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Background: Radiation-induced meningiomas represent a late side effect of cranial radiation therapy. The most widely used diagnostic criteria, despite the lack of a standard description, is a meningioma that develops in a previously irradiated area following a predetermined time interval. Case presentation: We present four cases of late-onset cranial atypical meningiomas following childhood cranial radiotherapy. Four patients (two females and two males) between 4 and 13 years of age at the time of cranial irradiation developed secondary intracranial meningioma after a latency period of 8–34 years. Surgical resection of the tumors was performed, and histopathological examination revealed a diagnosis of atypical meningioma in all four patients. Conclusion: Radiation-induced tumors continue to be a significant side effect of radiotherapy and radiosurgery, and they are frequently identified as recurrent, numerous, and more aggressive. Prolonged follow-up should definitely not be ignored in patients with antecedents of radiotherapy for a primary cerebral tumor or cranial irradiation for an early age malignancy. [ABSTRACT FROM AUTHOR]

Data from animal experiments show that the radiation-related risk of cancer decreases if the dose rate is reduced, even though the cumulative dose is unchanged (i.e., a dose-rate effect); however, the underlying mechanism is not well understood. To explore factors underlying the dose-rate effect observed in experimental rat mammary carcinogenesis, we developed a mathematical model that accounts for cellular dynamics during carcinogenesis, and then examined whether the model predicts cancer incidence. A mathematical model of multistage carcinogenesis involving radiation-induced cell death and mutagenesis was constructed using differential equations. The mutation rate was changed depending on the dose rate. The model also considered competition among cells with various mutation levels. The main parameters of the model were determined using previous experimental data. The parameters of the model were consistent with experimental observations. A dose-rate effect on carcinogenesis became apparent when the relationship between dose rate and mutation rate was linear quadratic or quadratic. The dose-rate effect became prominent when cells with more mutations preferentially compensated for the radiation-induced death of cells with fewer mutations. The phenomenon by which mutated cells gain a competitive advantage over normal cells is known as super-competition. Here, we identified super-competition as a novel mechanism underlying the dose-rate effects on carcinogenesis. The data also confirmed the relevance of the shape of the relationship between dose rate and the mutation rate. Thus, this study provides new evidence for the mechanism underlying the dose-rate effect, which is important for predicting the cancer-related risks of low-dose-rate irradiation. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study investigated the lifetime attributable risk (LAR) of radiation-induced breast cancer from mammography screening in Dubai. It aimed to explore the relationship between breast thickness, patient age, and the associated radiation dose during mammographic examinations. Methods: A retrospective analysis was conducted on 2601 patients aged 40 to 69 across five screening facilities in Dubai's healthcare system. Due to a low correlation between the mean glandular dose (MGD) and breast thickness, both glandular and non-glandular doses were included in calculations as the organ dose (OD). This comprehensive approach examined the impact of whole breast tissue on risk assessments. Key exposure parameters such as the kilovoltage peak (kVp), milliampere-seconds (mAs), and source-to-skin distance were extracted from the dose survey. Results: Our findings reveal that the organ dose increases with breast thickness, emphasizing the need for dose optimization in denser tissues. The LAR decreases with age across all thickness categories, but higher initial LAR values were seen in younger patients with thicker tissue. This study emphasizes the increased sensitivity of younger women, who usually have denser breast tissue, to radiation-induced cancer risks. Conclusions: Personalized screening protocols considering age and breast thickness are crucial for balancing early cancer detection benefits with radiation risks. Future research should improve mammography protocols, explore alternative methods, and consider generic testing for young high-risk patients to mitigate risks while maintaining diagnostic efficacy. [ABSTRACT FROM AUTHOR]

AbstractPurposeConclusionRadiation exposures do not seem to increase the proportion of mice dying from tumors, but rather cause a shift in the appearance of spontaneous cancers, allowing them to appear earlier, and hence produce a life shortening effect. Then, it was possible to estimate the effect of the dose rate on the carcinogenic effects of radiation using life shortening effects as a measure.The dose response for the induction of life shortening was linear under acute exposure conditions, which indicates that the response under chronic exposure conditions is also likely to be linear, and hence the dose rate factor (DRF) would be constant throughout the dose. Furthermore, the life shortening effect decreased sharply with an increase in age at exposure. To separate the dose rate effect from the effects of age under long-term exposure conditions, a thought experiment was designed which consisted of 8 repeated exposures to an acute 1 Gy dose at intervals of 50 days with an assumption that the effect is additive, and the results were compared with those observed in a chronic continuous exposure experiment (20 mGy per day for 400 days, for a total of 8 Gy: Tanaka et al. 2003). The results showed 211 days of life shortening in the former and 120 days in the latter, which provided a DRF of 1.8 (211/120). If one assumes that a tissue reaction is the primary cause of radiation carcinogenesis, the contrasting two concepts, radiation hormesis and linear-non-threshold model at low doses, would become compatible. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer (LC) is the leading cause of cancer-related mortality in Thailand, particularly in the Chiang Mai province. Beyond cigarette smoking, long-term exposure to indoor radon is a significant risk factor for the development of LC. In Kong Khaek, a subdistrict of the Mae Chaem district in Chiang Mai, the average indoor radon activity concentration exceeds both global and national averages. Understanding the impact of chronic low-dose radiation exposure on human populations living in high-background radiation areas is crucial. However, no specific biomarkers are currently available to detect LC resulting from prolonged exposure to indoor radon. Background: Indoor radon is a significant risk factor for the development of LC. This study aimed to identify potential biomarkers for LC risk in high background radiation areas using a metabolomics approach (UHPLC-HRMS). Methods: Based on the indoor radon activity concentration measurements in the Kong Khaek subdistrict, serum samples were collected from 45 nonsmoker or former smoker participants, comprising 15 LC patients and 30 matched healthy controls (low- and high-radon groups, respectively). Results: A total of 90 and 111 differential metabolites were identified in the LC group compared with the low- and high-radon groups, respectively, using criteria such as a variable importance in projection (VIP) of >1, a fold change (FC) of >1 or <0.5, and a p value of <0.05. Receiver operating characteristic (ROC) curves (an AUC of ≥ 0.9) indicated that 30 and 21 of these metabolites had the potential to serve as biomarkers of LC development in the low- and high-radon groups, respectively. The KEGG pathway enrichment analysis suggested that D-sphingosine may have been a candidate biomarker associated with LC in both groups. Conclusions: Overall, this study provides new insights into metabolic biomarkers for screening LC development in high-risk individuals with prolonged exposure to indoor radon. Further large-scale studies are needed to validate our results. [ABSTRACT FROM AUTHOR]

We previously reported endogenous activation of the DNA damage response (DDR) in the epidermis surrounding basal cell carcinoma resected from Nagasaki atomic bomb survivors, suggesting the presence of genomic instability (GIN) in the survivors as a late effect of radiation. Dual-color immunofluorescence (IF) analysis of TP53-binding protein-1 (53BP1) and a proliferative indicator, Ki-67, to elucidate GIN in tumor tissues revealed that abnormal 53BP1 expression is closely associated with carcinogenesis in several organs. The present study aimed to confirm the presence of radiation-induced GIN in the non-neoplastic epidermis of patients with radiation-induced skin cancer. Formalin-fixed paraffin-embedded tissues were obtained from all participants between 2008 and 2019 at the Nagasaki University Hospital. 53BP1 nuclear expression was examined using dual-color IF analysis with Ki-67 expression to assess the extent and integrity of the DDR. Expressions of gamma-H2AX, p53 and p21 were also analyzed using the dual-color IF analysis for their association with 53BP1. The results of this study provide evidence for sporadic activation of the DDR in medically irradiated and ultraviolet-exposed epidermis as a long-lasting radiation effect, which is a predisposition to skin cancer. Furthermore, the incidence of abnormal 53BP1 expression in cancer cells was higher than in non-neoplastic epidermal cells surrounding cancer, suggesting a correlation between the type of 53BP1 and the malignant potential of skin tumors. This study highlights the usefulness of dual-color IF for 53BP1 (and Ki-67) as an indicator to estimate the level of GIN as a long-lasting health effect of radiation exposure. [ABSTRACT FROM AUTHOR]

The use of radiological procedures has enormously advanced cardiology. People with heart disease are exposed to ionizing radiation. Exposure to ionizing radiation increases lifetime cancer risk with a dose-proportional hazard according to the linear no-threshold model adopted for radioprotection purposes. In the USA, the average citizen accumulates a median annual medical radiation exposure of 2.29 millisievert per year per capita as of the radiologic year 2016, corresponding to the dose exposure of 115 chest X-rays. Cardiology studies often involve high exposures per procedure accounting for ∼30–50% of cumulative medical radiation exposures. Malignancy is more incident in the most radiosensitive organs receiving the largest organ dose from cardiac interventions and cardiovascular imaging testing, such as the lung, bone marrow, and female breast. The latency period between radiation exposure and cancer is thought to be at least 2 years for leukaemia and 5 years for all solid cancers, and differences are more likely to emerge in cardiology studies with longer follow-up and inclusion of non-cardiovascular endpoints such as cancer incidence. In cardiological studies, excess cancers are observed 3–12 years following exposure, with longer follow-up times showing greater differences in cancer incidence. The presumed associated excess cancer risk needs greater study. These exposures provide a unique opportunity to expand our knowledge of the relationship between exposure to ionizing radiation and cancer risk. Future trials comparing interventional fluoroscopy vs. optimal medical therapy or open surgery should include a cancer incidence endpoint. [ABSTRACT FROM AUTHOR]

