Cardiovascular Risk Estimation Is Suboptimal in People With HIV.

BACKGROUND: Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts. METHODS AND RESULTS: CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c-statistics ranging from 0.78 to 0.90) and moderate for men (c-statistics ranging from 0.71 to 0.72). CONCLUSIONS: Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV-specific and sex-specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.

Hypertension Severity and Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer (WF-97415 UPBEAT).

BACKGROUND: Hypertension is a risk factor for experiencing left ventricular ejection fraction (LVEF) declines during receipt of potentially cardiotoxic breast cancer (BC) treatment. We sought to determine whether the hypertension stage is associated with LVEF decline during BC treatment. METHODS: Across 24 centers, cardiac magnetic resonance measures of LVEF and brachial arterial blood pressure (BP) measurements were performed in women with stages I to III BC before and 3 months after initiating potentially cardiotoxic chemotherapy. Using multivariable analysis, we assessed in a blinded fashion the association between 3-month ΔLVEF and precancer treatment American Heart Association/American College of Cardiology stages of hypertension. RESULTS: Among 204 women, age averaged 56±1 years with 75% being White and 20% of Black race. Participants received anthracycline (45.6%), trastuzumab (22.5%), cyclophosphamide (52.9%), or paclitaxel (50%). After accounting for pretreatment LVEF, diabetes status, tobacco use, age, the number of antihypertensive medications, and body mass index, those with stage II hypertension experienced an LVEF decline of -2.89% ([95% CI, -0.69% to -5.19%]; P=0.01) relative to individuals with normal BP. Other stages saw nonsignificant declines relative to normal BP to elevated BP (-1.63% [95% CI, -0.62% to 3.88%]; P=0.16) and stage I hypertension (-0.94% [95% CI, -0.90% to 2.78%]; P=0.32). CONCLUSIONS: Compared with women receiving treatment for BC with normal BP, there is a stronger association of decline in LVEF in women with stage II hypertension relative to women with other hypertension stages. This raises the possibility that stage along with hypertension presence may be associated with an increased risk for the LVEF decline among women receiving potentially cardiotoxic chemotherapy for BC. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02791581 and NCT01719562.

Radiotherapy for Advanced Hodgkin Lymphoma with Initial Bulk: A Combined Analysis of Two Randomized Trials.

Purpose: The role of consolidative radiation therapy (RT) in patients with advanced Hodgkin lymphoma with initial bulk is unclear. GITIL/FIL HD0607 and FIL HD0801, 2 randomized controlled trials with similar design and methodologies, did not identify a benefit to consolidative RT after a metabolic complete response to 6 cycles of doxorubicin, bleomycin, vinblastine and dacarbazine. However, their limited sample sizes reduced statistical power to detect a small but clinically meaningful benefit to RT. Methods and Materials: In a secondary analysis of these 2 phase 3 trials, reconstructed patient data were used to compare outcomes for early and complete responders randomized to no RT or RT to the site(s) of initial bulk. Estimates of progression-free survival (PFS) in the intent-to-treat (ITT) and per-protocol (PP) analyses were generated using the combined data and compared between groups using the log-rank test. Results: A total of 412 patients were included in the ITT analysis, and 373 patients were included in the PP analysis. Median age was 30 to 32 years, 42% of patients were stage IIB, and 73% of bulky sites were located in the mediastinum. For the no RT versus RT groups, 5-year ITT PFS estimates were 90.1% versus 90.1%, respectively (P = .81). Five-year PP PFS rates were 90.9% versus 92.9%, respectively (P = .31). There was no observed difference between no RT and RT groups in subgroups according to size of bulky disease: 5 to 7 cm (P = .78), 7 to 10 cm (P = .25), and >10 cm (P = .69). Conclusions: In this combined analysis of 2 randomized phase 3 clinical trials, consolidative RT to initial sites of bulky nodal involvement was not associated with a PFS benefit in patients with advanced Hodgkin lymphoma in metabolic complete response after 2 and 6 cycles of doxorubicin, bleomycin, vinblastine and dacarbazine.

Impact of Anti-Estrogen Therapy on Early Cardiovascular Referrals, Tests and Medications in Premenopausal Women with Operable Breast Cancer.

