Estimation of the optimal radiotherapy utilization rate for childhood neuroblastoma.

BACKGROUND AND PURPOSE: The optimal utilization rate of radiotherapy (oRUR) serves as a benchmark for assessing service demand and improving access to cancer care. While it is estimated that approximately 50 % of adult cancer patients require external beam radiotherapy during their treatment, there is a scarcity of data regarding the optimal use of radiotherapy in pediatric cancer. In this study, we adopted an established method and developed a model to estimate the oRUR in childhood neuroblastoma. MATERIALS AND METHODS: We developed a decision tree model to calculate the oRUR using indications for radiotherapy and corresponding epidemiological data collected through systematic review and meta-analysis. Sensitivity analyses were performed to evaluate the impact of variations in radiotherapy indications between treatment protocols and variables in the model. We calculated and compared the oRUR for global, high-income, and low- and middle-income settings. RESULTS: The oRUR for pediatric neuroblastoma was 64 % (95 % CI: 58 %-71 %) in the global setting, 50 % in high-income countries, and 68 % in low- and middle-income countries. The impact of variation in radiotherapy indications between major international treatment protocols was negligible. CONCLUSION: The knowledge of oRUR is crucial for evaluating current practices, identifying gaps in access, and planning future radiotherapy services for treating childhood cancer. Based on our results, 64 % of children with neuroblastoma have an indication for radiotherapy. Patients in low- and middle-income countries have more indications for radiotherapy than those in high-income countries, due to a more adverse tumour stage distribution caused by limited access to healthcare resources.

Longitudinal Costs of Image-Guided Intensity-Modulated Radiation Therapy Versus Three-Dimensional Conformal Radiation: Lessons From Phase III PARCER Trial for Shaping Resource-Stratified Guidelines in Low- and Middle-Income Countries.

PURPOSE: The PARCER trial provided level I evidence for image-guided intensity-modulated radiation therapy (IG-IMRT) in patients with cervical cancer. Further information regarding long-term financial impact is imperative for adoption into the National Cancer Grid of India cervical cancer resource-stratified guidelines. METHODS: Patient data from the PARCER trial were analyzed to evaluate the cost implications of transitioning to IG-IMRT. Lacking differences in outcomes between the three-dimensional conformal radiation (3D-CRT) and IG-IMRT, differences in treatment costs, adverse event incidence, and toxicity management costs were examined. The overall financial impact was estimated by adding the treatment costs, toxicity management, and wage loss. This was extrapolated nationally to determine if a transition to IG-IMRT would be feasible for the Indian health care system. RESULTS: Of the 300 patients in the PARCER trial, 93 faced grades ≥2 adverse events (3D-CRT = 59, IG-IMRT = 34). Patients in the 3D-CRT and IG-IMRT arms spent an average of 2.39 years and 1.96 years in toxicity, respectively. The average toxicity management and the yearly financial impact per patient were, respectively, 1.50 and 1.44 times higher for 3D-CRT patients compared with IG-IMRT patients. Extrapolation to the national level showed that treatment with 3D-CRT led to a 2.88 times higher cost ratio when compared with treatment with IG-IMRT. CONCLUSION: Although the initial costs of IG-IMRT are high, on the basis of longitudinal data, it is financially inefficient to treat with 3D-CRT. Resource-stratified guidelines should include longitudinal health intervention costs rather than solely initial costs for policy decisions to implement advanced radiation technology.

Brachytherapy Workflow Practices: Analysis of Different Workflow Scenarios in Patients With Cervical Cancer and Impact on IGBT Implementation-An IAEA Study.