During a nuclear accident, numerous products of nuclear fission are released, including isotopes of radioactive iodine. Among them is iodine-131, with a half-life of 8.02 days, which emits β radiation. For decades, it has been effectively and safely used in medicine. However, in the event of a nuclear accident, uncontrolled exposure can have harmful biological effects. The main sources of internal contamination with iodine-131 are contaminated air, food and water. The most exposed organ is the thyroid gland, where radioactive iodine accumulates via the Na+/I− symporter (NIS). NIS does not distinguish between radioactive iodine isotopes and the stable isotope iodine-127, which is essential for the synthesis of thyroid hormones. Exposure to radioactive iodine during a nuclear accident is primarily associated with papillary thyroid cancer, whose incidence begins to increase a few years after exposure. Children and adolescents are at the highest risk, and the risk is particularly significant for individuals living in iodine-deficient areas. Ensuring an adequate iodine supply is therefore crucial for lowering the risk of the harmful effects of exposure to radioactive iodine at the population level. Protecting the thyroid with potassium iodide tablets significantly reduces radiation exposure, as stable iodine prevents the entry of radioactive iodine into the thyroid. Such protection is effective only within a narrow time window - a few hours before and after the exposure and is recommended only for those under 40 years of age, as the risks of excessive iodine intake outweigh the potential benefits in older individuals. [ABSTRACT FROM AUTHOR]

The high rate of recurrence after radiation therapy in triple-negative breast cancer (TNBC) indicates that novel approaches and targets are needed to enhance radiosensitivity. Here, we report that neuropilin-2 (NRP2), a receptor for vascular endothelial growth factor (VEGF) that is enriched on subpopulations of TNBC cells with stem cell properties, is an effective therapeutic target for sensitizing TNBC to radiotherapy. Specifically, VEGF/NRP2 signaling induces nitric oxide synthase 2 (NOS2) transcription by a mechanism dependent on Gli1. NRP2-expressing tumor cells serve as a hub to produce nitric oxide (NO), an autocrine and paracrine signaling metabolite, which promotes cysteine-nitrosylation of Kelch-like ECH-associated protein 1 (KEAP1) and, consequently, nuclear factor erythroid 2-related factor 2-mediated (NFE2L2-mediated) transcription of antioxidant response genes. Inhibiting VEGF binding to NRP2, using a humanized mAb, results in NFE2L2 degradation via KEAP1, rendering cell lines and organoids vulnerable to irradiation. Importantly, treatment of patient-derived xenografts with the NRP2 mAb and radiation resulted in significant tumor necrosis and regression compared with radiation alone. Together, these findings reveal a targetable mechanism of radioresistance, and they support the use of NRP2 mAb as an effective radiosensitizer in TNBC. [ABSTRACT FROM AUTHOR]

Radiotherapy is a pivotal treatment for lung cancer, significantly impacting tumor control and patient quality of life. Despite its benefits, the molecular mechanisms underlying radiotherapy-induced biological alterations in lung cancer cells remain inadequately understood. In this study, we employed a mass spectrometry-based lipidomics approach to investigate lipid profile changes in a lung cancer mouse model post-radiation. Lewis lung carcinoma (LLC) cells were injected into C57BL/6J mice, followed by radiation treatment with varying split doses. Our results showed an increase in sterol lipids and a decrease in glycerolipids, specifically triacylglycerides, indicating disrupted lipid storage. Additionally, we observed significant changes in glycerophospholipid unsaturation, suggesting a remodeling of membrane properties that may influence cell survival. Linear regression analysis demonstrated a significant negative correlation between glycerophospholipid unsaturation index and tumor weight, indicating a potential role in radiation-induced tumor cell death. These findings provide new insights into the lipid metabolic pathways affected by radiotherapy and could inform the development of improved therapeutic strategies for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Ionising radiation (IR) is a form of energy that travels as electromagnetic waves or particles. While it is vital in medical and occupational health settings, IR can also damage DNA, leading to mutations, chromosomal aberrations, and transcriptional changes that disrupt the functions of certain cell regulators, genes, and transcription factors. These disruptions can alter functions critical for cancer development, progression, and treatment response. Additionally, IR can affect various cellular proteins and their regulators within different cell signalling pathways, resulting in physiological changes that may promote cancer development, progression, and resistance to treatment. Understanding these impacts is crucial for developing strategies to mitigate the harmful effects of IR exposure and improve cancer treatment outcomes. This review focuses on specific genes and protein biomarkers regulated in response to chronic IR exposure, and how their regulation impacts disease onset, progression, and treatment response. [ABSTRACT FROM AUTHOR]

The lifetime attributable risk (LAR) of cancer caused by radiation exposure is crucial when deciding on radiological protection measures or protective actions for nuclear emergency preparedness and response. Although a model for estimating LAR among the Japanese population has been developed based on epidemiological data from A-bomb survivors, a flexible projection code implementing this model must be developed. This study investigated existing codes to contribute to the development of a projection code. Based on these investigations, we compared their LAR calculation results and explored the causes of their differences. [ABSTRACT FROM AUTHOR]

Cancer risks attributable to low-dose and low-dose-rate radiation are a serious concern for public health. Radiation risk assessment is based on lifespan studies among Hiroshima–Nagasaki A-bomb survivors; however, there are statistical limitations due to a small sample size for low-dose radiation. Therefore, basic biological studies are helpful in understanding the mechanism of radiation carcinogenesis. The detrimental effects of ionising radiation (IR) are caused by reactive oxygen species (ROS)-mediated oxidative DNA damage. IR-induced delayed ROS are produced in the electron transport chain reaction of the mitochondrial complex. Thus, mitochondria are a source of ROS and a primary target for ROS attacks. Consequently, mitochondrial dysfunction is thought to be a key event in the metabolic changes of cancer cells and is important in radiation-induced carcinogenesis. In this paper, we present recent findings on radiation carcinogenesis effect assessment, focusing on mitochondrial function as stress sensors. [ABSTRACT FROM AUTHOR]

To investigate how absorbed doses to mastication structures in modern radiotherapy (RT) technique for head and neck cancer (HNC) compared with earlier RT techniques and with published trismus tolerance doses. To compare the incidence of radiation-induced trismus by earlier and newer RT techniques. This study investigated two HNC patient cohorts treated with RT in 2007–2012 (three-dimensional conformal radiotherapy [3DCRT] and/or intensity-modulated radiotherapy [IMRT]; n =121 [ Cohort 1 ]) and 2017–2020 (volumetric-modulated arc therapy [VMAT]; n =124 [ Cohort 2 ]). All patients underwent RT without mastication structure–sparing intent, had normal mouth-opening ability before RT, and were prospectively assessed. Trismus was defined as the maximal interincisal opening ≤35 mm at any follow-up (3-, 6-, and 12-months post-RT). The temporomandibular joints (TMJs), masseter, and medial/lateral pterygoid muscles were delineated on the planning CT:s. Mean doses were compared between cohorts, and evaluated with respect to published trismus tolerance doses. P values ≤ 0.05 indicated statistical significance. Within 12 months post RT, 74/121 (61%) of patients in Cohort 1 had experienced trismus compared to 11/124 (9%) in Cohort 2. Averaged mean doses (±S.D.) for the masseter muscles were 35.2±8.3 Gy in Cohort 1 and 20.2±8.7 Gy in Cohort 2 (P <0.001). Corresponding numbers were 19.1±16.2 and 4.3±4.3 Gy for the TMJs, 53.7±10.1 and 40.2±16.8 Gy for the medial pterygoid muscles, and 29.2±18.7 and 9.2±8.4 Gy for the lateral pterygoid muscles (all P <0.001). Masseter muscle doses were below tolerance doses in 23% of patients in Cohort 1 compared with 90% in Cohort 2. The corresponding numbers were 52% and 96% for the TMJs, 8% and 36% for the medial pterygoid muscles and 72% and 100% for the lateral pterygoid muscles. Mastication structure mean doses by more recent RT techniques were generally below proposed tolerance doses, with dose reductions of 10–20 Gy compared with earlier techniques. Modern RT without mastication-structure-sparing intent resulted in below 10% of HNC patients experiencing trismus compared with 60% treated with earlier techniques. • Modern radiotherapy can substantially spare organs-at-risk in head and neck cancer. • Mastication-structure mean radiation doses were reduced by 10–20 Gy. • These dose reductions were accompanied by a trismus reduction from 60% to 10%. [ABSTRACT FROM AUTHOR]

