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The unique optoelectronic properties of metal halide perovskite quantum dots (QDs) make them promising candidates for applications in light-emitting diodes (LEDs), scintillators, and other photonic devices. The automated micropipetting synthesis platform equipped with an optical reader enables the opportunity for high throughput synthesis and photoluminescent (PL) characterization of metal halide perovskite QDs for the first time. Here, we explore the compositional dependence of the PL behavior and stability of the combinatorial library of cesium lead halide (CsPbX3) perovskites QDs via the automated platform. To study the stability of synthesized QDs in the binary and ternary configurations, we study the time-dependent PL properties using previously developed machine learning analysis. To systematically explore the PL behavior in the ternary CsPbX3 QDs system, we introduce the Bayesian inference framework that allows the probabilistic fit of multiple models to the PL data and establishes both optimal model and model parameter robustly. Furthermore, these behaviors can be used as a control parameter for the navigation of the multidimensional compositional spaces in automated synthesis. This analysis shows the nonuniformity of the PL peak behavior in the ternary CsPbX3 QDs system. Further, the analysis confirms narrow size distribution and good quality of CsPbBr3 QDs alloyed with low concentrations of iodide and chloride. We note that Bayesian Inference fit parameters can be further used as a control signal for navigation of the chemical spaces in automated synthesis.

Purpose: To evaluate the prognostic significance of different descriptive parameters in head-and-neck cancer patients undergoing pretreatment [F-18] fluoro-D-glucose-positron emission tomography (FDG-PET) imaging. Patients and Methods: Head-and-neck cancer patients who underwent FDG-PET before a course of curative intent radiotherapy were retrospectively analyzed. FDG-PET imaging parameters included maximum (SUV(max)), and mean (SUV(mean)) standard uptake values, and total lesion glycolysis (TLG). Tumors and lymph nodes were defined on co-registered axial computed tomography (CT) slices. SUV(max) and SUV(mean) were measured within these anatomic regions. The relationships between pretreatment SUV(max), SUV(mean), and TLG for the primary site and lymph nodes were assessed using a univariate analysis for disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS). Kaplan-Meier survival curves were generated and compared via the log-rank method. SUV data were analyzed as continuous variables. Results: A total of 88 patients was assessed. Two-year OS, LRC, DMFS, and DFS for the entire cohort were 85%, 78%, 81%, and 70%, respectively. Median SUV(max) for the primary tumor and lymph nodes was 15.4 and 12.2, respectively. Median SUV(mean) for the primary tumor and lymph nodes was 7 and 5.2, respectively. Median TLG was 770. Increasing pretreatment SUV(mean) of the primary tumor was associated with decreased disease-free survival (p = 0.01). Neither SUV(max) in the primary tumor or lymph nodes nor TLG was prognostic for any of the clinical endpoints. Patients with pretreatment tumor SUV(mean) that exceeded the median value (7) of the cohort demonstrated inferior 2-year DFS relative to patients with SUV(mean) ≤ the median value of the cohort, 58% vs. 82%, respectively, p = 0.03. Conclusion: Increasing SUV(mean) in the primary tumor was associated with inferior DFS. Although not routinely reported, pretreatment SUV(mean) may be a useful prognostic FDG-PET parameter and should be further evaluated prospectively. [ABSTRACT FROM AUTHOR]

Background: Firearm violence is a significant public health issue. However, it is unclear if there is an association between the Social Vulnerability Index (SVI) and the intent of both fatal and nonfatal firearm injuries, and if these associations are modified by community race and ethnic composition. This study examines the association between community-level social vulnerability and firearm injury incidence in North Carolina (NC) using 2021-2022 emergency medical services (EMS) data. Additionally, it investigates how these associations vary by the intent of injury (assault, self-inflicted, and unintentional), and whether they are modified by community racial/ethnic composition., Methods: This cross-sectional study utilized NC EMS data, capturing firearm incidents from January 1, 2021, to December 31, 2022. The SVI from the Centers for Disease Control and Prevention (CDC) was used to assess community-level vulnerability. The SVI's racial/ethnic minority status component was removed for stratification analysis. Firearm injury rates were calculated per 100,000 population, and negative binomial regression models were used to estimate Incidence Rate Ratios (IRRs) for different SVI levels and intents of firearm injuries., Results: During the study period, we identified 7,250 EMS encounters at non-healthcare locations related to firearm injuries, encompassing 2,648 NC census tracts. Assault was the leading cause of firearm injuries (n = 3,799), followed by self-inflicted (n = 1,498), and unintentional injuries (n = 722). High-SVI communities had significantly higher rates of firearm injuries compared to low-SVI communities, particularly for assault-related injuries. When the minority status component was excluded from SVI, racial/ethnic minority status emerged as a significant modifier, with higher rates of firearm injuries being observed in communities with larger racial/ethnic minority populations., Conclusion: Community-level social vulnerability is significantly associated with firearm injury incidence, with the effect being more pronounced in racial/ethnic minority communities. These findings underscore the need for targeted public health interventions that address underlying social determinants of health (e.g., access to education) to reduce firearm violence. Future research should further explore the intersection of social vulnerability and racial/ethnic composition to develop effective prevention strategies., (© 2024. The Author(s).)

Enhancing the efficacy of immunotherapy in brain metastases (BrM) requires an improved understanding of the immune composition of BrM and how this is affected by radiation and dexamethasone. Our two-arm pilot study (NCT04895592) allocated 26 patients with BrM to either low (Arm A) or high (Arm B) dose peri-operative dexamethasone followed by pre-operative stereotactic radiosurgery (pSRS) and resection (n= 13 per arm). The primary endpoint, a safety analysis at 4 months, was met. The secondary clinical endpoints of overall survival, distant brain failure, leptomeningeal disease and local recurrence at 12-months were 66%, 37.3%, 6%, and 0% respectively and were not significantly different between arms (p= 0.7739, p= 0.3884, p= 0.3469). Immunological data from two large retrospective BrM datasets and confirmed by correlates from both arms of this pSRS prospective trial revealed that BrM CD8 T cells were composed of predominantly PD1+ TCF1+ stem-like and PD1+ TCF1-TIM3+ effector-like cells. Clustering of TCF1+ CD8 T cells with antigen presenting cells in immune niches was prognostic for local control, even without pSRS. Following pSRS, CD8 T cell and immune niche density were transiently reduced compared to untreated BrM, followed by a rebound 6+ days post pSRS with an increased frequency of TCF1- effector-like cells. In sum, pSRS is safe and therapeutically beneficial, and these data provide a framework for how pSRS may be leveraged to maximize intracranial CD8 T cell responses., (© 2024. The Author(s).)

