US Cancer Research Articles

Discharge outcomes in COVID and non-COVID cohorts of hospitalized patients with cancer: A comparative analysis in the first year of the COVID-19 pandemic.

e23063 Background: This research aimed to assess and compare the discharge outcomes in two cohorts of hospitalized oncology patients – those with COVID-19 and those without COVID-19 in the initial year of COVID pandemic. Methods: This study compared the length of hospital stay, 30-day readmission, in-hospital mortality, death within 30 days of admission, and death within 90 days of admission between the COVID cohort and the non-COVID cohort, based on prospectively collected hospitalization data from March 2020 to February 2021 at a prominent US cancer center. Results: The study included 4,225 oncology patients, with 551 having COVID-19. Aged on average around 61, both cohorts showed similar gender distribution and were predominantly White or Caucasian, with the most common cancers being hematological. Patients in the COVID cohort experienced a significantly extended hospital stay with a mean length of 12.2 days versus 8.27 days for the non-COVID cohort (p < 0.001). The median stay was also longer for the COVID cohort at 8 days [1, 103] compared to 5 days [1, 141] for the non-COVID cohort. The COVID cohort had a lower 30-day readmission rate post-discharge at 66.6% compared to 71.7% in the non-COVID cohort, with the difference being statistically significant (p = 0.015). Within the COVID cohort, a smaller proportion of patients were readmitted within 30 days of discharge (66.6%), as opposed to the non-COVID cohort (71.7%), with a p-value of 0.015. Although the COVID cohort experienced a higher rate of in-hospital mortality at 11.3% compared to 6.9% in the non-COVID cohort (p < 0.001), there were no significant differences in the rates of death within 30 days of admission (COVID cohort: 25.6% vs. non-COVID cohort: 27.6%, p = 0.349) or within 90 days of admission (COVID cohort: 28.9% vs. non-COVID cohort: 31.7%, p = 0.195) between the two cohorts. Conclusions: Oncology patients with COVID-19 faced longer hospital stays and higher in-hospital mortality rates than those without COVID-19. However, the COVID-19 cohort had a lower rate of readmission within 30 days after discharge. Despite the greater severity of hospitalization for COVID-19 patients, the mortality rates 30 and 90 days post-admission did not significantly differ from those without COVID-19. These findings underscore the need for intensified care and monitoring of hospitalized oncology patients with COVID-19, while also acknowledging the comparable longer-term survival between the cohorts.

Mapping disparities in head and neck cancer care: Geospatial analysis of social vulnerability and healthcare access in the US.

e23112 Background: Ensuring equitable access to head and neck (H&N) cancer care across the US is vital for optimal patient outcomes. This study explores the impact of social vulnerability on disparities in access to H&N multidisciplinary specialist care by US region and metro status. Methods: Oncologists and a subset of H&N cancer specialist practice locations were extracted from the National Provider Index, American Society of Clinical Oncology, and US News and World Report. Travel time using the fastest transportation mode from population-weighted county centroids to the nearest H&N cancer specialist (surgical, radiation, or medical oncologist) was computed using Travel Time API. Cancer data were obtained from United States Cancer Statistics and Surveillance, Epidemiology, and End Results (SEER). Regression analysis assessed impact of aspects of social vulnerability from the Social Vulnerability Index (SVI) on travel time. A disparity index incorporating travel time, county-level H&N cancer incidence, and SVI was developed to quantify disparities at the county-level. Results: In total, 18,241 medical, 6,387 radiation, and 2,564 surgical oncologists were identified, of which 346 medical, 308 radiation, and 453 surgical oncologists self-identified as H&N specialists. Regression analysis indicated that low household income and lack of insurance within counties significantly increased travel time ( p < .001) after controlling for US region, metro status, cancer rate, and other county-level factors. The disparity index identified counties with highest and lowest disparity (Table 1). Conclusions: Key findings highlight specific counties with higher vulnerability, primarily rural counties in the West and Southeast, and underscores the influence of social vulnerability on access to care. After accounting for US region and metro status, aspects of social vulnerability still predict travel time, with low household income and lack of insurance being the most impactful. Identified disparities in care may provide targets for interventions and policies aimed at reducing access inequalities, such as outreach programs and allocation of resources to underserved areas. [Table: see text]

Electronic clinical quality measure (eCQM) concordance and quality care disparities among patients with breast cancer (BC).

