bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of local inflammation in patients with uterine fibroids and endometrial cancer.
Authors: Zykova Tatiana A. , Zlatnik Elena Yu. , Nikitina Vera P. , Shevyakova Elena A. , Zhenilo Oksana E. , Verenikina Ekaterina V. , Ivanova Viktoria A. , Kruze Polina A. , Ardzha Anna Yu. 
Published: June 2021

e17561 Background: Contribution of local inflammation to the course of endometrial cancer (EC) is of interest since it may aggravate the disease. Methods: The study included 25 women aged 62+1.6 years with histologically verified EC (group 1a), 29 women aged 48+8.4 years with uterine fibroids (UF) (group 1b) and 13 non-cancer women aged 42+2.3 years (group 2, controls). Vaginal swabs were taken prior to antitumor treatment. Relative expression of genes encoding the synthesis of IL1B, IL10, IL18, TNFA, TLR4, GATA3, and CD68 in comparison with the reference gene B2M was determined by Real-time PCR using the ImmunoQuantex kit (Russia). An integral parameter of an inflammation index was calculated using binary logistics, and the ratios of the listed indicators were also calculated. 12 parameters were analyzed in total. Groups Ia and Ib were compared with healthy people (p1) and with each other (p2). Results: 4 of 12 studied parameters in EC patients differed from control; no differences were found in UF patients. 7 statistically significant differences were registered between EC and UF. Relative expression of the gene encoding the synthesis of IL10 was maximal in EC (2.8+0.2 vs. 1.8+0.3 in healthy women (p1= 0.006) and 1.8+0.2 in UF (p2= 0.002)). The IL10/IL18 ratio in EC statistically significantly exceeded the ratios in UF patients and in healthy women (61.4+21.7 (p1= 0.003), 46.3+32.2 (p2< 0.001) and 53.7+47.1 respectively). The TNFA/IL18 ratio in EC patients was also higher than in UF patients (1.1+0.7 vs. 0.5+0.2 (p2= 0.035)) due to higher TNFA levels (3.7+0.1 vs. 3.3+0.1 (p2= 0.006)), one of which effects includes stimulation of neoangiogenesis. The ratio of TLR4/GATA3, on the contrary, was lower in EC than in UF (0.7+0.3 and 1.5+0.9 respectively (p2= 0.001). Apparently, it characterized antimicrobial immunity because both of these genes are involved in the response to PAMP (TLR4) and in the genesis of intraepithelial lymphocytes related to innate immunity, as well as in the development of a humoral response via stimulation of Th2 (GATA3). The latter, in addition, is involved in the ontogenesis some organs, including the vagina and uterus. The highest TLR4/GATA3 ratio was found in UF, which, in our opinion, indicated the predominance of the inflammatory process in UF and local immunosuppression in EC. The inflammation index determined with the ImmunoQuantex test system did not differ between the studied groups of women. Conclusions: Some differences were observed in local reactions of immunity and inflammation in benign and malignant uterine tumors, involving the prevalence of immunosuppressive and angiogenic factors in EC and inflammatory factors in UF.
Cost-effectiveness (CE) analysis of pembrolizumab as first-line (1L) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the United States (US).
Authors: Ramakrishnan Karthik , Jain Disha , Gandhi Jyotika , Chirovsky Diana Romana , Borse Rebekah 
Published: June 2021