Advances in the multidisciplinary care of early stage resectable NSCLC (rNSCLC) are emerging at an unprecedented pace. Numerous phase 3 trials produced results that have transformed patient outcomes for the better, yet these findings also require important modifications to the patient treatment journey trajectory and reorganization of care pathways. Perhaps, most notably, the need for multispecialty collaboration for this patient population has never been greater. These rapid advances have inevitably left us with important gaps in knowledge for which definitive answers will only become available in several years. To this end, the International Association for the Study of Lung Cancer commissioned a diverse multidisciplinary international expert panel to evaluate the current landscape and provide diagnostic, staging, and therapeutic recommendations for patients with rNSCLC, with particular emphasis on patients with American Joint Committee on Cancer-Union for International Cancer Control TNM eighth edition stages II and III disease. Using a team-based approach, we generated 19 recommendations, of which all but one achieved greater than 85% consensus among panel members. A public voting process was initiated, which successfully validated and provided qualitative nuance to our recommendations. Highlights include the following: (1) the critical importance of a multidisciplinary approach to the evaluation of patients with rNSCLC driven by shared clinical decision-making of a multispecialty team of expert providers; (2) biomarker testing for rNSCLC; (3) a preference for neoadjuvant chemoimmunotherapy for stage III rNSCLC; (4) equipoise regarding the optimal management of patients with stage II between upfront surgery followed by adjuvant therapy and neoadjuvant or perioperative strategies; and (5) the robust preference for adjuvant targeted therapy for patients with rNSCLC and sensitizing EGFR and ALK tumor alterations. Our primary goals were to provide practical recommendations sensitive to the global differences in biology and resources for patients with rNSCLC and to provide expert consensus guidance tailored to the individualized patient needs, goals, and preferences in their cancer care journey as these are areas where physicians must make daily clinical decisions in the absence of definitive data. These recommendations will continue to evolve as the treatment landscape for rNSCLC expands and more knowledge is acquired on the best therapeutic approach in specific patient and disease subgroups., Competing Interests: Disclosure Dr. Spicer reports receiving grants or contracts from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Amgen, Roche, Regeneron, and Pfizer; consulting fees from AstraZeneca, Bristol-Myers Squibb, Eisai, Daiichi Sankyo, and Merck Sharp & Dohme; honoraria from AstraZeneca, Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, and Pfizer; meeting support from AstraZeneca, Bristol-Myers Squibb, and Merck Sharp & Dohme; data safety monitoring board for AstraZeneca; and receipt of other services from AstraZeneca, Bristol-Myers Squibb, and Merck Sharp & Dohme, outside the submitted work. Dr. Cascone reports receiving speaker fees and/or honoraria from the American Society for Clinical Oncology Post, AstraZeneca, Bio Ascend, Bristol-Myers Squibb, Clinical Care Options, IDEOlogy Health, Medical Educator Consortium, Medscape, OncLive, PEAK Medical, PeerView, Physicians' Education Resource, Society for Immunotherapy of Cancer, and Targeted Oncology; advisory role/consulting fees from Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Mark Foundation for Cancer Research, Merck, oNKo-innate, Pfizer, RAPT Therapeutics, and Regeneron; and institutional research funding from AstraZeneca and Bristol-Myers Squibb, outside the submitted work. Dr.Ahn reports receiving consulting fees from AstraZeneca, Alpha Pharmaceuticals, Genxin, and Pfizer; and honoraria from Takeda, Roche, Merck, Merck Sharp & Dohme, AstraZeneca, Amgen, Boronoi, Arcus, Daiichi Sankyo, Bayer, and Janssen, outside the submitted work. Dr.Dacic reports receiving consulting fees from AstraZeneca, Genentech, and Medscape, outside the submitted work. Dr. Felip reports receiving consulting fees from AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Genmab, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Turning Point, and Daiichi Sankyo; honoraria from Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, PeerVoice, Pfizer, Sanofi, Takeda, and Touch Oncology; travel support from AstraZeneca, Janssen, and Roche; and other from Grifols as an independent member of the board, outside the submitted work. Dr. Forde reports receiving grants or contracts from AstraZeneca, Bristol-Myers Squibb, Novartis, Regeneron, and BioNTech; consulting fees from Ascendis, AstraZeneca, Bristol-Myers Squibb, Curevac, Novartis, Regeneron, G1, Genlux, Genentech, Gritstone, Merck, Janssen, F Star, Sanofi, Amgen, Fosun, Teva, Synthekine, Flame, Iteos, and Tavotek. Dr. Higgins reports receiving grants or contracts from Jazz Pharmaceuticals, RefleXion Medicalx; consulting fees from AstraZeneca and Janssen; positions on the NRG Oncology Board of Directors and RTOG Foundation Board of Directors; and stock or stock options in Picture Health. Dr. Kris reports receiving grant or contracts from BerGenBio, Merus, AstraZeneca, Mirati, Pfizer, Janssen, Sanofi, and Novartis; honoraria from Pfizer and AstraZeneca; and personal fees from AstraZeneca and Roche/Genentech, outside the submitted work. Dr. Mitsudomi reports receiving grants or contracts from Boehringer Ingelheim, AstraZeneca, Chugai, Pfizer, Ono, Daiichi Sankyo, and Eli Lilly; consulting fees from AstraZeneca, Novartis, Chugai, Boehringer Ingelheim, Pfizer, Merck Sharp & Dohme, Thermo Fisher, Roche Diagnostics, Bristol-Myers Squibb, Ono Pharmaceuticals, Taiho, Takeda, Janssen, Daiichi Sankyo, and Regeneron; honoraria from AstraZeneca, Chugai, Boehringer Ingelheim, Pfizer, Taiho, Eli Lilly, Daiichi Sankyo, Thermo Fisher, Merck Sharp & Dohme, Bristol-Myers Squibb, Ono Pharmaceuticals, Invitae, Guardant, Novartis, Amgen, Merck biopharma, and Kyorin; data safety monitoring board for Taiho Pharmaceutical, outside the submitted work. Dr. Provencio reports receiving grants or contracts from Bristol-Myers Squibb, AstraZeneca, Roche, Janssen, and Takeda; consulting fees from Bristol-Myers Squibb, Roche, AstraZeneca, Merck Sharp & Dohme, and Takeda; honoraria from Bristol-Myers Squibb, Takeda, Roche, AstraZeneca, and Merck Sharp & Dohme; and meeting attendance support from Merck Sharp & Dohme, Roche, and Bristol-Myers Squibb, outside the submitted work. Dr. Senan reports receiving grants or contracts from AstraZeneca, Merck Sharp & Dohme, and Bristol-Myers Squibb; consulting fees from AstraZeneca and Bristol-Myers Squibb; honoraria from AstraZeneca; advisory board participation for AstraZeneca and Merck Sharp & Dohme; and membership on ETOP scientific committee, outside the submitted work. Dr. Solomon reports receiving travel support from IASLC to attend meeting related to manuscript; consulting fees from AstraZeneca, Bristol-Myers Squibb, Eli Lily, Merck Sharp & Dohme, Pfizer, Roche, GlaxoSmithKline, Janssen, and Amgen; honoraria from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, and GlaxoSmithKline; unpaid leadership roles at the IASLC, Thoracic Oncology Group of Australasia, and Cancer Council of Victoria. Dr. Tsao reports receiving travel support from IASLC to attend meeting related to manuscript; grants or contracts from AstraZeneca, Bayer, and Lily; consulting fees from AstraZeneca, Bayer, Amgen, AbbVie, Regeneron, Sanofi, Daiichi Sankyo, and Lily; honoraria from AbbVie and Sanofi; and board of directors for IASLC. Dr. Tsuboi reports receiving grant from AstraZeneca KK, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb KK, Novartis Japan, BMG KK, MiRXES, and Johnson & Johnson Japan; honoraria from Amgen KK, Johnson & Johnson Japan, AstraZeneca KK, Eli Lilly Japan, Chugai Pharmaceutical Co., Ltd., Taiho Pharma, Medtronic Japan, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme KK, Bristol-Myers Squibb KK, Daiichi Sanko KK, and Novalis; advisory committee participation for Chugai Pharmaceutical Co., Ltd., and AstraZeneca KK; and Board of Directors for Japan Lung Cancer Society (JLCS), Bronchology Committee Chair for JLCS, and Educational Committee working group chair for IASLC, outside the submitted work. Dr. Wakelee reports receiving grants or contracts from ACEA Biosciences, Arrys Therapeutics, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Genentech/Roche, Merck, Novartis, SeaGen, Xcovery, and Helsinn; advisory board participation for AstraZeneca, Blueprint, Mirati, Merck, and Genentech/Roche; and leadership positions on the IASLC Board of Directors and ECOG-ACRIN executive committee. Dr. Wu reports receiving grants and contracts form AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Henqrui, and Roche; honoraria from AstraZeneca, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, and Sanofi; and unpaid leadership role for Chinese Thoracic Oncology Group. Dr. Yang reports receiving personal fees and other from Amgen, Bayer Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Merck KGaA, Merck Sharp & Dohme, Novartis, Roche/Genentech, Takeda Oncology, and Yuhan Pharmaceuticals; grants, personal fees, and other from AstraZeneca; other from Eli Lilly; personal fees from Ono Pharmaceuticals and Pfizer; and other from JNJ, Puma Technology, Gilead, and GlaxoSmithKline, outside the submitted work. Dr. Zhou reports receiving consulting fees from Innovent Biologics, Hengrui, Qila, and TopAlliance Biosciences; honoraria from Lily China, Sanofi, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Alice, C-Stone, LUYE Pharma, TopAlliance Biosciences, Amoy Diagnostics, and AnHeart. Dr. Kelly reports receiving grants from AstraZeneca, during the conduct of the study; grants and personal fees from Genentech and Bristol-Myers Squibb; and personal fees from AstraZeneca, outside the submitted work. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: The multidisciplinary American Radium Society Thoracic Committee was assigned to create appropriate use criteria on cardiac toxicity prevention and management for patients undergoing radiotherapy., Methods: A systematic review of the current literature was conducted. Case variants of patients with thoracic malignancies undergoing radiation were created based on presence or absence of cardiovascular risk factors and treatment-related risks assessed by dose exposure to the heart and cardiac substructures. Modified Delphi methodology was used to evaluate the variants and procedures, with less than or equal to three rating points from median defining agreement/consensus., Results: A total of six variants were evaluated. The panel felt that patients with cardiac comorbidities at high risk for radiation-related cardiac toxicity should undergo a prescreening cardiac-focused history and physical (H&P) examination, electrocardiogram, cardiac imaging including an echocardiogram, and referral to a cardiologist/cardio-oncologist. Recommendations for those without cardiac comorbidities at low risk for cardiac toxicity were to undergo a baseline H&P examination only. Conversely, those without cardiac comorbidities but at high risk for radiation-related cardiac toxicity were recommended to undergo a prescreening electrocardiogram, in addition to a H&P examination. For patients with cardiac comorbidities at low risk for cardiac toxicity, the panel felt that prescreening and postscreening tests may be appropriate., Conclusions: The American Radium Society Thoracic appropriate use criteria panel has developed multidisciplinary consensus guidelines for cardiac toxicity prevention, surveillance, and management after thoracic radiotherapy based on cardiac comorbidities at presentation and risk of radiation-related cardiac toxicity., Competing Interests: Disclosure All panelists were required to declare all conflicts of interest for the previous 36 months before initiating work on this document. These complete disclosure forms are retained by the American Radium Society in perpetuity. The American Radium Society Appropriate Use Criteria Steering Committee reviewed these disclosures with the chair and co-chair of this document and approved participation of the panelists before starting development of this work., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Definitive radiation therapy is considered standard therapy for medically inoperable early-stage NSCLC. Nevertheless, for patients with tumors located near structures such as the proximal tracheobronchial tree, esophagus, heart, spinal cord, and brachial plexus, the optimal management regimen is controversial. The objective was to develop expert multidisciplinary consensus guidelines on managing medically inoperable NSCLC located in a central or ultracentral location relative to critical organs at risk., Methods: Case variants regarding centrally and ultracentrally located lung tumors were developed by the 15-member multidisciplinary American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) expert panel. A comprehensive review of the English medical literature was performed from January 1 1946 to December 31 2023 to inform consensus guidelines. Modified Delphi methods were used by the panel to evaluate the variants and procedures, with at least three rating points from median defining agreement/consensus. The guideline was then approved by the ARS Executive Committee and released for public comment per established ARS procedures., Results: The Thoracic ARS AUC Panel identified 90 relevant references and obtained consensus in all variants. Radiotherapy alone was considered appropriate, with additional immunotherapy to be considered primarily in the clinical trial setting. Hypofractionated radiotherapy in eight to 18 fractions was considered appropriate for ultracentral lesions near the proximal tracheobronchial tree, upper trachea, and esophagus. For other ultracentral lesions near the heart, great vessels, brachial plexus, and spine, or for non-ultracentral but still central lesions, five-fraction stereotactic body radiation therapy was also considered an appropriate option. Intensity-modulated radiotherapy was considered appropriate and three-dimensional-conformal radiotherapy inappropriate for all variants. Other treatment planning techniques to decrease the risk of overdosing critical organs at risk were also considered., Conclusions: The ARS Thoracic AUC panel has developed multidisciplinary consensus guidelines for various presentations of stage I NSCLC in a central or ultracentral location., Competing Interests: Disclosure Dr. Park reported personal fees AstraZeneca, Bristol-Myers Squibb, Daichii Sankyo, G1 Therapeutics, Galera Medical, RefleXion Medical, Regeneron, and research funding from Merck Sharp & Dohme. Dr. Rimner reported grants from Varian Medical Systems, AstraZeneca, Merck, Boehringer Ingelheim, Pfizer, and National Institutes of Health and personal fees from AstraZeneca, Merck, and MoreHealth. Dr. Chang reported grants from Bristol Myers Squibb and personal fees from Varian Medical Systems and IBA. Dr. Chun reported personal fees from AstraZeneca, Norton Healthcare, Binaytara Foundation, ViewRay, Japanese Society for Radiation Oncology, Hong Kong Precision Oncology Society, and Curio Science. Dr. Donington reported personal fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Roche/Genentech. Dr. Edelman reported personal fees from AstraZeneca, Takeda, Glaxo Smith Kline, Omega Therapeutics, Novocure, InterVenn, WindMil, Seattle Genetics, Regeneron/Sanofi, Flame Consulting, Proventus Consulting, GE Healthcare Consulting, BioAlta Consulting, Replimmune Consulting, Coherus Consulting, and AnHeart. Dr. Gubens reported personal fees from AnHeart, AstraZeneca, Atreca, Bristol-Myers Squibb, Cardinal Health, Genzyme, Genentech/Roche, Gilead, Guardant, Invitae, iTeos, Merus, Sanofi, Summit, and Surface and grants from Amgen, JNJ, Merck, OncoMed, and Trizell. Dr. Higgins reported grants from Jazz Pharmaceuticals and other support from AstraZeneca, Janssen Pharmaceuticals, and RefleXion Medical. Dr. Iyengar reported other support from Incyte and AstraZeneca. Dr. Movsas reported grants from Varian Research, Philips Research, and ViewRay Research. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Numerous systematic reviews (SR) and meta-analyses (MA) on low calorie sweeteners (LCS) have been published in recent years, concluding that LCS have beneficial, neutral, or detrimental effects on various health outcomes, depending on the review., Objectives: The objective of this overview of reviews was to determine how the methodologies of SR investigating the association between LCS consumption and body weight (BW) influence their findings and whether MA results can provide a consistent estimated effect., Methods: Systematic searches of PubMed, Scopus, and Cochrane Library were conducted in November 2022 to identify SR of randomized controlled trials (RCT) or non-randomized studies (NRS) investigating the association between LCS consumption and BW. The methods, MA results, and conclusions were extracted from each eligible SR., Results: Of the 985 search results, 20 SR evaluated the association between LCS and BW, drawing from publications of 75 RCT, 42 prospective cohort studies, and 10 cross-sectional studies. There was a considerable lack of overlap of studies included within each SR attributed, in part, to the inclusion of studies based on design; thus, each SR synthesized results from distinctly different studies. Evidence synthesis methods were heterogeneous and often opaque, making it difficult to determine why results from certain studies were excluded or why disparate results were observed between SR., Conclusions: SR investigating the effect of LCS on BW implement different methodologies to answer allegedly the same question, drawing from a different set of heterogeneous studies, ignoring the basic assumptions required for MA, resulting in disparate results and conclusions. Previous MA show the large effects of study design, which results in inconsistent estimates of the effect of LCS on BW between MA of RCT and NRS. Given the availability of long-term RCT, these studies should be the basis of determining causal relationships (or lack thereof) between LCS and BW. This trial was registered at PROSPERO as CRD42022351200., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cancer patients are commonly affected by fatigue. Herein, we sought to examine epigenetic modifications (i.e., DNA methylation) related to fatigue in peripheral blood among patients during and after treatment for head and neck cancer (HNC). Further, we determined whether these modifications were associated with gene expression and inflammatory protein markers, which we have previously linked to fatigue in HNC. This prospective, longitudinal study enrolled eligible patients with data collected at pre-radiotherapy, end of radiotherapy, and six months and one-year post-radiotherapy. Fatigue data were reported by patients using the Multidimensional Fatigue Inventory (MFI)-20. DNA methylation (Illumina MethylationEPIC) and gene expression (Applied Biosystems Clariom S) arrays and assays for seven inflammatory markers (R&D Systems multiplex) were performed. Mixed models and enrichment analyses were applied to establish the associations. A total of 386 methylation loci were associated with fatigue among 145 patients (False Discovery Rate [FDR] < 0.05). Enrichment analyses showed the involvement of genes related to immune and inflammatory responses, insulin and lipid metabolism, neuropsychological disorders, and tumors. We further identified 16 methylation-gene expression pairs (FDR < 0.05), which were linked to immune and inflammatory responses and lipid metabolism. Ninety-one percent (351) of the 386 methylation loci were also significantly associated with inflammatory markers (e.g., interleukin 6, c-reactive protein; FDR < 0.05), which further mediated the association between methylation and fatigue (FDR < 0.05). These data suggest that epigenetic modifications associated with inflammation and immunometabolism, in conjunction with relevant gene expression and protein markers, are potential targets for treating fatigue in HNC patients. The findings also merit future prospective studies in other cancer populations as well as interventional investigations., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS)., Objective: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation., Design, Setting, and Participants: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023., Intervention: Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks., Main Outcomes and Measures: The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers., Results: A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed., Conclusions and Relevance: This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation., Trial Registration: ClinicalTrials.gov Identifier: NCT03521570.