PURPOSE: The workflow of brachytherapy (BT) is an essential aspect of treatment to consider in image-guided brachytherapy (IGBT). It has an overarching effect influencing patient throughput and the number of cancer treatments that can be performed as it occupies equipment, space, and personnel. There is limited research addressing this issue. Under the International Atomic Energy Agency's Coordinated Research Activity titled IGBT for cervix cancer: An implementation study, our study analyzes various scenarios in the clinical workflow of BT delivery for cervical cancer. It aims to determine the extent to which these scenarios allow the routine implementation of IGBT. With this information, current barriers and individualized adaptations to efficient workflows can be identified to enhance the global application of IGBT, leading to better cervical cancer treatment. MATERIALS AND METHODS: A web-based poll of questions regarding practices in BT workflow was presented to 62 participants from low-, lower middle-, upper middle-, and high-income countries (19 countries). RESULTS: This study highlighted diversity in BT practices across countries, income levels, and regions. It identified variations in workflow, patient throughput, and resource availability, which can have implications for the efficiency and quality of BT treatments. Scenario A, utilizing multiple locations for the steps of the BT procedure, was the most commonly used. The availability of resources, such as imaging devices and trained personnel, varied among the participating centers and remained challenging for IGBT implementation and sustainability. CONCLUSION: The design of the BT facility plays a vital role in improving efficiency, with a dedicated BT suite contributing to an efficient workflow but limiting patient throughput, especially for high-volume centers. Although IGBT is effective, its implementation requires consideration of various logistical challenges and should be individualized.

Thoughts, perceptions and concerns of coastal residents regarding the discharge of tritium-containing treated water from the Fukushima Daiichi Nuclear Power Plant into the Pacific Ocean.

BACKGROUND: As a part of the decontamination process after the Fukushima Daiichi Nuclear Power Plant accident of 2011, 1.32 million tonnes of tritium-containing water will be discharged from the power plant into the Pacific Ocean. Although radiobiological impacts of the treated water discharge on the public and the environment were reported to be minimal, Tomioka and Okuma locals expressed unease regarding the long-term recovery of their towns, which are economically dependent on the agricultural, fishery, and tourism sectors. This study presents thoughts, perceptions and concerns of Tomioka and Okuma locals regarding the discharge of FDNPP-treated water containing tritium into the Pacific Ocean to facilitate a more inclusive decision-making process that respects local stakeholder interests. METHODS: Conducted from November to December 2022, surveys were mailed to current residents and evacuees aged 20 years or older registered with the town councils. RESULTS: Out of 1268 included responses, 71.5% were from those > 65 years. 65.6% were unemployed, 76.2% routinely visited hospitals, and 85.5% did not live with children. 61% did not want to return to Okuma/Tomioka. Anxiety about radiation-related health effects (38.7%), consuming food produced in Okuma/Tomioka (48.0%) and genetic effects (45.3%) were low. >50% reported poor physical and mental health. 40% were acceptive, 31.4% were unsure, and 29.7% objected to the discharge plans. Multinomial regression analysis revealed that, compared to acceptive responders, those who objected were more likely to be female, unemployed, and have anxiety about radiation-related genetic effects and poor mental health. Unsure responders were similarly more likely to be female, anxious about radiation-related genetic effects and have poor mental health. CONCLUSION: The poor mental health of the locals, connected to high levels of risk perception and anxiety about the loss of economic opportunities related to the discharge plans, must be addressed. The 30-year discharge process could handicap local industries and hamper post-disaster socioeconomic recovery due to the circulation of false rumours among consumers. These results highlight the need to actively involve residents in the towns' recovery process to address local concerns. The focus should be on the judicious combination of transparent science with the human aspect of recovery and narratives highlighting dialogues between local stakeholders and experts to enable the locals and the general public to make informed decisions about their protection and future.

Transitioning India to advanced image based adaptive brachytherapy: a national impact analysis of upgrading National Cancer Grid cervix cancer guidelines.

