Radiation Dose-Volume-Response Relationships for Adverse Events in Childhood Cancer Survivors: Introduction to the Scientific Issues in PENTEC.

At its very core, radiation oncology involves a trade-off between the benefits and risks of exposing tumors and normal tissue to relatively high doses of ionizing radiation. This trade-off is particularly critical in childhood cancer survivors (CCS), in whom both benefits and risks can be hugely consequential due to the long life expectancy if the primary cancer is controlled. Estimating the normal tissue-related risks of a specific radiation therapy plan in an individual patient relies on predictive mathematical modeling of empirical data on adverse events. The Pediatric Normal-Tissue Effects in the Clinic (PENTEC) collaborative network was formed to summarize and, when possible, to synthesize dose-volume-response relationships for a range of adverse events incident in CCS based on the literature. Normal-tissue clinical radiation biology in children is particularly challenging for many reasons: (1) Childhood malignancies are relatively uncommon-constituting approximately 1% of new incident cancers in the United States-and biologically heterogeneous, leading to many small series in the literature and large variability within and between series. This creates challenges in synthesizing data across series. (2) CCS are at an elevated risk for a range of adverse health events that are not specific to radiation therapy. Thus, excess relative or absolute risk compared with a reference population becomes the appropriate metric. (3) Various study designs and quantities to express risk are found in the literature, and these are summarized. (4) Adverse effects in CCS often occur 30, 50, or more years after therapy. This limits the information content of series with even very extended follow-up, and lifetime risk estimates are typically extrapolations that become dependent on the mathematical model used. (5) The long latent period means that retrospective dosimetry is required, as individual computed tomography-based radiation therapy plans gradually became available after 1980. (6) Many individual patient-level factors affect outcomes, including age at exposure, attained age, lifestyle exposures, health behaviors, other treatment modalities, dose, fractionation, and dose distribution. (7) Prospective databases with individual patient-level data and radiation dosimetry are being built and will facilitate advances in dose-volume-response modeling. We discuss these challenges and attempts to overcome them in the setting of PENTEC.

Reporting Standards for Complication Studies of Radiation Therapy for Pediatric Cancer: Lessons From PENTEC.

The major aim of Pediatric Normal Tissue Effects in the Clinic (PENTEC) was to synthesize quantitative published dose/-volume/toxicity data in pediatric radiation therapy. Such systematic reviews are often challenging because of the lack of standardization and difficulty of reporting outcomes, clinical factors, and treatment details in journal articles. This has clinical consequences: optimization of treatment plans must balance between the risks of toxicity and local failure; counseling patients and their parents requires knowledge of the excess risks encountered after a specific treatment. Studies addressing outcomes after pediatric radiation therapy are particularly challenging because: (a) survivors may live for decades after treatment, and the latency time to toxicity can be very long; (b) children's maturation can be affected by radiation, depending on the developmental status of the organs involved at time of treatment; and (c) treatment regimens frequently involve chemotherapies, possibly modifying and adding to the toxicity of radiation. Here we discuss: basic reporting strategies to account for the actuarial nature of the complications; the reporting of modeling of abnormal development; and the need for standardized, comprehensively reported data sets and multivariate models (ie, accounting for the simultaneous effects of radiation dose, age, developmental status at time of treatment, and chemotherapy dose). We encourage the use of tools that facilitate comprehensive reporting, for example, electronic supplements for journal articles. Finally, we stress the need for clinicians to be able to trust artificial intelligence models of outcome of radiation therapy, which requires transparency, rigor, reproducibility, and comprehensive reporting. Adopting the reporting methods discussed here and in the individual PENTEC articles will increase the clinical and scientific usefulness of individual reports and associated pooled analyses.

Advances in personalized radiotherapy.

Radiotherapy is a mainstay of cancer treatment. The clinical response to radiotherapy is heterogeneous, from a complete response to early progression. Recent studies have explored the importance of patient characteristics in response to radiotherapy. In this editorial, we invite contributions for a BMC Cancer collection of articles titled 'Advances in personalized radiotherapy' towards the improvement of treatment response.

Second Chance for Cure: Stereotactic Ablative Radiotherapy in Oligometastatic Disease.