Purpose: The recently proposed Integrated Physical Optimization Intensity Modulated Proton Therapy (IPO-IMPT) framework allows simultaneous optimization of dose, dose rate, and linear energy transfer (LET) for ultra-high dose rate (FLASH) treatment planning. Finding solutions to IPO-IMPT is difficult because of computational intensiveness. Nevertheless, an inverse solution that simultaneously specifies the geometry of a sparse filter and weights of a proton intensity map is desirable for both clinical and preclinical applications. Such solutions can reduce effective biologic dose to organs at risk in patients with cancer as well as reduce the number of animal irradiations needed to derive extra biologic dose models in preclinical studies., Methods and Materials: Unlike the initial forward heuristic, this inverse IPO-IMPT solution includes simultaneous optimization of sparse range compensation, sparse range modulation, and spot intensity. The daunting computational tasks vital to this endeavor were resolved iteratively with a distributed computing framework to enable Simultaneous Intensity and Energy Modulation and Compensation (SIEMAC). SIEMAC was demonstrated on a human patient with central lung cancer and a minipig., Results: SIEMAC simultaneously improves maps of spot intensities and patient-field-specific sparse range compensators and range modulators. For the patient with lung cancer, at our maximum nozzle current of 300 nA, dose rate coverage above 100 Gy/s increased from 57% to 96% in the lung and from 93% to 100% in the heart, and LET coverage above 4 keV/µm dropped from 68% to 9% in the lung and from 26% to <1% in the heart. For a simple minipig plan, the full-width half-maximum of the dose, dose rate, and LET distributions decreased by 30%, 1.6%, and 57%, respectively, again with similar target dose coverage, thus reducing uncertainty in these quantities for preclinical studies., Conclusions: The inverse solution to IPO-IMPT demonstrated the capability to simultaneously modulate subspot proton energy and intensity distributions for clinical and preclinical studies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: The treatment of locally advanced non-small cell lung cancer (LA-NSCLC) has been informed by more than 5 decades of clinical trials and other relevant literature. However, controversies remain regarding the application of various radiation and systemic therapies in commonly encountered clinical scenarios., Objective: To develop case-referenced consensus and evidence-based guidelines to inform clinical practice in unresectable LA-NSCLC., Evidence Review: The American Radium Society (ARS) Appropriate Use Criteria (AUC) Thoracic Committee guideline is an evidence-based consensus document assessing various clinical scenarios associated with LA-NSCLC. A systematic review of the literature with evidence ratings was conducted to inform the appropriateness of treatment recommendations by the ARS AUC Thoracic Committee for the management of unresectable LA-NSCLC., Findings: Treatment appropriateness of a variety of LA-NSCLC scenarios was assessed by a consensus-based modified Delphi approach using a range of 3 points to 9 points to denote consensus agreement. Committee recommendations were vetted by the ARS AUC Executive Committee and a 2-week public comment period before official approval and adoption. Standard of care management of good prognosis LA-NSCLC consists of combined concurrent radical (60-70 Gy) platinum-based chemoradiation followed by consolidation durvalumab immunotherapy (for patients without progression). Planning and delivery of locally advanced lung cancer radiotherapy usually should be performed using intensity-modulated radiotherapy techniques. A variety of palliative and radical fractionation schedules are available to treat patients with poor performance and/or pulmonary status. The salvage therapy for a local recurrence after successful primary management is complex and likely requires both multidisciplinary input and shared decision-making with the patient., Conclusions and Relevance: Evidence-based guidance on the management of various unresectable LA-NSCLC scenarios is provided by the ARS AUC to optimize multidisciplinary patient care for this challenging patient population.

Purpose: Emerging data have illuminated the impact of effective radiation dose to immune cells (EDIC) on outcomes in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT). Hypothesizing that intensity-modulated proton therapy (IMPT) may reduce EDIC versus IMRT, we conducted a dosimetric analysis of patients treated at our institution., Materials and Methods: Data were retrospectively collected for 12 patients with locally advanced, unresectable NSCLC diagnosed between 2019 and 2021 who had physician-approved IMRT and IMPT plans. Data to calculate EDIC from both Jin et al (PMID: 34944813) and Ladbury et al's (PMID: 31175902) models were abstracted. Paired t tests were utilized to compare the difference in mean EDIC between IMPT and IMRT plans., Results: IMPT decreased EDIC for 11 of 12 patients (91.7%). The mean EDIC per the Jin model was significantly lower with IMPT than IMRT (3.04 GyE vs 4.99 Gy, P  < .001). Similarly, the mean EDIC per the Ladbury model was significantly lower with IMPT than IMRT (4.50 GyE vs 7.60 Gy, P  < .002). Modeled 2-year overall survival was significantly longer with IMPT than IMRT (median 71% vs 63%; P  = .03)., Conclusion: IMPT offers a statistically significant reduction in EDIC compared to IMRT. Given the emergence of EDIC as a modifiable prognostic factor in treatment planning, our dosimetric study highlights a potential role for IMPT to address an unmet need in improving oncologic outcomes in patients with locoregionally advanced NSCLC., (© 2024 The Author(s).)