Background: High-dose-rate image guided brachytherapy (IGBT) for cervical cancer leads to improved local control and reduced toxicity and is a critical component of treatment. However, transition to IGBT requires capacity upscaling. An institutional activity mapping and national impact analysis of such a transition were undertaken to understand feasibility. Methods: Between September 2020 and March 2021, activity mapping was conducted in a high-volume centre that triaged cervical cancer patients for brachytherapy into four workflows; A: two-dimensional (2D) X-Ray point A-based intracavitary brachytherapy, B: CT point A-based intracavitary brachytherapy, C: MRI/CT-volume based intracavitary brachytherapy, D: MRI/CT volume-based intracavitary +/- interstitial brachytherapy. Clinical process time mapping was performed, and case scenarios for transition were modelled at the institutional and national levels based on available incidence and infrastructure levels. Treatment capacity changes were calculated, and potential strategies for workflow reorganisation were proposed. Findings: Eighty-four patients were included in the study. The total time taken for the workflows A, B, C, and D were 176 min (57-208), 224 min (74-260), 267 min (101-302), and 348 min (232-383), respectively. The transition from workflow A to D through sequential steps led to 35%, 49%, and 64% loss of treatment capacity in the index institution. Solutions such as 10-hour or 12-hour overlapping shifts increased treatment capacity by 25% and 50% and performing single implants and delivering multiple fractions increased capacity by 100%. Twenty-three Indian states and Union Territories are predicted to be able to transition to advanced workflows. For four Indian states, it may be detrimental considering the current infrastructure level, and eight Indian states lacked brachytherapy access. Further financial investment is required in the latter 12 states for transition to advanced workflows. Interpretation: Our study demonstrates that unplanned transition to IGBT can lead to treatment capacity loss and increase in waiting lists to access treatment. The proposed solutions of workflow reorganisation, using strategies such as single brachytherapy applicator implant and delivering multiple treatment fractions can improve access to treatment for women with cervix cancer in resource-strained and high patient-volume settings. We recommend state-wise solutions for the upscale from conventional 2D workflows to IGBT, subject to the availability of skilled personnel, infrastructure and training. Financial investments may be needed in some states to achieve this goal. Funding: International Atomic Energy Agency (IAEA) supported the salary of VH through project E33042 that focussed on implementation strategies of image guided brachytherapy.

Changes in the Intention to Return and the Related Risk Perception Among Residents and Evacuees of Tomioka Town 11 Years After the Fukushima Nuclear Accident.

OBJECTIVE: This study examined temporal trends in risk perception and intention to return to Tomioka among residents and evacuees with the aim of aiding community recovery. METHODS: Responses to questionnaires distributed in 2017 and 2021 were compared regarding demographic information, intention to return to Tomioka, desire to consult radiation experts, and risk perception such as anxiety about food consumption, drinking tap water, self-health, and genetic effects. Questionnaires were distributed to all persons registered with the Tomioka town council, both current residents and evacuees. RESULTS: In 2021, the proportion of responders who had already returned/ wanted to return and those who did not want to return increased by 3.2% and 6.8% respectively, and the proportion unsure about returning decreased by 10.1%. Anxiety for self-health decreased by 15.4%, for genetic effects decreased by 24.4%, for food consumption decreased by 30.9%, and the latter 2 remained significant factors among responders unsure of returning and among those who did not want to return in 2021. CONCLUSIONS: Risk perception for food and genetic effects was significantly associated with uncertainty about returning or not returning. There is a need for continual monitoring of risk perception trends and implementation of targeted risk communication strategies.

Frequency of visits to Tomioka town and related factors among evacuees more than a decade after the Fukushima Daiichi Nuclear Power Plant accident.

This study aimed to clarify the frequency of visits (FOV) to Tomioka town, Japan, and related factors among evacuees more than a decade after the Fukushima Daiichi Nuclear Power Plant accident. A questionnaire survey was conducted on residents (age ≥ 18 years) who had residence cards in August 2021. Of the 2260 respondents, the FOV to Tomioka was as follows: 926 (41.0%) more than twice a year (Group 1 [G1]), 841 (37.2%) once a year (G2) and 493 (21.8%) no visits (G3). About 70% of the respondents who had decided not to return to Tomioka visited once a year or more. No significant differences in the FOV or radiation risk perception were found between groups. Multinomial logistic regression analysis using G3 as a reference revealed independent associations between living inside Fukushima in G1 (odds ratio [OR] = 5.4, 95% confidence interval [CI]: 4.1-7.3; P < 0.01) and G2 (OR = 2.3, 95% CI: 1.8-3.0, P < 0.01), undecided about returning in G1 (OR = 2.5, 95% CI: 1.9-3.3, P < 0.01), females in G1 (OR = 2.0, 95% CI: 1.6-2.6, P < 0.01) and motivation to learn more about tritiated water in G2 (OR = 1.8, 95% CI: 1.3-2.4, P < 0.01). Overall, 80% of the residents had visited Tomioka within a decade after the accident. These findings suggest the need to continue the effective dissemination of information about the effects of a nuclear accident and the subsequent decommissioning process to evacuees after evacuation orders have been lifted.