PURPOSE: Local ablative therapy, such as radiotherapy or surgery, plays a key role in treatment of patients with oligometastatic disease. Stereotactic ablative body radiotherapy (SABR) comes to the fore as a safe and effective treatment for patients with a limited number of metastases, even those located in hard-to-reach body sites. Many researchers have suggested that metastatsis-directed therapy could improve long-term progression-free survival (PFS) and overall survival (OS) in patients with oligometastases. PATIENTS AND METHODS: This was a retrospective, single-arm, observational study conducted between July 2015 and February 2022. In our institute, 60 patients with controlled primary tumors and one to five metastases were treated with SABR. Prescribed radiation doses ranged from 12 to 60 Gy administered in one to seven fractions. We aimed to determine whether metastatic-directed therapy using SABR for all oligometastases affects OS and PFS and whether the primary tumor or metastatic site influences OS/PFS. RESULTS: The most common primary malignancy types were prostate (n = 14), colorectal (n = 10), lung (n = 7), and breast cancers (n = 6). The median follow-up was 30 months, ranging from 9 to 79. The 1-, 3-, and 5-year PFS and OS rates were 54.9%, 37.0%, and 37.0% and 98.3%, 84.4%, and 73.8%, respectively, and the median time to first progression was 15 (range, 2-32) months. Twenty-four (40%) patients had no recurrence. In our analysis, primary tumor site was not an independent prognostic factor. The metastatic site may influence on patient outcome in cases of localized bone and liver metastases. CONCLUSION: In our retrospective analysis, SABR was associated with favorable levels of PFS and OS in patients with oligometastases. The limitations of our study were lacking high-level evidence, and randomized studies to compare SABR and palliative standard of care are mandatory.

Imaging Assessment of Radiation Therapy-Related Normal Tissue Injury in Children: A PENTEC Visionary Statement.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium has made significant contributions to understanding and mitigating the adverse effects of childhood cancer therapy. This review addresses the role of diagnostic imaging in detecting, screening, and comprehending radiation therapy-related late effects in children, drawing insights from individual organ-specific PENTEC reports. We further explore how the development of imaging biomarkers for key organ systems, alongside technical advancements and translational imaging approaches, may enhance the systematic application of imaging evaluations in childhood cancer survivors. Moreover, the review critically examines knowledge gaps and identifies technical and practical limitations of existing imaging modalities in the pediatric population. Addressing these challenges may expand access to, minimize the risk of, and optimize the real-world application of, new imaging techniques. The PENTEC team envisions this document as a roadmap for the future development of imaging strategies in childhood cancer survivors, with the overarching goal of improving long-term health outcomes and quality of life for this vulnerable population.

Safety and Tolerability of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy.

Importance: In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy. Objective: To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach). Design, Setting, and Participants: This cohort study included adults with solid tumors treated with a 1.5-T MR-Linac enrolled in Multi Outcome Evaluation for Radiation Therapy Using the MR-Linac (MOMENTUM), a large prospective international study of MRgRT between February 2019 and October 2021. Included were adults with solid tumors treated with a 1.5-T MR-Linac. Data were collected in Canada, Denmark, The Netherlands, United Kingdom, and the US. Data were analyzed in August 2023. Exposure: All patients underwent MRgRT using a 1.5-T MR-Linac. Radiation prescriptions were consistent with institutional standards of care. Main Outcomes and Measures: Patterns of care, tolerability, and technical feasibility (ie, treatment completed as planned). Acute high-grade radiotherapy-related toxic effects (ie, grade 3 or higher toxic effects according to Common Terminology Criteria for Adverse Events version 5.0) occurring within the first 3 months after treatment delivery. Results: In total, 1793 treatment courses (1772 patients) were included (median patient age, 69 years [range, 22-91 years]; 1384 male [77.2%]). Among 41 different treatment sites, common sites were prostate (745 [41.6%]), metastatic lymph nodes (233 [13.0%]), and brain (189 [10.5%]). ATS was used in 1050 courses (58.6%). MRgRT was completed as planned in 1720 treatment courses (95.9%). Patient withdrawal caused 5 patients (0.3%) to discontinue treatment. The incidence of radiotherapy-related grade 3 toxic effects was 1.4% (95% CI, 0.9%-2.0%) in the entire cohort and 0.4% (95% CI, 0.1%-1.0%) in the subset of patients treated with ATS. There were no radiotherapy-related grade 4 or 5 toxic effects. Conclusions and Relevance: In this cohort study of patients treated on a 1.5-T MR-Linac, radiotherapy was safe and well tolerated. Online adaptation of the radiation plan at each treatment session to account for anatomic variations was associated with a low risk of acute grade 3 toxic effects.

