bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibodies and cell immunity after vaccination with tozinameran (BNT162b2) in workers of National Comprehensive Cancer Center (NCCC) in Slovakia.
Authors: Palacka Patrik , Polanova Monika , Svobodova Alena , Zigmond Jan , Zanchetta Katarina , Gombarova Vlasta , Vulganova Martina , Slopovsky Jan , Obertova Jana , Mego Michal , Drgona Lubos , Pechan Juraj 
Published: June 2022

e18774 Background: Vaccination remains the leading strategy against Covid-19 worldwide. BNT 162b2 (tozinameran) belongs among first licensed vaccines with good efficacy. However, the role of monitoring both, antibodies and cell immunity after vaccination remains unclear. Methods: We conducted a 6-month prospective study involving vaccinated workers of NCCC in Slovakia who were tested for the presence of neutralizing antibodies and cell immunity after second dose of tozinameran. SARS-CoV-2 IgG antibodies were detected by the Atellica IM sCOVG, a fully automated 2-step sandwich immunoassay using indirect chemiluminescent technology. Blood samples were tested by two IGRA tests (Quantiferon RUO and CoviFeron) to assess interferon-γ (IFN-γ) responses to SARS CoV-2 spike protein antigen and nucleocapsid protein antigen. Results were stratified by gender and body mass index. P values for categorical variables were calculated using χ2 or Fishers exact test. P values for continuous variables were calculated using T test and Wilcoxon-Mann-Whitney test. Value of statistical significance was set to 0.05. Data were analyzed using SAS 9.4 software. Results: Medical records of 94 respondents (71 females) were analyzed. Mean age was 40.2 years (23 – 62 years) and mean body mass index (BMI) ± standard error of mean (SEM) was 26.4±2.7 (21.3 – 31.7). Twenty-two (23.4 %) respondents had Covid-19 before first, 5 (5.3 %) before second, and 2 (2.15 %) after second dose of vaccine (P < 0.0001). IgG were tested 24.4±5.0, 50.2±12.1, and 187.9±12.8 days after second vaccination. IgG index progressively decline with corresponding values 126.81±40.34, 93.55±51.29, and 17.68±29.07 (P < 0.0001). Mean time from second vaccination to cell immunity testing was 157.2±101.3 days. Forty-eight (51.1 %) of respondents had negative, 6 (6.4 %) border line, and 40 (42.6 %) positive cell immunity (P < 0.0001). Conclusions: Our study confirmed the efficacy of tozinameran despite both, rapid decline of antibodies and absence of cell immunity in majority of subjects.
Trends and disparities in the treatment of older adults with colon cancer.
Authors: Ding Philip Q. , Brenner Darren R , O'Sullivan Dylan E. , Cheung Winson Y. 
Published: June 2022

e18776 Background: Adults aged ≥70 years represent approximately half of all patients diagnosed with colon cancer (CC), but undertreatment in this population persists. Recent guidelines have aimed to reduce age-related biases in the treatment of CC and emphasized the importance of personalizing management with comprehensive geriatric assessments (CGAs). Therefore, we hypothesized that age-related disparities in the curative-intent treatment of CC would improve over time. Methods: This was a retrospective, population-based cohort study of adults diagnosed with CC between 2010 and 2018 in Alberta, Canada. The study data included patient demographics and clinical characteristics collected through the Alberta Cancer Registry and electronic medical records. Patients were stratified by age: < 70 and ≥70 years. Cox proportional hazard models (CPHM) were generated to evaluate the associations and interaction between age groups and treatment status on disease-specific survival (DSS), after adjusting for important covariates. Multivariable logistic regression was used to identify time trends and predictors of treatment receipt. Results: A total of 10,838 patients were included, of whom 5,176 (48%) were aged ≥70 years and 2,468 (23%) had stage IV CC at initial diagnosis. Older age was associated with greater comorbidity and less advanced disease ( p < 0.001, standardized mean difference > 0.1 for both). The vast majority (87%) of patients in the overall cohort received surgery while 34% received systemic therapy. In multivariable CPHM, older age was associated with lower DSS (HR 1.42, 95%CI 1.31-1.54, p < 0.001) while surgery and systemic therapy were each associated with higher DSS (HR 0.30, 95%CI 0.27-0.33, p < 0.001; HR 0.40, 95%CI 0.37-0.43, p < 0.001; respectively). However, the interaction between age and treatment status was not statistically significant ( p = 0.78 for surgery; p = 0.17 for systemic therapy). Compared to the younger age group, the odds of receiving surgery and systemic therapy were 3 and 5 times lower, respectively, among older patients (OR 0.27, 95%CI 0.18-0.40, p < 0.001; OR 0.18, 95%CI 0.16-0.20, p < 0.001; respectively). In addition to younger age, predictors of surgery receipt included less comorbidity and stage II/III vs I disease, whereas predictors of systemic therapy receipt included male sex, southern residence, higher neighbourhood income, less comorbidity, and stage III vs IV disease ( p < 0.05 for all). There were no statistically significant correlations between year of diagnosis and treatment receipt ( ptrend = 0.07 for surgery; ptrend = 0.26 for systemic therapy). Conclusions: Surgery and systemic therapy continue to improve CC outcomes regardless of age. However, rates of curative-intent treatment for CC were consistently lower in patients aged ≥70 years, with minimal changes over time. Better integration of CGAs into routine care may be needed to reduce persistent age-related treatment disparities.