Stereotactic radiosurgery (SRS) is an established treatment for brain arteriovenous malformations (AVMs), but outcomes between pediatric and adult populations are not well compared. We conducted a systematic review and meta-analysis comparing SRS outcomes for pediatric versus adult AVMs. PubMed was searched for studies reporting SRS outcomes for pediatric or adult AVMs up to January 2024. Primary outcome was obliteration rate, with secondary outcomes including post-SRS hemorrhage, symptomatic radiation-induced changes (RICs), and permanent RICs. Pooled estimates were calculated using random effects models. Analysis included 22 studies with 3469 patients (1316 pediatric, 2153 adult). Pooled obliteration rate was 63% (95% confidence interval: 56%-70%) overall, with no significant difference between pediatric (61%) and adult (67%) cohorts (P = 0.38). Post-SRS hemorrhage rates were similar (5% pediatric, 6% adult, P = 0.60). Symptomatic RICs occurred in 9% (95% confidence interval: 6%-13%) overall, with 10% in both cohorts (P = 0.91). Permanent RIC rates were 4% in pediatric and 3% in adult cohorts (P = 0.43). Cyst formation (0.6%) and radiation-induced tumors (0.2%) were rare. All-cause mortality was significantly lower in the pediatric cohort (2.6% vs. 9.8%, P = 0.003). Hemorrhagic AVM presentation was inversely correlated with symptomatic RICs across both groups. SRS is a reasonable treatment option for appropriately selected AVM patients in both pediatric and adult populations, offering comparable obliteration rates and adverse event profiles. The lower mortality in pediatric patients underscores the importance of early intervention in this population given their high cumulative lifetime rupture risks. [ABSTRACT FROM AUTHOR]

Age at exposure is a critical modifier of the risk of radiation-induced cancer. However, the effects of age on radiation-induced carcinogenesis remain poorly understood. In this study, we focused on tissue stem cells using Lgr5-eGFP-ires-CreERT2 mice to compare radiation-induced DNA damage responses between Lgr5+ and Lgr5- intestinal stem cells. Three-dimensional immunostaining analyses demonstrated that radiation induced apoptosis and the mitotic index more efficiently in adult Lgr5- stem cells than in adult Lgr5+ stem cells but not in infants, regardless of Lgr5 expression. Supporting this evidence, rapid and transient p53 activation occurred after irradiation in adult intestinal crypts but not in infants. RNA sequencing revealed greater variability in gene expression in adult Lgr5+ stem cells than in infant Lgr5+ stem cells after irradiation. Notably, the cell cycle and DNA repair pathways were more enriched in adult stem cells than in infant stem cells after irradiation. Our findings suggest that radiation-induced DNA damage responses in mouse intestinal crypts differ between infants and adults, potentially contributing to the age-dependent susceptibility to radiation carcinogenesis. [ABSTRACT FROM AUTHOR]

Mouse models are vital for assessing risk from environmental carcinogens, including ionizing radiation, yet the interspecies difference in the dose response precludes direct application of experimental evidence to humans. Herein, we take a mathematical approach to delineate the mechanism underlying the human–mouse difference in radiation‐related cancer risk. We used a multistage carcinogenesis model assuming a mutational action of radiation to analyze previous data on cancer mortality in the Japanese atomic bomb survivors and in lifespan mouse experiments. Theoretically, the model predicted that exposure will chronologically shift the age‐related increase in cancer risk forward by a period corresponding to the time in which the spontaneous mutational process generates the same mutational burden as that the exposure generates. This model appropriately fitted both human and mouse data and suggested a linear dose response for the time shift. The effect per dose decreased with increasing age at exposure similarly between humans and mice on a per‐lifespan basis (0.72‐ and 0.71‐fold, respectively, for every tenth lifetime). The time shift per dose was larger by two orders of magnitude in humans (7.8 and 0.046 years per Gy for humans and mice, respectively, when exposed at ~35% of their lifetime). The difference was mostly explained by the two orders of magnitude difference in spontaneous somatic mutation rates between the species plus the species‐independent radiation‐induced mutation rate. Thus, the findings delineate the mechanism underlying the interspecies difference in radiation‐associated cancer mortality and may lead to the use of experimental evidence for risk prediction in humans. [ABSTRACT FROM AUTHOR]

Background: Tumor-immune interactions shape a developing tumor and its tumor immune microenvironment (TIME) resulting in either well-infiltrated, immunologically inflamed tumor beds, or immune deserts with low levels of infiltration. The pre-treatment immune make-up of the TIME is associated with treatment outcome; immunologically inflamed tumors generally exhibit better responses to radio- and immunotherapy than non-inflamed tumors. However, radiotherapy is known to induce opposing immunological consequences, resulting in both immunostimulatory and inhibitory responses. In fact, it is thought that the radiation-induced tumoricidal immune response is curtailed by subsequent applications of radiation. It is thus conceivable that spatially fractionated radiotherapy (SFRT), administered through GRID blocks (SFRT-GRID) or lattice radiotherapy to create areas of low or high dose exposure, may create protective reservoirs of the tumor immune microenvironment, thereby preserving anti-tumor immune responses that are pivotal for radiation success. Methods: We have developed an agent-based model (ABM) of tumor-immune interactions to investigate the immunological consequences and clinical outcomes after 2 Gy × 35 whole tumor radiation therapy (WTRT) and SFRT-GRID. The ABM is conceptually calibrated such that untreated tumors escape immune surveillance and grow to clinical detection. Individual ABM simulations are initialized from four distinct multiplex immunohistochemistry (mIHC) slides, and immune related parameter rates are generated using Latin Hypercube Sampling. Results: In silico simulations suggest that radiation-induced cancer cell death alone is insufficient to clear a tumor with WTRT. However, explicit consideration of radiation-induced anti-tumor immunity synergizes with radiation cytotoxicity to eradicate tumors. Similarly, SFRT-GRID is successful with radiation-induced anti-tumor immunity, and, for some pre-treatment TIME compositions and modeling parameters, SFRT-GRID might be superior to WTRT in providing tumor control. Conclusion: This study demonstrates the pivotal role of the radiation-induced anti-tumor immunity. Prolonged fractionated treatment schedules may counteract early immune recruitment, which may be protected by SFRT-facilitated immune reservoirs. Different biological responses and treatment outcomes are observed based on pre-treatment TIME composition and model parameters. A rigorous analysis and model calibration for different tumor types and immune infiltration states is required before any conclusions can be drawn for clinical translation. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the current scoping review is to identify the studies reporting ototoxicity monitoring in individuals with head and neck cancer (HNC) undergoing radiation therapy and/or chemoradiation therapy across the world. The specific objectives were to identify and report the test protocol used, identify the most common timeline of follow-up, and identify barriers and facilitators influencing the implementation of the monitoring program. Method: A comprehensive search was conducted across six electronic databases, including PubMed, Embase, Web of Science, Scopus, Google Scholar, and ProQuest. The scoping review method adhered to relevant guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) and frameworks. The database search was carried out by two independent researchers, and studies were selected based on specific inclusion and exclusion criteria. Results: This scoping review identified 13 studies that fulfilled the inclusion criteria of this study. Only one study reported findings from the perspective of ototoxicity monitoring. Another study explicitly mentioned that ototoxicity monitoring was a standard of care in their hospital. Only one study reported using the relevant guidelines for monitoring ototoxicity. Specialized tests such as high-frequency audiometry, distortion product otoacoustic emissions, and vestibular tests were rarely used. Ototoxicity monitoring was influenced by awareness-related factors, technical factors, treatment-related factors, and organizational factors. Conclusions: Research on ototoxicity monitoring programs is in its early stages, highlighting the need for standardized practices and multidisciplinary collaboration to enhance health care services for HNC patients. A standardized approach, improved awareness, and the incorporation of patient perspectives are crucial to enhancing ototoxicity monitoring in HNC patients. [ABSTRACT FROM AUTHOR]

This article provides an overview of the advancements and practical applications of magnetic resonance imaging (MRI) in diagnosing and treating musculoskeletal disorders. It discusses the benefits of MRI, including its excellent soft tissue contrast and multiplanar capabilities, as well as the technical developments that have improved its resolution and acquisition time. The article also acknowledges the challenges and limitations of MRI, such as long acquisition times and difficulties imaging tissues near hardware. It emphasizes the importance of considering practicality and feasibility in clinical settings, while also addressing various aspects of MRI imaging, including reducing distortion artifacts, patient safety considerations, workflow efficiency, and the need for increased access to MRI scanners, particularly in low- and middle-income countries. The authors call for ongoing research and technological advancements to further enhance the field of MRI imaging. [Extracted from the article]

