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.

Review of the Accident Compensation Corporation's radiation therapy injury claims, 1 July 2009-30 June 2019.

AIM: The aim of this study was to review and report on radiation therapy injury claims lodged with the Accident Compensation Corporation (ACC) in New Zealand in the last decade. METHODS: ACC's treatment injury database was used to identify injury claims decided between 1 July 2009 and 30 June 2019. The associated structured and unstructured data, including claim lodgement information and medical records, were reviewed. RESULTS: Of 121,168 treatment injuries, only 975 (0.8%) were radiation therapy injury claims, with 519 claims accepted for cover. Most declined claims were considered "ordinary consequences of treatment" rather than treatment injuries. Of the 519 accepted claims, ACC classified 21 as fatal and eight as serious, which indicates a need for lifelong ACC support. Injuries correlated with the age and gender of the most common cancers treated with radiation therapy in New Zealand. More treatment injury claims were submitted and accepted for New Zealand European patients compared with Maori and Pasifika patients. CONCLUSION: Radiation therapy injury claims make up a very small proportion of the total number of ACC treatment injury claims. A better understanding of the claim process may assist injured individuals better by improving appropriate claim lodgement and claim acceptance rates.

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.

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.

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.

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.

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.

Long-Term Disease Burden and Survivorship Issues After Surgery and Radiotherapy of Intracranial Meningioma Patients.

BACKGROUND: Many intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention. OBJECTIVE: To assess the long-term (≥5 yr) disease burden of meningioma patients. METHODS: In this multicenter cross-sectional study, patients ≥5 yr after intervention (including active magnetic resonance imaging (MRI) surveillance) were included and assessed for HRQoL (Short-Form Health Survey 36), neurocognitive functioning (neuropsychological assessment), anxiety and depression (Hospital Anxiety and Depression Scale), and work productivity (Short Form-Health and Labour Questionnaire). Multivariable and propensity score regression analyses were used to compare patients and controls, and different treatment strategies corrected for possible confounders. Clinically relevant differences were reported. RESULTS: At a median of 9 yr follow-up after intervention, meningioma patients (n = 190) reported more limitations due to physical (difference 12.5 points, P = .008) and emotional (13.3 points, P = .002) health problems compared with controls. Patients also had an increased risk to suffer from anxiety (odds ratio [OR]: 2.6, 95% CI: 1.2-5.7) and depression (OR: 3.7, 95% CI: 1.3-10.5). Neurocognitive deficits were found in 43% of patients. Although postoperative complications, radiotherapy, and reresection were associated with worse verbal memory, attention, and executive functioning when compared to patients resected once, the only clinically relevant association was between reresection and worse attention (-2.11, 95% CI: -3.52 to -0.07). Patients of working age less often had a paid job (48%) compared with the working-age Dutch population (72%) and reported more obstacles at work compared with controls. CONCLUSION: In the long term, a large proportion of meningioma patients have impaired HRQoL, neurocognitive deficits, and high levels of anxiety or depression. Patients treated with 1 resection have the best neurocognitive functioning.

Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial.

BACKGROUND: We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial. METHODS: FAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1-3, pN0-1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1·6% excess for five-fraction schedules (critical hazard ratio [HR] of 1·81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132. FINDINGS: Between Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71·5 months (IQR 71·3 to 71·7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0·86 (95% CI 0·51 to 1·44) for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2·1% (1·4 to 3·1); estimated absolute differences versus 40 Gy in 15 fractions were -0·3% (-1·0 to 0·9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior five-fraction schedule: p=0·0022 vs 40 Gy in 15 fractions) and -0·7% (-1·3 to 0·3) for 26 Gy in five fractions (p=0·00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9·9%) 40 Gy patients, 155 (15·4%) of 1005 27 Gy patients, and 121 of 1020 (11·9%) 26 Gy patients. Across all clinician assessments from 1-5 years, odds ratios versus 40 Gy in 15 fractions were 1·55 (95% CI 1·32 to 1·83, p<0·0001) for 27 Gy in five fractions and 1·12 (0·94 to 1·34, p=0·20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy. INTERPRETATION: 26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

A Monte Carlo model for organ dose reconstruction of patients in pencil beam scanning (PBS) proton therapy for epidemiologic studies of late effects.