Diagnoses, treatment, and utilization changes in oncology patients before and during COVID-19.
Authors: Wang Miao , Lardeux Sylvie , Avalos-Reyes Elisea , Johnson Kjel Andrew 
Published: June 2022

e18779 Background: COVID-19 has had an unprecedented impact on the healthcare system. During the pandemic, cancer patients experienced delayed diagnoses, interruptions in care and suboptimal care. This study aimed to understand the impact of COVID-19 on breast, lung, colon and prostate cancer patients’ diagnoses, treatment and utilization during the pandemic. Methods: This is a retrospective cohort study of breast, lung, colon and prostate cancer patients insured by a large Commercial and Medicare health plan in the United States. To assess the impact of COVID-19 on newly diagnosed treatment and utilization rates, we compareda pre-COVID period (March 1 to December 31, 2019) to a COVID period (March 1 to December 31, 2020) to assess how COVID-19 impacted diagnoses and treatment. We defined a new cancer diagnosis as a patient with medical insurance but no paid claim for cancer for at least six months before the initial claim with a cancer diagnosis. We utilized both medical and pharmacy claims to identify utilization patterns. The newly diagnosed rate and cancer diagnosis claims were normalized by total membership in the given year by line of business. Results: This study included 113,795 patients in 2019 and 112,837 patients in 2020. The newly diagnosed rate decreased by 4% (2.2 to 2.1 per 1000 patients) (p = 0.0014) for Commercial and 3% (16.2 to 15.8 per 1000 patients) (p < 0.001) for Medicare patients. Patients with infused chemotherapy treatments, among patients with cancer diagnoses, increased by 4% (9.6% to 10%) (p = 0.02) for Medicare patients but not for Commercial patients. Among patients with infused treatments, there were no significant changes in average number of infusions per patient for Commercial and Medicare patients (all p > 0.05). In 2020, there was a 2% decrease in infused treatments in the hospital setting (52% to 50%; p < 0.01) for Medicare patients; it remained stable for Commercial patients. There was also a switch from infused drugs to oral drugs for Commercial (2.4%, p < 0.001) and Medicare patients (2.0%, p < 0.001). From March to May 2020, there was a 31-35% decrease (p < 0.001) in new cancer diagnoses for Commercial and Medicare patients with a rebound in the last six months of 2020. There was an 18-21% decrease (p < 0.001) in the percentage of existing cancer patients with cancer claims during this time, reflecting a decrease in utilization. Conclusions: During the COVID-19 pandemic, we observed significant decreases in cancer diagnoses and utilization rates among new and existing Commercial and Medicare patients; however, chemotherapy treatments increased for Medicare patients during this time. We observed site of care changes in patients undergoing infused treatments. While new cancer diagnoses and utilization rates declined during the pandemic’s height, both rates quickly rebounded in the last months of 2020. As the COVID-19 pandemic continues to evolve, care for patients with cancer will need to evolve as well.
Evaluation of the use of COVID-19 vaccines in patients treated with immunotherapy.