"Current", "heated rods", and "hot vapour": why patients refuse radiotherapy as a treatment modality for cancer in northern Sri Lanka.

PURPOSE: Significant proportions of patients either refuse or discontinue radiotherapy, even in the curative setting, leading to poor clinical outcomes. This study explores patient perceptions that underlie decisions to refuse/discontinue radiotherapy at a cancer care facility in northern Sri Lanka. METHODS: An exploratory descriptive qualitative study was carried out among 14 purposively selected patients with cancer who refused/discontinued radiotherapy. In-depth semi-structured interviews were transcribed in Tamil, translated into English, coded, and thematically analyzed. RESULTS: All participants referred to radiotherapy as "current" with several understanding the procedure to involve electricity, heat, or hot vapour. Many pointed to gaps in information provided by healthcare providers, who were perceived to focus on side effects without explaining the procedure. In the absence of these crucial details, patients relied on family members and acquaintances for information, often based on second or third-hand accounts of experiences with radiotherapy. Many felt pressured by family to refuse radiation, feared radiation, or felt ashamed to ask questions, while for others COVID-19 was an impediment. All but three participants regretted their decision, claiming they would recommend radiation to patients with cancer, especially when it is offered with curative intent. CONCLUSION: Patients with cancer who refused/discontinued radiation therapy have significant information needs. While human resource deficits need to be addressed in low-resource settings like northern Sri Lanka, providing better supportive cancer care could improve clinical outcomes and save healthcare resources that would otherwise be wasted on patient preparation for radiotherapy.

[Spatially fractionated radiotherapy : introduction into clinical practice]. / Radiothérapie fractionnée dans l'espace : introduction en pratique clinique.

Spatially fractionated radiotherapy is a new concept involving partial irradiation of tumor volumes. Different techniques are described: mini-beam and micro-beam radiotherapy (pre-clinical) and LATTICE radiotherapy (L-RT) (clinical). Although L-RT is emergent in clinical practice and its evidence is still limited, it has still revealed excellent outcomes. At least three clinical situations can be discussed: definitive palliative radiotherapy, dose escalation (boost) or salvage radiotherapy. The interaction between L-RT and the immune system is still under investigation. Preclinical observations have already demonstrated a strong interaction, with tumor response dependent on immune system stimulation and the generation of an abscopal effect.

La radiothérapie fractionnée dans l'espace est un nouveau concept consistant en une irradiation partielle des volumes tumoraux. Plusieurs techniques sont ainsi décrites : les radiothérapies mini-beam et micro-beam (pré-clinique) et la radiothérapie LATTICE (L-RT) (clinique). Bien que la L-RT soit relativement nouvelle dans la pratique clinique et que les preuves quant à son utilisation soient encore limitées, elle montre des résultats prometteurs. Au moins trois situations cliniques peuvent être examinées en détail : la radiothérapie palliative définitive, l'escalade de dose (boost) ou encore la radiothérapie de sauvetage. L'interaction entre la L-RT et le système immunitaire est encore en cours d'investigation, mais des observations précliniques ont déjà démontré une interaction forte, avec notamment la dépendance de la réponse tumorale à la stimulation du système immunitaire et la génération d'un effet abscopal.

A review and bibliometric analysis of global research on proton radiotherapy.