e18013 Background: Pembrolizumab received FDA approval in 1L R/M HNSCC as monotherapy (P) in patients with combined positive score (CPS) ≥1, and in combination with platinum + 5-Fluorouracil (5-FU) chemotherapy (P + C) in the total population, based on KEYNOTE 048 (KN048) trial. Taking a US payer perspective, we evaluated the CE of P and P + C versus KN048 trial comparator cetuximab + platinum + 5-FU (EXTREME regimen), and other comparators commonly used in the US (i.e. cisplatin+docetaxel+cetuximab [TPEx regimen], platinum + paclitaxel/taxane [Pt + T] and platinum+5-FU [Pt + F]). Methods: A 3-state partitioned-survival model was used to project costs and outcomes over 20 years with a 3% annual discount rate. For P, P + C and EXTREME, health state occupancy was based on KN048 trial results with long-term parametric extrapolation of progression-free survival (PFS) and overall survival (OS) guided by statistical criteria. A network meta-analysis (NMA) was applied to the P and P + C interventions in KN048 to project the PFS and OS outcomes for other comparators. The time on treatment (ToT) for P, P+C and EXTREME was derived from the KN048 trial, whereas for other comparators, ToT was approximated by PFS. Costs of 1L and subsequent treatments, disease management, adverse event, and terminal care were included. Utilities were derived using the EuroQoL five-dimension data from KN048 and a US value set. Results: CE ratios, total and incremental costs and quality-adjusted life years (QALYs) from the base case analysis are summarized in the table below. P was more effective and less costly (i.e. dominant) versus EXTREME and TPEx. P + C was highly cost-effective versus EXTREME ($1,789/QALY) and TPEx regimen (dominant). CE ratios for both P and P + C versus all comparators were below a $100,000/QALY willingness-to-pay threshold. Probabilistic sensitivity analysis also showed a 100% CE probability for P and P + C at the $100,000/QALY threshold. Conclusions: P and P + C are cost-effective treatment options in the US with CE ratios below $100,000/QALY gained versus commonly used therapies in 1L R/M HNSCC.[Table: see text]
Prognostic nomogram for pediatric nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.
Authors: Zhang Yizhuo , Hong Ye , Chen Huimou , Wu Yanpeng , Zhu Jia , Huang Junting , Wang Juan , Sun Feifei , Que Yi , Zhang Lian , Chen Binbin , Lu Suying 
Published: June 2021

e18036 Background: There was no prognostic nomogram model exclusive for pediatric nasopharyngeal carcinoma (NPC). This study aimed to establish a nomogram, incorporating clinical characteristics and MRI features, for predicting progression-free survival (PFS) and overall survival (OS) in pediatric NPC. Methods: Children with nonmetastatic NPC treated with intensity-modulated radiotherapy (IMRT) in Sun Yat-sen University cancer center in China between 2004 to 2018 were enrolled and separated in a 3:1 ratio into a training cohort and a validation cohort. The data of the training cohort were analyzed to identify the variables independently associated with PFS and OS, and these variables were used to construct the prognostic nomogram. The predictive accuracy and discriminative capability of the nomogram were evaluated by the calibration curve and the concordance index (C-index). The nomogram was validated in the validation cohort. Results: A total of 200 patients were enrolled: 152 in the training cohort and 48 in the validation cohort. Age, serum lactate dehydrogenase level, and invasion of the clivus were the independent prognostic factors for PFS in the training cohort. The C-index of the nomogram constructed using these variables was 0.86. The calibration curve showed consistency between the nomogram prediction and the actual observation for 5-, 6- and 7-year PFS. In the validation cohort, the C-index of the nomogram was 0.64, and the calibration curve showed good consistency between the nomogram and actual observation for 5-, 6- and 7-year PFS. For OS, no independent prognostic factors were identified. Conclusions: The prognostic nomogram could be a useful tool for predicting PFS in pediatric NPC patients treated with IMRT.
Neoadjuvant intraarterial cytoreductive chemotherapy for lacrimal gland adenoid cystic carcinoma: A 33-year single-institution experience.
Authors: Costa Philippos Apolinario , Pelaez Daniel , Tse David , Benedetto Pasquale W. 
Published: June 2021

e18051 Background: Lacrimal gland adenoid cystic carcinoma (LGACC) has historically been associated with a poor prognosis even in localized disease, with the survival of 56% at 5 years and 49% at 10 years. In 1988, our group treated the first patient with neoadjuvant intra-arterial chemotherapy (IACC) followed by adjuvant chemoradiation. Since then, we use this protocol as the standard approach for localized LGACC. Herein, we aim to analyze the clinical characteristics and outcomes of LGACC patients at a single academic institution treated with the protocol to provide information on this approach's efficacy. Methods: We prospectively assessed all patients with pathologically confirmed LGACC treated at Bascom Palmer, Sylvester Comprehensive Cancer Center, or Jackson Memorial Hospital between 1988 and 2021. We calculated overall survival (OS) using the Kaplan-Meier and Cox proportional-hazards modeling methods with Log-Rank Test to estimate the 95% confidence interval. Results: 42 LGACC patients were identified, and 37 (88%) underwent IACC, with 2 (5%) being metastatic at the time of the protocol. In our cohort, the median follow-up was 10 years, 21 (56%) were men, and the median age at diagnosis was 42 (range 20-72). The average tumor size was 3cm (range 0.8-7.6). The dominant histological pattern was cribriform (n = 23, 54%), followed by basaloid (n = 6, 14%) and solid (n = 6, 14%). 16 patients underwent whole genome sequencing, and the most common mutations found were NOTCH1 (n = 7, 41%), ATM (n = 4, 25%), BPTF (n = 4, 25%), FGFR 2 (n = 3, 18%), Frem3 (n = 3, 18%), and NOTCH2 (n = 3, 18%), with additional biomarker data forthcoming. The 5, and 10-year survival rates were 85% (95% CI 73–97) and 71% (95% CI 53-89), respectively, giving and overall mean survival of 23 years (95% CI 19–28). The risk of death was higher with a tumor size larger than 3 cm and with bone invasion (HR: 6.5 and 7.5 respectively; P < 0.05). Conclusions: Despite the historically described poor prognosis, patients with LGACC treated with IACC have an excellent prognosis. Future research on tumor molecular characteristics might identify susceptibility to targeted therapies such as NOTCH or FGFR inhibitors that could be incorporated into the IACC protocol, further extending its benefits.
Racial/ethnic disparities in oropharyngeal cancer outcomes among males in the United States (2005-2016): A population-based retrospective cohort study.
Authors: Villalona Seiichi , Stroup Antoinette , Villalona Satsuki , Ferrante Jeanne 
Published: June 2021