Carbon ion radiotherapy (CIRT) for pediatric cancer is currently limited because of the unknown risk of induction of secondary cancers. Medulloblastoma of Ptch1+/– mice offers a unique experimental system for radiation-induced carcinogenesis, in which tumors are classified into spontaneous and radiation-induced subtypes based on their features of loss of heterozygosity (LOH) that affect the wild-type Ptch1 allele. The present study aims to investigate in young Ptch1+/– mice the carcinogenic effect, and its age dependence, of the low-linear energy transfer (LET, ∼13 keV/µm) carbon ions, to which normal tissues in front of the tumor are exposed during therapy. We irradiated Ptch1+/– mice at postnatal day (P) 1, 4, or 10 with 290 MeV/u carbon ions (0.05–0.5 Gy; LET, 13 keV/µm) and monitored them for medulloblastoma development. Loss of heterozygosity of seven genetic markers on chromosome 13 (where Ptch1 resides) was studied to classify the tumors. Carbon ion exposure induced medulloblastoma most effectively at P1. The LOH patterns of tumors were either telomeric or interstitial, the latter occurring almost exclusively in the irradiated groups, allowing the use of interstitial LOH as a biomarker of radiation-induced tumors. Radiation-induced tumors developed during a narrow age window (most strongly at P1 and only moderately at P4, with suppressed tumorigenesis at P10). Calculated using previous results using 137Cs gamma rays, the values for relative biological effectiveness (RBE) regarding radiation-induced tumors were 4.1 (3.4, 4.8) and 4.3 (3.3, 5.2) (mean and 95% confidence interval) for exposure at P1 and 4, respectively. Thus, the RBE of carbon ions for medulloblastoma induction in Ptch1+/– mice was higher than the generally recognized RBE of 1–2 for cell killing, chromosome aberrations, and skin reactions. [ABSTRACT FROM AUTHOR]

The Planning and Acting Network for Low Dose Radiation Research in Japan (PLANET) was established in 2017 in response to the need for an all-Japan network of experts. It serves as an academic platform to propose strategies and facilitate collaboration to improve quantitative estimation of health risks from ionizing radiation at low-doses and low-dose-rates. PLANET established Working Group 1 (Dose-Rate Effects in Animal Experiments) to consolidate findings from animal experiments on dose-rate effects in carcinogenesis. Considering international trends in this field as well as the situation in Japan, PLANET updated its priority research areas for Japanese low-dose radiation research in 2023 to include (i) characterization of low-dose and low-dose-rate radiation risk, (ii) factors to be considered for individualization of radiation risk, (iii) biological mechanisms of low-dose and low-dose-rate radiation effects and (iv) integration of epidemiology and biology. In this context, PLANET established Working Group 2 (Dose and Dose-Rate Mapping for Radiation Risk Studies) to identify the range of doses and dose rates at which observable effects on different endpoints have been reported; Working Group 3 (Species- and Organ-Specific Dose-Rate Effects) to consider the relevance of stem cell dynamics in radiation carcinogenesis of different species and organs; and Working Group 4 (Research Mapping for Radiation-Related Carcinogenesis) to sort out relevant studies, including those on non-mutagenic effects, and to identify priority research areas. These PLANET activities will be used to improve the risk assessment and to contribute to the revision of the next main recommendations of the International Commission on Radiological Protection. [ABSTRACT FROM AUTHOR]

Introduction: Screening and diagnostic mammography are associated with some risk of radiation-induced breast cancer. This study was conducted to establish the National Diagnostic Reference Levels (NDRLs) for digital diagnostic and screening mammography in Uganda to achieve breast radiation dose optimization. Methods: A cross-sectional study was conducted among female participants recruited by consecutive sampling from three selected hospitals with digital mammography in Uganda. The study variables extracted from the mammography machines were exposure factors, compressed breast thickness (CBT), and Average Glandular Dose (AGD) of two standard mammogram views. The stratified National DRL was derived by calculating the 75th percentile of the AGD across all the samples at various CBT ranges for both screening and diagnostic mammography in craniocaudal (CC) and mediolateral oblique (MLO) views. Results: We included 300 participants with mean ages of 50.28±9.32 and 47.45±13.45 years for the screening and diagnostic mammography, respectively. There were statistically significant positive correlations between AGD and exposure factors (mAs, kVp) (all p-values<0.0001). For screening mammography, mAs demonstrated a strong positive correlation (r = 0.8369 in CC, 0.8133 in MLO), whereas kVp showed a positive correlation with relatively lower coefficients (r = 0.3700 in CC, 0.3080 in MLO). For diagnostic mammography, mAs exhibited an even stronger positive correlation (r = 0.8987 in CC, 0.8762 in MLO), and kVp maintained a positive correlation with somewhat lower coefficients (r = 0.4954 in CC, 0.3597 in MLO). In screening mammography, for CBT within the range of (7–39) mm, the NDRLs were (1.5mGy, 1.66mGy) in CC) and MLO views. For CBT in the range of (40–59) mm, the NDRLs were (1.78mGy, 1.87mGy), and for CBT in the range of (60–99) mm, the NDRLs were (2.18mGy, 2.22mGy). For diagnostic mammography, the NDRLs were established as (1.7mGy, 1.91mGy), (2.00mGy, 2.09mGy), and (2.63mGy, 2.81mGy) for CBT ranges of (7–39) mm, (40–59) mm, and (60–99) mm, respectively. Conclusion: The NDRLs for digital screening and diagnostic mammography in Uganda have been proposed for the first time. The NDRL values in mammography should be specific to CBT ranges and mammographic views for both diagnostic and screening mammography. [ABSTRACT FROM AUTHOR]

Radiation treatment, particularly at a young age, creates theoretical risk for long-term adverse radiation effects, including the development of malignancy. The literature is sparse on radiation-induced vestibular schwannomas (VSs). A retrospective review was performed for cases of suspected radiation-induced VS at 2 high-volume centers. Only cases where radiation included coverage of the posterior fossa were included with those diagnosed within 3 years of radiation treatment being excluded. Patient and tumor characteristics were collected. A systematic literature review was also performed for any previously published series on radiation-induced VS. Eight cases of radiation-induced VS were identified with a median follow-up 125 months (range 7–131). The median age at incident radiation was 15 years (range 2–46). The median age at VS diagnosis was 57 years (range 26–83) with median interval from radiation to diagnosis of 51-years (range 15–66). The median tumor size was 6 mm (range 3–21). Two patients underwent surgical resection. Lesions were described as soft and highly vascular, with medium to high adherence to the facial nerve. Five articles with a total of 52 patients were identified, median age at VS diagnosis was 42-years (range 23–73) with a median interval from radiation to diagnosis of 19 years (range 15–23). The development of VS following radiation exposure appears rare and our understanding of the condition remains incomplete. Further studies are required to determine the best management of these patients and determine whether there is a causative relationship between radiation exposure and the development of VS. [ABSTRACT FROM AUTHOR]

Screening mammography is considered to be the most effective means for the early detection of breast cancer. However, epidemiological studies suggest that longitudinal exposure to screening mammography may raise breast cancer radiation-induced risk, which begs the need for optimization and internal auditing. The present work aims to establish a comprehensive well-structured Diagnostic Reference Level (DRL) system that can be confidently used to highlight healthcare centers in need of urgent action, as well as cases exceeding the dose notification level. Screening mammographies from a total of 2048 women who underwent screening mammography at seven different healthcare centers were collected and retrospectively analyzed. The typical DRL for each healthcare center was established and defined as per (A) bilateral image view (left craniocaudal (LCC), right craniocaudal (RCC), left mediolateral oblique (LMLO), and right mediolateral oblique (RMLO)) and (B) structured compressed breast thickness (CBT) criteria. Following this, the local DRL value was established per the bilateral image views for each CBT group. Screening mammography data from a total of 8877 images were used to build this comprehensive DRL system (LCC: 2163, RCC: 2206, LMLO: 2288, and RMLO: 2220). CBTs were classified into eight groups of <20 mm, 20–29 mm, 30–39 mm, 40–49 mm, 50–59 mm, 60–69 mm, 70–79 mm, 80–89 mm, and 90–110 mm. Using the Kruskal–Wallis test, significant dose differences were observed between all seven healthcare centers offering screening mammography. The local DRL values defined per bilateral image views for the CBT group 60–69 mm were (1.24 LCC, 1.23 RCC, 1.34 LMLO, and 1.32 RMLO) mGy. The local DRL defined per bilateral image view for a specific CBT highlighted at least one healthcare center in need of optimization. Such comprehensive DRL system is efficient, easy to use, and very clinically effective. [ABSTRACT FROM AUTHOR]

