bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency and outcomes of molecularly guided off-label targeted agent prescriptions in the VA National Precision Oncology Program (NPOP).
Authors: Vashistha Vishal , Guo Aixia , Katsoulakis Evangelia , Price Meghan , Ahmed Sara , Kelley Michael J.
Published: June 2022

e18676

Background: The increasing availability of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) has led to substantial improvements in outcomes among cancer pts with actionable mutations. CGP has led to identification of both on-label (level 1) variants, for which TAs have known efficacy, and off-label variants with lesser strength of supporting data. We sought to evaluate real-world prescription patterns and outcomes of off-label TA prescriptions among pts who underwent CGP. Methods: The NPOP database and VA Corporate Data Warehouse were queried to identify pts who had underwent CGP between February 2019 and December 2021 and were prescribed at least 1 of 73 TAs before January 2022. TAs prescribed for FDA-approved indications not relying on CGP as a companion diagnostic were excluded. OncoKB was used to annotate gene variants and evaluated against prescriptions to select pts who received off-label TAs. The frequency of off-label TA use, and for those treated > 4 weeks, rate of pts treated for 6 months or longer, median treatment duration and overall survival (OS) were computed. Results: Of the 18686 patients who underwent CGP, 2107 (11%) were prescribed any TA, and 191 (1%) were prescribed off-label TAs, with 31 receiving multiple concurrent or sequential off-label TAs. Mean age was 65.5 years, and 88% were male. TAs were most often prescribed for cancers of unknown primary (CUP, 29), NSCLC (24), and colorectal cancer (22). Frequency of off-label prescriptions was highest for pts who completed CGP for thyroid cancer (9%), breast cancer (8%), and CUP (2%). Most common variants involved BRAF (21%), ERBB2 (18%), BRCA1/BRCA2/ATM (9%), and PIK3CA (6%). Among all 164 pts treated > 4 weeks, 40% received TAs for 6 months or longer, including 50%, 47%, and 46% of pts bearing BRAF-, ERBB2-, and PIK3CA-mutant disease, respectively. Median therapy duration and OS was 141 [78.5 – 317, IQR] days and 181 [96.5 – 304.5, IQR] days, respectively. Conclusions: Though overall use of off-label TAs following CGP is low, nearly 10% of advanced thyroid and breast cancer patients are prescribed TAs for off-label indications. Forty percent of all pts receiving off-label TAs continue for at least 6 months, with higher rates for pts bearing BRAF-, ERBB2-, and PIK3CA-mutant disease. CGP-guided off-label treatment approaches offer unique options for advanced stage cancer with amenable molecular profiles.
National claims data analysis of outcomes of hospitalized cancer patients without COVID-19 infection during versus prior to the COVID-19 pandemic.
Authors: Caswell-Jin Jennifer Lee , Nemati Shafaee Maryam , Liu Mina , Xiao Lan , John Esther M , Bondy Melissa , Kurian Allison W.
Published: June 2022

e18679

Background: There has been growing concern regarding the impact of the COVID-19 pandemic on health care delivery and disruption of care to cancer patients. Reductions in cancer surgeries, delays in administration of life saving chemo and radiation therapies, and lower rates of cancer-related hospitalizations have been reported. While cancer patients with COVID-19 infection have poor hospitalization outcomes, less is known about the outcomes of hospitalized cancer patients without the infection. This study aimed to describe the impact of the COVID-19 pandemic on outcomes of the most common cancer-related hospital admissions for patients without COVID-19 infection at a national level using insurance claims. Given the concern for disruptions in their care, we hypothesized that hospitalized cancer patients may have worse outcomes. Methods: We used the Optum Clinformatics Data Mart, consisting of claims records linked to electronic health records, including an average of 8 million adult Americans per year enrolled for at least 6 months. We identified cancer-related hospitalizations from 02/2018-05/2021 and included patients with at least of one of these cancer types: breast, prostate, bladder, ovarian, cervical, lung, colorectal, esophageal, liver, small intestine, gastric, or gallbladder cancer. Patients with cancer-related hospitalization who had COVID-19 infection were excluded. The main outcome was “severe adverse outcome” and included at least one of the following: mortality during or within 30 days of hospitalization, mechanical ventilation during hospitalization, intensive care unit admission, or discharge to hospice. We used Poisson regression to compare the number of hospitalizations before (2/1/2018-1/30/2020) and during (2/1/2020-5/30/2021) the pandemic and a Chi-squared test to compare the proportion of cancer-related hospitalizations with severe adverse outcomes over that time period in 4-month intervals and across cancer types, gender, (male vs female) and geography (the 9 Census Bureau regions). Results: There were 82,796 cancer-related hospitalizations in the period 2/2018-05/2021. A slightly higher proportion of cancer-related hospitalizations resulted in a severe adverse outcome during the pandemic as compared to prior to the pandemic (41.8% vs 40.9%; p = 0.012). There were no differences by cancer site, gender, or geography. The number of hospitalizations was lower during vs prior to the pandemic (p < 0.0001). Conclusions: The number of cancer-related hospitalizations during the pandemic was lower compared to before the, and a slightly higher proportion of those hospitalized experienced severe adverse outcomes among insured U.S. cancer patients without COVID-19 infection. The lower number of cancer-related hospitalizations during the pandemic warrants further investigation.
Recurring event survival analyses: A methodological approach to model recurring event data in cancer patients receiving multiple lines of therapy.
Authors: Galaznik Aaron , Dudley William , Coombs Nicholas
Published: June 2022