INTRODUCTION: Premenopausal women with high-risk hormone receptor (HR)-positive breast cancer often receive ovarian function suppression (OFS) and anti-estrogen therapy which induces near complete estrogen deprivation (NCED). This treatment improves recurrence-free survival but may increase cardiovascular risk. We sought to identify patterns of cardiovascular care and outcomes in premenopausal women with operable breast cancer. METHODS: Premenopausal women ≤ 50 years of age with stage I-III HR-positive or triple negative breast cancer (TNBC) were identified by retrospective review. We categorized women into 3 groups based on anti-estrogen therapy approach: NCED (HR + OFS), anti-estrogen therapy without OFS (HRnoOFS), and no anti-estrogen therapy (TNBC). Baseline characteristics, post-diagnosis cardiovascular events and cardiovascular actions (tests, referrals and medications) were recorded. Categorical variables were compared among the groups using chi-square and Fisher's exact tests; continuous outcomes were compared using ANOVA. RESULTS: 82, 83, and 52 women were identified in the HR + OFS, HRnoOFS, and TNBC groups respectively; mean follow-up was 5.0 years. Mean number of cardiovascular actions per year were highest in the HR + OFS group compared with HRnoOFS and TNBC groups (0.35 vs. 0.20 and 0.27, respectively; P = .036). The HR + OFS group had significantly more referrals and tests per year than the other groups. Cardiovascular medication initiation did not differ among groups. CONCLUSIONS: In this early follow-up period, there were meaningful numbers of cardiovascular actions, with women on NCED experiencing the most per year. Future work should seek to further understand the impact of anti-estrogen therapy on the cardiovascular health of premenopausal women and test strategies to mitigate cardiotoxicity.

Clinical Prediction Models Combining Routine Clinical Measures Have High Accuracy in Identifying Youth-Onset Type 2 Diabetes Defined by Maintained Endogenous Insulin Secretion: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: With high prevalence of obesity and overlapping features between diabetes subtypes, accurately classifying youth-onset diabetes can be challenging. We aimed to develop prediction models that, using characteristics available at diabetes diagnosis, can identify youth who will retain endogenous insulin secretion at levels consistent with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We studied 2,966 youth with diabetes in the prospective SEARCH for Diabetes in Youth study (diagnosis age ≤19 years) to develop prediction models to identify participants with fasting C-peptide ≥250 pmol/L (≥0.75 ng/mL) after >3 years' (median 74 months) diabetes duration. Models included clinical measures at the baseline visit, at a mean diabetes duration of 11 months (age, BMI, sex, waist circumference, HDL cholesterol), with and without islet autoantibodies (GADA, IA-2A) and a Type 1 Diabetes Genetic Risk Score (T1DGRS). RESULTS: Models using routine clinical measures with or without autoantibodies and T1DGRS were highly accurate in identifying participants with C-peptide ≥0.75 ng/mL (17% of participants; 2.3% and 53% of those with and without positive autoantibodies) (area under the receiver operating characteristic curve [AUCROC] 0.95-0.98). In internal validation, optimism was very low, with excellent calibration (slope 0.995-0.999). Models retained high performance for predicting retained C-peptide in older youth with obesity (AUCROC 0.88-0.96) and in subgroups defined by self-reported race/ethnicity (AUCROC 0.88-0.97), autoantibody status (AUCROC 0.87-0.96), and clinically diagnosed diabetes types (AUCROC 0.81-0.92). CONCLUSIONS: Prediction models combining routine clinical measures at diabetes diagnosis, with or without islet autoantibodies or T1DGRS, can accurately identify youth with diabetes who maintain endogenous insulin secretion in the range associated with T2D.

Clinical outcomes of oropharyngeal squamous cell carcinoma stratified by human papillomavirus subtype: A systematic review and meta-analysis.

PURPOSE: We aim to determine if there is a survival difference between patients with oropharyngeal squamous cell carcinoma (OPSCC) associated with human papillomavirus (HPV) 16 versus HPV-non16 subtypes. PATIENT AND METHODS: Databases were queried for full length, peer-reviewed, English language, articles published between 01/01/1980 and 06/08/2022. Studies reporting clinical outcomes of OPSCC associated with HPV16 and HPV-non16 subtypes with at least 10 patients were included. Primary outcome was the overall survival (OS) of patients with HPV16- versus HPV-non16-associated OPSCC. Secondary outcomes were recurrence-free survival (RFS) and pooled rate of p16 positivity by immunohistochemistry (IHC). RESULTS: A total of 9 studies met inclusion criteria and included 1,310 patients with HPV16 and 219 with HPV-non16 subtypes of OPSCC. The prevalence of HPV-non16 was 14.3 %. The pooled 5-year OS rates for patients with HPV16 and HPV-non16 were 83.4 %(95 % CI 77.8-89.0 %) and 69.3 %(95 % CI 58.5-80.1 %), respectively. OS at 5 years was significantly worse for HPV-non16 subtype, compared to HPV16 (log odds ratio [OR] -0.54, p = 0.008). There was a trend towards worse 5-year RFS with HPV-non16 compared to HPV16 (log OR -0.55, p = 0.063). Patients with HPV-non16 disease were less likely to be p16 positive by IHC (log OR -0.91, p = 0.02). CONCLUSION: Patients with HPV-non16OPSCC may experience worse OS and were less likely to be p16 positive compared to patients with HPV16 disease. While future prospective validation is warranted, routine assessment of both p16 IHC and HPV subtype could be considered prior to pursuing treatment de-escalation for HPV-associated OPSCC.

Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study.

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and 2 CCTA scans during the 2-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026 to 2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

Intensity-Modulated Radiation Therapy for Early-Stage Squamous Cell Carcinoma of the Glottic Larynx: A Systematic Review and Meta-Analysis.

PURPOSE: Early-stage squamous cell carcinoma of the glottic larynx is commonly treated with 2-dimensional or 3-dimensional conventional radiation therapy (CRT). Despite its use in other head and neck cancers, intensity-modulated radiation therapy (IMRT) remains controversial in this patient population. METHODS AND MATERIALS: A systematic review was performed by querying 3 databases (Pubmed, Embase, Web of Science) for articles published between December 1, 2000 and September 2, 2022. Included studies reported outcomes in at least 10 patients treated with IMRT for early-stage glottic cancer. Data were extracted and reported following PRISMA standards. Pooled outcomes were estimated using random-effects models. Primary outcome was the rate of local failure (LF) following IMRT. Secondary outcomes included rates of regional failure (RF) following IMRT and rates of LF and RF following CRT. RESULTS: A total of 15 studies (14 retrospective, 1 prospective) consisting of 2083 patients were identified. IMRT was used in 873 patients (64% T1, 28% T2). Multiple treatment (partial larynx, single vocal cord carotid sparing) and image-guided radiation therapy techniques were used. The pooled crude rate of LF was 7.6% (95% confidence inverval [CI], 3.6%-11.5%) and actuarial LF rates at 3 and 5 years were 6.3% (95% CI, 2.2%-10.3%) and 9.0% (95% CI, 4.4%-13.5%), respectively. The pooled crude rate of RF after IMRT was 1.5% (95% CI, 0.5%-2.5%). On metaregression analysis, increased rate of LF was significantly associated with T2 disease (P < .001) and grade 2 to 3 histology (P < .001). Treatment with CRT was reported in 738 patients (76% T1, 22% T2). Among the studies reporting outcomes of both modalities, there was no significant difference in LF (log odds ratio; P = .12) or RF (log odds ratio; P = .58) between IMRT or CRT. CONCLUSIONS: In patients with early-stage glottic cancer, retrospective data suggests local and regional control are similar for patients treated with IMRT and CRT. Additional prospective studies with uniform methods of volume delineation and image guidance are needed to confirm the efficacy of IMRT.

Quad-shot-immunotherapy: quad-shot radiotherapy with pembrolizumab for advanced/recurrent head and neck cancer.

Effective treatments for advanced/recurrent head and neck squamous-cell carcinoma are limited. For cases not curable by conventional local therapies, the immune checkpoint inhibitor pembrolizumab shows modest response rates. Quad-shot, a hypofractionated palliative radiotherapy regimen (14.8 Gy in four twice-daily fractions), can provide symptomatic relief, contributes to local control and may potentiate the effects of immune checkpoint inhibitors. In this study, 15 patients with advanced/recurrent head and neck squamous-cell carcinoma will be treated with pembrolizumab combined with up to three administrations of quad-shot before cycles four, eight and 13. Outcomes include disease response, survival and treatment toxicity. Correlative multiomics analysis of blood and saliva will identify molecular biomarkers of response to immune checkpoint inhibitor and the immune-related impact of quad-shot. Clinical trial registration: This study (WFBCCC 60320) is registered on NCT04454489 (ClinicalTrials.gov).

Advanced and recurrent head and neck cancers are difficult to treat. Most patients receive systemic therapies, such as chemotherapy or immunotherapy, with modest rates of cancer control. We aim to test the effectiveness of an immunotherapy drug called pembrolizumab in combination with a type of low-dose radiation therapy called quad-shot. Patients will receive pembrolizumab every 3 weeks and will be treated with one to three low-dose radiation therapy courses targeted at their cancer in the head and neck approximately every 12 weeks. We plan to measure how well the cancer responds to treatment, how long this response lasts, how long patients survive and treatment side effects.