Thyroid cancer incidence increases worldwide annually, primarily due to factors such as ionizing radiation (IR), iodine intake, and genetics. Papillary carcinoma of the thyroid (PTC) accounts for about 80% of thyroid cancer cases. RET/PTC1 (coiled‐coil domain containing 6 [CCDC6]‐rearranged during transfection) rearrangement is a distinctive feature in over 70% of thyroid cancers who exposed to low doses of IR in Chernobyl and Hiroshima‒Nagasaki atomic bombings. This study aims to elucidate mechanism between RET/PTC1 rearrangement and IR in PTC. N‐thy‐ori‐3‐1 cells were subjected to varying doses of IR (2/1/0.5/0.2/0.1/0.05 Gy) of IR at different days, and result showed low‐dose IR‐induced RET/PTC1 rearrangement in a dose‐dependent manner. RET/PTC1 has been observed to promote PTC both in vivo and in vitro. To delineate the role of different DNA repair pathways, SCR7, RI‐1, and Olaparib were employed to inhibit non‐homologous end joining (NHEJ), homologous recombination (HR), and microhomology‐mediated end joining (MMEJ), respectively. Notably, inhibiting NHEJ enhanced HR repair efficiency and reduced IR‐induced RET/PTC1 rearrangement. Conversely, inhibiting HR increased NHEJ repair efficiency and subsequent RET/PTC1 rearrangement. The MMEJ did not show a markable role in this progress. Additionally, inhibiting DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs) decreased the efficiency of NHEJ and thus reduced IR‐induced RET/PTC1 rearrangement. To conclude, the data suggest that NHEJ, rather than HR or MMEJ, is the critical cause of IR‐induced RET/PTC1 rearrangement. Targeting DNA‐PKcs to inhibit the NHEJ has emerged as a promising therapeutic strategy for addressing IR‐induced RET/PTC1 rearrangement in PTC. [ABSTRACT FROM AUTHOR]

Introduction: FLASH radiotherapy (RT) has emerged as a promising modality, demonstrating both a normal tissue sparing effect and anticancer efficacy. We have previously reported on the safety and efficacy of single fraction FLASH RT in the treatment of oral tumors in canine cancer patients, showing tumor response but also a risk of radiation-induced severe late adverse effects (osteoradionecrosis) for doses ≥35 Gy. Accordingly, the objective in this study was to investigate if single fraction high dose FLASH RT is safe for treating non-oral tumors. Methods: Privately-owned dogs with superficial tumors or microscopic residual disease were included. Treatment was generally delivered as a single fraction of 15-35 Gy 10 MeV electron FLASH RT, although two dogs were re-irradiated at a later timepoint. Follow-up visits were conducted up to 12 months post- treatment to evaluate treatment efficiency and adverse effects. Results: Fourteen dogs with 16 tumors were included, of which nine tumors were treated for gross disease whilst seven tumors were treated post-surgery for microscopic residual disease. Four treatment sites treated with 35 Gy had ulceration post irradiation, which was graded as severe adverse effect. Only mild adverse effects were observed for the remaining treatment sites. None of the patients with microscopic disease experienced recurrence (0/7), and all patients with macroscopic disease showed either a complete (5/9) or a partial response (4/9). Five dogs were euthanized due to clinical disease progression. Discussion: Our study demonstrates that single fraction high dose FLASH RT is generally safe, with few severe adverse effects, particularly in areas less susceptible to radiation-induced damage. In addition, our study indicates that FLASH has anti-tumor efficacy in a clinical setting. No osteoradionecrosis was observed in this study, although other types of high-grade adverse effects including ulcer-formations were observed for the highest delivered dose (35 Gy). Overall, we conclude that osteoradionecrosis following single fraction, high dose FLASH does not appear to be a general problem for non-oral tumor locations. Also, as has been shown previously for oral tumors, 30 Gy appeared to be the maximum safe dose to deliver with single fraction FLASH RT. [ABSTRACT FROM AUTHOR]

This study aimed to develop a normal tissue complication probability (NTCP) model to estimate the risk of severe radiation-induced lymphopenia (SRIL; absolute lymphocyte count [ALC] < 500/μL) by using the blood dose of patients with hepatocellular carcinoma (HCC). We retrospectively collected data from 75 patients with HCC who received radiation therapy (RT) between 2015 and 2018. The hematological dose framework calculated blood dose-volume histograms (DVHs) using a predefined blood flow model, organ DVHs, the number of treatment fractions, and beam delivery time. A Lyman-Kutcher-Burman model with a generalized equivalent dose was used to establish the NTCP model, reflecting the whole-blood DVHs. Optimization of the Lyman-Kutcher-Burman parameters was conducted by minimizing a negative log-likelihood function. There were 6, 4, 18, 33, and 14 patients in the groups with radiation-induced lymphopenia grades 0, 1, 2, 3, and 4, respectively. The median pre- and post-RT ALC values were 1410/μL (range, 520-3710/μL) and 470/μL (range, 60-1760/μL), respectively. There was a correlation between mean blood dose and ALC depletion (Pearson r = −0.664; P <.001). The average mean blood doses in each radiation-induced lymphopenia group were 2.90 Gy (95% CI, 1.96-3.85 Gy) for grade 0 to 1, 5.29 Gy (95% CI, 4.12-6.45 Gy) for grade 2, 8.81 Gy (95% CI, 7.55-10.07 Gy) for grade 3, and 11.69 Gy (95% CI, 9.82-17.57 Gy) for grade 4. When applying the developed NTCP model to predict SRIL, the area under the receiver operating characteristic curve and Brier score values were 0.89 and 0.12, respectively. We developed the first NTCP model based on whole-blood DVHs for estimating SRIL after abdominal RT in patients with HCC. Our results showed a strong correlation between blood dose and ALC depletion, suggesting the potential to predict the risk of SRIL occurrence using blood dose. [ABSTRACT FROM AUTHOR]

Darier's disease (DD) is an autosomal dominant genodermatosis characterized by hyperkeratotic papules, often accompanied by scaling and crusting. Managing DD presents significant challenges due to the absence of an effective cure, with only symptom targeting treatments currently available. This study presents a case of refractory DD that showed poor response to established pharmacological treatments but demonstrated improvement with low-dose superficial X-ray radiotherapy (SRT). The radiation was delivered as a single 200 cGy treatment, which visibly improved the condition. Considering the different degrees of side effects, sequelae, and risk of developing radiation-induced cancer after exposure to moderate levels of radiation, it may be considered that we attempt to treat recalcitrant DD initially by applying a low dose of radiation in order to mitigate these undesired side effects. If larger doses or additional courses are necessary due to inadequate response, the risks and benefits must be carefully evaluated and discussed with patients. [ABSTRACT FROM AUTHOR]

Fractionated total body irradiation (TBI) with X-rays induces thymic lymphoma/leukemia (TL) in C57BL/6 mice. Radiation-induced mouse TL (RITL) can be prevented by bone marrow transplantation (BMT) of unirradiated BM cells. However, the mechanisms underlying the prevention of RITL with BMT remain unclear. Here, we show that BMT restores thymic T-cell differentiation in mice subjected to TBI. TBI (four times of 1.8 Gy X-rays weekly) was conducted with C57BL/6 mice. BMT was performed immediately after the last irradiation of TBI in mice by transplantation of BM cells isolated from enhanced green fluorescence protein (eGFP) transgenic mice. Thymic cell numbers were drastically decreased in TBI and TBI + BMT mice compared to those in non-irradiated mice. Flow cytometry showed a dramatic decrease in double negative (DN, CD4−CD8−) thymocytes, especially DN2 (CD25+CD44+) and DN3 (CD25+CD44−) subpopulations, in the TBI mice on Day 10 after the last irradiation. In contrast, the DN2 and DN3 populations were recovered in TBI + BMT mice. Interestingly, these restored DN2 and DN3 cells mainly differentiated from eGFP-negative recipient cells but not from eGFP-positive donor cells, suggesting that transplanted BM cells may interact with recipient cells to restore thymic T-cell development in the RITL model. Taken together, our findings highlight the significance of restoring thymic T-cell differentiation by BMT in RITL prevention. [ABSTRACT FROM AUTHOR]

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Introduction: Pediatric patients have an increased risk of radiation-induced malignancies due to their ongoing development and long remaining life span. Thus, optimization of PET protocols is an important task in pediatric nuclear medicine. Long axial field-of-view (LAFOV) PET/CT has shown a significant increase in sensitivity, which provides an ideal opportunity for reduction of injected tracer activity in the pediatric population. In this study we aim to evaluate the clinical performance of a 2-[18F]FDG-tracer reduction from 3 MBq/kg to 1.5 MBq/kg on the Biograph Vision Quadra LAFOV PET/CT. Materials and methods: The first 50 pediatric patients referred for clinical whole-body PET/CT with 1.5 MBq/kg 2-[18F]FDG, were included. A standard pediatric protocol was applied. Five reconstructions were created with various time, filter and iteration settings. Image noise was computed as coefficient-ofvariance (COV = SD/mean standardized-uptake-value) calculated from a spherical 20--50 mm (diameter) liver volume-of-interest. Sets of reconstructions were reviewed by one nuclear medicine physicians, who reported image lesions on a pre-defined list of sites. Paired comparison analysis was performed with significance at PB < 0.05 (Bonferroni corrected). Results: All reconstructions, except one, achieved a COVmean (0.08--0.15) equal to or lower than current clinical acceptable values (COVref ≤ 0.15). Image noise significantly improved with increasing acquisition time, lowering iterations (i) from 6i to 4i (both with five subsets) and when applying a 2 mm Gauss filter (PB < 0.001). Significant difference in lesion detection was seen from 150s to 300s and from 150s to 600s (PB = 0.006--0.007). 99% of all lesions rated as malignant could be found on the 150s reconstruction, while 100% was found on the 300s, when compared to the 600s reconstruction. Conclusion: Injected activity and scan time can be reduced to 1.5 MBq/kg 2-[18F] FDG with 5 min acquisition time on LAFOV PET/CT, while maintaining clinical performance in the pediatric population. These results can help limit radiation exposure to patients and personnel as well as shorten total scan time, which can help increase patient comfort, lessen the need for sedation and provide individually tailored scans. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. It has been known for some considerable time that radiation is associated with excess risk of CVD. A recent systematic review of radiation and CVD highlighted substantial inter-study heterogeneity in effect, possibly a result of confounding or modifications of radiation effect by non-radiation factors, in particular by the major lifestyle/environmental/medical risk factors and latent period. Methods: We assessed effects of confounding by lifestyle/environmental/medical risk factors on radiation-associated CVD and investigated evidence for modifying effects of these variables on CVD radiation dose–response, using data assembled for a recent systematic review. Results: There are 43 epidemiologic studies which are informative on effects of adjustment for confounding or risk modifying factors on radiation-associated CVD. Of these 22 were studies of groups exposed to substantial doses of medical radiation for therapy or diagnosis. The remaining 21 studies were of groups exposed at much lower levels of dose and/or dose rate. Only four studies suggest substantial effects of adjustment for lifestyle/environmental/medical risk factors on radiation risk of CVD; however, there were also substantial uncertainties in the estimates in all of these studies. There are fewer suggestions of effects that modify the radiation dose response; only two studies, both at lower levels of dose, report the most serious level of modifying effect. Conclusions: There are still large uncertainties about confounding factors or lifestyle/environmental/medical variables that may influence radiation-associated CVD, although indications are that there are not many studies in which there are substantial confounding effects of these risk factors. [ABSTRACT FROM AUTHOR]