Timing of eating (TOE) and energy intake (TOEI) has important implications for chronic disease risk beyond diet quality. The 2020 Dietary Guidelines Advisory Committee recommended developing consistent terminology to address the lack of TOE/TOEI standardization. The primary objective of this methodological systematic review was to characterize the conceptualization and assessment of TOE/TOEI within the chronic disease literature (International Prospective Register of Systematic Reviews registration number: CRD42021236621). Literature searches in Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, Embase, PubMed, and Scopus were limited to English language publications from 2000 to August 2022. Eligible studies reported the association between TOE/TOEI and obesity, cardiovascular disease, type 2 diabetes mellitus, cancer, or a related clinical risk factor among adults (≥19 y) in observational and intervention studies. A qualitative synthesis described and compared TOE/TOEI conceptualization, definitions, and assessment methods across studies. Of the 7579 unique publications identified, 259 studies (observational [51.4 %], intervention [47.5 %], or both [1.2 %]) were eligible for inclusion. Key findings indicated that most studies (49.6 %) were conducted in the context of obesity and body weight. TOE/TOEI variables or assigned conditions conceptualized interrelated aspects of time and eating or energy intake in varying ways. Common TOE/TOEI conceptualizations included the following: 1) timepoint (specific time to represent when intake occurs, such as time of breakfast [74.8 %]); 2) duration (length of time or interval when intake does/does not occur, such as "eating window" [56.5 %]); 3) distribution (proportion of daily intake at a given time interval, such as "percentage of energy before noon" [29.8 %]); and 4) cluster (grouping individuals based on temporal ingestive characteristics [5.0 %]). Assessment, definition, and operationalization of 24-h TOE/TOEI variables varied widely across studies. Observational studies most often used surveys or questionnaires (28.9 %), whereas interventions used virtual or in-person meetings (23.8 %) to assess TOE/TOEI adherence. Overall, the diversity of terminology and methods solidifies the need for standardization to guide future research in chrononutrition and to facilitate inter-study comparisons., (Published by Elsevier Inc.)

Background: The PACIFIC trial established consolidative durvalumab after concurrent chemoradiation as standard-of-care in patients with stage III or unresectable non-small cell lung cancer (NSCLC). Black patients, however, comprised just 2% (n = 14) of randomized patients in this trial, warranting real-world evaluation of the PACIFIC regimen in these patients., Methods: This single-institution, multi-site study included 105 patients with unresectable stage II/III NSCLC treated with concurrent chemoradiation followed by durvalumab between 2017 and 2021. Overall survival (OS), progression-free survival (PFS), and grade ≥3 pneumonitis-free survival (PNFS) were compared between Black and non-Black patients using Kaplan-Meier and Cox regression analyses., Results: A total of 105 patients with a median follow-up of 22.8 months (interquartile range, 11.3-37.3 months) were identified for analysis, including 57 Black (54.3%) and 48 (45.7%) non-Black patients. The mean radiation prescription dose was higher among Black patients (61.5 ± 2.9 Gy vs. 60.5 ± 1.9 Gy; p = .031), but other treatment characteristics were balanced between groups. The median OS (not-reached vs. 39.7 months; p = .379) and PFS (31.6 months vs. 19.3 months; p = .332) were not statistically different between groups. Eight (14.0%) Black patients discontinued durvalumab due to toxicity compared to 13 (27.1%) non-Black patients (p = .096). The grade ≥3 pneumonitis rate was similar between Black and non-Black patients (12.3% vs. 12.5%; p = .973), and there was no significant difference in time to grade ≥3 PNFS (p = .904). Three (5.3%) Black patients and one (2.1%) non-Black patient developed grade 5 pneumonitis., Conclusions: The efficacy and tolerability of consolidative durvalumab after chemoradiation appears to be comparable between Black and non-Black patients., (© 2023 American Cancer Society.)

Objective: Patients with head and neck cancer (HNC) experience psychoneurological symptoms (PNS, i.e., depression, fatigue, sleep disturbance, pain, and cognitive dysfunction) during intensity-modulated radiotherapy (IMRT) that negatively impact their functional status, quality of life, and overall survival. The underlying mechanisms for PNS are still not fully understood. This study aimed to examine differentially expressed genes and pathways related to PNS for patients undergoing IMRT (i.e., before, end of, 6 months, and 12 months after IMRT)., Methods: Participants included 142 patients with HNC (mean age 58.9 ± 10.3 years, 72.5% male, 83.1% White). Total RNA extracted from blood leukocytes were used for genome-wide gene expression assays. Linear mixed effects model was used to examine the association between PNS and gene expression across time. Gene Ontology (GO) enrichment analysis was employed to identify pathways related to PNS., Results: A total of 1352 genes (162 upregulated, 1190 downregulated) were significantly associated with PNS across time (false discovery rate (FDR) < 0.05). Among these genes, 112 GO terms were identified (FDR < 0.05). The top 20 GO terms among the significant upregulated genes were related to immune and inflammatory responses, while the top 20 GO terms among the significant downregulated genes were associated with telomere maintenance., Conclusion: This study is the first to identify genes and pathways linked to immune and inflammatory responses and telomere maintenance that are associated with PNS in patients with HNC receiving IMRT. Inflammation and aging markers may be candidate biomarkers for PNS. Understanding biological markers may produce targets for novel interventions., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest or competing interests to disclose. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Peer review in the form of chart rounds is a critical component of quality assurance and safety in radiation therapy treatments. Radiation therapy departments have undergone significant changes that impose challenges to meaningful review, including institutional growth and increasing use of virtual environment. We discuss the implementation of a novel chart rounds (NCR) format and application adapted to modern peer review needs at a single high-volume multisite National Cancer Institute designated cancer center., Methods and Materials: A working group was created to improve upon the prior institutional chart rounds format (standard chart rounds or SCR). Using a novel in-house application and format redesign, an NCR was created and implemented to accomplish stated goals. Data regarding the SCR and NCR system were then extracted for review., Results: SCR consisted of 2- 90-minute weekly sessions held to review plans across all disease sites, review of 49 plans per hour on average. NCR uses 1-hour long sessions divided by disease site, enabling additional time to be spent per patient (11 plans per hour on average) and more robust discussion. The NCR application is able to automate a list of plans requiring peer review from the institutional treatment planning system. The novel application incorporates features that enable efficient and accurate review of plans in the virtual setting across multiple sites. A systematic scoring system is integrated into the application to record feedback. Over 5 months of use of the NCR, 1160 plans have been reviewed with 143 scored as requiring minor changes, 32 requiring major changes and 307 with comments. Major changes triggered treatment replan. Feedback from scoring is incorporated into physician workflow to ensure changes are addressed., Conclusion: The presented NCR format and application enables standardized and highly reliable peer review of radiation therapy plans that is robust across a variety of complex planning scenarios and could be implemented globally., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Our objective was to convene interdisciplinary experts from government, academia, and industry to develop a Research Roadmap to identify research priorities about processed food intake and risk for obesity and cardiometabolic diseases (CMD) among United States populations. We convened attendees at various career stages with diverse viewpoints in the field. We held a "Food Processing Primer" to build foundational knowledge of how and why foods are processed, followed by presentations about how processed foods may affect energy intake, obesity, and CMD risk. Breakout groups discussed potential mechanistic and confounding explanations for associations between processed foods and obesity and CMD risk. Facilitators created research questions (RQs) based on key themes from discussions. Different breakout groups convened to discuss what is known and unknown for each RQ and to develop sub-RQs to address gaps. Workshop attendees focused on ultra-processed foods (UPFs; Nova Group 4) because the preponderance of evidence is based on this classification system. Yet, heterogeneity and subjectivity in UPF classification was a challenge for RQ development. The 6 RQs were: 1) What objective methods or measures could further categorize UPFs, considering food processing, formulation, and the interaction of the two? 2) How can exposure assessment of UPF intake be improved? 3) Does UPF intake influence risk for obesity or CMDs, independent of diet quality? 4) What, if any, attributes of UPFs influence ingestive behavior and contribute to excess energy intake? 5) What, if any, attributes of UPFs contribute to clinically meaningful metabolic responses? 6) What, if any, external environmental factors lead people to consume high amounts of UPFs? Uncertainty and complexity around UPF intake warrant further complementary and interdisciplinary causal, mechanistic, and methodological research related to obesity and CMD risk to understand the utility of applying classification by degree of processing to foods in the United States., (Published by Elsevier Inc.)

The influence of individual macro- and micronutrients on absenteeism in the United States is largely unknown. The objective of this study was to determine whether nutritional status or nutrient intake were associated with absenteeism from school and work due to illness or injury. Data from NHANES 2003-2008 were used to assess nutrient intake from food and food plus supplements, nutritional biomarker levels, and school and work absenteeism per year in children and adults. Negative binomial regression models were used to predict mean days of missed work per year and to estimate incidence rate ratios (IRRs) of absenteeism by nutrient biomarker status. Of 7429 children, 77% reported missing school days (mean 4.0 days). Of 8252 adults, 51% reported missing work days (mean 4.9 days). Children and adults who reported more absent days had a significantly lower intake of protein and several essential micronutrients from the diet. When nutrients from supplements were included, this negative association was retained for protein, selenium, choline, and DHA in children and for protein, selenium, vitamin K, choline, potassium, fiber, octadecatrienoic acid, and lycopene in adults. Future studies are needed to ascertain whether dietary interventions, such as access to healthier food options and/or dietary supplements, can reduce absenteeism.