e18576 Background: The incidence of male oropharyngeal cancers (OPCa) has increased rapidly during the past two decades in the United States. Little is known regarding differences in OPCa incidence and outcomes by race/ethnicity and human papillomavirus (HPV) status. Methods: Population-based retrospective cohort study of 175,843 males diagnosed in U.S. with OPCa from 2005-2016 in the North American Association of Central Cancer Registries. Outcomes included: incidence trends of OPCa by race/ethnicity [Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic, Other] and histology-based HPV status; late-stage diagnosis; 5-year cumulative and mean survival; and mortality (cause-specific, all cause). Results: The majority of male OPCa were HPV-related (92.2%) and in NHW (83.6%), with marked increase in late-stage HPV-related OPCa among NHW. No difference in late-stage diagnosis was observed between NHW, NHB (aOR, 0.99, 95% CI, 0.94-1.04), and Hispanics (aOR, 0.98, 95% CI, 0.92-1.04), while other race had lower odds of late-stage diagnosis (aOR 0.87, 95% CI, 0.79-1.01). HPV-related cancers (aOR, 3.47, 95% CI, 3.33-3.62), Medicaid (aOR, 1.37, 95% CI, 1.28-1.46) and no insurance (aOR, 1.44, 95% CI, 1.32-1.56) were independent predictors of late-stage diagnosis. NHB (69.72 months, 95% CI, 68.14-71.31) and Hispanics (91.89 months, 95% CI, 89.87-93.91) had lower unadjusted mean survival in HPV-related OPCa relative to NHW (99.63 months, 95% CI, 99.18-100.07; p < 0.01). Higher cancer-specific mortality was observed among NHB (aHR, 1.79, 95% CI, 1.71-1.86), Hispanics (aHR, 1.07, 95% CI, 1.01-1.14), HPV-related OPCa (aHR, 1.17, 95% CI, 1.11-1.24), age > 54 years, insurances other than private, residence in counties with higher poverty, and geographic regions other than the Northeast. Adjusting for treatment attenuated associations but did not eliminate the observed cancer-specific mortality, except in Hispanics and residence in the South. Conclusions: There has been a sharp increase in HPV-related late-stage OPCa among NHW males over the past decade. Despite no racial/ethnic differences in late-stage diagnosis, NHB had highest mortality that was not explained by treatment. HPV vaccination and possibly, oral cancer screening should be promoted, especially in NHW males. Further research is needed to elucidate comorbidities and possible biologic mechanisms responsible for the higher OPCa mortality among NHB males.
Patient adherence to LungRADS recommendations at an academic institution.
Authors: Lin Yannan , Zhang Tianran , Hsu William , Aberle Denise R. , Prosper Ashley 
Published: June 2021