Introduction: Therapy‐induced senescent cancer and stromal cells secrete cytokines and growth factors to promote tumor progression. Therefore, senescent cells may be novel targets for tumor treatment. Near‐infrared photoimmunotherapy (NIR‐PIT) is a highly tumor‐selective therapy that employs conjugates of a molecular‐targeting antibody and photoabsorber. Thus, NIR‐PIT has the potential to be applied as a novel senolytic therapy. This study aims to investigate the efficacy of NIR‐PIT treatment on senescent cancer and stromal cells. Methods: Two cancer cell lines (human lung adenocarcinoma A549 cells and human pancreatic cancer MIA PaCa‐2 cells) and two normal cell lines (mouse fibroblast transfected with human epidermal growth factor receptor 2 [HER2] cells and human fibroblast WI38 cells) were used. The cytotoxicity of NIR‐PIT was evaluated using anti‐epidermal growth factor receptor (EGFR) antibody panitumumab and anti‐HER2 antibody transtuzumab. Results: Cellular senescence was induced in A549 and MIA PaCa‐2 cells by 10 Gy γ‐irradiation. The up‐regulation of cellular senescence markers and characteristic morphological changes in senescent cells, including enlargement, flattening, and multinucleation, were observed in cancer cells after 5 days of γ‐irradiation. Then, NIR‐PIT targeting EGFR was performed on these senescent cancer cells. The NIR‐PIT induced morphological changes, including bleb formation, swelling, and the inflow of extracellular fluid, and induced a significant decrease in cellular viability. These results suggested that NIR‐PIT may induce cytotoxicity using the same mechanism in senescent cancer cells. In addition, similar morphological changes were also induced in radiation‐induced senescent 3T3‐HER2 fibroblasts by NIR‐PIT targeting human epidermal growth factor receptor 2. Conclusion: NIR‐PIT eliminates both senescent cancer and stromal cells in vitro suggesting it may be a novel strategy for tumor treatment. [ABSTRACT FROM AUTHOR]

Introduction: While there are many papers on maternal and foetal radiation doses from computed tomography pulmonary angiography (CTPA) and ventilation/perfusion (V/Q) lung scanning examinations for diagnosing pulmonary embolism in pregnant patients, few have used clinical data to examine the patient lifetime attributable risk (LAR) of different cancer types. This paper aims to estimate the cancer risk from maternal radiation doses from CTPA and V/Q examinations and associated foetal doses. Methods: Dosimetric data were determined for 267 pregnant patients who received CTPA and/or V/Q examinations over 8 years. Organ and foetal doses were determined using software allowing patient size variations for CTPA and using two different activity‐to‐organ dose conversion methods for V/Q scans. The LAR of cancer incidence was estimated using International Commission on Radiological Protection (ICRP) modelling including estimates of detriment. Results: Estimated total cancer incidence was 23 and 22 cases per 100,000 for CTPA and V/Q examinations, respectively, with detriment estimates of 18 and 20 cases. Cancer incidence was evenly divided between lung and breast cancer for CTPA with lung cancer being 80% of all cancer for V/Q. The median foetal doses were 0.03 mSv for CTPA and 0.29 mSv for V/Q. Significant differences in estimated foetal dose for V/Q scans were obtained by the two different methods used. The differences in dose between the modes of CTPA scan acquisition highlight the importance of optimisation. Conclusion: Maternal cancer incidence and detriment were remarkably similar for each examination. Optimisation of examinations is critical for low‐dose outcomes, particularly for CTPA examination. [ABSTRACT FROM AUTHOR]

It has long been thought that the carcinogenic effect of radiation resulted from the induction of oncogenic mutations which then led to an increase in the proportion of cancer-bearing individuals. However, even as early as the 1960s, there were indications that the carcinogenic effect of radiation might result from the induction of an earlier onset of cancer. Recently, the former notion was challenged by its inability to explain time-dependent decline of the relative risk following an exposure to radiation, and a parallel shift of mouse survival curves toward younger ages following an exposure to radiation. The two observations are clearly understood if it is assumed only that a radiation exposure causes an earlier onset of spontaneously occurring cancers. In the present study, a critical review was conducted which examined papers that showed dose responses which apparently supported the mutation induction theory of radiation carcinogenesis. It was found that there were two types of misleading experimental designs: one consisted of studies in which observations were prematurely terminated, and which consequently hid a complete story of radiation carcinogenesis. The other set of papers used age adjustments which were derived from the idea that the life shortening effect of radiation needs to be compensated for since tumor mortality becomes higher among older subjects. This type of adjustment appeared reasonable but was found actually to be a different form of description on an earlier onset of cancer following radiation exposures. In mouse experiments, radiation exposures did not lead to the induction of a large increase in the proportion of tumor deaths when life-long observations were made. Human epidemiologic data are also in line with the earlier onset hypothesis of radiation action. It should be cautioned, however, that the earlier onset model applies only to malignancies whose mortality increases rapidly with the increase of age and does not apply to diseases of short latency such as childhood leukemia and thyroid cancers. [ABSTRACT FROM AUTHOR]

In this Pediatric Normal Tissue Effects in the Clinic (PENTEC) vision paper, challenges and opportunities in the assessment of subsequent neoplasms (SNs) from radiation therapy (RT) are presented and discussed in the context of technology advancement. The paper discusses the current knowledge of SN risks associated with historic, contemporary, and future RT technologies. Opportunities for research and SN mitigation strategies in pediatric patients with cancer are reviewed. Present experience with radiation carcinogenesis is from populations exposed during widely different scenarios. Knowledge gaps exist within clinical cohorts and follow-up; dose-response and volume effects; dose-rate and fractionation effects; radiation quality and proton/particle therapy; age considerations; susceptibility of specific tissues; and risks related to genetic predisposition. The biological mechanisms associated with local and patient-level risks are largely unknown. Future cancer care is expected to involve several available RT technologies, necessitating evidence and strategies to assess the performance of competing treatments. It is essential to maximize the utilization of existing follow-up while planning for prospective data collection, including standardized registration of individual treatment information with linkage across patient databases. [ABSTRACT FROM AUTHOR]

The PENTEC (Pediatric Normal Tissue Effects in the Clinic) task force aimed to quantify effects of radiation therapy (RT) dose to the female reproductive organs after treatment for childhood cancer. Relevant studies published 1970 to 2017 were identified systematically through PubMed, Medline, and Cochrane databases with additional articles before 2021 identified by the group. Two large studies reported sufficient data to allow modeling of acute ovarian failure (AOF; loss of function ≤5 year from diagnosis) and premature ovarian insufficiency (POI; loss of function at attained age <40 years) based on maximum dose to least affected ovary. Although normal tissue complication probability modeling was not feasible for the uterus due to limited data, the relationship between ultrasound-measured uterine volume and estimated amount of RT was plotted. Limited data regarding vaginal toxicity were available. The risk of AOF increases with RT dose to least affected ovary, alkylating agent cumulative dose (cyclophosphamide equivalent dose [CED] in g/m2), age at RT, and stem cell transplantation: Two Gy to the least affected ovary resulted in AOF risk of 1% to 5% (CED = 0, risk increasing with age), 4% to 7% (CED = 10 g/m2, risk increasing with age), and 6% to 13% (CED = 30 g/m2, risk increasing with age). For patients aged 1 and 20 years at time of RT, AOF risk was ≥50% at doses of 24 Gy and 20 Gy with no alkylating chemotherapy, 22.5 Gy and 17 Gy with intermediate alkylator dose (10 g/m2), and 17 Gy and 13 Gy with high alkylator dose (30 g/m2). Risk of POI increases with survivor (attained) age (rather than age at time of RT), radiation dose to least affected ovary, and alkylator dose. Data review suggested that higher radiation doses to the uterus are associated with uterine toxicity, with uterine size considerably restricted after 12 Gy. Vaginal radiation in children is associated with high toxicity risk, although dose-volume data are not available for quantification. Risk of AOF increases with age at RT, CED exposure, and RT dose; risk of POI likewise increases with RT dose, CED exposure, and survivor age. Both AOF and POI are expected to affect fertility and estrogen production. Data suggest that RT uterine dose >12 Gy may be associated with uterine size restriction. Adult literature suggests that maintaining vaginal dose <5 Gy may limit toxicity. Treatment of life-threatening malignancy remains a priority over reproductive preservation; however, when possible, radiation and surgical techniques should be considered to minimize dose to least affected ovary, uterus, and vagina. Survivors should receive endocrine and gynecologic support; those desiring pregnancy should be counseled early to maximize reproductive options. [ABSTRACT FROM AUTHOR]