Fatigue among patients with head and neck cancer (HNC) has been associated with higher inflammation. Short-chain fatty acids (SCFAs) have been shown to have anti-inflammatory and immunoregulatory effects. Therefore, this study aimed to examine the association between SCFAs and fatigue among patients with HNC undergoing treatment with radiotherapy with or without concurrent chemotherapy. Plasma SCFAs and the Multidimensional Fatigue Inventory-20 were collected prior to and one month after the completion of treatment in 59 HNC patients. The genome-wide gene expression profile was obtained from blood leukocytes prior to treatment. Lower butyrate concentrations were significantly associated with higher fatigue (p = 0.013) independent of time of assessment, controlling for covariates. A similar relationship was observed for iso/valerate (p = 0.025). Comparison of gene expression in individuals with the top and bottom 33% of butyrate or iso/valerate concentrations prior to radiotherapy revealed 1,088 and 881 significantly differentially expressed genes, respectively (raw p < 0.05). The top 10 Gene Ontology terms from the enrichment analyses revealed the involvement of pathways related to cytokines and lipid and fatty acid biosynthesis. These findings suggest that SCFAs may regulate inflammatory and immunometabolic responses and, thereby, reduce inflammatory-related symptoms, such as fatigue., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to explore the associations among physical activity (PA), inflammatory markers, and quality of life (QoL) from preradiotherapy to 1-year postradiotherapy for patients with head and neck cancer (HNC)., Methods: This was an observational longitudinal study. Mixed-effect models incorporating within-subject correlation were used to examine the relationship among the three key variables., Results: Aerobically active patients had significantly lower levels of sTNFR2 (but not other inflammatory markers) than aerobically inactive patients. Being aerobically active and lower inflammation were independently associated with better total QoL scores after adjusting covariates. The trend was similar for patients engaged in strength exercises., Conclusions: Being aerobically active was associated with lower inflammation as represented by sTNFR2 but not with other inflammatory markers. Higher PA (aerobic and strength) and lower inflammation were linked to better QoL. More research is warranted to validate the association among PA, inflammation, and QoL., (© 2023 Wiley Periodicals LLC.)

Purpose: Current guidelines recommend surgery as standard of care for primary lung neuroendocrine tumor (LNET). Given that LNET is a rare clinical entity, there is a lack of literature regarding treatment of LNET with stereotactic body radiation therapy (SBRT). We hypothesized that SBRT could lead to effective locoregional tumor control and long-term outcomes., Methods and Materials: We retrospectively reviewed 48 tumors in 46 patients from 11 institutions with a histologically confirmed diagnosis of LNET, treated with primary radiation therapy. Data were collected for patients treated nonoperatively with primary radiation therapy between 2006 and 2020. Patient records were reviewed for lesion characteristics and clinical risk factors. Kaplan-Meier analysis, log-rank tests, and Cox multivariate models were used to compare outcomes., Results: Median age at treatment was 71 years and mean tumor size was 2 cm. Thirty-two lesions were typical carcinoid histology, 7 were atypical, and 9 were indeterminate. The most common SBRT fractionation schedule was 50 to 60 Gy in 5 daily fractions. Overall survival at 3, 6, and 9 years was 64%, 43%, and 26%, respectively. Progression-free survival at 3, 6, and 9 years was 88%, 78%, and 78%, respectively. Local control at 3, 6, and 9 years was 97%, 91%, and 91%, respectively. There was 1 regional recurrence in a paraesophageal lymph node. No grade 3 or higher toxicity was identified., Conclusions: This is the largest series evaluating outcomes in patients with LNET treated with SBRT. This treatment is well tolerated, provides excellent locoregional control, and should be offered as an alternative to surgical resection for patients with early-stage LNET, particularly those who may not be ideal surgical candidates., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Thymic carcinoma is rare, and its oncologic management is controversial due to a paucity of prospective data. For this reason, multidisciplinary consensus guidelines are crucial to guide oncologic management., Objective: To develop expert multidisciplinary consensus guidelines on the management of common presentations of thymic carcinoma., Evidence Review: Case variants spanning the spectrum of stage I to IV thymic carcinoma were developed by the 15-member multidisciplinary American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) expert panel to address management controversies. A comprehensive review of the English-language medical literature from 1980 to 2021 was performed to inform consensus guidelines. Variants and procedures were evaluated by the panel using modified Delphi methodology. Agreement/consensus was defined as less than or equal to 3 rating points from median. Consensus recommendations were then approved by the ARS Executive Committee and subject to public comment per established ARS procedures., Findings: The ARS Thoracic AUC panel identified 89 relevant references and obtained consensus for all procedures evaluated for thymic carcinoma. Minimally invasive thymectomy was rated as usually inappropriate (regardless of stage) due to the infiltrative nature of thymic carcinomas. There was consensus that conventionally fractionated radiation (1.8-2 Gy daily) to a dose of 45 to 60 Gy adjuvantly and 60 to 66 Gy in the definitive setting is appropriate and that elective nodal irradiation is inappropriate. For radiation technique, the panel recommended use of intensity-modulated radiation therapy or proton therapy (rather than 3-dimensional conformal radiotherapy) to reduce radiation exposure to the heart and lungs., Conclusions and Relevance: The ARS Thoracic AUC panel has developed multidisciplinary consensus guidelines for various presentations of thymic carcinoma, perhaps the most well referenced on the topic.

Purpose: Head and neck cancer (HNC) patients may experience multiple co-occurring neuropsychological symptoms (NPS) cluster, including fatigue, depression, pain, sleep disturbance, and cognitive impairment. While inflammation has been attributed as a key mechanism for some of these symptoms, its association with the NPS as a cluster of symptoms is unknown. Thus, the aim of this study was to examine the association between peripheral inflammation and NPS cluster among HNC patients over cancer treatment (radiotherapy with or without chemotherapy)., Methods: HNC patients were recruited and followed at pre-treatment, end of treatment, three months and one-year post-treatment. Plasma inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNFA), soluble tumor necrosis factor receptor-2 (sTNFR2), interleukin-1 beta (IL1-β), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemotactic protein-1 (MCP-1), and interleukin-1 receptor antagonist (IL-1RA) and patient-reported NPS cluster were collected at the 4 time points. Associations between inflammatory markers and the NPS cluster were analyzed using linear mixed-effects models and generalized estimating equations (GEE) models controlling covariates., Results: 147 HNC patients were eligible for analysis. 56% of the patients received chemoradiotherapy as treatment. The highest NPS cluster score was reported at the end of treatment, which gradually decreased over time. An increase in inflammatory markers including CRP, sTNFR2, IL-6 and IL-1RA was associated with higher continuous NPS cluster scores (p<0.001, p = 0.003, p<0.001, p<0.001; respectively). GEE further confirmed that patients with at least two moderate symptoms had elevated sTNFR2, IL-6, and IL-1RA (p = 0.017, p = 0.038, p = 0.008; respectively). Notably, this positive association between NPS cluster and inflammatory markers was still significant at one-year post-treatment for CRP (p = 0.001), sTNFR2 (p = 0.006), and IL-1RA (p = 0.043)., Conclusions: Most HNC patients experienced NPS clusters over time, especially immediately after the end of treatment. Elevated inflammation, as represented by inflammatory markers, was strongly associated with worse NPS cluster over time; this trend was also notable at one-year post-treatment. Our findings suggest that peripheral inflammation plays a pivotal role in the NPS cluster over cancer treatment, including long-term follow-ups. Interventions on reducing peripheral inflammation may contribute to alleviating the NPS cluster in cancer patients., Competing Interests: None., (© 2023 The Authors.)