Significant efforts such as the Pediatric Proton/Photon Consortium Registry (PPCR) involving multiple proton therapy centers have been made to conduct collaborative studies evaluating outcomes following proton therapy. As a groundwork dosimetry effort for the late effect investigation, we developed a Monte Carlo (MC) model of proton pencil beam scanning (PBS) to estimate organ/tissue doses of pediatric patients at the Maryland Proton Treatment Center (MPTC), one of the proton centers involved in the PPCR. The MC beam modeling was performed using the TOPAS (TOol for PArticle Simulation) MC code and commissioned to match measurement data within 1% for range, and 0.3 mm for spot sizes. The established MC model was then tested by calculating organ/tissue doses for sample intracranial and craniospinal irradiations on whole-body pediatric computational human phantoms. The simulated dose distributions were compared with the treatment planning system dose distributions, showing the 3 mm/3% gamma index passing rates of 94%-99%, validating our simulations with the MC model. The calculated organ/tissue doses per prescribed doses for the craniospinal irradiations (1 mGy Gy-1 to 1 Gy Gy-1) were generally much higher than those for the intracranial irradiations (2.1 µGy Gy-1 to 0.1 Gy Gy-1), which is due to the larger field coverage of the craniospinal irradiations. The largest difference was observed at the adrenal dose, i.e. ∼3000 times. In addition, the calculated organ/tissue doses were compared with those calculated with a simplified MC model, showing that the beam properties (i.e. spot size, spot divergence, mean energy, and energy spread) do not significantly influence dose calculations despite the limited irradiation cases. This implies that the use of the MC model commissioned to the MPTC measurement data might be dosimetrically acceptable for patient dose reconstructions at other proton centers particularly when their measurement data are unavailable. The developed MC model will be used to reconstruct organ/tissue doses for MPTC pediatric patients collected in the PPCR.

Whole-brain radiotherapy plus sequential or simultaneous integrated boost for the treatment of a limited number of brain metastases in non-small cell lung cancer: A single-institution study.

BACKGROUND: To compare the survival outcomes and neurocognitive dysfunction in non-small cell lung cancer (NSCLC) patients with brain metastases (BM ≤10) treated by whole-brain radiotherapy (WBRT) with sequential integrated boost (SEB) or simultaneous integrated boost (SIB). MATERIALS: Fifty-two NSCLC patients with a limited number of BMs were retrospectively analyzed. Twenty cases received WBRT+SEB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*3 fractions; SEB group), and 32 cases received WBRT+SIB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*10 fractions; SIB group). The survival and mini-mental state examination (MMSE) scores were compared between the groups. RESULTS: The cumulative 1-, 2-, and 3-year survival rates in the SEB vs SIB groups were 60.0% vs 47.8%, 41.1% vs 19.1%, and 27.4% vs 0%, respectively. The median survival times in the SEB and SIB groups were 15 and 10 months, respectively. The difference in survival rate was significant (P = .046). Subgroup analysis revealed that 1-, 2-, and 3-year survival rates and median survival time in the SEB group were significantly superior to those of the SIB group, especially for male patients (age <60 years) with 1-2 BMs (P < .05). The MMSE score of the SEB group at 3 months after radiation was higher than that of the SIB group (P < .05). Nevertheless, WBRT+SEB required a longer treatment time and greater cost (P < .005). CONCLUSIONS: WBRT + SEB results in better survival outcomes than WBRT+SIB, especially for male patients (age <60 years) with 1-2 BMs. WBRT+SEB also appeared to induce less neurocognitive impairment than WBRT+SIB.

Assessment of the nuclear medicine personnel occupational exposure to radioiodine.

PURPOSE: To physically and cytogenetically screen medical personnel of Department of Endocrinology and Nuclear Medicine, Holy Cross Cancer Center, Kielce, Poland (DENM) who are occupationally exposed to 131I. MATERIALS AND METHODS: The exposure was monitored by whole-body and finger ring dosimeters. The thyroid iodine intake was measured by a whole-body spectrometer equipped with two semiconductor gamma radiation detectors. A cytokinesis-block micronucleus assay and the premature chromosome condensation technique were used to assess the aberration score. Cytogenetic analyses were carried out on a group of 29 workers and were compared to 32 controls (healthy donors), matched for gender and age. RESULTS: On average, the exposed group showed a significantly higher frequency of genetic damage and a higher proliferation index compared to the control group. Smoking status, age and duration of exposure influenced the observed effects in both groups. No differences in measured biomarkers were observed after stratification of the exposed group into two subgroups based on the measured 131I activity below and above 6 Bq. CONCLUSION: The findings suggest that radiation protection principles based on whole-body and finger ring dosimetry, supported by activity measurements with a whole-body spectrometer, may be insufficient to monitor the absorbed dose estimation of the nuclear medicine staff who are occupationally exposed to 131I. Furthermore, their future health risks are influenced by confounders. Direct assessments comparing physical and biological dose estimations on the larger group are needed to accurately monitor occupational radiation exposure.

The growing concern of radiation dose in paediatric dental and maxillofacial CBCT: an easy guide for daily practice.