e23237 Background: BC mortality is decreasing steadily, yet disparities in treatment and outcomes persist. eCQMs are metrics specified in a standard electronic format using data from electronic health records (EHR) and other systems to measure care quality. CancerLinQ is a health technology platform aggregating EHR data from ~7M patients (pts) seen in US oncology practices and cancer centers. This analysis assesses odds of non-concordance with 4 BC-specific eCQMs in CancerLinQ. Methods: Pts actively treated for BC in 2021 in CancerLinQ data were included in this study. The following four practice-level eCQMs were assessed as proportions of BC pts who: eCQM1 – Undergo HER2 testing eCQM2 – Are < age 70 with early-stage, hormone receptor (HR) negative BC who receive combination chemotherapy < 4 months of dx eCQM3 – Have early-stage, HER2+ BC and receive trastuzumab eCQM4 – Have early-stage, HR+ BC and receive tamoxifen or an aromatase inhibitor (AI) < 1-year of dx Ethnicity, race, age at dx, pt/practice rural status, and practice type were assessed as covariates. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were calculated for associations among study variables and receipt of guideline non-concordant care. Results: aORs (95% CI) of pt characteristics were compared to reference groups - non-Hispanic, white, age at dx 60-69, married, urban: eCQM1 (N = 21296): For unknown ethnicity, aOR (95% CI) = 1.5 (1.3 1.6); unknown race = 1.3 (1.2, 1.5); age 70-79 = 1.1 (1.0, 1.2), age 80-89 = 1.4 (1.2, 1.5), age > 90 = 1.5 (1.1, 2.2); formerly married/partnered = 1.2 (1.1, 1.3), thus having greater odds of non-concordance. Age 40-49, aOR (95% CI) = 0.9 (0.8, 0.986), had lower odds of non-concordance. eCQM2 (N = 1259): For unknown ethnicity, aOR (95% CI) = 1.9 (1.2, 3.1); Asian = 2.9 (1.7, 4.9) or other race = 2.3 (1.2, 4.1); and formerly married/partnered = 1.7 (1.2, 2.6), thus having greater odds of non-concordance. Pts age < 40 = 0.6 (0.3, 0.9) had lower odds of non-concordance. eCQM3 (N = 1341): Age > 80, aOR (95% CI) = 3.8 (1.5, 9.1), had greater odds of non-concordance. eCQM4 (N = 5063): For age < 40, aOR (95% CI) = 2.9 (2.1, 4.1), age 40-49 = 1.6 (1.2, 2.0), and age 50-59 = 1.5 (1.2, 1.9); and formerly married/partnered = 1.3 (1.1, 1.7), thus having greater odds of non-concordance. Conclusions: As expected, pts < 40 had greater odds of receiving chemotherapy and pts > 80 had lower odds of receiving trastuzumab, possibly due to cardiotoxicity concerns. Although all women with early-stage HR+ BC are potential tamoxifen/AI candidates, pts < 60 with early-stage HR+ BC had greater odds of not receiving tamoxifen/AI compared to those age 60-69. Additionally, divorced, separated, or widowed pts had greater odds of non-concordant care in 3 of 4 of eCQMs assessed. Our findings demonstrate the ability of eCQMs to identify clinical subgroups more likely to receive non-concordant care who may be eligible for targeted interventions.

Statins among US adults and cancer: where the future liaises?

Statins among US adults and cancer: where the future liaises?

Abstract PO2-16-05: ESR1 mutations (ESR1mut) in HR(+)HER2(-)patients with metastatic breast cancer (MBC): prevalence along treatment course and predictive value for endocrine therapy (ET) resistance in real-world practice