To evaluate the effects of arc geometry on lung stereotactic body radiation therapy (SBRT) plan quality, using collision check software to select safe beam angles. Thirty lung SBRT cases were replanned 10Gy x 5 using 4 volumetric modulated arc therapy (VMAT) geometries: coplanar lateral (cpLAT), coplanar oblique (cpOBL), noncoplanar lateral (ncpLAT) and noncoplanar oblique (ncpOBL). Lateral arcs spanned 180° on the affected side whereas the 180° oblique arcs crossed midline to spare healthy tissues. Couch angles were separated by 30° on noncoplanar plans. Clearance was verified with Radformation CollisionCheck software. Optimization objectives were the same across the four plans for each case. Planning target volume (PTV) coverage was set to 95% and then plans were evaluated for dose conformity, healthy tissue doses, and monitor units. Clinically treated plans were used to benchmark the results. The volumes of the 25%, 50% and 75% isodoses were smaller with noncoplanar than coplanar arcs. The volume of the 50% isodose line relative to the PTV (CI50%) was as follows: clinical 3.75±0.72, cpLAT 3.39 ± 0.37, cpOBL 3.36 ± 0.34, ncpLAT 3.02 ± 0.21 and ncpOBL 3.02 ± 0.22. The Wilcoxon signed rank test with Bonferroni correction showed p < 0.005 in all CI50% comparisons except between the cpLat and cpObl arcs and between the ncpLat and ncpObl arcs. The best lung sparing was achieved using ncpObl arcs, which was statistically significant (p < 0.001) compared with the other four plans at V12.5Gy, V13.5Gy and V20Gy. Chest wall V30Gy was significantly better using noncoplanar arcs in comparison to the other plan types (p < 0.001). The best heart sparing at V10Gy from the ncpOBL arcs was significant compared with the clinical and cpLat plans (p < 0.005). Arc geometry has a substantial effect on lung SBRT plan quality. Noncoplanar arcs were superior to coplanar arcs at compacting the dose distribution at the 25%, 50% and 75% isodose levels, thereby reducing the dose to healthy tissues. Further healthy tissue sparing was achieved using oblique arcs that minimize the pathlength through healthy tissues and avoid organs at risk. The dosimetric advantages of the noncoplanar and oblique arcs require careful beam angle selection during treatment planning to avoid collisions during treatment, which may be facilitated by commercial software., (Copyright © 2023 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Introduction: Cardiac radioablation (CR) is a noninvasive treatment option for patients with refractory ventricular tachycardia (VT) during which high doses of radiation, typically 25 Gy, are delivered to myocardial scar. In this study, we investigate motion from cardiac cycle and evaluate the dosimetric impact in a cohort of patients treated with CR., Methods: This retrospective study included eight patients treated at our institution who had respiratory-correlated and ECG-gated 4DCT scans acquired within 2 weeks of CR. Deformable image registration was applied between maximum systole (SYS) and diastole (DIAS) CTs to assess cardiac motion. The average respiratory-correlated CT (AVG resp ) was deformably registered to the average cardiac (AVG cardiac ), SYS, and DIAS CTs, and contours were propagated using the deformation vector fields (DVFs). Finally, the original treatment plan was recalculated on the deformed AVG resp CT for dosimetric assessment., Results: Motion magnitudes were measured as the mean (SD) value over the DVFs within each structure. Displacement during the cardiac cycle for all chambers was 1.4 (0.9) mm medially/laterally (ML), 1.6 (1.0) mm anteriorly/posteriorly (AP), and 3.0 (2.8) mm superiorly/inferiorly (SI). Displacement for the 12 distinct clinical target volumes (CTVs) was 1.7 (1.5) mm ML, 2.4 (1.1) mm AP, and 2.1 (1.5) SI. Displacements between the AVG resp and AVG cardiac scans were 4.2 (2.0) mm SI and 5.8 (1.4) mm total. Dose recalculations showed that cardiac motion may impact dosimetry, with dose to 95% of the CTV dropping from 27.0 (1.3) Gy on the AVG resp to 20.5 (7.1) Gy as estimated on the AVG cardiac ., Conclusions: Cardiac CTV motion in this patient cohort is on average below 3 mm, location-dependent, and when not accounted for in treatment planning may impact target coverage. Further study is needed to assess the impact of cardiac motion on clinical outcomes., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: Established prognostic factors for head and neck squamous cell carcinoma (HNSCC) mostly consist of clinical and tumor features assessed before treatment. We report a novel application of DNA methylation in peripheral blood before and after radiation therapy to further improve outcomes stratification., Methods and Materials: Peripheral blood samples from patients with nonmetastatic HNSCC were obtained for methylation analysis 1 week before and 1 month after radiation therapy. Patients were randomized 1:1 to a Discovery Cohort or a Validation Cohort. In the Discovery Cohort, associations between genome-wide methylation change (posttreatment minus pretreatment) and recurrence-free survival (RFS) as well as overall survival (OS) were evaluated using Cox regression. A methylation risk score (MRS) was then constructed from methylation levels at the top associated sites, filtered for residing within the regulatory regions of genes expressed in cells of hematopoietic lineage. The prognostic value of MRS was separately assessed in the Discovery and Validation Cohorts., Results: Between December 2013 and September 2018, 115 patients participated in this study. Human papilloma virus negative status, oral cavity cancer, gastrostomy tube insertion, and higher neutrophil count before radiation therapy were associated with shorter RFS and OS (P < .05). Genes downstream of the methylation sites comprising MRS are HIF1A, SF1, LGALS9, and FUT5, involved in hypoxia response, blood cell maturation, and immune modulation. High MRS (in the top third) was significantly associated with worse RFS (hazard ratio [HR], 7.1; 95% confidence interval [CI], 1.4-35.5; P = .016) and OS (HR, 15.9; 95% CI, 1.6-153.6; P = .017) in the Discovery Cohort, independent of the aforementioned risk factors. These findings were replicated in the Validation Cohort, for which high MRS also independently predicted worse RFS (HR, 10.2; 95%, CI 2.4-43.4; P = .002) and OS (HR, 3.7; 95% CI, 1.3-10.4; P = .015)., Conclusions: We successfully trained and validated a signature of DNA methylation in peripheral blood before and after radiation therapy that stratified outcomes among patients with HNSCC, implicating the potential for genomics-tailored surveillance and consolidation treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Tobacco cessation is a critical but challenging intervention for cancer patients. Our National Cancer Institute-designated Comprehensive Cancer Center instituted a tobacco cessation program in 2019. This manuscript reports on the first 2 years of our experience., Methods: Patients were referred to the program by their care team, and a certified tobacco treatment specialist contacted patients remotely and provided behavioral therapy and coordinated pharmacotherapy. We retrospectively captured data from patients with a cancer diagnosis referred to the tobacco cessation program. Univariate and multivariable logistic regression analyses with the backward elimination approach were performed to determine factors associated with patient acceptance of referral to the tobacco cessation program. Tobacco cessation rates after referral to the program were also captured., Results: Between July 2019 and August 2021, 194 patients were referred to the tobacco cessation program. Of the 194 patients referred, 93 agreed to enroll in the tobacco cessation program (47.9%), of which 84 requested pharmacotherapy (90.3%). Twenty-four were able to cease tobacco use (25.8%). Only 7 patients out of the 101 patients (6.9%) who declined cessation services were successful (p < 0.001). On univariate logistic regression, race (p = 0.027) and marital status (p = 0.020) were associated with referral acceptance. On multivariable analysis, single patients (odds ratio [OR] = 0.33) and Caucasian patients (OR = 0.43) were less likely to accept a referral., Conclusions: Access to tobacco cessation services is a critical component of comprehensive cancer care. Our experience highlights the need to understand patient-specific factors associated with engagement with a tobacco cessation program during cancer treatment. The use of pharmacotherapy is also a critical component of successful tobacco cessation., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: As immunotherapy has improved distant metastasis-free survival (DMFS) in Non-Small Cell Lung Cancer (NSCLC), isolated locoregional recurrences have increased. However, management of locoregional recurrences can be challenging. We report our institutional experience with definitive intent re-irradiation using Intensity Modulated Proton Therapy (IMPT)., Method: Retrospective cohort study of recurrent or second primary NSCLC or LS-SCLC treated with IMPT. Kaplan-Meier method and log-rank test were used for time-to-event analyses., Results: 22 patients were treated from 2019 to 2021. After first course of radiation (median 60 Gy, range 45-70 Gy), 45% received adjuvant immunotherapy. IMPT re-irradiation began a median of 28.2 months (8.8-172.9 months) after initial radiotherapy. The median IMPT dose was 60 GyE (44-60 GyE). 36% received concurrent chemotherapy with IMPT and 18% received immunotherapy after IMPT. The median patient's IMPT lung mean dose was 5.3 GyE (0.9-13.9 GyE) and 5 patients had cumulative esophagus max dose >100 GyE with 1-year overall survival (OS) 68%, 1-year local control 80%, 1-year progression free survival 45%, and 1-year DMFS 60%. Higher IMPT (HR 1.4; 95% CI 1.1-1.7, p=0.01) and initial radiotherapy mean lung doses (HR 1.3; 95% CI 1.0-1.6, p=0.04) were associated with worse OS. Two patients developed Grade 3 pneumonitis or dermatitis, one patient developed Grade 2 pneumonitis, and seven patients developed Grade 1 toxicity. There were no Grade 4 or 5 toxicities., Discussion: Definitive IMPT re-irradiation for lung cancer can prolong disease control with limited toxicity, particularly in the immunotherapy era., Competing Interests: KH and JB report as potential commercial or financial conflicts of interest the following relationships: AstraZeneca consultant/advisory board RefleXion Medical funded research, advisory board, Jazz pharmaceuticals funded research, Ultimate Opinions in medicine honorarium. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Janopaul-Naylor, Cao, McCall, Switchenko, Tian, Chen, Stokes, Kesarwala, McDonald, Shelton, Bradley and Higgins.)

Purpose: To assess the resulting dosimetry characteristics of simulation and planning techniques for proton stereotactic body radiation therapy (SBRT) of primary and secondary liver tumors., Methods: Consecutive patients treated under volumetric daily image guidance with liver proton SBRT between September 2019 and March 2022 at Emory Proton Therapy Center were included in this study. Prescriptions ranged from 40 Gy to 60 Gy in 3- or 5-fraction regimens, and motion management techniques were used when target motion exceeded 5 mm. 4D robust optimization was used when necessary. Dosimetry evaluation was conducted for ITV V100, D99, Dmax, and liver-ITV mean dose and D700cc. Statistical analysis was performed using independent-samples Mann-Whitney U tests., Results: Thirty-six tumors from 29 patients were treated. Proton therapy for primary and secondary liver tumors using motion management techniques and robust optimization resulted in high target coverage and low doses to critical organs. The median ITV V100% was 100.0%, and the median ITV D99% was 111.3%. The median liver-ITV mean dose and D700cc were 499 cGy and 5.7 cGy, respectively. The median conformity index (CI) was 1.03, and the median R50 was 2.56. Except for ITV D99% (primary 118.1% vs. secondary 107.2%, p = 0.005), there were no significant differences in age, ITV volume, ITV V100%, ITV maximum dose, liver-ITV mean dose, or D700cc between primary and secondary tumor groups., Conclusion: The study demonstrated that proton therapy with motion management techniques and robust optimization achieves excellent target coverage with low normal liver doses for primary and secondary liver tumors. The results showed high target coverage, high conformality, and low doses to the liver., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors have nothing to disclose., (© 2023 Old City Publishing, Inc.)