e18693

Background: In cancer treatment, patients often receive multiple rounds of treatment, or Lines of Therapy (LoT). The time between start of a LOT and change to a new LOT is an important outcome in clinical oncology, for understanding disease progression and anticipating response to further treatment. Research questions may focus on the associations between duration of an LOT (the dependent variable) and independent variables of interest, such as time-invariant demographic (gender, age, race) and clinical factors (comorbidities, stage of disease) as well as time-varying factors such as Patient Reported Outcomes (PRO’s), resource utilization, and adverse events. These associations can be tested empirically with traditional “survival analyses”, more generally known as time-to-event when there is a single event (such as 5-year survival). The analyses, however, may become more complex when patients experience more than one LOT. This is due to the possibility that the Time-to-Events may be correlated within an individual patient, similarly to how outcome variables are correlated in other repeated measures designs. If this correlation is not captured in the modeling, the validity of parameters estimates may be in doubt. Thus, it is important to analyze the data using methods which account for the within-person correlation among LOT durations through the use of “Recurring Event” survival analyses. Methods: This methodological presentation will report an example of a real world “Recurring Event” analysis in a study of Multiple Myeloma patients who received one or more than one LOT. The study data set was derived from users of PROmpt®, an application for remote patient reporting and provider symptom management. Patient characteristics and treatment history were assessed by survey and review of patient EMR records. 80 patients were identified, with a treatment history of receiving between 1 and 19 LOT’s (mean = 5.2). Time invariant predictors are age, gender, and frailty (employing the Modified Geriatric Assessment). Time varying variables are the incidence of hematological and non-hematological toxicities. Results: The presentation will provide: an overview of how to interpret the model parameters, a discussion of the data structure required by the modeling, and a series of results in which LOT durations are analyzed as first independent and then when modeled as a “Recurring Event” analysis. The results are examined across different modeling strategies to illustrate a model testing approach, as well as to quantitatively demonstrate the impact on survival analysis results when incorporating “recurring event” methodology. Conclusions: The intent of the presentation is to alert researchers to the need to analyze Time-To-Event models using a recurring event framework when patients experience recurring events in order to produce valid and generalizable parameters.
Hospital readmission after a breast cancer-related admission among breast cancer patients with and without heart failure.
Authors: Park Chanhyun , Lee Hyesung , Jensen Brian C. , Schonberg Mara A.
Published: June 2022