Abstract Background: ET combined with CDK4/6 inhibitors (CDKi) is the standard of care for HR(+)HER2(-) patients with MBC. ESR1mut is an acquired resistance mechanism to ET, especially aromatase inhibitors (AI). The prevalence and behavior of ESR1mut in patients receiving the selective estrogen receptor degrader (SERD) fulvestrant remains in question. This study aimed to characterize the prevalence of ESR1mut at start of successive lines of therapy and to evaluate clinical outcomes of ET by ESR1 status in 1st line therapy in real-world practice. Methods: This study included patients with HR(+)HER2(-) MBC who underwent genomic testing using Foundation Medicine tissue or liquid comprehensive genomic profiling (CGP) assays, with specimens collected within 60 days of therapy initiation. Patient clinical data was obtained by the nationwide (US-based) de-identified Flatiron Health and Foundation Medicine real-world clinicogenomic breast database (FH-FMI CGDB), originated from ~280 US cancer clinics (~800 sites of care) between 01/2011 and 04/2023. ESR1mut prevalence was calculated in tissue and liquid samples collected in the 1st, 2nd, and 3rd lines of therapy. Real-world progression free-survival (rwPFS), time to treatment discontinuation (rwTTD), and overall survival (rwOS) were compared between patients who received AI + CDKi and between patients receiving fulvestrant + CDKi 1st line therapy [ESR1mut vs. ESR1 wild-type (wt) by tissue CGP] by Cox models. Multivariable analyses adjusted for adjuvant therapy, age, ECOG, menopausal status, histology, stage at diagnosis, metastatic site, and specific ESR1mut (Y537S, D538G, E380W, or others) were performed. Results: The prevalence of ESR1mut in tissue samples collected in 1st, 2nd, and 3rd lines of therapy was 7.9% (n=159/2004), 26.4% (n=66/250), and 34.0% (n=68/200), respectively. The prevalence of ESR1mut in liquid samples collected in the 1st, 2nd, and 3rd lines of therapy was 11.6% (n=30/259) 34.4% (n=63/183), and 35.9% (n=42/117), respectively. Among patients receiving AI + CDKi 1st line therapy (n=485), those with ESR1mut vs. ESR1wt had less favorable rwPFS [median 6.1 vs. 20.8 months, hazard ratio (HR) 2.36, 95% CI 1.35-4.14, p=0.003]. rwTTD and rwOS assessments were consistent with the magnitude of effect of rwPFS. Among patients receiving fulvestrant + CDKi 1st line therapy (n=302), those with ESR1mut vs. ESR1wt had less favorable rwPFS (median 10.5 vs. 14.5 months, HR 1.5, 95% CI 1.05-2.15, p=0.025), but no difference was observed for rwTTD and rwOS (p >0.05). Notably, the multivariable analyses found the independent association of ESR1mut and less favorable rwPFS (HR 2.18, 95% CI 1.15-4.1, p=0.018), rwTTD (HR 3.34, 95% CI, 1.84-6.1, p< 0.001), and rwOS (HR 2.46, 95% CI 1.04-5.9, p=0.041) in patients receiving AI + CDKi. The multivariable analyses confirmed no association between ESR1mut and outcomes in patients receiving fulvestrant + CDKi (p >0.05). No substantial differential associations were observed between specific ESR1mut and clinical outcomes in the multivariable analyses. Conclusion: In our dataset, ESR1mut is prevalent in about 8-11% of baseline tissue and liquid samples of patients with HR(+)HER2(-) MBC. Baseline ESR1mut is associated with less favorable outcomes in patients receiving AI + CDKi 1st line therapy, but not in patients receiving fulvestrant + CDKi. Specific ESR1mut do not seem to be associated with different outcomes to ET. ESR1mut prevalence increased during treatment course. Further investigation is warranted to determine optimal endocrine partner with CDKi based upon ESR1 status, particularly with development of oral SERDs. Citation Format: Manali Bhave, Julia Quintanilha, Ryon Graf, Takara Scott, Hanna Tukachinsky, Gerald Li, Alexa Schrock, Geoffrey Oxnard, Mia Levy, Kevin Kalinsky. ESR1 mutations (ESR1mut) in HR(+)HER2(-)patients with metastatic breast cancer (MBC): prevalence along treatment course and predictive value for endocrine therapy (ET) resistance in real-world practice [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-05.

Abstract PO4-17-11: Normalized Breast Cancer Survival Outcomes in U.S. Tumor Registries