Association of ipsilateral radiation therapy with contralateral lymph node failure in patients with squamous cell carcinoma of the oral cavity: A systematic review and meta-analysis.

BACKGROUND: Ipsilateral neck radiotherapy (INRT) is controversial in some patients with oral cavity cancer due to concern for contralateral neck failure (CNF). METHODS: A systematic review was performed and data were extracted following PRISMA guidelines. Outcomes were the rate of CNF following INRT and the rates of CNF by AJCC 7th ed. tumor and nodal staging. RESULTS: Fifteen studies consisting of 1825 patients were identified. Among the 805 patients treated with INRT, the rate of CNF was 5.7%. Patients with T4 tumors constituted 56% of all CNF cases. The rate of CNF increased by N stage (N0: 1.2%; N1: 3.8%; N2-N3: 17.4%) and was significantly higher for patients with N2-N3 than N0-N1 disease (p < 0.001). DISCUSSION: INRT is associated with an overall low risk of CNF in well-selected patients with N0-N1 disease. Patients with N2-3 and/or T4 disease should receive bilateral RT due to increased risk of CNF following INRT.

Plasma Progerin in Patients With Hutchinson-Gilford Progeria Syndrome: Immunoassay Development and Clinical Evaluation.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare, fatal, premature aging disease caused by a toxic protein called progerin. Circulating progerin has not been previously detected, precluding research using readily available biological samples. This study aimed to develop a plasma progerin assay to evaluate progerin's quantity, response to progerin-targeted therapy, and relationship to patient survival. METHODS: Biological samples were collected by The Progeria Research Foundation Cell and Tissue Bank from a non-HGPS cohort cross-sectionally and a HGPS cohort longitudinally. HGPS donations occurred at baseline and intermittently while treated with farnesylation inhibitors lonafarnib±pravastatin and zoledronate, within 3 sequential open-label clinical trials at Boston Children's Hospital totaling >10 years of treatment. An ultrasensitive single-molecule counting progerin immunoassay was developed with prespecified performance parameters. Intra- and interpatient group statistics were descriptive. The relationship between progerin and survival was assessed by using joint modeling with time-dependent slopes parameterization. RESULTS: The assay's dynamic detection range was 59 to 30 000 pg/mL (R2=0.9987). There was no lamin A cross-reactivity. Mean plasma progerin in non-HGPS participants (n=69; 39 male, 30 female; age, 0.2-71.3 years) was 351±251 pg/mL, and in drug-naive participants with HGPS (n=74; 37 female, 37 male; age, 2.1-17.5 years) was 33 261±12 346 pg/mL, reflecting a 95-fold increase in affected children (P<0.0001). Progerin levels did not differ by sex (P=0.99). Lonafarnib treatment resulted in an average per-visit progerin decrease from baseline of between 35% to 62% (all P<0.005); effects were not augmented by adding pravastatin and zoledronate. Progerin levels fell within 4 months of therapy and remained lower for up to 10 years. The magnitude of progerin decrease positively associated with patient survival (P<0.0001; ie, 15 000 pg/mL decrease yields a 63.9% decreased risk of death). For any given decrease in progerin, life expectancy incrementally increased with longer treatment duration. CONCLUSIONS: A sensitive, quantitative immunoassay for progerin was developed and used to demonstrate high progerin levels in HGPS plasma that decreased with lonafarnib therapy. The extent of improved survival was associated with both the magnitude of progerin decrease and duration at lower levels. Thus, plasma progerin is a biomarker for HGPS whose reduction enables short- and long-term assessment of progerin-targeted treatment efficacy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifiers: NCT00879034 and NCT00916747.

Family History of Modifiable Risk Factors and Association With Future Cardiovascular Disease.