e18717

Background: Breast cancer and heart failure (HF) are both costly conditions that lead to increased hospitalization. Little is known about hospital readmission among breast cancer patients with comorbid HF. We aimed to compare rates and causes of readmission among women hospitalized for breast cancer, between those with and without comorbid HF. Methods: This cross-sectional study, using the 2015–2018 Nationwide Readmissions Database (NRD), includes hospitalized women with a primary diagnosis code for breast cancer. The primary independent variable was the presence of comorbid HF. The dependent variables were 30-day and 90-day hospital readmission after hospital discharge. Women with HF were matched to women without HF by age group (18-49, 60-64, 65-79, ≥ 80 years). Multivariate logistic regression was used to assess the association between HF and hospital readmission rate while controlling for covariates. Subgroup analyses were conducted by age group. Results: Among 172,434 hospitalized women with breast cancer, 11.9% (n = 20,102) had HF; of which 8.8% were readmitted at 30 days and 15.9% at 90 days. Before matching, mean age (SD) of women with HF was 73.9 (SD +/-11.6) years and was 62.8 (+/-14.1) years in those without HF; after matching the mean age was 71.5 (+/-11.4) years for both groups. In multivariate analyses, comorbid HF was associated with a 14% increase in the 30-day readmission rate and a 20% increase in the 90-day readmission rate. HF was associated with an increased risk of readmission for women with breast cancer who were ≥ 65 years, but not for those < 65 years. Among those with HF who were ≥ 65 years, the most common cause of readmission was HF; among those with HF who were < 65 years, the most common cause of readmission was breast cancer. Conclusions: HF substantially increased the risk of hospital readmission for older women breast cancer. Timely inpatient and post-discharge management of HF, particularly for older women, will improve health outcomes and reduce the economic burden among patients with breast cancer.[Table: see text]
How to promote the sharing of RWS data in China's second-tier cities?
Authors: Wang Shasha , Wang Fang , Zeng Zhen , Gao Fang , Qin Haifeng
Published: June 2022

e18719

Background: Real world studies(RWS) measure the actual effects of treatment, not the efficacy in trials, making conclusions from real world studies more extrapolative. Clinical SCI papers are primarily based on the exploration of real-world clinical practice. We investigated the status of SCI papers published by 500 front-line clinicians, hoping to find some effective ways to promote the sharing of clinical research results in the real world. Methods: From December 2021 to January 2022, 500 front-line clinicians in 26 cities completed a 20-question online survey. Results: All of respondents were attending physicians in second-tier cities, and 7% of respondents were Bachelors, 61.8% were Masters and 31.2% were Doctors. The survey indicated surprising 83.1% of the respondents had no experience in SCI paper publication. Those(56.0%) had trouble getting paper published. Among all the respondents, 29.6% did not know the grade and submission requirements of SCI journals, 27.1% have no idea how to operate it, 24.9% had insufficient knowledge of medical statistics, 7.8% were not clear about the research design requirements for papers submitted to SCI journals. The major reasons(88.2%) for the above situation was no opportunity to receive professional systematic training. In terms of expecting help, 63.2% of patients expected to receive systematic lectures from the SCI editorial board，and 25.1% expected their peers to share their experiences in turning RWS data to paper. Conclusions: The survey indicated the ability improvement of paper publication was helpful to promote the sharing of clinical research results in the real world, and further benefit more patients.
COVID-19 vaccination status and clinical outcomes in solid cancer patients treated with immune checkpoint inhibitors.
Authors: Khaddour Karam , Meeder Natalie , Kamel Josette Mary , Babwah Amaara , Nguyen Ryan Huu-Tuan , Wang Heidy , Liu Li C. , Feldman Lawrence Eric , Jain Shikha , Weinberg Frank
Published: June 2022

e18731

Background: Immune checkpoint inhibitors (ICI) constitute the mainstay of treatment in several unresectable locally advanced and metastatic solid cancers. mRNA COVID-19 vaccines are immunogenic and can modulate intrinsic host immunostimulatory properties however the effect of COVID-19 mRNA vaccination on outcomes in patients receiving ICI is not well understood. This study examines the outcomes in cancer patients receiving ICI according to their vaccination status. Methods: From January 2021 to December 2021, we identified adult patients with locally advanced and metastatic solid tumors at the University of Illinois Hospital & Health Sciences System who had received at least one dose of ICI, either as monotherapy or in combination with chemotherapy or targeted therapy, in any line of cancer treatment. Patients were stratified by COVID-19 vaccination status and treatment type (monotherapy versus combined chemoimmunotherapy). Endpoints included immune-related adverse events (IRAEs), progression-free survival (PFS) from ICI initiation and overall survival (OS). Results: Among 89 patients meeting these inclusion criteria, the mean age at diagnosis was 66 years, patient sex was about equally split (female 50.5% to male 49.5%), most patients were minorities (including 58.4% African American), vaccinated (78.7%), had lung cancer (57.3%), were stage IV (71.1%), and had received ICI monotherapy (67.4%). There were no significant differences in the rate of IRAEs between vaccinated and non-vaccinated patients ( p= 0.53). Patients who received ICI monotherapy had higher rates of IRAEs ( p< 0.001). There was no difference in PFS between vaccinated and non-vaccinated patients ( p= 0.7) and no difference in OS between vaccinated and non-vaccinated patients ( p= 0.59). Conclusions: In this real-world sample of patients with advanced solid cancers who received ICI there were no significant differences in IRAEs, PFS or OS between vaccinated and non-vaccinated patients, which may be due to the relatively small sample size. Larger real-world datasets with long-term follow-up are needed to study the effect of mRNA COVID-19 vaccination on outcomes in advanced cancer patients receiving ICI.
Incidence of severe and febrile neutropenia in cancer patients treated with myelosuppressive chemotherapy in real clinical oncology practice: Preliminary results from the FLAME study.
Authors: Snegovoy Anton , Kononenko Inessa , Chernova Alexandra , Shepel Artem , Kaleikina Liliya , Shalina Anna , Sharov Sergey , Pavlova Elena , Goldshmidt Petr , Dergunov Alexander , Safin Rustem , Pimonova Irina , Yukalchuk Denis , Soroka Svetlana , Mikhaluk Viktorya , Vladimirova Liubov Yu , Yavorskaya Marina , Starostina Tatiyana , Tkachenko Svetlana , Sorokina Irina
Published: June 2022