Comparison of quality of life between elderly and non-elderly adult residents in Okuma town, Japan, in a post-disaster setting.

With the growing elderly population who are susceptible to poor health, improvement of their quality of life is essential. In the post-disaster setting of the 2011 Fukushima Dai-ichi nuclear power plant (FDNPP) accident, affected municipalities such as Okuma town commenced their recovery processes and lifted evacuation orders in 2019. This study examines the differences in self-reported mental and physical health status, social functioning, risk perception, and intention to return between elderly (age ≥65 years) and non-elderly (age 20-64 years) residents. Questionnaires were distributed to current residents and evacuees of Okuma. Results revealed that the elderly had a 1.4 times higher odds ratio (95%CI 1.0-1.8, p = 0.034) for having anxiety regarding radiation-related health effects on future generations and a 1.3 times higher odds ratio (95%CI 1.1-1.5, p = 0.001) for wanting to know about the release of FDNPP-treated water into the environment than the younger group. Elderly residents also demonstrated a 2.2 times higher odds ratio for reporting poor physical health than younger residents. Clearing misconceptions and disseminating coherent information will reduce risk perception among this group. Further in-depth research regarding the disposal of FDNPP-treated water and its perceived risks is required. Health promotion through the encouragement of social participation, improvement of surroundings to facilitate healthy behaviors, and enhanced access to health services will improve the quality of life of elderly Okuma residents.

Value of Geographical Information Systems in Analyzing Geographic Accessibility to Inform Radiotherapy Planning: A Systematic Review.

PURPOSE: Vulnerable populations face geographical barriers in accessing radiotherapy (RT) facilities, resulting in heterogeneity of care received and cancer burden faced. We aimed to explore the current use of Geographical Information Systems (GIS) in access to RT and use these findings to create sustainable solutions against barriers for access in low- and middle-income countries. MATERIALS AND METHODS: A systematic review using the PRISMA search strategy was done for studies using GIS to explore outcomes among patients with cancer. Included studies were reviewed and classified into three umbrella categories of how GIS has been used in studying access to RT. RESULTS: Forty articles were included in the final review. Thirty-eight articles were set in high-income countries and two in upper-middle-income countries. Included studies were published from 2000 to 2020, and were comprised of patients with all-cancers combined, breast, colon, skin, lung, prostate, ovarian, and rectal carcinoma patients. Studies were categorized under three groups on the basis of how they used GIS in their analyses: to describe geographic access to RT, to associate geographic access to RT with outcomes, and for RT planning. Most studies fell under multiple categories. CONCLUSION: Although this field is relative nascent, there is a wide array of functions possible through GIS for RT planning, including identifying high-risk populations, improving access in high-need areas, and providing valuable information for future resource allocation. GIS should be incorporated in future studies, especially set in low- and middle-income countries, which evaluate access to RT.

Effects of dietary interventions on telomere dynamics.

Telomeres play a critical role in maintaining cellular fate through tight regulation of cell division and DNA damage or repair. Over the years, it is established that biological ageing is defined by a gradual derangement in functionality, productivity, and robustness of biological processes. The link between telomeres and ageing is highlighted when derangement in telomere biology often leads to premature ageing and concomitant accompaniment of numerous age-associated diseases. Unfortunately, given that ageing is a biologically complicated intricacy, measures to reduce morbidity and improve longevity are still largely in the infancy stage. Recently, it was discovered that dietary habits and interventions might play a role in promoting successful healthy ageing. The intricate relationship between dietary components and its potential to protect the integrity of telomeres may provide unprecedented health benefits and protection against age-related pathologies. However, more focused prospective and follow-up studies with and without interventions are needed to unequivocally link dietary interventions with telomere maintenance in humans. This review aims to summarise recent findings that investigate the roles of nutrition on telomere biology and provide enough evidence for further studies to consider the topic of nutrigenomics and its contributions toward healthy ageing and concomitant strategy against age-associated diseases.