Background A parental history of cardiovascular disease (CVD) confers greater risk of future CVD among offspring. Whether the presence of parental modifiable risk factors contribute to or modify CVD risk in offspring is unclear. Methods and Results We studied 6278 parent-child trios in the multigenerational longitudinal Framingham Heart Study. We assessed parental history of CVD and modifiable risk factors (smoking, hypertension, diabetes, obesity, and hyperlipidemia). Multivariable Cox models were used to evaluate the association of parental history and future CVD among offspring. Among 6278 individuals (mean age 45±11 years), 44% had at least 1 parent with history of CVD. Over a median follow-up of 15 years, 353 major CVD events occurred among offspring. Parental history of CVD conferred 1.7-fold increased hazard of future CVD (hazard ratio [HR], 1.71 [95% CI, 1.33-2.21]). Parental obesity and smoking status were associated with higher hazard of future CVD (obesity: HR, 1.32 [95% CI, 1.06-1.64]; smoking: HR, 1.34 [95% CI, 1.07-1.68], attenuated after adjusting for offspring smoking status). By contrast, parental history of hypertension, diabetes, and hypercholesterolemia were not associated with future CVD in offspring (P>0.05 for all). Furthermore, parental risk factors did not modify the association of parental CVD history on future offspring CVD risk. Conclusions Parental history of obesity and smoking were associated with a higher hazard of future CVD in offspring. By contrast, other parental modifiable risk factors did not alter offspring CVD risk. In addition to parental CVD, the presence of parental obesity should prompt a focus on disease prevention.

Estimating incidence of type 1 and type 2 diabetes using prevalence data: the SEARCH for Diabetes in Youth study.

BACKGROUND: Incidence is one of the most important epidemiologic indices in surveillance. However, determining incidence is complex and requires time-consuming cohort studies or registries with date of diagnosis. Estimating incidence from prevalence using mathematical relationships may facilitate surveillance efforts. The aim of this study was to examine whether a partial differential equation (PDE) can be used to estimate diabetes incidence from prevalence in youth. METHODS: We used age-, sex-, and race/ethnicity-specific estimates of prevalence in 2001 and 2009 as reported in the SEARCH for Diabetes in Youth study. Using these data, a PDE was applied to estimate the average incidence rates of type 1 and type 2 diabetes for the period between 2001 and 2009. Estimates were compared to annual incidence rates observed in SEARCH. Precision of the estimates was evaluated using 95% bootstrap confidence intervals. RESULTS: Despite the long period between prevalence measures, the estimated average incidence rates mirror the average of the observed annual incidence rates. Absolute values of the age-standardized sex- and type-specific mean relative errors are below 8%. CONCLUSIONS: Incidence of diabetes can be accurately estimated from prevalence. Since only cross-sectional prevalence data is required, employing this methodology in future studies may result in considerable cost savings.

Association of Unilateral Radiotherapy With Contralateral Lymph Node Failure Among Patients With Squamous Cell Carcinoma of the Tonsil: A Systematic Review and Meta-analysis.

Importance: Ipsilateral neck radiotherapy (RT) is controversial in some patients with tonsil cancer due to concern for nodal failure within the contralateral nonirradiated neck (hereinafter referred to as contralateral neck failure [CNF]). Objective: To determine the rate of CNF following ipsilateral neck RT in patients with tonsil cancer. Data Sources: Databases including PubMed, Embase, Web of Science, and Cochrane Library were queried for peer-reviewed, English language articles published between January 1, 1980, and December 31, 2021. Study Selection: Studies reporting rates of CNF from at least 20 patients treated with ipsilateral neck RT. Studies were excluded if they lacked full text, reported results from databases or systematic reviews, or did not provide RT details. Data Extraction and Synthesis: Data were extracted following the PRISMA reporting guideline. Study quality was assessed using criteria from a methodological index for nonrandomized studies. Pooled outcomes were estimated using random-effects models. Main Outcomes and Measures: Primary outcome was the pooled rate of CNF following ipsilateral neck RT. Secondary outcomes were the pooled rates of CNF by tumor and nodal staging categories from the 7th edition of the AJCC Cancer Staging Manual and rates of toxic effects. Results: A total of 17 studies (16 retrospective and 1 prospective) including 1487 unique patients were identified. The pooled risk of CNF was 1.9% (95% CI, 1.2%-2.6%). The rate of CNF by tumor (T) category was as follows: 1.3% (95% CI, 0.3%-2.3%) for T1; 3.0% (95% CI, 1.6%-4.4%) for T2; 11.3% (95% CI, 3.3%-19.2%) for T3; and 16.0% (95% CI, -7.8% to 39.8%) for T4. Patients with T3 to T4 tumors had a significantly higher rate of CNF than those with T1 to T2 tumors (11.5% [95% CI, 3.9%-19.1%] vs 1.8% [95% CI, 1.0%-2.6%]; P < .001). The rate of CNF by nodal (N) category was 1.2% (95% CI, 0.1%-2.2%) for N0; 4.8% (95% CI, 2.4%-7.2%) for N1; 3.1% (95% CI, 0.4%-5.8%) for N2a; 3.1% (95% CI, 1.2%-4.9%) for N2b; and 0 (95% CI, not applicable) for N3. Rates of CNF were similar for patients with N2b to N3 and N0 to N2a disease (3.0% [95% CI, 1.2%-4.7%] vs 1.7% [95% CI, 0.6%-2.8%], respectively; P = .07). Compared with bilateral RT, ipsilateral RT was associated with increased risk of CNF (log odds ratio, 1.29 [95% CI, 0.09-2.48]; P = .04). The crude rates of xerostomia of grade 3 or greater and feeding tube use were 0.9% (95% CI, -0.2% to 1.9%) and 13.3% (95% CI, 8.3%-18.3%), respectively. Conclusions and Relevance: In this systematic review and meta-analysis, ipsilateral neck RT was associated with a low rate of CNF in patients with small, lateralized tonsil cancers. Bilateral neck RT was associated with lower risk of CNF compared with ipsilateral neck RT. Patients with tumors of a higher T category were at increased risk for CNF following ipsilateral neck RT, and advanced nodal stage was not associated with CNF. Rates of toxic effects appeared favorable in patients treated with ipsilateral neck RT.