e18740

Background: Febrile neutropenia (FN) is a life-threatening complication of myelosuppressive chemotherapy (CT). It can lead to infections, subsequent hospitalizations, treatment delays, dose reductions, and additional health care costs. According to guidelines, use of granulocyte colony-stimulating factors (G-CSF) prevents FN. However, in clinical practice, the need for G-CSF use has not been defined due to the lack of national reports on neutropenic complications (NC). Methods: FLAME is the first Russian retrospective non-randomized non-interventional study designed to include 515 patients (pts) with solid tumors receiving myelosuppressive CT with or without targeting and immuno-oncology drugs. The primary objective of this study is to define the actual incidence of NC in clinical practice and to identify patients at high risk of FN. In addition, this study is intended to demonstrate the unmet need for G-CSF prophylaxis of FN. Patients who completed at least the first 2 cycles of treatment in frame of the course between the 1st’Aug 2020 till 30th’October 2021 were eligible to be included in the study. Results: Data were obtained from 492 pts recruited from cancer hospitals throughout Russia. Their characteristics were as follows: median age 56.5; male/female: 36.5%/63.5%. Among 492 pts with various malignancies, 65% had stage III or IV. Breast (68%), colorectal (10%), urogynecological cancer (10%) were the most common. The remaining were gastrointestinal cancer, lung cancer, sarcoma, and CUP. Clinically significant comorbidities were reported in 53.6% of pts. Thirty percent of patients had ≥1 risk factor for FN based on individual and CT analysis. From 29 different CT regimens, 14% had a high risk of FN. Primary prophylaxis was given only to 44.1% pts with a high risk of FN [empegfilgrastim (Extimia®) 19,1%, filgrastim 25%]. The duration of filgrastim administration was 1 to 3 days in 81% of cases. Treatment of NC with corticosteroids and others was prescribed in 12.8% of cases. Three percent (3%) and 3.8% of pts had FN and dose-limiting neutropenia, respectively. Delayed CT at the second cycle was performed in 27%. The dose of CT was reduced by 20-25% in 8.3% of patients. Conclusions: Preliminary results from this study suggest that the risk of FN is higher from the start of CT. Delaying and reducing the dose of CT is still typical for oncologists. This practice is associated with low adherence to guidelines. Further efforts are needed to decrease the risk of NC in clinical practice.
Real-world evidence on predictors of survival for hormone-positive and triple-negative advanced breast cancer by treatment and BRCA status in the United States.
Authors: Zhang Dongmu , Raskin Leon , Sebby Wendy , He Lei , Pawar Sandeep , Narod Steven A , Olopade Olufunmilayo I. , Liede Alexander
Published: June 2022