Introduction: Patients receiving stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) are typically inoperable, in concordance with guidelines that advocate surgical resection as preferred treatment for operable patients. This differential treatment allocation complicates retrospective comparisons of surgery with SBRT by introducing the potential for confounding by operability., Methods: PubMed was queried for manuscripts reporting primary data from retrospective comparisons of overall survival (OS) between patients undergoing surgery versus SBRT for early-stage NSCLC. Each manuscript was categorized for two outcomes: (1) whether treatment allocation was based on a determination of patient operability, and (2) whether a direct OS comparison between operable SBRT patients and surgically treated patients was included. Associations with variables of interest were measured with statistical significance prespecified at p < 0.10., Results: From 3,072 manuscripts identified in our query, sixty-one analyses met screening criteria. Twenty-one (34 %) reported operability status influencing treatment allocation. These were more likely to be published in journals with a surgical focus (52 vs 20 %) and impact factor < 5 (81 vs 58 %), and to contain cohorts from institutional datasets (81 vs 55 %), and to have a radiation oncologist as first (43 vs 25 %) or senior (43 vs 28 %) author. Seven (11 %) manuscripts featured a direct OS comparison between SBRT and surgery., Conclusion: Nearly-two-thirds of peer-reviewed retrospective studies that have compared OS between surgery and SBRT for early-stage NSCLC lack information on patient operability status, and nearly 90% lack a direct comparison between operable SBRT patients and those receiving surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Numerous governmental and health organizations recommend reduced intake of added sugars due to the health risks associated with excess intake, including the risk of obesity. Some organizations further recommend avoiding dietary sweetness, regardless of the source. A scoping review and evidence map were completed to characterize the research that investigated associations between dietary sweetness and body weight. The aim was to identify and map published studies that have investigated total dietary sweetness, sweet food/beverages, sugar, or sweetener intake, and body weight-related outcomes and/or energy intake. Using preregistered search terms (osf.io/my7pb), 36,779 publications (duplicates removed) were identified from PubMed, Cochrane Library, and Scopus and screened for inclusion. Eligible studies were clinical trials, longitudinal cohorts, case-control studies, cross-sectional studies, and systematic reviews conducted among adults (age ≥18 y), which were performed to investigate associations between dietary sweetness, sweet foods/beverages, sugar, or sweetener (energetic or nonenergetic) intake and body weight, BMI, adiposity, and/or energy intake. A total of 833 eligible publications were identified, detailing 804 studies. Only 7 studies (0.9% of included studies; 2 clinical trials, 4 cross-sectional studies, and 1 with another design type) investigated associations between total dietary sweetness and body weight-related outcome and/or energy intake. An additional 608 (75.6%) studies investigated intakes of sweet foods/beverages, sugar, or sweetener, and body weight-related outcomes and/or energy intake, including 225 clinical trials, 81 longitudinal cohorts, 4 case-control studies, and 280 cross-sectional studies. Most studies (90.6%) did not measure the sweetness of the diet or individual foods consumed. Ninety-two (11.4%) publications reported data from studies on dietary patterns that included sweet foods/beverages alongside other dietary components and 97 (12.1%) systematic reviews addressed different but related research questions. Although there is a breadth of evidence from studies that have investigated associations between intakes of sweet foods and beverages, sugars, and sweeteners and body weight, there is a limited depth of evidence on the association between total dietary sweetness and body weight., (Published by Oxford University Press on behalf of the American Society for Nutrition 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Dairy products are a rich source of nutrients of public health concern, though most women do not meet the recommended intake of 3 cup-eq/day. Aim: The objective of this analysis was to examine micronutrient adequacy among pregnant women in the US by level of dairy consumption. Methods: Pregnant women (n  =  791) ages 20-44 years in NHANES 2003-2016 were categorized by level of dairy consumption (<1, 1 to <2, 2 to <3, and ≥3 cup-eq/day). Usual micronutrient intakes and prevalence of intakes below the Estimated Average Requirement (EAR) or above the Adequate Intake level (AI) were calculated from food alone and food plus dietary supplements using the National Cancer Institute method. Diet quality was assessed with the Healthy Eating Index 2015 (HEI-2015). Results: Pregnant women consuming ≥3 cup-eq/day of dairy were more likely to meet the potassium AI than women consuming lower levels. Compared to women consuming ≥3 cup-eq/day of dairy, women consuming <1 or 1 to <2 cup-eq/day were more likely to have inadequate intake of vitamin D, magnesium, zinc, and vitamin A from foods plus supplements. Compared to women consuming ≥3 cup-eq/day of dairy, women consuming <1 cup-eq/day were more likely to have inadequate intake of calcium and riboflavin. The median urinary iodine concentration (UIC) among pregnant women consuming ≥3 cup-eq/day of dairy was 220 ng/mL compared with median UICs of 98-135 mg/mL among women consuming the lowest levels. Pregnant women consuming ≥3 cup-eq/day of dairy had the highest intake of sodium (mg/day) and saturated fat intake evaluated as a HEI-2015 component. Conclusions: Consumption of recommended levels of dairy products may help pregnant women achieve adequate intakes of select micronutrients.

Background: Patients with head and neck cancer experience psychoneurological symptoms (PNS) (i.e., depression, fatigue, sleep disturbance, pain, and cognitive dysfunction) during intensity-modulated radiotherapy (IMRT) that decrease their functional status, quality of life, and survival rates. The purpose of this study was to examine and visualize the relationships among PNS within networks over time and evaluate for demographic and clinical characteristics associated with symptom networks., Methods: A total of 172 patients (mean age, 59.8 ± 9.9 years; 73.8%, male; 79.4%, White) completed symptom questionnaires four times, namely, before IMRT (T1), 1 month (T2), 3 months (T3), and 12 months (T4) post IMRT. Network analysis was used to examine the symptom-symptom relationships among PNS. Centrality indices, including strength, closeness, and betweenness, were used to describe the degrees of symptom network interconnections. Network comparison test was used to assess the differences between two symptom networks., Results: Depression was associated with the other four symptoms, and fatigue was associated with the other three symptoms across the four assessments. Based on the centrality indices, depression (r strength  = 1.3-1.4, r closeness  = 0.06-0.08, r betweeness  = 4-10) was the core symptom in all symptom networks, followed by fatigue. Female gender, higher levels of stress, and no alcohol use were associated with stronger symptom networks in network global strength before IMRT., Conclusion: Network analysis provides a novel approach to gain insights into the relationships among self-reported PNS and identify the core symptoms and associated characteristics. Clinicians may use this information to develop symptom management interventions that target core symptoms and interconnections within a network., Lay Summary: This study describes the symptom-symptom relationships for five common symptoms in patients with head and neck cancer receiving radiotherapy. Depression and fatigue appeared to be two core symptoms that were connected with sleep disturbance, pain, and cognitive dysfunction within a network. Several characteristics (i.e., female, higher stress, no alcohol use) were associated with stronger symptom networks., (© 2022 American Cancer Society.)

Objectives: Diet is an important factor in gestational health. Many pregnant women have suboptimal diets and dairy foods are an excellent source of key nutrients. The aim of this work was to investigate the relationships between dairy consumption (cup equivalents/day) or diet quality assessed using the Healthy Eating Index-2015 and gestational diabetes mellitus (GDM) or gestational weight gain (GWG) among pregnant women in the United States (US)., Methods: Study populations were subsets of pregnant, non-lactating women (20-44 years) in the National Health and Nutrition Examination Surveys 2003-2016, which was approved by the National Center for Health Statistics Research Ethics Review Board. GDM and GWG were classified according to national guidelines. General characteristics were compared across categories of dietary variables. Adjusted regression models estimated associations between diet and GDM and GWG., Results: No statistically significant linear associations between dairy consumption or diet quality and GDM or GWG were observed., Conclusions for Practice: Future research should aim to address the limitations of the current cross-sectional analyses and further elucidate the underlying relationships between diet and gestational health., (© 2022. The Author(s).)

Background/purpose: Higher estimated radiation doses to immune cells (EDIC) have correlated with worse overall survival (OS) in patients with locally-advanced non-small cell lung cancer (NSCLC) prior to the PACIFIC trial, which established consolidative durvalumab as standard-of-care. Here, we examine the prognostic impact of EDIC in the durvalumab era., Materials/methods: This single-institution, multi-center study included patients with unresectable stage II/III NSCLC treated with chemoradiation followed by durvalumab. Associations between EDIC [analyzed continuously and categorically (≤6 Gy vs > 6 Gy)] and OS, progression-free survival (PFS), and locoregional control (LRC) were evaluated by Kaplan-Meier and Cox proportional methods., Results: 100 patients were included with median follow-up of 23.7 months. The EDIC > 6 Gy group had a significantly greater percentage of stage IIIB/IIIC disease (76.0 % vs 32.6 %; p < 0.001) and larger tumor volumes (170 cc vs 42 cc; p < 0.001). There were no differences in early durvalumab discontinuation from toxicity (24.1 % vs 15.2 %; p = 0.27). Median OS was shorter among the EDIC > 6 Gy group (29.6 months vs not reached; p < 0.001). On multivariate analysis, EDIC > 6 Gy correlated with worse OS (HR: 4.15, 95 %CI: 1.52-11.33; p = 0.006), PFS (HR: 3.79; 95 %CI: 1.80-8.0; p < 0.001), and LRC (HR: 2.66, 95 %CI: 1.15-6.18; p = 0.023). Analyzed as a continuous variable, higher EDIC was associated with worse OS (HR: 1.34; 95 %CI: 1.16-1.57; p < 0.001), PFS (HR: 1.52; 95 %CI: 1.29-1.79; p < 0.001), and LRC (HR: 1.34, 95 %CI: 1.13-1.60; p = 0.007)., Conclusions: In the immunotherapy era, EDIC is an independent predictor of OS and disease control in locally advanced NSCLC, warranting investigation into techniques to reduce dose to the immune compartment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Accrual to oncology clinical trials remains a challenge, particularly during the COVID-19 pandemic. For late phase clinical trials funded by the National Cancer Institute, the development of these research protocols is a resource-intensive process; however, mechanisms to optimize patient accrual after trial activation are underdeveloped across the National Clinical Trial Network (NCTN). Low patient accrual can lead to the premature closure of clinical trials and can ultimately delay the availability of new, potentially life-saving therapies in oncology., Objective: The purpose of this study is to formally create an easily implemented tool kit of resources for investigators of oncology clinical trials within the NCTN, specifically the NRG Oncology cooperative group, in order to optimize patient accrual., Methods: NRG Oncology sought to formally develop a tool kit of resources to use at specific time points during the lifetime of NRG Oncology clinical trials. The tools are clearly described and involve the facilitation of engagement of the study principal investigator with the scientific and patient advocate community during the planning, activation, and accrual periods. Social media tools are also leveraged to enhance such engagement. The principal investigator (PI) tool kit was created in 2019 and thereafter piloted with the NRG Oncology/Alliance NRG-LU005 phase II or III trial in small-cell lung cancer. The PI tool kit was developed by the NRG Oncology Protocol Operations Management committee and was tested with the NRG/Alliance LU005 randomized trial within the NCTN., Results: NRG Oncology/Alliance NRG-LU005 has seen robust enrollment, currently 127% of the projected accrual. Importantly, many of the tool kit elements are already being used in ongoing NRG Oncology trials, with 56% of active NRG trials using at least one element of the PI tool kit and all in-development trials offered the resource. This underscores the feasibility and potential benefits of deploying the PI tool kit across all NRG Oncology trials moving forward., Conclusions: While clinical trial accrual can be challenging, the PI tool kit has been shown to augment accrual in a low-cost and easily implementable fashion. It could be widely and consistently deployed across the NCTN to improve accrual in oncology clinical trials., Trial Registration: ClinicalTrials.gov NCT03811002; https://clinicaltrials.gov/ct2/show/NCT03811002., (©Kristin A Higgins, Alexandra Thomas, Nancy Soto, Rebecca Paulus, Thomas J George, Thomas B Julian, Sharon Hartson Stine, Merry Jennifer Markham, Maria Werner-Wasik. Originally published in JMIR Cancer (https://cancer.jmir.org), 25.08.2022.)