e18592 Background: The National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer mortality when screened with low dose computed tomography (LDCT) as opposed to chest radiography. Notably, participants’ adherence to the screening protocol was 90%. To date, published evidence on the adherence of patients enrolled in clinical lung cancer screening (LCS) programs to LungRADS recommendations is limited. We investigate the adherence rate at our institution and determine the predictors of non-adherence to LungRADS recommendations. Methods: We performed a retrospective analysis on patients aged 50-80 years at time of baseline screen with initial screening exam at our institution between Jan 1, 2015 and Jan 12, 2021. Patients were excluded if 1) their follow-up period was insufficient to determine adherence as of Jan 28, 2021, 2) the follow-up recommendation was inconsistent with LungRADS guidelines, or 3) they died before the expected follow-up date. Adherence was defined as completion of recommended or more invasive follow-up at our institution within 12 months for LungRADS 0, 15 months for LungRADS 1/2, 9 months for LungRADS 3, 5 months for LungRADS 4A, and 3 months for LungRADS 4B/4X. A univariate logistic regression was used to determine predictors of non-adherence. Results: Among the 2120 eligible patients, 1266 (60%) were male and 854 (40%) were female with a median age of 65 at the baseline screen. One thousand four hundred and seventy-seven (70%) patients identified as White, 286 (13%) declared another racial group, and 357 (17%) did not disclose their race. One hundred and nine (5%) patients identified as Hispanic and 165 (8%) patients did not state their ethnicity. There were 1113 (53%) former smokers, 748 (35%) current smokers, and 259 (12%) patients of unspecified smoking status. Median tobacco exposure was 30 pack years (range 0.15 to 240). Fifty-seven percent of patients had private or commercial insurance while 39% had Medicare as primary insurance (3 patients were unspecified). The distribution of baseline LungRADS scores was 0: < 1%, 1: 14%, 2: 71%, 3: 7%, 4A: 4%, 4B: 2%, and 4X: < 1%. Overall adherence was 31% with 0: 38%, 1: 21%, 2: 27%, 3: 46%, 4A: 68%, 4B: 80%, and 4X: 100%. Of the 1463 non-adherent patients, 528 completed a follow-up exam beyond the expected date while 935 did not have any follow-up before the end of the study. Patients who were over 65 at baseline screen (OR = 1.34, 95% CI: 1.11, 1.61), former smokers (OR = 1.24, 95% CI: 1.02, 1.52), had Medicare insurance (OR = 1.35 95% CI: 1.12, 1.63), or had LungRADS 3/4 (referent: LR 1/2, OR = 4.29, 95% CI: 3.32, 5.55) were more likely to be adherent. Conclusions: Patient adherence to LungRADS recommendations at time of baseline screen in clinical practice is suboptimal, particularly among those with negative screens (LungRADS 1/2), with a non-adherence rate of > 70%. Baseline LungRADS scores, age, smoking status, and insurance are predictive of LCS non-adherence.
A Retrospective audit comparing the neutropenic complications in the Pre-COVID and COVID era from a tertiary care center.
Authors: Warrier Narayanankutty , Chandramohan Deepa , Vallathol Dilip Harindran , Parameswaran Prasanth V. , K. V. Sajeevan , P. S. Sreedharan 
Published: June 2021

e18619 Background: The COVID era has shown a rise in Intensive Care Unit (ICU) admissions. This is mainly due to COVID related complications. On the contrary, the public around the world have become more aware about maintaining proper hygiene by wearing masks , using hand wash and keeping themselves clean. As an audit, we conducted a retrospective analysis comparing neutropenic complications during the pre COVID and COVID times at our tertiary care cancer hospital. Methods: We collected data of febrile neutropenia admissions in ICU from March to July 2019-Non Covid (NC) and March to July 2020-Covid (C). The data collection was done including data on nadir total WBC count, use of GCSF, positive cultures, type of malignancy and deaths. The statistical analysis was done using SPSS software version 22. Results: There were 15 patients in the NC dataset and 18 patients in the C dataset. The mean age of NC was 59 (SD-9.2) and that of C was 57. 3 (SD-14). The age and sex were comparable in both the groups. The number of solid organ malignancies constituted 5 (33.33%) in NC set and 8 (44.44%) in C set. The hematological malignancies constituted 10 in each of C and NC sets. Gram negative sepsis was seen in 26.67% and 22.22% in NC and C dataset respectively. There were 4 (26.67%) deaths in NC group and 5 (27.28%) C group. Growth factors were received by 9 (60%) patients in NC group and 15 (83.3%) patients in the C group (p=0.0005). There was no significant difference in the admission, complication and death rates in ICU when comparing the two groups. These results have been depicted in Table. Conclusions: Despite the precautions taken by community during the COVID times, we conclude that there was no significant difference in the neutropenic complications. It also suggests that most of the neutropenic infections are related to the person’s immunity rather than community transmission. The study limitation is that this is a single center study but further audits and prospective studies are warranted in this regard. Keywords - COVID, Non COVID, Neutropenia, Intensive Care Unit. [Table: see text]
30-day readmission after TAVR (Transcatheter Aortic Valve Replacement (TAVR) in patients with malignancy.
Authors: Upadhyay Banskota Shristi Upadhyay , Salazar Miguel , Gauto Estefania , Macchi Hugo , Shrestha Prajwal , Khanal Nabin 
Published: June 2021