Abstract Background The largest U.S. tumor registries, NCDB (National Cancer Database) and SEER (Surveillance, Epidemiology, and End Results Program), are vital sources of epidemiological data and are frequently utilized in research. Although the NCDB includes the majority of patients diagnosed with breast cancer, it is a hospital-based registry. In contrast, SEER is a population-based registry, but includes less than half of all breast cancer patients diagnosed each year. While the US Cancer Statistics Public Use Database (USCS) captures nearly all breast cancers, treatment and survival data are not included. As such, we sought to normalize the NCDB and SEER populations to mirror the USCS population and examine survival outcomes after normalization. Methods All patients diagnosed with stage I-IV breast cancer (2010-2018) were selected from the NCDB and SEER. Frequencies of patients by select characteristics were exported from the USCS. Rates from the USCS were then used to normalize the NCDB and SEER cohorts, using patient weighted frequencies for age, sex, race/ethnicity, tumor biomarkers [estrogen receptor (ER), HER2], and extent of disease (local, regional, distant; anatomic staging data not available in USCS). Of note, the USCS does not have individual patient-level data (only summary data for select variables), and thus, weighted frequencies were used for normalization. The weighted frequencies were calculated based on the total number of patients in the USCS database divided by the total number of patients in the NCDB or SEER separately for each variable (age, sex, race/ethnicity, etc). Weighted and unweighted data were summarized with N (%). Unweighted patient and disease characteristics (crude data) were compared using Chi-square tests. Overall survival (OS) was estimated using the Kaplan-Meier method before and after normalization. Results The USCS cohort included 2,473,739 patients; the NCDB included 1,441,556 and SEER 504,938. The median followup was 54.9 months for NCDB and 57 months for SEER. There were minimal differences between the cohorts based on age (age < 50y: USCS 18.1%, NCDB 19.3%, SEER 18.9%) or sex (female: USCS 99.1%, NCDB 99.1%, SEER 99.3%). However, there were notable differences in the racial/ethnic composition; non-Hispanic White: USCS 75%, NCDB 78.2%, SEER 68.2%; non-Hispanic Black: USCS 11.4%, NCDB 11.4%, SEER 9.9%; Hispanic: USCS 8.3%, NCDB 5.9%, SEER 11.7%; p< 0.001 for USCS vs NCDB and USCS vs SEER). There were minimal differences in tumor biomarkers (ER+: USCS 82.9%, NCDB 83%, SEER 84.9%; HER2+: USCS 14.5%, NCDB 14.1%, SEER 13.8%), but significant differences in extent of disease (local: USCS 66.1%, NCDB 80.2%, SEER 68.4%; distant: USCS 6%, NCDB 3.9%, SEER 3.9%; p< 0.001 for USCS vs NCDB and USCS vs SEER). For the variables that were similar without weighting (age, sex, tumor biomarkers), OS was also similar after weighting (Table). After normalizing the NCDB based on race, 8-year OS remained comparable (crude 77.2% vs weighted 77.3%); similar findings were noted after normalizing SEER (crude 75.8% vs weighted 75.3%). After normalizing the NCDB based on extent of disease, 8-year OS was notably worse (crude 77.2% vs weighted 74.2%); similar findings were noted for SEER (crude 75.8% vs weighted 74.4%). Conclusions While national tumor registries afford researchers the opportunity to study large breast cancer cohorts, they do not always fully represent the entire breast cancer population. This limitation should be considered when working with these data sets. Table. Citation Format: Tori Chanenchuk, Kerri-Anne Crowell, Samantha Thomas, Rachel Greenup, Jennifer Plichta. Normalized Breast Cancer Survival Outcomes in U.S. Tumor Registries [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-11.

Disparities in Cancer Stage Outcomes by Catchment Areas for a Comprehensive Cancer Center

The National Cancer Institute comprehensive cancer centers (CCCs) lack spatial and temporal evaluation of their self-designated catchment areas. To identify disparities in cancer stage at diagnosis within and outside a CCC's catchment area across a 10-year period using spatial and statistical analyses. This cross-sectional, population-based study conducted between 2010 and 2019 utilized cancer registry data for the Johns Hopkins Sidney Kimmel CCC (SKCCC). Eligible participants included patients with cancer in the contiguous US who received treatment for cancer, a diagnosis of cancer, or both at SKCCC. Patients were geocoded to zip code tabulation areas (ZCTAs). Individual-level variables included sociodemographic characteristics, smoking and alcohol use, treatment type, cancer site, and insurance type. Data analysis was performed between March and July 2023. Distance between SKCCC and ZCTAs were computed to generate a catchment area of the closest 75% of patients and outer zones in 5% increments for comparison. The primary outcome was cancer stage at diagnosis, defined as early-stage, late-stage, or unknown stage. Multinomial logistic regression was used to determine associations of catchment area with stage at diagnosis. This study had a total of 94 007 participants (46 009 male [48.94%] and 47 998 female [51.06%]; 30 195 aged 22-45 years [32.12%]; 4209 Asian [4.48%]; 2408 Hispanic [2.56%]; 16 004 non-Hispanic Black [17.02%]; 69 052 non-Hispanic White [73.45%]; and 2334 with other or unknown race or ethnicity [2.48%]), including 47 245 patients (50.26%) who received a diagnosis of early-stage cancer, 19 491 (20.73%) who received a diagnosis of late-stage cancer , and 27 271 (29.01%) with unknown stage. Living outside the main catchment area was associated with higher odds of late-stage cancers for those who received only a diagnosis (odds ratio [OR], 1.50; 95% CI, 1.10-2.05) or only treatment (OR, 1.44; 95% CI, 1.28-1.61) at SKCCC. Non-Hispanic Black patients (OR, 1.16; 95% CI, 1.10-1.23) and those with Medicaid (OR, 1.65; 95% CI, 1.46-1.86) and no insurance at time of treatment (OR, 2.12; 95% CI, 1.79-2.51) also had higher odds of receiving a late-stage cancer diagnosis. In this cross-sectional study of CCC data from 2010 to 2019, patients residing outside the main catchment area, non-Hispanic Black patients, and patients with Medicaid or no insurance had higher odds of late-stage diagnoses. These findings suggest that disadvantaged populations and those living outside of the main catchment area of a CCC may face barriers to screening and treatment. Care-sharing agreements among CCCs could address these issues.