OBJECTIVES: To provide an indication-based and scanner-specific radiation dose and risk guide for paediatric patients undergoing dental and maxillofacial cone beam computed tomography (CBCT) examinations. METHODS: Five commercially available scanners were simulated in EGSnrc Monte Carlo (MC) code. Dedicated, in-house built, head and neck voxel models, each consisting of 22 segmented organs, were used in the study. Organ doses and life attributable risk (LAR) for cancer incidence were assessed for males and females, aged 5 to 14 years old, for every clinically available protocol: central upper and lower incisors, upper and lower premolars, upper and lower jaws, cleft palate, temporal bone, sinus, dentomaxillofacial complex, and face and skull imaging. Dose results were normalised to the x-ray tube load (mAs) and logarithmic curves were fit to organ dose and risk versus age data. RESULTS: Females demonstrated higher LAR values in all cases. A well-established dose decreasing pattern with increasing age-at-exposure was observed. Central upper incisor protocols were those with the lowest risk, contrary to skull protocols which provided the highest LAR values. Salivary glands and oral mucosa were the highest irradiated organs in all cases, followed by extrathoracic tissue (ET) in protocols where the entire nasal cavity was inside the primary field. The dose to thyroid was considerably high for younger patients. CONCLUSIONS: This work provides an extensive dose assessment guide for 5 dental CBCTs, enabling detailed dose assessment for every paediatric patient. KEY POINTS: • Radiation dose concerns due to the growing use of paediatric dental and maxillofacial CBCT underline the need for justification that should in part be based on radiation exposure in radiology. • Patient-specific dose calculations based on Monte Carlo simulations and head-neck paediatric voxel models overcome the limitations of conventional thermoluminescent dosimeter (TLD) dosimetry and provide proper guidance for justification of CBCT exposures. • Monte Carlo simulations with head-neck models reveal an organ dose and radiation risk decreasing pattern with increasing age at exposure, and with decreasing size of the scanning volume of interest (field of view).

Research plans in Europe for radiation health hazard assessment in exploratory space missions.

The European Space Agency (ESA) is currently expanding its efforts in identifying requirements and promoting research towards optimizing radiation protection of astronauts. Space agencies use common limits for tissue (deterministic) effects on the International Space Station. However, the agencies have in place different career radiation exposure limits (for stochastic effects) for astronauts in low-Earth orbit missions. Moreover, no specific limits for interplanetary missions are issued. Harmonization of risk models and dose limits for exploratory-class missions are now operational priorities, in view of the short-term plans for international exploratory-class human missions. The purpose of this paper is to report on the activity of the ESA Topical Team on space radiation research, whose task was to identify the most pertinent research requirements for improved space radiation protection and to develop a European space radiation risk model, to contribute to the efforts to reach international consensus on dose limits for deep space. The Topical Team recommended ESA to promote the development of a space radiation risk model based on European-specific expertise in: transport codes, radiobiological modelling, risk assessment, and uncertainty analysis. The model should provide cancer and non-cancer radiation risks for crews implementing exploratory missions. ESA should then support the International Commission on Radiological Protection to harmonize international models and dose limits in deep space, and guarantee continuous support in Europe for accelerator-based research configured to improve the models and develop risk mitigation strategies.

A Critical Assessment of the Linear No-Threshold Hypothesis: Its Validity and Applicability for Use in Risk Assessment and Radiation Protection.

The Society of Nuclear Medicine and Molecular Imaging convened a task group to examine the evidence for the risk of carcinogenesis from low-dose radiation exposure and to assess evidence in the scientific literature related to the overall validity of the linear no-threshold (LNT) hypothesis and its applicability for use in risk assessment and radiation protection. In the low-dose and dose-rate region, the group concluded that the LNT hypothesis is invalid as it is not supported by the available scientific evidence and, instead, is actually refuted by published epidemiology and radiation biology. The task group concluded that the evidence does not support the use of LNT either for risk assessment or radiation protection in the low-dose and dose-rate region.

Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti-PD-1 antibodies.

BACKGROUND: Brain radiotherapy is used in the management of melanoma brain metastases (MBM) and can result in radionecrosis. Anti-PD-1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radionecrosis in longer-term survivors with MBM treated with this combination. METHODS: Patients with MBM treated with radiotherapy and anti-PD-1 who survived >1 year were identified to determine radionecrosis incidence (Cohort A, n = 135). Cohort A plus additional radionecrosis cases were examined for factors associated with radionecrosis and management (Cohort B, n = 148). RESULTS: From Cohort A, 17% developed radionecrosis, with a cumulative incidence at 2 years of 18%. Using Cohort B, multivariable analysis confirmed an association between radionecrosis and elevated lactate dehydrogenase (p = 0.0496) and prior treatment with ipilimumab (p = 0.0319). Radionecrosis was diagnosed based on MRI (100%), symptoms (69%) and pathology (56%). Treatment included corticosteroids, bevacizumab and neurosurgery. CONCLUSIONS: Radionecrosis is a significant toxicity in longer-term melanoma survivors with MBM treated with anti-PD-1 and radiotherapy. Identification of those at risk of radionecrosis who may avoid radiotherapy is required.