Authors: Man Yun , Rompelman Garrett , Chen Angela , Giobbie-Hurder Anita , Buchbinder Elizabeth Iannotti 
Published: June 2022

e18781 Background: Immunotherapy can boost a patient’s immune system to bring about anti-tumor activity and may theoretically exaggerate the inflammatory immune response to infection or vaccinations. Conversely, vaccination may enhance immune activity in patients on immunotherapy. Currently, there are limited safety data in patients treated with immunotherapy who received COVID-19 vaccines. Methods: An IRB-approved retrospective review of Dana-Farber Cancer Institute patients treated with PD-1 checkpoint inhibitors and received COVID-19 vaccines was performed. The primary endpoint was the incidence rate of immune-related adverse events (irAEs) pre- and post- COVID-19 vaccinations. An Electronic Health Record search identified all patients who completed COVID-19 vaccines between 12/1/2020 and 3/31/2021 and received anti-PD-1 monotherapy between 10/1/2020 and 5/31/2021. Medical record review identified timing, occurrence, and grading of irAEs as defined by clinicians or Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Results: A total of 229 patients were included in the study. The most common underlying cancers were lung (32%) and melanoma (26%). The majority of patients had Pfizer-BioNTech COVID-19 vaccine; 64% of all patients received the third dose of vaccine. The median duration of treatment was 15 months, and median duration of follow-up was 19 months. Among the study cohort, 120 irAEs occurred before vaccination (any grade); 30 (25%) were grade 1, 35 (29%) were grade 2, 11 (9%) were grade 3 or 4, and 44 (37%) were ungraded. The main types of irAEs were skin toxicities (37% of all irAEs) followed by thyroid dysfunction (22%) and colitis (11%). Of the 75 irAEs that occurred after vaccination, 24 (32%) were grade 1, 16 (21%) were grade 2, 16 (21%) were grade 3 or 4, and 19 (26%) were ungraded. The main irAEs types were skin toxicity (31% of all irAEs) followed by thyroid dysfunction (13%) and hepatic toxicity (12 %). The all-grade pre- and post-vaccine irAE incidence rates per 100 patient-months were 4.13 and 5.09, respectively. Within this cohort, there were 0.96 (95% CI -0.362-2.284, p = 0.15) more irAEs post vaccine per 100 patient-months of anti-PD-1 therapy. Conclusions: The data weakly suggested that there is a higher incidence of irAEs post COVID-19 vaccine; however, the comparison did not achieve statistical significance. Further analysis of other patient characteristics will help to determine if any specific patterns are observed.[Table: see text]
First-line (1L) treatment patterns in advanced non-small cell lung cancer (NSCLC) patients (pts) who are elderly or have compromised performance status (PS).
Authors: Judd Julia , Handorf Elizabeth A. , Gupta Brinda , Edelman Martin Joseph 
Published: June 2022

e18783 Background: Previous studies demonstrated that pts > 80 years (80+), or compromised PS (ECOG PS > 2, PS 2+) are frequently not treated for advanced NSCLC, despite studies demonstrating survival benefit with active therapy. We hypothesized that new therapies (e.g., immunotherapy) have changed practice in these populations. Here, we present new subgroup analysis in pts 80+ or PS2+. Methods: We conducted a retrospective, observational cohort study using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database to describe 1L treatment patterns from 2011 to 2020 in pts with advanced NSCLC. Pts 80+ could only be included from 2015 as the database suppressed birth years prior to 1935 due to privacy protection. Pts were excluded if there was a > 90-day post-diagnosis gap in EHR data. Treatment groups included PD-1/PD-L1 inhibitor single agent, chemoimmunotherapy, platinum-based doublet +/- VEGF inhibitors (VEGFi), single agent chemotherapy and tyrosine kinase inhibitors (TKIs). Descriptive statistics were used to analyze treatment patterns by year, and the relationship between 1L treatments and variables of interest were tested using Cochran-Armitage trend tests. Results: Of 58,145 pts with advanced NSCLC in the database, 6,528 were 80+ (2015+) and 8,611 had PS2+ at diagnosis (2011+). While the proportion of pts who did not receive any documented treatment has decreased for those 80+ (p < 0.0001), the proportion remains the same in pts with PS2+ (p = 0.78; Table). There was rapid uptake of PD-1/PD-L1 inhibitors as well as chemoimmunotherapy upon FDA approvals in 2016 and 2018, respectively. This correlated with a rapid decrease in platinum-doublet chemotherapy +/- VEGFi and single agent chemotherapy use. Single agent immunotherapy was favored in pts 80+ (Table). TKIs accounted for 9-11% of treatment employed in pts 80+ and 6-8% in pts with PS2+, without notable change across the study period. Conclusions: Real world data from 2011 to 2020 demonstrates rapid incorporation of immunotherapy into 1L treatment for NSCLC pts who are 80+ or PS2+. A substantial proportion of pts in these subgroups (32.8% and 35.1%, respectively) still do not receive treatment. [Table: see text]
Breast cancer after reduction mammoplasty: A population-based analysis of incidence, treatment, and screening patterns.