Association of patient socioeconomic status with outcomes after palliative treatment for disseminated cancer.

Palliative treatment has been associated with improved quality of life and survival for a wide variety of metastatic cancers. However, it is unclear whether the benefits of palliative treatment are uniformly experienced across the US cancer population. We evaluated patterns and outcomes of palliative treatment based on socioeconomic, sociodemographic and treating facility characteristics. Patients diagnosed between 2008 and 2019 with Stage IV primary cancer of nine organ sites were analyzed in the National Cancer Database. The association between identified variables, and outcomes concerning the administration of palliative treatment were analyzed with multivariable logistic regression and Cox proportional hazard models. Overall 238,995 (23.6%) of Stage IV patients received palliative treatment, which increased over time for all cancers (from 20.7% in 2008 to 25.6% in 2019). Palliative treatment utilization differed significantly by region (West less than Northeast, OR: 0.55 [0.54-0.56], p < 0.001) and insurance payer status (uninsured greater than private insurance, OR: 1.35 [1.32-1.39], p < 0.001). Black race and Hispanic ethnicity were also associated with lower rates of palliative treatment compared to White and non-Hispanics respectively (OR for Blacks: 0.91 [0.90-0.93], p < 0.001 and OR for Hispanics: 0.79 [0.77-0.81] p < 0.001). There are important differences in the utilization of palliative treatment across different populations in the United States. A better understanding of variability in palliative treatment use and outcomes may identify opportunities to improve informed decision making and optimize quality of care at the end-of-life.

Trends in financial payments from industry to US cancer centers, 2014-2021.

Industry payments to US cancer centers are poorly understood. US National Cancer Institute (NCI)-designated comprehensive cancer centers were identified (n = 51). Industry payments to NCI-designated comprehensive cancer centers from 2014 to 2021 were obtained from Open Payments and National Institutes of Health (NIH) grant funding from NIH Research Portfolio Online Reporting Tools (RePORT). Given our focus on cancer centers, we measured the subset of industry payments related to cancer drugs specifically and the subset of NIH funding from the NCI. Despite a pandemic-related decline in 2020-2021, cancer-related industry payments to NCI-designated comprehensive cancer centers increased from $482 million in 2014 to $972 million in 2021. Over the same period, NCI research grant funding increased from $2 481 million to $2 724 million. The large majority of nonresearch payments were royalties and licensing payments. Industry payments to NCI-designated comprehensive cancer centers increased substantially more than NCI funding in recent years but were also more variable. These trends raise concerns regarding the influence and instability of industry payments.

Association of food insecurity with overall and disease-specific mortality among cancer survivors in the US.