e18754

Background: Factors that affect overall survival (OS) for women with metastatic or recurrent breast cancer (BC) and BRCA1 or BRCA2 mutations (BRCA+) are a matter of debate. We analyzed electronic health records (EHR) from centers across the US to examine the effect of bilateral salpingo oophorectomy (BSO) and other factors on OS across treatment and molecular subtypes with emphasis on hormone-positive (HR+) and triple-negative BC (TNBC). Methods: A cohort of women diagnosed with stage 3 or 4 HR+ or TNBC from 1-Jan-2015 to 31-Dec-2019 was identified from EHR (Tempus Labs, Chicago, IL). BRCA+ was confirmed from medical notes and laboratory reports. A comparator group included HR+ and TNBC with no record of BRCA testing (Non-BRCA). Kaplan-Meier and Cox proportional hazards were used to evaluate predictors of OS from earliest diagnosis in multivariate models by BRCA status and molecular phenotype; treatment exposure (any time), mastectomy and BSO were treated as time-dependent variables. Results: We identified 1227 women with median age of 53 years (range 18-89) at BC diagnosis and median follow up of 26.1 months (max > 26 years) and 358 deaths. Two-thirds had distant visceral or bone metastases, almost 60% were recurrent after original stage 1-3 BC; 302 women were stage 3 and 296 stage 4 at BC. The BRCA+ cohort included 439 women (195 BRCA1, 220 BRCA2, 24 “BRCA” mutation; 265 HR+, 142 TNBC) and median age at BC was 46 years (44 BRCA1, 47 BRCA2). Non-BRCA cohort consisted of 788 women with a median age of 57 at BC (378 HR+, 341 TNBC). BRCA+ had longer OS than non-BRCA ( P= 0.0001); HR+ had longer OS than TNBC ( P= 0.0001). For 331 TNBC, chemotherapeutic regimens were most common first line treatment; few (17%) received third line and 31% had no evidence of receiving systemic therapy. Age ≤50, BRCA+, and mastectomy were associated with increased OS in HR+; BRCA+ status and mastectomy were predictors of increased OS whereas platinum-based chemotherapy was associated with decreased OS in TNBC (Table). Across molecular subtypes, BSO was not an independent predictor of OS and most women (92%) had BSO after BC diagnosis. Conclusions: Regardless of BRCA status, women with advanced TNBC were almost exclusively treated with chemotherapy, which highlights the remaining unmet need for effective treatment options. Taking timing of BSO and other interventions into account is critical to understanding their effects of BC mortality.[Table: see text]
Review of health care access duration among cancer patients at a large health plan.
Authors: Rutter Wilbur , Cavers William , Prakash Shivaani , Avalos-Reyes Elisea , Johnson Kjel Andrew
Published: June 2022

e18758

Background: Cancer patients have unique, long-term health care needs and access to timely and affordable care is essential. Little is known about cancer patients’ propensity to leave their health plan during and after treatment. This study aimed to examine health care access duration among cancer survivors. Methods: Adult patients diagnosed with cancer between 11/1/2015 and 10/31/2016 were identified and followed until 11/1/2021. Control patients were identified as adults with no cancer diagnosis between 11/1/2015 and 11/1/2021. Patients with skin cancer were excluded due to limited care requirements. The primary outcomes were annual patient churn and median length of health plan enrollment duration. Propensity score (PS) matching was conducted between the groups utilizing patient demographics to balance comorbidities between groups. Comorbidity was described with the National Cancer Institute comorbidity index (NCI CI). Appropriate descriptive statistics were calculated and Cox proportional hazards (CPH) models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Overall, 3.2 million patients met the eligibility criteria, with 18% having cancer. Significant differences in the unmatched population were found, with the cancer group being older and having more comorbidities (p < 0.001). Following PS matching, the differences in underlying demographic variables were minimal, despite being statistically significant. Unadjusted annual churn rate, defined as the percent of cancer patients leaving the health plan per year, averaged 25.44% overall, with the non-cancer group experiencing more churn most years (Table). Median length of health plan enrollment duration was 716 days (Interquartile range (IQR) = 819) overall, with the cancer group having less median duration than the non-cancer group in the matched analysis (713 [IQR 808] vs. 717 [IQR 822], p < 0.001). After adjusting for the variables in the model, having a cancer diagnosis was associated with decreased risk of health plan disenrollment in multivariate CPH regression (HR 0.987 [95% CI 0.983 – 0.991]). Additional factors that increased the risk of disenrollment included: male gender (HR 1.011 [1.008-1.015]), Medicare eligibility (HR 1.290 [1.279-1.301]) and increasing NCI CI (1.124 [1.118-1.129]). Conclusions: Cancer patients experienced less churn from their health plan over a five-year follow-up. They were less at risk for disenrollment at any time than non-cancer patients when confounders are accounted for in multivariate modeling.[Table: see text]
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.