Monitoring pulmonary health in Swiss childhood cancer survivors.

BACKGROUND: Childhood cancer survivors are at increased risk for pulmonary morbidity and mortality. International guidelines recommend pulmonary function tests (PFT) during follow-up care. This nationwide study assessed how many children received PFT within 5 years after pulmotoxic treatment in Switzerland, types of tests, and predictors for testing. METHODS: We included all children from the Swiss Childhood Cancer Registry who were diagnosed with cancer from 1990 to 2013 at age 0-16 years, survived for ≥2 years from diagnosis, and had pulmotoxic chemotherapy with bleomycin, busulfan, nitrosoureas, and/or chest radiotherapy. We searched medical records in all Swiss pediatric oncology clinics for PFT (spirometry, plethysmography, diffusion capacity of carbon monoxide [DLCO]) and treatment details. RESULTS: We found medical records for 372 children, of whom 147 had pulmotoxic chemotherapy and 323 chest radiotherapy. Only 185 had plethysmography and/or spirometry (50%), 122 had DLCO (33%). Testing varied by cancer center from 3% to 79% (P = 0.001). Central nervous system tumor survivors and those not treated according to study protocols had less plethysmography and/or spirometry (odds ratio (OR) 0.3 and 0.3), lymphoma survivors and those who were symptomatic had more PFT (plethysmography and/or spirometry: OR 5.9 and 8.7; DLCO: OR 3.4 and 2.3). Cumulative incidence (CuI) of PFT was 52% in the first 5 years after pulmotoxic treatment; most of the tests were done in the first 2 years after treatment (CuI 44%). CONCLUSION: Only half of the survivors exposed to pulmotoxic treatment have been followed up with PFT in Switzerland. We need to optimize, update, and implement monitoring guidelines.

Case Study of the Minimum Provable Risk Considering the Variation in Background Risk: Effect of Residual Risk on Epidemiological Studies and a Comparative Assessment of Fatal Disease Risk Due to Radiation Exposure.

In order to prove a small increment in a risk of concern in an epidemiological study, a large sample of a population is generally required. Since the background risk of an end point of interest, such as cancer mortality, is affected by various factors, such as lifestyle (diet, smoking, etc.), adjustment for such factors is necessary. However, it is impossible to inclusively and completely adjust for such factors; therefore, uncertainty in the background risk remains for control and exposed populations, indicating that there is a minimum limit to the lower bound for the provable risk regardless of the sample size. In this case study, we developed and discussed the minimum provable risk considering the uncertainty in background risk for hypothetical populations by referring to recent Japanese statistical information to grasp the extent of the minimum provable risk. Risk of fatal diseases due to radiation exposure, which has recently been the focus of radiological protection, was also examined by comparative assessment of the minimum provable risk for cancer and circulatory diseases. It was estimated that the minimum provable risk for circulatory disease mortality was much greater than that for cancer mortality, approximately five to seven times larger; circulatory disease mortality is more difficult to prove as a radiation risk than cancer mortality under the conditions used in this case study.

Hospital burden of long-term genitourinary and gastrointestinal toxicity after radical radiotherapy for prostate cancer.

INTRODUCTION: Treatment options for prostate cancer (PCa) include radical radiotherapy (RT) and radical prostatectomy, both of which have comparable oncological outcomes. The aim of this study was to investigate the hospital burden of long-term genitourinary and gastrointestinal toxicity among patients with PCa who were treated with radiotherapy at our institution. METHODS: The radiotherapy department database was used retrospectively to identify all patients who underwent radiotherapy for PCa from January 2006 to January 2008. The patient administration system from each public hospital in the region was interrogated and all patient points of contact were recorded. Minimum follow up was 5 years. Individual patient charts were reviewed and factors that might influence outcomes were documented. RESULTS: We identified 112 patients. The mean age at diagnosis was 66 (44-76) and the median PSA was 12.1 (3.2-38). The mean duration of follow-up was 7.8 yrs. Twenty-three patients (20%) presented to the Emergency Department (ED) with late onset toxicity. Nine patients had more than 2 ED attendances. Twenty-five patients (22%) were investigated for genitourinary toxicity. Forty-seven patients (42%) underwent investigation for gastrointestinal side-effects and 45% of these required argon therapy (21/47). CONCLUSION: We found a significant hospital burden related to the management of gastrointestinal and genitourinary toxicity post radical radiotherapy for prostate cancer. As health care reforms gain momentum, policy makers must take into account the considerable longitudinal health care cost related to radiotherapy. It is also important that patients are counselled carefully in relation to potential long-term side-effects.