Proton beam therapy (PBT) has great advantages as tumor radiotherapy and is progressively becoming a more prevalent choice for individuals undergoing radiation therapy. The objective of this review is to pinpoint collaborative efforts among countries and institutions, while also exploring the hot topics and future outlook in the field of PBT. Data from publications were downloaded from the Web of Science Core Collection. CiteSpace and Excel 2016 were used to conduct the bibliometric and knowledge map analysis. A total of 6516 publications were identified, with the total number of articles steadily increasing and the United States being the most productive country. Harvard University took the lead in contributing the highest number of publications. Paganetti Harald published the most articles and had the most cocitations. PHYS MED BIOL published the greatest number of PBT-related articles, while INT J RADIAT ONCOL received the most citations. Paganetti Harald, 2012, PHYS MED BIOL can be classified as classic literature due to its high citation rate. We believe that research on technology development, dose calculation and relative biological effectiveness were the knowledge bases in this field. Future research hotspots may include clinical trials, flash radiotherapy, and immunotherapy.

Mechanisms of Action in FLASH Radiotherapy: A Comprehensive Review of Physicochemical and Biological Processes on Cancerous and Normal Cells.

The advent of FLASH radiotherapy (FLASH-RT) has brought forth a paradigm shift in cancer treatment, showcasing remarkable normal cell sparing effects with ultra-high dose rates (>40 Gy/s). This review delves into the multifaceted mechanisms underpinning the efficacy of FLASH effect, examining both physicochemical and biological hypotheses in cell biophysics. The physicochemical process encompasses oxygen depletion, reactive oxygen species, and free radical recombination. In parallel, the biological process explores the FLASH effect on the immune system and on blood vessels in treatment sites such as the brain, lung, gastrointestinal tract, skin, and subcutaneous tissue. This review investigated the selective targeting of cancer cells and the modulation of the tumor microenvironment through FLASH-RT. Examining these mechanisms, we explore the implications and challenges of integrating FLASH-RT into cancer treatment. The potential to spare normal cells, boost the immune response, and modify the tumor vasculature offers new therapeutic strategies. Despite progress in understanding FLASH-RT, this review highlights knowledge gaps, emphasizing the need for further research to optimize its clinical applications. The synthesis of physicochemical and biological insights serves as a comprehensive resource for cell biology, molecular biology, and biophysics researchers and clinicians navigating the evolution of FLASH-RT in cancer therapy.

Quantification of the environmental impact of radiotherapy and associated secondary human health effects: a multi-institutional retrospective analysis and simulation.

BACKGROUND: The health-care industry is a substantial contributor to global greenhouse gas emissions, yet the specific environmental impact of radiotherapy, a cornerstone of cancer treatment, remains under-explored. We aimed to quantify the emissions associated with the delivery of radiotherapy in the USA and propose a framework for reducing the environmental impact of oncology care. METHODS: In this multi-institutional retrospective analysis and simulation study, we conducted a lifecycle assessment of external beam radiotherapy (EBRT) for ten anatomical disease sites, adhering to the International Organization for Standardization's standards ISO 14040 and ISO 14044. We analysed retrospective data from Jan 1, 2017, to Oct 1, 2023, encompassing patient and staff travel, medical supplies, and equipment and building energy use associated with the use of EBRT at four academic institutions in the USA. The primary objective was to measure the environmental impacts across ten categories: greenhouse gases (expressed as kg of carbon dioxide equivalents [CO2e]), ozone depletion, smog formation, acidification, eutrophication, carcinogenic and non-carcinogenic potential, respiratory effects, fossil fuel depletion, and ecotoxicity. Human health effects secondary to these environmental impacts were also estimated as disability-adjusted life years. We also assessed the potential benefits of hypofractionated regimens for breast and genitourinary (ie, prostate and bladder) cancers on US greenhouse gas emissions using an analytic model based on the 2014 US National Cancer Database for fractionation patterns and patient commute distances. FINDINGS: We estimated that the mean greenhouse gas emissions associated with a standard 25-fraction EBRT course were 4310 kg CO2e (SD 2910), which corresponded to 0·0035 disability-adjusted life years per treatment course. Transit and building energy usage accounted for 25·73% (1110 kg CO2e) and 73·95% of (3190 kg CO2e) of total greenhouse gas emissions, respectively, whereas supplies contributed only 0·32% (14 kg CO2e). Across the other environmental impact categories, most of the environmental impact also stemmed from patient transit and energy use within facilities, with little environmental impact contributed by supplies used. Hypofractionated treatment simulations suggested a substantial reduction in greenhouse gas emissions-by up to 42% for breast and 77% for genitourinary cancer-and environmental impacts more broadly. INTERPRETATION: This comprehensive lifecycle assessment of EBRT delineates the environmental and secondary health impacts of radiotherapy, and underscores the urgent need for sustainable practices in oncology. The findings serve as a reference for future decarbonisation efforts in cancer care and show the potential environmental benefits of modifying treatment protocols (when clinical equipoise exists). They also highlight strategic opportunities to mitigate the ecological footprint in an era of escalating climate change and increasing cancer prevalence. FUNDING: Mount Zion Health Fund.