Point-A vs. volume-based brachytherapy for the treatment of cervix cancer: A meta-analysis.

BACKGROUND & PURPOSE: To report disease-free survival (DFS) for volume-based and point-A based brachytherapy (BT) in locally advanced cervical cancer. MATERIALS & METHODS: We conducted a meta-analysis of studies assessing the effects of point-A and volume-based brachytherapy on 3-year DFS. Studies including stage I-IVA cervical cancer patients were included if standard treatment of concomitant chemo-radiotherapy and high-dose- or pulsed dose rate BT was delivered. The primary outcome was 3-year DFS, and secondary outcomes were 3-year local control (LC), 3-year overall survival (OS) and late toxicity. A random-effects subgroup meta-analysis was done. RESULTS: In total, 5499 studies were screened, of which 24 studies with 5488 patients were eligible. There was significant heterogeneity among point-A studies (1538 patients) (I2 = 82%, p < 0.05) relative to volume-based studies (3950 patients) (I2 = 58, p = 0.01). The 3-year DFS for point-A and volume-based studies were 67% (95% CI 60%-73%) and 79% (95% CI 76%-82%) respectively (p = 0.001). Three-year LC for point-A and volume-based studies were 86% (95% CI 81%-90%) and 92% (91%-94%) respectively (p = 0.01). The difference in 3-year OS (72% vs. 79%, p = 0.12) was not statistically significant. The proportion of prospectively enrolled patients was 23% for point-A studies and 33% for volume-based studies. There was no difference in late grade 3 or higher gastrointestinal (3% vs. 4%, p = 0.76) genitourinary toxicities (3% vs. 3% p = 0.45) between the two groups. CONCLUSION: Volume-based BT results in superior 3-year DFS and 3-year LC. In the absence of randomized trials, this meta-analysis provides the best evidence regarding transition to 3D planning.

Educational dialogue on public perception of nuclear radiation.

PURPOSE: Across the world, nuclear radiation and its effects on the population has been the topic of back-burner debates, given the strong emotional connotations involved. We believe that education is crucial for people to make informed decisions regarding nuclear energy. With a science-technology-society (STS) approach, a seminar-style educational module on Radiation and Society was formulated at Tembusu College, National University of Singapore (NUS) in 2015. This primarily aimed to equip students with the necessary analytical tools to assess evidence and thus, evaluate existing assumptions on radiation/nuclear power/nuclear energy, the effects on mankind and societal perception of radiation. METHODS: Radiation and Society was a seminar-style module which consisted of weekly 3-hour interactive sessions for 13 weeks. Throughout the semester, students were acquainted with themes and concepts related to radiation and society, such as the historical dimensions, radiation science, role in medicine, the psychology of radiation fear, existing radiation myths, complexities in radiation disaster response, communication of risks and emergency preparedness. Discussions during the sessions covered a variety of topics, including ionizing radiation as a result of nuclear fall-out, historical contextualization of nuclear fear, and uses of radiation in (bio)medicine, STS and science communication. Field visits to research reactors and cancer centers were arranged to showcase the diverse applications of nuclear radiation. Experts involved in various related spheres of influence shared their perspectives on matters such as technological developments in emergency preparedness, nuclear reactors, and societal impacts. RESULTS: The interactive facilitator-student sessions helped educate young minds about nuclear radiation. A post-course survey was conducted to obtain opinions of students on their perceptions of reliability and safety of nuclear energy, effectiveness of the seminar, and where radiation ranked relative to alternative energy sources. Overall findings of the survey indicated that although nuclear energy was perceived as a safe and reliable substitute, renewable energy was considered a better option. Participants felt that, as per the learning objectives, the sessions were effective in improving awareness regarding nuclear energy. CONCLUSION: This seminar-style module equipped students with the analytical tools required to critically assess sources of knowledge and social perceptions of radiation. In addition to the concluding perceptions toward nuclear energy from the post-course survey, a pre-module/course survey to reveal changes in student attitudes is planned to aid refinement of the course in future iterations. Such educational efforts will allow students to be aware of both the pros and cons of nuclear radiation and thus, construct informed opinions.