To investigate the association of food insecurity with overall and disease-specific mortality among US cancer survivors. Data from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were used to examine the impact of food insecurity on mortality risks among cancer survivors in the US. Study participants aged ≥ 20years who had a history of cancer and completed the Adult Food Security Survey Module were included. Mortality data [all-cause, cancer, and cardiovascular (CVD) specific] through December 31, 2019 were obtained through linkage to the National Death Index. Using multivariable Cox proportional hazard regression, hazard ratios of mortality based on food security status were estimated. Among 5032 cancer survivors (mean age 62.5years; 58.0% women; 86.2% non-Hispanic White), 596 (8.8%) reported food insecurity. Overall, 1913 deaths occurred (609 cancer deaths and 420 CVD deaths) during the median follow-up of 6.8years. After adjusting for age, food insecurity was associated with a higher risk of overall (HR = 1.93; 95% CI = 1.56-2.39), CVD-specific (HR = 1.95; 95% CI = 1.24-3.05), and cancer-specific (HR = 1.70; 95% CI = 1.20-2.42) mortality (P < 0.001). However, after adjusting for socioeconomic characteristics and health-related factors (physical activity, diet quality measured by healthy eating index), the association between food insecurity and overall mortality was no longer statistically significant. Food insecurity was associated with a greater risk of overall mortality among cancer survivors. Further studies are needed to confirm these findings and evaluate whether the observed association represents a causal phenomenon and, if so, whether the effect is modifiable with food assistance programs.

A population-based study of COVID-19 mortality risk in US cancer patients.

In this study, we provide the largest analysis to date of a US-based cancer cohort to characterize death from COVID-19. A total of 4 020 669 patients across 15 subtypes living with cancer in 2020 and included in the National Cancer Institute's Surveillance, Epidemiology, and End Results database were abstracted. We investigated prognostic factors for death due to COVID-19 using a Cox proportional hazards model and calculated hazard ratios (HRs). Standardized mortality ratios were calculated using observed mortality counts from Surveillance, Epidemiology, and End Results and expected mortality based on US mortality rates. A total of 291 323 patients died, with 14 821 (5.1%) deaths attributed to COVID-19 infection. The COVID-19 disease-specific mortality rate was 11.81/10 000-persons years, and the standardized mortality ratio of COVID-19 was 2.30 (95% confidence interval [CI] = 2.26 to 2.34; P < .0001). COVID-19 ranked as the second leading cause of death following ischemic heart disease (5.2%) among 26 noncancer causes of death. Patients who are older (80 years and older vs 49 years and younger: HR = 21.47, 95% CI = 19.34 to 23.83), male (vs female: HR = 1.46, 95% CI = 1.40 to 1.51), unmarried (vs married: HR = 1.47, 95% CI = 1.42 to 1.53), and Hispanic or non-Hispanic African American (vs non-Hispanic White: HR = 2.04, 95% CI = 1.94 to 2.14 and HR = 2.03, 95% CI = 1.94 to 2.14, respectively) were at greatest risk of COVID-19 mortality. We observed that people living with cancer are at 2 times greater risk of dying from COVID-19 compared with the general US population. This work may be used by physicians and public health officials in the creation of survivorship programs that mitigate the risk of COVID-19 mortality.

Incidence and Presenting Characteristics of Angiosarcoma in the US, 2001-2020

Angiosarcoma is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed. To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US. This retrospective cross-sectional study used data from the US Cancer Statistics (USCS) National Program of Cancer Registries-Surveillance, Epidemiology, and End Results Combined Database, which captures more than 99% of newly diagnosed cancers in the US. The study included all 19 289 patients in the US with a new diagnosis of angiosarcoma between 2001 and 2020 captured in the USCS database. Statistical analysis was performed from June to September 2023. Incidence of angiosarcoma, demographics of patients with angiosarcoma, and extent of disease at presentation. The study included 19 289 patients (median age, 71 years [IQR, 59-80 years]; 10 506 women [54.5%]) with a new diagnosis of angiosarcoma. The US incidence of angiosarcoma doubled between 2001 (657 cases) and 2019 (1312 cases), reflecting both an increase in the adjusted incidence rate of 1.6% per year (P = .001), to 3.3 cases per 1 000 000 person-years (95% CI, 3.1-3.5 cases per 1 000 000 person-years), and an increase in the population at risk. In 2020, the reported incidence rate (3.0 cases per 1 000 000 person-years) and cases of angiosarcoma (n = 1159) were modestly lower than in 2019. Overall, 72.3% of cases of angiosarcoma (n = 13 955) were cutaneous, subcutaneous, or breast angiosarcomas; 24.4% were visceral (n = 4701); and 3.3% were located in unknown or rare primary sites (n = 633). Secondary breast and chest wall angiosarcomas among women represented the largest contribution to increasing incidence. Among breast angiosarcomas, 99.2% (2684 of 2705) were in women and 71.9% (1944 of 2705) were secondary. A total of 80.4% of chest wall or thorax cases among women (1861 of 2316) were secondary vs 26.5% among men (112 of 422), and 63.9% of upper extremity cases among women (205 of 321) were secondary vs 26.8% (56 of 209) among men (P = .001). Rates of secondary angiosarcoma in the abdomen and lower extremities were similar between men and women. The incidence rate of visceral angiosarcoma was also found to be increasing (1.5% per year; P = .001). This cross-sectional study describes angiosarcoma presentation patterns and incidence rates in the US over a 20-year period and shows that the number of cases in men and women increased, with the greatest increase among women with secondary angiosarcoma of the chest, breast, and upper extremity. These data increase awareness of a rare but highly morbid disease and highlight the need for improved early detection of angiosarcoma among patients at high risk, such as women with a history of breast cancer.