Dosimetric Validation of Treatment Planning System for Volumetric Modulated Arc Therapy Using AAPM Medical Physics Practice Guideline 5.b.

AIM: To assess the precision of dose calculations for Volumetric Modulated Arc Therapy (VMAT) using megavoltage (MV) photon beams, we validated the accuracy of two algorithms: AUROS XB and Analytical Anisotropic Algorithm (AAA). This validation will encompass both flattening filter (FF) and flattening filter-free beam (FFF) modes, using AAPM Medical Physics Practice Guideline (MPPG 5b). MATERIALS AND METHODS: VMAT validation tests were generated for 6 MV FF and 6 MV FFF beams using the AAA and AXB algorithms in the Eclipse V.15.1 treatment planning system (TPS). Corresponding measurements were performed on a linear accelerator using a diode detector and a radiation field analyzer. Point dose (PD) and in-vivo measurements were conducted using an A1SL ion chamber and (TLD) from Thermofisher, respectively. The Rando Phantom was employed for end-to-end (E2E) tests. RESULTS: The mean difference (MD) between the TPS-calculated values and the measured values for the PDD and output factors were within 1% and 0.5%, respectively, for both 6 MV FF and 6 MV FFF. In the TG 119 sets, the MD for PD with both AAA and AXB was <0.9%. For the TG 244 sets, the minimum, maximum, and mean deviations in PD for both 6 MV FF and 6 MV FFF beams were 0.3%, 1.4% and 0.8% respectively. In the E2E test, using the Rando Phantom, the MD between the TLD dose and the TPS dose was within 0.08% for both 6 MV FF (p=1.0) and 6 MV FFF (0.018) beams. CONCLUSION: The accuracy of the TPS and its algorithms (AAA and AXB) has been successfully validated. The recommended tests included in the VMAT/IMRT validation section proved invaluable for verifying the PDD, output factors, and the feasibility of complex clinical cases. E2E tests were instrumental in validating the entire workflow from CT simulation to treatment delivery.

Effectiveness and Safety of Carbon Ion Radiotherapy in Solid Tumors: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aimed to investigate the effectiveness of carbon ion radiotherapy (CIRT) compared to that of conventional radiotherapy in patients with various types of solid tumors. MATERIALS AND METHODS: We systematically searched eight electronic databases from inception until August 2022 in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The comparative effectiveness of the different treatment options was assessed by a random-effects meta-analysis. RESULTS: This review included 34 comparative studies and three treatment groups. Overall, the meta-analysis indicated comparable local control rates between the CIRT and control groups [pooled risk ratio (RR)=1.02, 95% confidence interval (CI) 0.90-1.15]. The local control rate in the CIRT group was higher than that in the photon therapy group, but slightly lower than that in the proton radiation therpy (PRT) group. Additionally, the CIRT group had significantly higher overall survival (OS) (RR=1.19, 95% CI=1.01-1.42) and progression-free survival (PFS) (RR=1.50, 95% CI=1.01-2.21) rates compared to the control group. In the subgroup analysis, survival rates were similar between the CIRT and PRT groups. CONCLUSION: CIRT was associated with improved toxicity, local tumor control, OS, and PFS compared to conventional treatments. Therefore, CIRT was found to be a safe and effective option for achieving local control in patients with solid tumors.

Radiation Oncology Training in the Philippines: Bridging Gaps for Improved Cancer Care in Low- and Middle-Income Countries.