This study compared the risks for developing second primary cancers and cardiotoxicity following radiotherapy for thymoma. Three different 3D-CRT, IMRT, and VMAT plans were generated with 6 MV photons for 12 females with thymoma. Dose-volume histogram data were employed to estimate the second cancer risks using a mechanistic non-linear model. The radiation doses to the heart and cardiac substructures were combined with linear models to assess the probability of cardiotoxicity. The mean lifetime risk for lung, esophageal, thyroid, left breast, and right breast cancer induction was 4.34–4.49%, 0.30–0.31%, 0.05–0.07%, 2.06–2.30%, and 2.04–2.34%, respectively, depending upon the radiotherapy technique. The relative risk for major cardiac events, including myocardial infarction, coronary revascularization, and death, was 1.43–1.55, whereas that for chronic heart failure was 1.20–1.29. The IMRT and VMAT significantly reduced the risk for cardiotoxicity with respect to 3D-CRT (p ≤ 0.023). Small but significant reductions were observed for most organ-specific cancer risks with IMRT compared to conformal treatment (p ≤ 0.008). Similar decreases were detected only for esophageal and thyroid cancer with VMAT (p ≤ 0.033). No difference was found in the probability for radiation-induced lung cancer with the three techniques (p ≥ 0.06). Healthcare professionals may use these data to select the appropriate radiotherapy technique and restrict the risk of late effects. [ABSTRACT FROM AUTHOR]

The primary treatment for nasopharyngeal carcinoma (NPC) is radiotherapy. In rare cases, patients with NPC treated with radiotherapy may develop radiation-induced sarcoma (RIS), a malignant tumor, in the field of previous radiation. The prognosis is poor, and complete surgical resection is the only potentially curative treatment. We report a case of radiation-induced nasopharyngeal sarcoma after radiotherapy for NPC with suspected lung and liver metastases in a 69-year-old woman. [ABSTRACT FROM AUTHOR]

The article discusses the effects of ionizing radiation exposure on offspring and future generations. It highlights the concerns surrounding the potential harmful effects of radiation on prenatal development and reproductive health. The article references numerous studies and reports that have investigated the risks and consequences of radiation exposure, particularly during critical periods of pregnancy. It emphasizes the need for more research and data to better understand the complexities involved and calls for long-term epidemiological studies and advancements in genetic and molecular techniques. [Extracted from the article]

Background: The European-funded Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Pediatrics (HARMONIC) project aims to improve knowledge on the effects of medical exposure to ionizing radiation (IR) received during childhood. One of its objectives is to build a consolidated European cohort of pediatric patients who have undergone cardiac catheterization (Cath) procedures, with the goal of enhancing the assessment of long-term radiation-associated cancer risk. The purpose of our study is to provide a detailed description of the Italian cohort contributing to the HARMONIC project, including an analysis of cumulative IR exposure, reduction trend over the years and an overview of the prospective collection of biological samples for research in this vulnerable population. Methods: In a single-center retrospective cohort study, a total of 584 patients (323 males) with a median age of 6 (2–13) years, referred at the Pediatric Cardiology in Niguarda Hospital from January 2015 to October 2023, were included. Biological specimens from a subset of 60 patients were prospectively collected for biobanking at baseline, immediately post-procedure and after 12 months. Results: Two hundred fifty-nine (44%) patients were under 1 year old at their first procedure. The median KAP/weight was 0.09 Gy·cm2/kg (IQR: 0.03–0.20), and the median fluoroscopy time was 8.10 min (IQR: 4.00–16.25). KAP/weight ratio showed a positive correlation with the fluoroscopy time (Spearman's rho = 0.679, p < 0.001). Significant dose reduction was observed either after implementation of an upgraded technology system and a radiation training among staff. The Italian cohort includes 1858 different types of specimens for Harmonic biobank, including blood, plasma, serum, clot, cell pellet/lymphocytes, saliva. Conclusions: In the Italian Harmonic cohort, radiation dose in cardiac catheterization varies by age and procedure type. An institution's radiological protection strategy has contributed to a reduction in radiation dose over time. Biological samples provide a valuable resource for future research, offering an opportunity to identify potential early biomarkers for health surveillance and personalized risk assessment. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation-associated sarcomas pose a significant clinical challenge due to their complexity, aggressiveness, and poor prognosis. Our retrospective study is one of the largest descriptions of radiation-associated sarcomas, aiming to shed light on their clinicopathologic characteristics and highlight treatment approaches. Our research found a significant association between high radiation-associated sarcoma histologic grade and inferior clinical outcomes. We also found that localized radiation-associated sarcoma patients who underwent margin-negative resections lived significantly longer than their counterparts. Our analysis thus confirms the paramount role of tumor grade and the central importance of margin-negative oncologic resection in determining clinical outcomes for radiation-associated sarcomas. Radiation-associated sarcomas (RASs) are rare tumors with limited contemporary data to inform prognostication and management. We sought to identify the clinical presentation, patterns of care, and prognostic factors of RASs. RAS patients treated at a single institution from 2015 to 2021 were retrospectively reviewed for clinicopathologic variables, treatment strategies, and outcomes. Thirty-eight patients were identified with a median follow-up of 30.5 months. The median age at RAS diagnosis was 68.4 years (27.9–85.4), with a median latency from index radiotherapy (RT) of 9.1 years (3.7–46.3). RAS histologies included angiosarcoma (26%), undifferentiated pleomorphic sarcoma (21%), and osteosarcoma (18%). Most were high-grade (76%). Genomic profiling revealed low tumor mutational burden, frequent inactivating TP53 mutations (44%), CDKN2A deletions (26%), and MYC amplifications (22%), particularly in breast angiosarcomas. Of 38 patients, 33 presented with localized disease, 26 of whom were treated with curative intent. Overall, the median progression-free survival (PFS) was 9.5 months (1.4–34.7), and the overall survival (OS) was 11.1 months (0.6–31.6). Patients with localized vs. metastatic RASs had a longer PFS (HR, 3.0 [1.1–8.5]; p = 0.03) and OS (HR, 3.0 [1.04–8.68]; p = 0.03). Among localized RAS patients, high grade was associated with shorter OS (HR, 4.6 [1.04–20.30]; p = 0.03) and resection with longer OS (mean 58.8 vs. 6.1 months, HR, 0.1 [0.03–0.28]; p < 0.001). Among patients undergoing resection, negative margins were associated with improved OS (mean 71.0 vs. 15.5 months, HR, 5.1 [1.4–18.2]; p = 0.006). Patients with localized disease, particularly those undergoing R0 resection, demonstrated significantly better outcomes. Novel strategies are urgently needed to improve treatment outcomes in this challenging group of diseases. [ABSTRACT FROM AUTHOR]

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

Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches. Radiation-induced tumor vaccination is insufficient to elicit robust antitumor immune response. Here they combine chiral vidarabine monophosphate-gadolinium nanowires with immune checkpoint blockade therapy to synergistically induce antitumor immunity. Reviewer recognition: [ABSTRACT FROM AUTHOR]

Purpose: Intraoperative fluoroscopy use is essential during spinal fusion procedures. The amount of radiation dose should always be minimized. This study aimed to determine the feasibility of halving the frame rate from 12.5 to 6.25 frames per second (fps) and to quantify the reduction in the risk of developing radiation-induced cancer. Methods: This pilot study included 34 consecutive patients operated for open lumbar posterolateral fusion (PLF) with or without transforaminal lumbar interbody fusion (TLIF). C-arm modes were changed from half-dose (12.5 frames per second (fps), group I) to quarter-dose (6.25 fps, group II). Age, body mass index, surgical procedure, number of treated levels, and complications were collected. Kerma area product (KAP), cumulative air kerma (CAK), and fluoroscopy time were compared. Effective dose and radiation-induced cancer risk were estimated. Results: Eighteen and 16 patients were, respectively, included in group I and II. Demographic, surgical data, and fluoroscopy time were similar in both groups. However, CAK, KAP, and effective dose were significantly lower in group II, respectively, 0.56 versus 0.41 mGy (p = 0.03), 0.09 versus 0.06 Gy cm2 (p = 0.04), and 0.03 versus 0.02 mSv (p = 0.04). Radiation-induced cancer risk decreased by 47.7% from 1.49 × 10–6 to 7.77 × 10–7 after optimization. No complications were recorded in either group. Conclusion: This study demonstrates the feasibility of setting 6.25 fps for TLIF with and without PLF. By halving the fps, radiation-induced cancer risk could be almost divided by two, without compromising surgical outcome. Finally, after optimization, the risk of developing radiation-induced cancer was less than one in a million. [ABSTRACT FROM AUTHOR]