Profits over care? An analysis of the relationship between corporate capitalism in the healthcare industry and cancer mortality in the United States

The characteristic features of 21st-century corporate capitalism – monopoly and financialization – are increasingly being recognized by public health scholars as undermining the foundations of human health. While the “vectors” through which this is occurring are well known – poverty, inequality, climate change among others – locating the root cause of this process in the nature and institutions of contemporary capitalism is relatively new. Researchers have been somewhat slow to study the relationship between contemporary capitalism and human health. In this paper, we focus on one of the leading causes of death in the United States; cancer, and empirically estimate the relationship between various measures of financialization and monopoly in the US healthcare system and cancer mortality. The measures we focus on are for the hospital industry, the health insurance industry, and the pharmaceutical industry. Using a fixed effects model with different specifications and control variables, our analysis is at the state level for the years 2012–2019. These variables include data on population demographic controls, social and economic factors, and health behavior and clinical care. We compare Medicaid expansion states with non-Medicaid expansion states to investigate variations in state-level funded health insurance coverage. The results show a statistically significant positive correlation between the HHI index in the individual healthcare market and cancer mortality and the opioid dispensing rate and cancer mortality.

The impact of adjusting for hysterectomy prevalence on cervical cancer incidence rates and trends among women aged 30 years or older-United States, 2001-2019.

Hysterectomy protects against cervical cancer when the cervix is removed. However, measures of cervical cancer incidence often fail to exclude women with a hysterectomy from the population-at-risk denominator, underestimating and distorting disease burden. In this study, we estimated hysterectomy prevalence from the Behavioral Risk Factor Surveillance System surveys to remove the women who were not at risk of cervical cancer from the denominator and combined these estimates with the US Cancer Statistics data. From these data, we calculated age-specific and age-standardized incidence rates for women aged >30 years from 2001-2019, adjusted for hysterectomy prevalence. We calculated the difference between unadjusted and adjusted incidence rates and examined trends by histology, age, race and ethnicity, and geographic region using joinpoint regression. The hysterectomy-adjusted cervical cancer incidence rate from 2001-2019 was 16.7 per 100 000 women-34.6% higher than the unadjusted rate. After adjustment, incidence rates were higher by approximately 55% among Black women, 56% among those living in the East South Central division, and 90% among women aged 70-79 and ≥80 years. These findings underscore the importance of adjusting for hysterectomy prevalence to avoid underestimating cervical cancer incidence rates and masking disparities by age, race, and geographic region. This article is part of a Special Collection on Gynecological Cancers.

Abstract LB143: Environmental assessment of alcohol-related policies and practices at US cancer organizations

Abstract In 1998, the International Agency for Research on Cancer (IARC) declared that the consumption of alcoholic beverages was a class I carcinogen to humans; the designation was reaffirmed in 2007 and 2010. Despite this, approximately 4% of new cancer cases worldwide in 2020 were attributable to alcohol intake. Growing evidence indicates that alcohol use increases the risk of cancers of the upper aerodigestive tract (oral cavity, pharynx, esophagus, and larynx) and lower digestive tract (colon, rectum, and liver). Over half of the 6.3 million cases of these cancers are considered preventable, underscoring notable gaps regarding alcohol consumption and cancer prevention. Despite (1) the longstanding designation of alcohol as an established carcinogen, (2) an increasing and consistent body of data noting alcohol as a leading contributor to the global cancer burden, and (3) the publication of policy statements by authoritative sources, it is unclear whether cancer-focused institutions are aware of these facts or are acting on these data (i.e., implementing evidence-based policies and practices to limit alcohol-related cancer risks for their employees, guests, or the public). Driven by these data and shortfalls, we developed a 22-item survey to inquire about cancer organizations' interpretation of current literature, existing policies, decision-making processes, inclination to act, and perceived responsibility to lead in the realms of public education and policy implementation to mitigate alcohol-related cancer risks in the public’s interest. The survey will be sent to over 100 leading U.S. cancer organizations, including NCI-designated- and other major cancer centers, cancer-oriented professional organizations, and cancer-research organizations. It underwent rigorous testing for clarity, brevity, and expected response time, also drawing upon the expertise of five survey-science professionals. The study is under institutional review board (IRB) review, and we anticipate the survey’s distribution in the first quarter of the calendar year 2024. We expect to share the survey instrument and results during the meeting. Citation Format: Meghan Si, Stephanie Martch, Sanjay Shete, Ernest Hawk. Environmental assessment of alcohol-related policies and practices at US cancer organizations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB143.