Background: Dietary patterns developed by the USDA provide modest levels of protein (14-18% energy) within the Acceptable Macronutrient Distribution Range (AMDR) of 10-35% for adults, though diets providing a higher percentage of energy may be beneficial for some individuals. The purpose of this study was to determine if it is feasible to modify the Healthy U.S.-Style Eating Pattern ("HEP") to provide a higher percentage of energy from protein., Methods: Using the framework implemented by the USDA in developing the HEP, energy from protein was set at 20%, 25%, and 30%. Amounts of protein foods were proportionally increased while amounts of other foods were adjusted iteratively within specified parameters. The models also disaggregated total meat/poultry into fresh and processed forms to develop patterns maintaining current proportions, current levels, reduced, or no processed meat/poultry. Nutrient intakes were compared with nutrient goals for representative U.S. populations with 2,000 kcal needs (females 19-30 years, males 51-70 years), with 90% of the Recommended Dietary Allowance or Adequate Intake regarded as sufficient., Results: Dietary patterns with 20% energy from protein were constructed with minor deviations from the current 2,000 kcal HEP. Dietary patterns with 25% energy from protein were constructed for all levels of processed meat/poultry excluding the current proportion model, though relative to the current HEP the constructed patterns reflect substantial reductions in amounts of refined grains and starchy vegetables, and substantial increases in protein foods consumed as beans and peas, seafood, and soy products. It was not possible to develop a pattern with 30% energy from protein without reducing the percentage of energy from carbohydrate below the AMDR or non-compliance with other modeling constraints. Stepwise reductions in processed meat/poultry reduced sodium intake., Conclusions: It is feasible to develop dietary patterns in a 2,000 kcal diet while mirroring the HEP that meet recommended intakes of nutrients with 20% or 25% energy from protein, though the pattern with 25% energy from protein may be more idealistic than realistic. Reduced levels of processed meat/poultry may translate to lower sodium intake., (© 2022. The Author(s).)

Background: Operability is both a crucial determinant in treatment selection and a potential confounder in analyses comparing surgery with non-surgical approaches such as stereotactic body radiotherapy (SBRT). We aimed to assess the association between operability status and intervention with post-treatment mortality in early-stage non-small cell lung cancer (NSCLC)., Patients and Methods: We defined four groups of patients with cT1-T2N0M0 NSCLC diagnosed 2010 to 2014 from the National Cancer Database: SBRT patients deemed operable vs. inoperable and surgery patients receiving open vs. minimally-invasive approaches. Mortality rates at 30, 60, and 90 days post-treatment were calculated and compared., Results: We abstracted 80,108 patients, 0.8% undergoing SBRT and operable, 13.2% undergoing SBRT and inoperable, 52.4% undergoing open surgery, and 33.7% undergoing minimally-invasive surgery. Mortality rates were highest among open surgery patients and lowest among operable SBRT patients (2.0% vs. 0.2% at 30 days and 3.7% vs. 0.7% at 90 days), with intermediate results in the other two groups. These findings persisted on multivariate Cox regression: compared to patients undergoing minimally-invasive surgery, mortality risk was highest among open surgery patients (30 days HR 1.32, 95%CI 1.16-1.51; 90 days HR 1.36, 95%CI 1.24-1.50; both P < .001) and lowest among operable SBRT patients (30 days HR 0.09, 95%CI 0.01-0.64; 90 days HR 0.15, 95%CI 0.05-0.46; both P ≤ .016). These associations were maintained in a propensity score-matched subset., Conclusion: Operable patients undergoing SBRT experience minimal post-treatment mortality compared to their inoperable counterparts. These findings illustrate the potential for confounding by operability to bias results in cohort studies that compare surgical vs. non-surgical approaches in early-stage NSCLC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ultrasound imaging of the lung has played an important role in managing patients with COVID-19-associated pneumonia and acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, lung ultrasound (LUS) or point-of-care ultrasound (POCUS) has been a popular diagnostic tool due to its unique imaging capability and logistical advantages over chest X-ray and CT. Pneumonia/ARDS is associated with the sonographic appearances of pleural line irregularities and B-line artefacts, which are caused by interstitial thickening and inflammation, and increase in number with severity. Artificial intelligence (AI), particularly machine learning, is increasingly used as a critical tool that assists clinicians in LUS image reading and COVID-19 decision making. We conducted a systematic review from academic databases (PubMed and Google Scholar) and preprints on arXiv or TechRxiv of the state-of-the-art machine learning technologies for LUS images in COVID-19 diagnosis. Openly accessible LUS datasets are listed. Various machine learning architectures have been employed to evaluate LUS and showed high performance. This paper will summarize the current development of AI for COVID-19 management and the outlook for emerging trends of combining AI-based LUS with robotics, telehealth, and other techniques.

The treatment for locally advanced non-small-cell lung cancer has changed dramatically over the past several years, with consolidative immunotherapy after concurrent chemoradiation becoming the new standard of care. Five-year survival outcomes have substantially improved with this approach. Despite these advances, further improvements are needed as the majority of patients ultimately develop progression of disease. The next-generation immunotherapy trials are currently being conducted that include approaches such as concurrent immunotherapy and addition of other therapeutic agents in the concurrent and consolidative settings. Specific unmet needs continue to exist for patients who develop disease progression after concurrent chemoradiation and immunotherapy, as well as defining the best treatment for patients with driver mutations. Future directions also include refinement of radiation techniques to reduce toxicities as much as possible, as well as the use of circulating tumor DNA in the surveillance setting. The current scientific landscape shows promising approaches that may further improve outcomes for patients with locally advanced non-small-cell lung cancer., Competing Interests: Kristin A. HigginsHonoraria: PrecisCAConsulting or Advisory Role: AstraZeneca, Genentech, Varian Medical SystemsResearch Funding: Reflexion MedicalTravel, Accommodations, Expenses: AstraZeneca Sonam PuriConsulting or Advisory Role: AstraZeneca, G1 Therapeutics Jhanelle E. GrayHonoraria: Merck Sharp & Dohme, Axiom Healthcare Strategies, InivataConsulting or Advisory Role: Novartis, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, EMD Serono, Lilly, Sanofi, Merck Sharp & Dohme, Janssen Scientific AffairsResearch Funding: Array BioPharma, Merck, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Genentech/Roche, G1 Therapeutics, Novartis, Pfizer, Ludwig Institute for Cancer ResearchTravel, Accommodations, Expenses: Merck Sharp & Dohme, Inivata, Merck, EMD Serono, NovartisNo other potential conflicts of interest were reported.

Energy intake is the product of portion size (PS)-the energy content of an ingestive event-and ingestive frequency (IF)-the number of ingestive events per unit time. An uncompensated alteration in either PS or IF would result in a change in energy intake and body weight if maintained over time. The objective of this meta-analysis was to assess the independent effects of PS and IF on energy intake and body weight among healthy adults in randomized controlled trials (RCTs). A total of 9708 articles were identified in PubMed, Web of Science, Cochrane, and CINAHL databases. The articles were divided among 10 researchers; each article was screened for eligibility by 2-3 independent reviewers. Exclusion criteria included: populations <19 y and >65 y, unhealthy populations (i.e. participants with an acute or chronic disease), assessments <24 h and <4 wk in duration for trials investigating energy intake or body weight, respectively. Controlled feeding trials (i.e. fixed energy intake) that manipulated IF and PS in the same study intervention (IF/PS) were evaluated separately and for the body weight outcome only. Twenty-two studies (IF = 4, PS = 14, IF/PS = 4) met the inclusion criteria. There was an insufficient number of studies to assess the effect of IF, PS, or IF/PS on body weight. There was heterogeneity in the effect sizes among all comparisons (I2 ≥75%). Consuming larger portion sizes was associated with higher daily energy intake [295 kcal (202, 388), n = 24; weighted mean differences (WMD) (95% CI), n = comparisons], and increased frequency of ingestive events was associated with higher energy intake [203 kcal (76, 330), n = 10]. Results from RCTs support that larger PS and greater IF are both associated with higher energy consumption. However, there is insufficient information to determine chronic effects on body weight. This protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42018104757., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Purpose: Recent randomized studies have suggested improvements in progression-free and overall survival with the addition of stereotactic body radiation therapy (SBRT, also known as SABR) in patients with oligometastatic non-small cell lung cancer. Given the novelty and complexity of incorporating SBRT in the oligometastatic setting, the multidisciplinary American Radium Society Lung Cancer Panel was assigned to create appropriate use criteria on SBRT as part of consolidative local therapy for patients with oligometastatic and oligoprogressive non-small cell lung cancer., Methods and Materials: A review of the current literature was conducted from January 1, 2008, to December 25, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to systematically search the PubMed database to retrieve a comprehensive set of relevant articles., Results: Based on representation in existing randomized trials, the panel defined the term "oligometastasis" as ≤3 metastatic deposits (not including the primary tumor) in the previously untreated setting or after first-line systemic therapy after the initial diagnosis. "Oligoprogression" also referred to ≤3 discrete areas of progression in the setting of prior or ongoing receipt of systemic therapy. In all appropriate patients, the panel strongly recommends enrollment in a clinical trial whenever available. For oligometastatic disease, administering first-line systemic therapy followed by consolidative radiation therapy (to all sites plus the primary/nodal disease) is preferred over up-front radiation therapy. Owing to a dearth of data, the panel recommended that consolidative radiation therapy be considered on a case-by-case basis for 4 to 5 sites of oligometastatic disease, driver mutation-positive oligometastatic disease without progression on up-front targeted therapy, and oligoprogressive cases., Conclusions: Although SBRT/SABR appears to be both safe and effective in treating patients with limited metastatic sites of disease, many clinical circumstances require individualized management and strong multidisciplinary discussion on account of the limited existing data., (Copyright © 2021 Elsevier Inc. All rights reserved.)