Authors: Drohan Ashley , Quan May Lynn , Birdsell Dale , Kong Shiying , Xu Yuan 
Published: June 2022

e18785 Background: The incidence of breast cancer after reduction mammoplasty has been demonstrated to be lower than the general population in several large registry trials performed in primarily European populations; North American data is lacking. Tissue rearrangement during reduction mammoplasty may lead to abnormal breast imaging results postoperatively resulting in more challenging screening.The purpose of this study was to describe the incidence and treatment of breast cancer after reduction mammoplasty in a more contemporary Canadian population, and to better understand the use of breast cancer screening modalities in these patients. Methods: This population-based retrospective analysis utilized the Discharge Abstract Database held by the Canadian Institute for Health Information (CIHI) and the National Ambulatory Care Reporting System (NACRS) to identify all women 20 or older who underwent reduction mammoplasty in Alberta, Canada between 2003 and 2007. The incidence and treatment of breast cancer was compared among patients who underwent reduction mammoplasty and age-sex matched controls in Alberta. Imaging utilization post mammoplasty, including use of mammography, ultrasound and breast biopsy was also compared between these two groups. Results: A total of 8,021 patients over 20 years old underwent reduction mammoplasty during the study period. Patients were followed for an average of 12.6 years. Most women (6,417, 80%) underwent reduction mammoplasty surgery between the ages of 20-50. Compared to controls, women who underwent reduction mammoplasty had more comorbidities (Charlson Comorbidities > 1: 5.2% vs 4.2% controls, p < 0.0001). Overall, 89 (1.1%) patients who underwent reduction mammoplasty developed breast cancer after surgery, compared to 453 (1.9%) controls (p < 0.0001). Among patients diagnosed with breast cancer, there was no difference in patient characteristics, tumor size, histology and grade between the two groups. Fewer patients presented with metastatic disease after reduction mammoplasty (0% vs 5.1%, p = 0.043). The surgical treatment differed between groups; patients who underwent reduction mammoplasty were significantly more likely to undergo mastectomy for breast cancer (41.6% vs 1.5%, p < 0.0001). Women who underwent reduction were more likely to undergo mammography (66.7% vs 58.7%, p < 0.001), ultrasound (29.2% vs 26.2%, p < 0.0001) and biopsy for benign disease (7.2% vs 6%, p = 0.0001) compared to controls. Conclusions: Despite an increased frequency of breast cancer screening, the incidence of breast cancer is lower after reduction mammoplasty compared to women who did not undergo breast reduction. After a diagnosis of breast cancer, surgical treatment patterns differ between groups despite similarities in tumor characteristics, whereby mastectomy is more common in those who have undergone breast reduction.
Updated demographics at the only public oncology clinic in Belize.
Authors: Wong Wayne , Dickerson James , Sood Rupali , Valtis Yannis , Yacab Ramon Argenes , Lattin John , Garrity Philip , Bhatt Ami Siddharth , Huang Franklin W. 