PURPOSE: Radiation oncology in the Philippines, a large lower- and middle-income country in Southeast Asia, is facing a critical shortage in manpower, with only 113 radiation oncologists (ROs) over 55 radiotherapy (RT) centers serving 100 million population. Paramount to workforce expansion is ensuring that training programs can produce adequately trained specialists. In this study, we describe the current state of radiation oncology training programs in the Philippines. METHODS: This is a cross-sectional observational analysis of the nine radiation oncology residency training programs in the Philippines. Data were collected from a survey of the program directors, the Philippine Radiation Oncology Society database, and a PubMed literature search. RESULTS: Eight of the nine programs are in the National Capital Region. Since program standardization in 2005, there have been 82 four-year residency graduates, with up to 18 new graduates annually. Faculty-to-trainee ratio ranges from 0.5 to 2.67. In terms of technology, all programs have intensity-modulated RT and high-dose-rate brachytherapy, but only six are equipped with computed tomography-based image guidance and stereotactic capabilities. Clinical education schemes vary per institution regarding curriculum implementation, resident activities, and methods of evaluation. Required resident case logs are not met for lung, GI, genitourinary, bone and soft tissue, and hematologic malignancies. In total, there are only 22 resident-led publications from 10 unique individuals in two training programs. CONCLUSION: Program expansions are warranted to meet the projected demand for ROs in the Philippines, but training programs must first improve key aspects of staffing, technology, clinical education, and research. Addressing training challenges related to resource limitations necessitates local and international collaborations with higher-capacity centers to bridge gaps for continued quality improvement with the aim of ultimately delivering better overall cancer care.

Fibroblast Activation Protein Inhibitor Tracers and Their Preclinical, Translational, and Clinical Status in China.

Quinoline-based fibroblast activation protein (FAP) inhibitors (FAPIs) have recently emerged as a focal point in global nuclear medicine, underscored by their promising applications in cancer theranostics and the diagnosis of various nononcological conditions. This review offers an in-depth summary of the existing literature on the evolution and use of FAPI tracers in China, tracing their journey from preclinical to clinical research. Moreover, this review also assesses the diagnostic accuracy of FAPI PET for the most common cancers in China, analyzes its impact on oncologic management paradigms, and investigates the potential of FAP-targeted radionuclide therapy in patients with advanced or metastatic cancer. This review also summarizes studies using FAPI PET for nononcologic disorders in China. Thus, this qualitative overview presents a snapshot of China's engagement with FAPI tracers, aiming to guide future research endeavors.

Recent Advances in Radiotracers Targeting Novel Cancer-Specific Biomarkers in China: A Brief Overview.

Radiopharmaceuticals play a critical role in nuclear medicine, providing novel tools for specifically delivering radioisotopes for the diagnosis and treatment of cancers. As the starting point for developing radiopharmaceuticals, cancer-specific biomarkers are important and receive worldwide attention. This field in China is currently experiencing a rapid expansion, with multiple radiotracers targeting novel targets being developed and translated into clinical studies. This review provides a brief overview of the exploration of novel imaging targets, preclinical evaluation of their targeting ligands, and translational research in China from 2020 to 2023, for detecting cancer, guiding targeted therapy, and visualizing the immune microenvironment. We believe that China will play an even more important role in the development of nuclear medicine in the world in the future.

Nutritional Prognosis of Patients Submitted to Radiotherapy and Its Implications in Treatment.

Oncological patients show intense catabolic activity, as well as a susceptibility to higher nutritional risk and clinical complications. Thus, tools are used for monitoring prognosis. Our objective was to analyze the nutrition prognosis of patients who underwent radiotherapy, correlating it with outcomes and complications. We performed a retrospective transversal study based on secondary data from hospital records of patients who started radiotherapy between July 2022 and July 2023. We established Prognostic Scores through a combination of Prognostic Nutritional Index (PNI) and a Subjective Global Assessment (SGA), assessed at the beginning and end of treatment. Score 3 patients, with PNI ≤ 45.56 and an SGA outcome of malnutrition, initially presented a higher occurrence of odynophagia, later also being indicative of reduced diet volume, treatment interruption, and dysphagia. SGA alone showed sensitivity to altered diet volume, dysphagia, and xerostomia in the second assessment. Besides this, PNI ≤ 45.56 also indicated the use of alternative feeding routes, treatment interruption, and hospital discharge with more complications. We conclude that the scores could be used to indicate complications; however, further studies on combined biomarkers are necessary.