Investigations on the new mechanism of action for acetaldehyde-induced clastogenic effects in human lung fibroblasts.

Acetaldehyde (AA) has been classified as a probable human carcinogen by the International Agency for Research on Cancer (IARC, WHO) and by the US Environmental Protection Agency due to its ability to cause tumours following inhalation or alcohol consumption in animals. Humans are constantly exposed to AA through inhalation from the environment through cigarette smoke, vehicle fumes and industrial emissions as well as by persistent alcohol ingestion. Individuals with deficiencies in the enzymes that are involved in the metabolism of AA are more susceptible to its toxicity and constitute a vulnerable human population. Studies have shown that AA induces DNA damage and cytogenetic abnormalities. A study was undertaken to elucidate the clastogenic effects induced by AA and any preceding DNA damage that occurs in normal human lung fibroblasts as this will further validate the detrimental effects of inhalation exposure to AA. AA exposure induced DNA damage, involving DNA double strand breaks, which could possibly occur at the telomeric regions as well, resulting in a clastogenic effect and subsequent genomic instability, which contributed to the cell cycle arrest. The clastogenic effect induced by AA in human lung fibroblasts was evidenced by micronuclei induction and chromosomal aberrations, including those at the telomeric regions. Co-localisation between the DNA double strand breaks and telomeric regions was observed, suggesting possible induction of DNA double strand breaks due to AA exposure at the telomeric regions as a new mechanism beyond the clastogenic effect of AA. From the cell cycle profile following AA exposure, a G2/M phase arrest and a decrease in cell viability were also detected. Therefore, these effects due to AA exposure via inhalation may have implications in the development of carcinogenesis in humans.

α-ZrP Nanoreinforcement Overcomes the Trade-Off between Phosphoric Acid Dopability and Thermomechanical Properties: Nanocomposite HTPEM with Stable Fuel Cell Performance.

In recent times, high-temperature polymer electrolyte membranes (HTPEMs) have emerged as viable alternatives to the Nafion-based low-temperature-operated polymer electrolyte membrane fuel cells. This is owing to their higher tolerance to fuel impurities, efficient water management, and higher cathode kinetics. However, the most efficacious HTPEMs such as poly(benzimidazole) (PBI) or 2,5-poly(benzimidazole) (ABPBI), which rely on the extent of phosphoric acid (PA) doping level for fuel cell performance, suffer from poor mechanical properties at higher acid doping levels and dopant leaching during continuous operation. To overcome these issues, we report the synthesis of ABPBI membranes and fabrication of ABPBI-zirconium pyrophosphate (α-ZrP)-based nanocomposite membranes by an ex situ methodology using methane sulfonic acid as the solvent. The incorporation of hydrophilic α-ZrP into the membrane resulted in higher dopability of PA (6.5 mol) and proton conductivity (46 mS/cm) of the membranes (10 wt % of α-ZrP) as against the corresponding values of 3.6 mol and 27 mS/cm, respectively, for the pristine membrane. More remarkably, these property improvements could be achieved while simultaneously augmenting the thermomechanical properties and oxidative stability of the membranes. The unit-cell tests showed a marked improvement in the maximum power density for the nanocomposite membrane (335 mW/cm2 at 10 wt % α-ZrP content) over the pristine ABPBI membrane (200 mW/cm2). We also report for the first time the feasibility of a 100 W HTPEM fuel cell (HTPEMFC) stack operated with the nanocomposite membrane with an active area of 39 cm2. The HTPEMFC stack delivered a stable voltage and power output, with a voltage drop rate of 0.84 µV/h over a run time of 730 h.