A Risk-Adjusted Control Chart to Evaluate Intensity Modulated Radiation Therapy Plan Quality

Purpose: This study aimed to develop a quality control framework for intensity modulated radiation therapy plan evaluations that can account for variations in patient- and treatment-specific risk factors. Methods and Materials: Patient-specific risk factors, such as a patient’s anatomy and tumor dose requirements, affect organs-at-risk (OARs) dose-volume histograms (DVHs), which in turn affects plan quality and can potentially cause adverse effects. Treatment-specific risk factors, such as the use of chemotherapy and surgery, are clinically relevant when evaluating radiation therapy planning criteria. A risk-adjusted control chart was developed to identify unusual plan quality after accounting for patient- and treatment-specific risk factors. In this proof of concept, 6 OAR DVH points and average monitor units serve as proxies for plan quality. Eighteen risk factors are considered for modeling quality: planning target volume (PTV) and OAR cross-sectional areas; volumes, spreads, and surface areas; minimum and centroid distances between OARs and the PTV; 6 PTV DVH points; use of chemotherapy; and surgery. A total of 69 head and neck cases were used to demonstrate the application of risk-adjusted control charts, and the results were compared with the application of conventional control charts. Results: The risk-adjusted control chart remains robust to interpatient variations in the studied risk factors, unlike the conventional control chart. For the brainstem, the conventional chart signaled 4 patients with unusual (out-of-control) doses to 2% brainstem volume. However, the adjusted chart did not signal any plans after accounting for their risk factors. For the spinal cord doses to 2% brainstem volume, the conventional chart signaled 2 patients, and the adjusted chart signaled a separate patient after accounting for their risk factors. Similar adjustments were observed for the other DVH points when evaluating brainstem, spinal cord, ipsilateral parotid, and average monitor units. The adjustments can be directly attributed to the patient- and treatment-specific risk factors. Conclusions: A risk-adjusted control chart was developed to evaluate plan quality, which is robust to variations in patient- and treatment-specific parameters

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Comparative Analysis of US Guidelines for the Management of Cutaneous Squamous Cell and Basal Cell Carcinoma

Background. This study presents a comparative analysis of recently published guidelines to manage cutaneous squamous cell carcinoma (cSCC) and cutaneous basal cell carcinoma (cBCC) within the United States (US). Methods. A PubMed database search was performed for the time period between June 1, 2016, and December 1, 2022. A comprehensive comparison was performed in the following clinical interest areas: staging and risk stratification, management of primary tumor and regional nodes with curative intent, and palliative treatment. Results. Guidelines from 3 organizations were analyzed: the American Academy of Dermatology (AAD), the National Comprehensive Cancer Network (NCCN), and the American Society for Radiation Oncology (ASTRO). The guidelines used different methodologies to grade evidence, making comparison difficult. There was agreement that surgery is the preferred treatment for curative cBCC and cSCC. For patients ineligible for surgery, there was a consensus to recommend definitive radiation. AAD and NCCN recommended consideration of other topical modalities in selected low-risk cBCC. Postoperative radiation therapy (PORT) was uniformly recommended in patients with positive margins that could not be cleared with surgery and in patients with nerve invasion. The definition and extent of nerve invasion varied. All guidelines recommended surgery as the primary treatment in patients with lymph node metastases in a curative setting. The criteria used for PORT varied; NCCN and ASTRO used lymph node size, number of nodes, and extracapsular extension for recommending PORT. Both NCCN and ASTRO recommend consideration of systemic treatment along with PORT in patients with extracapsular extension. Conclusion: US guidelines provide contemporary and complementary information on the management of cBCC and cSCC. There are opportunities for research, particularly in the areas of staging, indications for adjuvant treatment in curative settings, extent of nerve invasion and prognosis, and the role of systemic treatments in curative and palliative settings

Emergence of MR-Linac in Radiation Oncology: Successes and Challenges of Riding on the MRgRT Bandwagon

The special issue of JCM on “Advances of MRI in Radiation Oncology” provides a unique forum for scientific literature related to MR imaging in radiation oncology. This issue covered many aspects, such as MR technology, motion management, economics, soft-tissue–air interface issues, and disease sites such as the pancreas, spine, sarcoma, prostate, head and neck, and rectum from both camps—the Unity and MRIdian systems. This paper provides additional information on the success and challenges of the two systems. A challenging aspect of this technology is low throughput and the monumental task of education and training that hinders its use for the majority of therapy centers. Additionally, the cost of this technology is too high for most institutions, and hence widespread use is still limited. This article highlights some of the difficulties and how to resolve them

Management of salivary gland malignancies: current and developing therapies

Salivary gland tumors are rare, clinically diverse neoplasms that represent less than 1% of all malignancies. In locoregional recurrent or metastatic disease, systemic therapy is the standard approach. While numerous small phase II studies have evaluated the activity of cytotoxic agents, either alone or in combination, the response rates are generally modest with objective response rates ranging from 15%–50%. Duration of response is cited in the range of 6–9 months. Given this, further evaluation of novel therapies is mandatory in these diseases. With the emergence of molecular targeted therapy, these tumors become optimal candidates for trials of investigational drugs and established drugs for new indications. Of note, given the often indolent nature of disease, only patients with progressive disease should be enrolled and treated on these clinical trials. Study designs must incorporate stringent inclusion criteria to enable accurate reporting of disease response and stabilization. With dedication and co-operation, patients with these rare neoplasms can be accrued to clinical trials and the establishment of new treatment guidelines will be forthcoming

Adaptability and Resilience of Academic Radiation Oncology Personnel and Procedures during COVID-19 Pandemic

Background: A comprehensive response to the unprecedented SARS-CoV-2 (COVID-19) challenges for public health and its impact on radiation oncology patients and personnel for resilience and adaptability is presented. Methods: The general recommendations included working remotely when feasible, implementation of screening/safety and personal protective equipment (PPE) guidelines, social distancing, regular cleaning of treatment environment, and testing for high-risk patients/procedures. All teaching conferences, tumor boards, and weekly chart rounds were conducted using a virtual platform. Additionally, specific recommendations were given to each section to ensure proper patient treatments. The impact of these measures, especially adaptability and resilience, were evaluated through specific questionnaire surveys. Results: These comprehensive COVID-19-related measures resulted in most staff expressing a consistent level of satisfaction in regard to personal safety, maintaining a safe work environment, continuing quality patient care, and continuing educational activities during the pandemic. There was a significant reduction in patient treatments and on-site patient visits with an appreciable increase in the number of telemedicine e-visits. Conclusions: Survey results demonstrated substantial adaptability and resilience, including in the rapid recovery of departmental activities during the reactivation phase. In the event of a future public health emergency, the measures implemented may be adopted with good outcomes by radiation oncology departments across the globe