A high-resolution large-area detector for quality assurance in radiotherapy.

Hadron therapy is an advanced radiation modality for treating cancer, which currently uses protons and carbon ions. Hadrons allow for a highly conformal dose distribution to the tumour, minimising the detrimental side-effects due to radiation received by healthy tissues. Treatment with hadrons requires sub-millimetre spatial resolution and high dosimetric accuracy. This paper discusses the design, fabrication and performance tests of a detector based on Gas Electron Multipliers (GEM) coupled to a matrix of thin-film transistors (TFT), with an active area of 60 × 80 mm2 and 200 ppi resolution. The experimental results show that this novel detector is able to detect low-energy (40 kVp X-rays), high-energy (6 MeV) photons used in conventional radiation therapy and protons and carbon ions of clinical energies used in hadron therapy. The GEM-TFT is a compact, fully scalable, radiation-hard detector that measures secondary electrons produced by the GEMs with sub-millimetre spatial resolution and a linear response for proton currents from 18 pA to 0.7 nA. Correcting known detector defects may aid in future studies on dose uniformity, LET dependence, and different gas mixture evaluation, improving the accuracy of QA in radiotherapy.

Travel-Time Disparities in Access to Proton Beam Therapy for Cancer Treatment.

Importance: Proton beam therapy is an emerging radiotherapy treatment for patients with cancer that may produce similar outcomes as traditional photon-based therapy for many cancers while delivering lower amounts of toxic radiation to surrounding tissue. Geographic proximity to a proton facility is a critical component of ensuring equitable access both for indicated diagnoses and ongoing clinical trials. Objective: To characterize the distribution of proton facilities in the US, quantify drive-time access for the population, and investigate the likelihood of long commutes for certain population subgroups. Design, Setting, and Participants: This population-based cross-sectional study analyzed travel times to proton facilities in the US. Census tract variables in the contiguous US were measured between January 1, 2017, and December 31, 2021. Statistical analysis was performed from September to November 2023. Exposures: Drive time in minutes to nearest proton facility. Population totals and prevalence of specific factors measured from the American Community Survey: age; race and ethnicity; insurance, disability, and income status; vehicle availability; broadband access; and urbanicity. Main Outcomes and Measures: Poor access to proton facilities was defined as having a drive-time commute of at least 4 hours to the nearest location. Median drive time and percentage of population with poor access were calculated for the entire population and by population subgroups. Univariable and multivariable odds of poor access were also calculated for certain population subgroups. Results: Geographic access was considered for 327 536 032 residents of the contiguous US (60 594 624 [18.5%] Hispanic, 17 974 186 [5.5%] non-Hispanic Asian, 40 146 994 [12.3%] non-Hispanic Black, and 195 265 639 [59.6%] non-Hispanic White; 282 031 819 [86.1%] resided in urban counties). The median (IQR) drive time to the nearest proton facility was 96.1 (39.6-195.3) minutes; 119.8 million US residents (36.6%) lived within a 1-hour drive of the nearest proton facility, and 53.6 million (16.4%) required a commute of at least 4 hours. Persons identifying as non-Hispanic White had the longest median (IQR) commute time at 109.8 (48.0-197.6) minutes. Multivariable analysis identified rurality (odds ratio [OR], 2.45 [95% CI, 2.27-2.64]), age 65 years or older (OR, 1.09 [95% CI, 1.06-1.11]), and living below the federal poverty line (OR, 1.22 [1.20-1.25]) as factors associated with commute times of at least 4 hours. Conclusions and Relevance: This cross-sectional study of drive-time access to proton beam therapy found that disparities in access existed among certain populations in the US. These results suggest that such disparities present a barrier to an emerging technology in cancer treatment and inhibit equitable access to ongoing clinical trials.