Projections of Type 1 and Type 2 Diabetes Burden in the U.S. Population Aged <20 Years Through 2060: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: To project the prevalence and number of youths with diabetes and trends in racial and ethnic disparities in the U.S. through 2060. RESEARCH DESIGN AND METHODS: Based on a mathematical model and data from the SEARCH for Diabetes in Youth study for calendar years 2002-2017, we projected the future prevalence of type 1 and type 2 diabetes among youth aged <20 years while considering different scenarios of future trends in incidence. RESULTS: The number of youths with diabetes will increase from 213,000 (95% CI 209,000; 218,000) (type 1 diabetes 185,000, type 2 diabetes 28,000) in 2017 to 239,000 (95% CI 209,000; 282,000) (type 1 diabetes 191,000, type 2 diabetes 48,000) in 2060 if the incidence remains constant as observed in 2017. Corresponding relative increases were 3% (95% CI -9%; 21%) for type 1 diabetes and 69% (95% CI 43%; 109%) for type 2 diabetes. Assuming that increasing trends in incidence observed between 2002 and 2017 continue, the projected number of youths with diabetes will be 526,000 (95% CI 335,000; 893,000) (type 1 diabetes 306,000, type 2 diabetes 220,000). Corresponding relative increases would be 65% (95% CI 12%; 158%) for type 1 diabetes and 673% (95% CI 362%; 1,341%) for type 2 diabetes. In both scenarios, substantial widening of racial and ethnic disparities in type 2 diabetes prevalence are expected, with the highest prevalence among non-Hispanic Black youth. CONCLUSIONS: The number of youths with diabetes in the U.S. is likely to substantially increase in future decades, which emphasizes the need for prevention to attenuate this trend.

Prevalence of Cardiovascular Diseases Among Breast Cancer Survivors: Findings From the NHANES 2003-2018.

PURPOSE: To examine the prevalence of cardiovascular diseases (CVD) among breast cancer (BC) survivors. DESIGN: Cross-sectional observational study using the data from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. SETTING: United States (US). SUBJECTS: A nationally representative sample of US women with a history of BC. MEASURES: Self-reported CVD status (i.e., coronary artery disease (CAD), heart failure, and stroke) and time of the CVD diagnosis were used to categorize BC survivors into three groups: No CVD, preexisting CVD, and post-acquired CVD after BC diagnosis. ANALYSIS: The prevalence of CVD among BC survivors were estimated by demographic characteristics. Complex sampling design of the NHANES was accounted to estimate the population-level prevalence. RESULTS: A total of 658 BC survivors were identified, representing 3.01% (≈3.4 million) of the US women aged ≥18 years old. Of those, ≈6% (≈.2 million) had preexisting CVD and ≈11% (≈.4 million) had at least one CVD diagnosed after BC diagnosis, with an average time elapsed ranging from ≈5 years for heart failure to ≈9 years for CAD and stroke. The prevalence of CVD among BC survivors differed by demographic characteristics including age, education, marital status, menopausal, and physical activity levels. CONCLUSION: Our findings suggest that BC survivors are at risk of suffering from CVD and public health strategies for the long-term management of CVD risk factors in this vulnerable population group is recommended.