Introduction: The study aimed to analyze and determine impact of the 3D-CRT fractionation on risk of secondary cancer. Material and Methods: This study used a patient-specific anthropomorphic phantom, and radiation was performed using the Three Dimensional-Conformal Radiation Therapy Field in Field (3D-CRT FinF) technique with conventional, hypofractionation, and hyperfractionation with a dose of 200 cGy, 260 cGy, and 160 cGy in 25, 16, and 30 fractions respectively. It focused on the contralateral breast, contralateral lung, and ipsilateral lung as Organs at Risk (OAR). In addition, the Dose Volume Histogram (DVH) value, normal tissue complication probability (NTCP), and risk of secondary cancer were evaluated. Results: The results showed that the average dose value (Dmean) for ipsilateral lung with hypofractionation was smaller than conventional and hyperfractionation of 1519.8, 1826.7, and 1753.6 cGy, respectively. Furthermore, hypofractionation also reduced radiobiological effects by 50% in the ipsilateral lung with an NTCP value of 0.01% compared to conventional and hyperfractionation with a value of 0.02%. Hypofractionation reduces the risk of secondary cancer in the contralateral breast, contralateral lung, and ipsilateral lung by 16.38, 17, and 22.31% compared to conventional fractionation and 12.75, 13.54, and 21.34% compared to hyperfractionation, respectively. Conclusion: The dose profiles in OAR was smaller in treatment planning with hypofractionation. EBT3 film verification results showed that the ipsilateral lung received more doses than planned, with an insignificant difference (p>0.05). In radiobiology, the ipsilateral lung has the highest probability of complications in treatment planning with conventional fractionation and hyperfractionation. [ABSTRACT FROM AUTHOR]

Introduction: Ultraviolet radiation (UVR) is the primary risk factor for keratinocyte carcinomas. Oral supplementation with nicotinamide (NAM) is reported to reduce the formation of new keratinocyte carcinomas. NAM's photoprotection is mediated by enhanced DNA repair. We wanted to explore whether NAM in combination with antiproliferative (metformin [Met]) or antioxidant (phloroglucinol [PG]) compounds could potentially enhance its photoprotective effects. Methods: Hairless mice (C3.Cg-Hrhr/TifBomTac) were treated orally with either a standard dose of NAM monotherapy (NAM-mono; 600 mg/kg) or NAM (400 mg/kg) combined with Met (200 mg/kg) (NAM-Met) or PG (75 mg/kg) (NAM-PG). Mice were irradiated with 3.5 standard erythema doses of UVR three times per week to induce tumour development. Photoprotective effects were based on (i) tumour onset of the first three tumours, (ii) skin photodamage, and (iii) DNA damage (cyclobutane pyrimidine dimers [CPDs] and pyrimidine-pyrimidone (6–4) photoproducts [6-4PPs]). Results: All mice treated with NAM demonstrated a delay in tumour onset and reduced tumour burden compared to the UV control group (NAM, NAM-Met, NAM-PG vs. UV control: p ≤ 0.015). NAM-mono and NAM-PG increased time until all three tumours with no difference between them, indicating a similar degree of photoprotection. NAM-mono had no effect on DNA damage compared to the UV control group (p > 0.05), whereas NAM-PG reduced 6-4PP lesions (p < 0.01) but not CPDs (p > 0.05) compared to NAM-mono. NAM-Met delayed the onset of the third tumour compared to the UV control but demonstrated a quicker onset compared to NAM-mono, suggesting inferior photoprotection compared to nicotinamide monotherapy. Conclusion: NAM-PG was as effective in delaying UVR-induced tumour onset as NAM-mono. The reduction in 6-4PP lesions may indicate that the mechanism of NAM-PG is better suited for photoprotection than NAM-mono. NAM-mono was superior to NAM-Met, indicating a dose dependency of NAM's photoprotection. These results highlight the potential for combining photoprotective compounds to enhance photoprotection. Plain Language Summary: Skin cancer is the most common type of cancer seen in the clinic. The amount of lifelong sun exposure and the degree of sunburns are important contributors to the development of skin cancer. Despite massive prevention campaigns promoting better sun habits by staying in the shade and applying sufficient sunscreen, skin cancer cases are still increasing. To address this, researchers are exploring different compounds for oral sun protection. In this study, we tested whether combining vitamin B3 (nicotinamide) with the well-known medication metformin or a known antioxidant called phloroglucinol could enhance its protection against sun-induced skin cancer. Hairless mice were given either nicotinamide alone or nicotinamide at a lower dose combined with either metformin or phloroglucinol through their drinking water and exposed to simulated sunlight 3 times per week to induce skin cancer. We show for the first time that mice treated with all three nicotinamide groups had a delay in skin cancer onset compared to sun-exposed control. Furthermore, we show that the nicotinamide and phloroglucinol combination provides the same sun protection as nicotinamide alone, whereas the combination with metformin did not. Notably, the nicotinamide combined with phloroglucinol provided a reduction in DNA damage, suggesting a better-suited mechanism of action for preventing skin cancer. Overall, the study indicates a potential strategy of combining compounds to enhance oral sun protection to prevent skin cancer. [ABSTRACT FROM AUTHOR]

Many patients with hepatocellular carcinoma (HCC) respond poorly to radiotherapy despite remarkable advances in treatment. A deeper insight into the mechanism of sensitivity of HCC to this therapy is urgently required. It is demonstrated that RECQL4 is upregulated in the malignant cells of patients with HCC. Elevated RECQL4 levels reduce the sensitivity of HCC to radiotherapy by repairing radiation‐induced double‐stranded DNA (dsDNA) fragments. Mechanistically, the inhibitory effect of RECQL4 on radiotherapy is due to the reduced recruitment of dendritic cells and CD8+ T cells in the tumor microenvironment (TME). RECQL4 disrupts the radiation‐induced transformation of the TME into a tumoricidal niche by inhibiting the cGAS‐STING pathway in dendritic cells. Knocking out STING in dendritic cells can block the impact of RECQL4 on HCC radiosensitivity. Notably, high RECQL4 expressions in HCC is significantly associated with poor prognosis in multiple independent cohorts. In conclusion, this study highlights how HCC‐derived RECQL4 disrupts cGAS‐STING pathway activation in dendritic cells through DNA repair, thus reducing the radiosensitivity of HCC. These findings provide new perspectives on the clinical treatment of HCC. [ABSTRACT FROM AUTHOR]

Radiotherapy-induced glioblastomas (RIGB) are a well-known late and rare complication of brain irradiation. Yet the clinical, radiological and molecular characteristics of these tumors are not well characterized. This was a retrospective multicentre study that analysed adult patients with newly diagnosed glioblastoma over a 10-year period. Patients with RIGB were identified according to Cahan's criteria for radiation-induced tumors. A case-control analysis was performed to compare known prognostic factors for overall survival (OS) with an independent cohort of IDH-1 wildtype de novo glioblastomas treated with standard temozolomide chemoradiotherapy. Survival analysis was performed by Cox proportional hazards regression. A total of 590 adult patients were diagnosed with glioblastoma. 19 patients (3%) had RIGB. The mean age of patients upon diagnosis was 48 years ± 15. The mean latency duration from radiotherapy to RIGB was 14 years ± 8. The mean total dose was 58Gy ± 10. One-third of patients (37%, 7/19) had nasopharyngeal cancer and a fifth (21%, 4/19) had primary intracranial germinoma. Compared to a cohort of 146 de novo glioblastoma patients, RIGB patients had a shorter median OS of 4.8 months versus 19.2 months (p-value: <.001). Over a third of RIGBs involved the cerebellum (37%, 7/19) and was higher than the control group (4%, 6/146; p-value: <.001). A fifth of RIGBs (21%, 3/19) were pMGMT methylated which was significantly fewer than the control group (49%, 71/146; p-value:.01). For RIGB patients (32%, 6/19) treated with re-irradiation, the one-year survival rate was 67% and only 8% for those without such treatment (p-value:.007). The propensity for RIGBs to develop in the cerebellum and to be pMGMT unmethylated may contribute to their poorer prognosis. When possible re-irradiation may offer a survival benefit. Nasopharyngeal cancer and germinomas accounted for the majority of original malignancies reflecting their prevalence among Southern Chinese. [ABSTRACT FROM AUTHOR]