Published: June 2022

e18787 Background: Belize is a middle-income Caribbean country without comprehensive cancer care capacity and poorly described cancer epidemiology. In 2020, we reported some of the first cancer demographics from the country. This was made possible by a capacity building partnership with the only public oncology clinic in the country at Karl Heusner Memorial Hospital (KHMH). Here we provide an update on demographic trends at this clinic. Methods: We performed a retrospective chart review of all available patient data at the KHMH clinic from December 2020 to December 2021. This was compared to data from the clinic’s founding in 2018 through its first 12 months. Results: From December 2020 through December 2021, the clinic saw 332 patients, an increase of 141% from the 236 patients seen over the first 12-month period of the clinic. In 2021, 250 (75%) patients had a confirmed pathologic diagnosis of cancer, with 78 (23%) remaining under clinical suspicion. This is in comparison to 63% of patients with a pathologic diagnosis in 2018. H&E staining alone remained the only publicly available pathologic service. Patients were predominantly female (67%) with a median age of 54 (Range: 2-95). The most common histologies (n = 332) were breast (29%), cervical (11%), colorectal (8%), prostate (4%), gastric (4%), and lung (3%). Of patients with histologically confirmed cancer, 221 (66%) were able to be fully staged. Patients predominantly presented with later stage disease (25% Stage III, 34% Stage IV). At the end of 2021, out of all patients tracked longitudinally over the year (n = 332), 24% remained in need of full diagnostic assessment, 34% were on curative treatment (predominantly cytotoxic chemotherapy), 22% were under surveillance, and 18% were receiving palliative chemotherapy or best supportive care due to advanced disease. This is in comparison to 2018, when there was no capacity to administer chemotherapy at KHMH and patients were referred to either private clinics or out of the country. Conclusions: The burden of cancer in Belize is significant and diverse. Compared to 2018, in 2021, the number of patients seen at KHMH increased 141%, as did the percentage of patients with histologically confirmed cancer (120% increase). Chemotherapy treatment was made possible through procurement of a chemotherapeutic stock at KHMH due to key partnerships with the Belizean government, hospital administration, and crucially, the only medical oncologist in the nation. This has led to chemotherapy being available at a public clinic in the country for the first time. Despite this progress, patients continue to present at late stages and many cannot access cancer care due to limited resources, cost, and low public awareness. This further affirms the need for infrastructure investment and early detection programs to improve cancer outcomes in Belize.
Sensitive detection of cancer using deep learning model of cfDNA genome-wide methylation data.
Authors: Kim Wan , Kim Minjung , Park Juntae , Park Sook Ryun , Kim Bo Hyun , Lee Jeong-Won , Oh Dongryul , Song Ki Byung , Jun Eunsung , Shim Ju Hyun , Lee Danbi , Jonggi Choi , Yoo Changhoon , Lee Tae-Rim , Ahn Jin Mo , Lee Junnam , Kim Dasom , Ki Chang Seok , Cho Eunhae 
Published: June 2022

e18789 Background: Methylation analysis of cfDNA has been used to diagnose cancer in its early stages. Previous research has concentrated on local methylation signals using cancer type specific methylation markers. We used not just methylation markers, but also global methylation patterns for sensitive cancer detection. Methods: We generated methylation data from cancer patients (N = 717) and normal controls (N = 190) using cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq, N = 907) and cell free whole genome enzymatic methyl seq (cfWGEM-seq, N = 162) from cancer patients (N = 137) and normal controls (N = 25). We analyzed at the Illumina 450K methylation microarray (N = 3,479) from The Cancer Genome Atlas (TCGA) to find differentially methylated regions (DMR) in 6 cancer types (breast, lung, liver, ovarian, esophageal, and pancreatic cancer). After determining the overlapping DMRs of each dataset, the best 1661 regions that differed the most between the cancer patient group and the normal group were left. The selected marker-based model was cross-validated using cfMeDIP samples separated into training, validation, and test sets. Additionally, global methylation count values of cfMeDIP-seq data were used to train convolutional neural network. Finally, the global methylation pattern deep learning algorithm and the marker-based algorithm were combined to detect cancer. Results: Deep learning models based on selected markers and global methylation patterns achieved test data accuracy of 0.88-0.92 and 0.90-0.91, respectively, with AUC 0.94-0.96 and 0.95-0.96. The ensemble model of two models showed test data accuracy 0.91-0.92 and AUC 0.96-0.97 with the detection of early stage of cancers (stage 1:detection rate of 88-100%, stage 2:detection rate of 75-100%, stage 3:detection rate of 90-97%, stage 4:detection rate of 92-100%). Conclusions: In this study, we selected best markers by using tissue methylation dataset (TCGA) and cfDNA methylation datasets (cfMeDIP-seq, cfWGEM-seq). To train cancer detection models, we used not only the DMR pattern but also the global methylation pattern. And the ensemble model that included these features outperformed a single model. In the field of early cancer detection, our models show potential.