e18620 Background: Hospital readmissions after cardiac procedures are increasingly the major focus of quality improvement efforts. Although some reflect appropriate care, others are potentially preventable readmissions (PPRs). We aim to describe the burden, timing, and factors associated with readmissions after transcatheter aortic valve replacement (TAVR) in patients with malignancy. Methods: We performed a retrospective study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for TAVR with a concomitant diagnosis of malignancy. We aimed to identify 30-day readmission rate, mortality, healthcare related utilization of resources and other independent predictors of readmission. Results: A total of 2,213 patients with malignancy underwent TAVR. The 30-days readmission rate was 16% (n=355). Main causes of readmissions were found to be heart failure, sepsis, acute hypercapnic respiratory failure, coronary artery disease with angina, and AKI with ATN. Readmitted patients were more likely to come from small metropolitan areas (43.1% vs 33.6, p≤0.01), micropolitan areas (1.4% vs 0.35%, p≤0.01), rural hospital (20.3% vs 8.8%, p≤0.01), non-teaching hospital (23.5% vs 9.1%, p≤0.01), and small sized hospitals (11.5% vs 4%, p≤0.01). Patients re-admitted were more likely to have malnutrition (8% vs 3.2%, p≤0.01), new VTEs (3.8% vs 0.6, p≤0.01), AKI (26% vs 13.6%, p≤0.01) and deaths (4.6% vs 1.7%, p≤0.01). The total health care in-hospital economic burden of readmission was $5.9 million in total charges and $25 million in total costs. Independent predictors of readmission were disposition to short-term skilled nursing facilities, home-health care, and sepsis. Conclusions: We concluded that readmissions after TAVR in patients with malignancy are associated with higher in-hospital mortality rate and pose a higher health care burden. We also identified risk factors that can be targeted to decrease readmissions after TAVR, health care burden, and patient mortality.[Table: see text]
Cardiotoxic safety communications after FDA approval of novel cancer therapies.
Authors: Bonsu Janice , Kola-Kehinde Onaopepo , Kim Lisa , Ruz Patrick , Lustberg Maryam B. , Brammer Jonathan Edward , Addison Daniel 
Published: June 2021

e18629 Background: Proliferation of novel anticancer therapies has dramatically improved survival. However, in practice, cardiovascular disease (CVD) events have become an increasing concern. Post-market safety communications by the US Food and Drug Administration (FDA) are a primary source of new safety information for patients and providers. Yet, the prevalence and factors associated with the issuance of CVD warnings among cancer therapies are unknown. Methods: Leveraging the Drugs@FDA database and publicly available FDA drug reviews, we identified all anticancer drugs given new-drug applications from 1998-2018. Characteristics related to approval, including drug class, therapeutic area, priority review status, accelerated approval status, orphan product status, regulatory review times, near-regulatory deadline approval status, and post-market safety events were evaluated. Post-market safety communications were defined as the composite of safety-related drug withdrawals and the issuance of black box label warnings or precautions. CVD was defined as heart failure, hypertension (HTN), coronary disease, myocardial infarction, stroke, thromboembolic disease, arrhythmia/electrocardiographic change, or sudden cardiac death. Multivariable logistic regression was used to assess for characteristics associated with the need for CVD safety communications. Results: Overall, there were 125 novel anticancer therapies, including 24 biologics, 10 immunotherapies, and 48 targeted drugs. There were 177 safety communications (41 black box warnings, 7 withdrawals, 4 dose adjustments, and 84 general warnings). Cardiac safety warnings were issued for 63 (51.2%) of therapies, including 23 (36.5% of all) black box warnings. CVD was the most common reason for a black box warning; Table. Among all CVD warnings, arrhythmias (21.6%) followed by heart failure (13.9%), thromboembolic disease (13.9%), uncontrolled HTN (11.8%), sudden CVD death (9.0%), ischemic disease (6.9%), stroke (4.9%), and other CVD events (12.5%) were found. In a multivariable model, only therapeutic class and prior in-class cardiotoxicity were associated with the issuance of CVD safety communications. Conclusions: Among novel cancer therapies, cardiac safety communications are prevalent.[Table: see text]