapy: Comparison of Risk-Adaptive Dose Schedules.

PURPOSE: High dose definitive radiation therapy (RT) alone is recommended to patients with cT1-3N0 non-small cell lung cancer, who are unfit for surgery or stereotactic RT. This study was conducted to evaluate the clinical outcomes and cost-effectiveness following RT alone using two different modest hypofractionation dose schemes. MATERIALS AND METHODS: Between 2001 and 2014, 124 patients underwent RT alone. From 2001 till 2010, 60 Gy in 20 fractions was delivered to 79 patients (group 1). Since 2011, 60 Gy in 20 fractions (group 2, 20 patients), and 60 Gy in 15 fractions (group 3, 25 patients) were selectively chosen depending on estimated risk of esophagitis. RESULTS: At follow-up of 16.7 months, 2-year rates of local control, progression-free survival, and overall survival were 62.6%, 39.1%, and 59.1%, respectively. Overall survival was significantly better in group 3 (p=0.002). In multivariate analyses, cT3 was the most powerful adverse factor affecting clinical outcomes. Incidence and severity of radiation pneumonitis were not different among groups, while no patients developed grade 2 esophagitis in group 3 (p=0.003). Under current Korean Health Insurance Policy, RT cost per person was 22.5% less in group 3 compared with others. CONCLUSION: The current study demonstrated that 60 Gy in 15 fractions instead of 60 Gy in 20 fractions resulted in comparable clinical outcomes with excellent safety, direct cost saving, and improved convenience to the patients with tumors located at ≥ 1.5 cm from the esophagus.

Shear Wave Elastography--A New Quantitative Assessment of Post-Irradiation Neck Fibrosis.

PURPOSE: Shear wave elastography (SWE) is a new technique which provides quantitative assessment of soft tissue stiffness. The aim of this study was to assess the reliability of SWE stiffness measurements and its usefulness in evaluating post-irradiation neck fibrosis. MATERIALS AND METHODS: 50 subjects (25 patients with previous radiotherapy to the neck and 25 sex and age-matched controls) were recruited for comparison of SWE stiffness measurements (Aixplorer, Supersonic Imagine). 30 subjects (16 healthy individuals and 14 post-irradiated patients) were recruited for a reliability study of SWE stiffness measurements. SWE stiffness measurements of the sternocleidomastoid muscle and the overlying subcutaneous tissues of the neck were made. The cross-sectional area and thickness of the sternocleidomastoid muscle and the overlying subcutaneous tissue thickness of the neck were also measured. The post-irradiation duration of the patients was recorded. RESULTS: The intraclass correlation coefficients for the intraoperator and interoperator reliability of deep and subcutaneous tissue SWE stiffness ranged from 0.90-0.99 and 0.77-0.94, respectively. The SWE stiffness measurements (mean +/- SD) of deep and subcutaneous tissues were significantly higher in the post-irradiated patients (64.6 ± 46.8 kPa and 63.9 ± 53.1 kPa, respectively) than the sex and age-matched controls (19.9 ± 7.8 kPa and 15.3 ± 8.37 respectively) (p < 0.001). The SWE stiffness increased with increasing post-irradiation therapy duration in the Kruskal Wallis test (p < 0.001) and correlated with muscle atrophy and subcutaneous tissue thinning (p < 0.01). CONCLUSION: SWE is a reliable technique and may potentially be an objective and specific tool in quantifying deep and subcutaneous tissue stiffness, which in turn reflects the severity of neck fibrosis.

Recent advances in radiation oncology: intensity-modulated radiotherapy, a clinical perspective.

Radiotherapy plays an important role in the treatment of various malignancies, and intensity-modulated radiotherapy (IMRT) is an attractive option because it can deliver precise conformal radiation doses to the target while minimizing the dose to adjacent normal tissues. IMRT provides a highly conformal dose distribution by modulating the intensity of the radiation beam. A number of malignancies have been targeted by IMRT; this work reviews published data on the major disease sites treated with IMRT. The dosimetric advantage of IMRT has resulted in the significant reduction of adverse effects in some tumors. However, there are few clinical trials comparing IMRT and three-dimensional conformal radiotherapy (3D-CRT), and no definite increase in survival or the loco-regional control rate by IMRT has been demonstrated in many malignancies. IMRT also requires greater time and resources to complete compared to 3D-CRT. In addition, the cost-effectiveness of IMRT versus 3D-CRT has not yet been established.