Trends in Oral Tongue Cancer Incidence in the US

Oral tongue cancer (OTC) incidence has increased rapidly among young (<50 years) non-Hispanic White individuals in the US during the past 2 decades; however, it is unknown if age-associated trajectories have persisted. To examine US trends in OTC incidence and project future case burden. This cross-sectional analysis of OTC incidence trends used the US Cancer Statistics Public Use Database, which covers approximately 98% of the US population, and included individuals with an OTC diagnosis reported to US cancer registries between January 1, 2001, and December 31, 2019. Sex, race and ethnicity, and age. Estimated average annual percentage change in OTC incidence from 2001 to 2019. Given the substantial incidence rate increases among non-Hispanic White individuals compared with those of racial and ethnic minority groups, subsequent analyses were restricted to non-Hispanic White individuals. Forecasted OTC incidence trends and case burden among non-Hispanic White individuals to 2034. There were 58 661 new cases of OTC identified between 2001 and 2019. Male individuals (57.6%), non-Hispanic White individuals (83.7%), those aged 60 years or older (58.0%), and individuals with localized stage disease at diagnosis (62.7%) comprised most cases. OTC incidence increased across all age, sex, and racial and ethnic groups, with marked increases observed among non-Hispanic White individuals (2.9% per year; 95% CI, 2.2%-3.7%). Increases among female individuals aged 50 to 59 years were most notable and significantly outpaced increases among younger non-Hispanic White female individuals (4.8% per year [95% CI, 4.1%-5.4%] vs 3.3% per year [95% CI, 2.7%-3.8%]). While all non-Hispanic White birth cohorts from 1925 to 1980 saw sustained increases, rates stabilized among female individuals born after 1980. Should trends continue, the burden of new OTC cases among non-Hispanic White individuals in the US is projected to shift more toward older individuals (from 33.1% to 49.3% among individuals aged 70 years or older) and female individuals (86% case increase vs 62% among male individuals). The results of this cross-sectional study suggest that the period of rapidly increasing OTC incidence among younger non-Hispanic White female individuals in the US is tempering and giving way to greater increases among older female individuals, suggesting a birth cohort effect may have been associated with previously observed trends. Recent increases among non-Hispanic White individuals 50 years or older of both sexes have matched or outpaced younger age groups. Continuing increases among older individuals, particularly female individuals, may be associated with a shift in the OTC patient profile over time.

Abstract 2250: Effects of loneliness on medical expenditures among US cancer survivors

Abstract Background: Social isolation in cancer survivors associates with diminished quality of life and worse survival. However, effects of loneliness on medical expenditure are understudied. We examined associations of loneliness with medical costs, and social/psychological/behavioral determinants of health (SDHs). Methods: We identified 1,866 cancer survivors from the 2021 Medical Expenditure Panel Survey. One has loneliness if answering ‘often’ for any of: feel lack companionship/left out/isolated from others. Two-part regression models assessed marginal effect of loneliness to annual total health care expenditure (cost) in cancer survivors, aged 18-64 (young) and ≥65 years (older), adjusting for age, sex, race, region, education, health insurance, comorbid illnesses, family income, unemployment, and activity limitation. Models were sequentially adjusted for every single SDH. Ordinal regression models assessed associations of loneliness with SDHs. Results: Over one-tenth of young (19%) and older (13%) cancer survivors reported loneliness. Loneliness was associated with higher cost in older cancer survivors (conditional coefficient (CC) 0.46, 0.12-0.81), but not young survivors (-0.14, -0.62-0.36). In both age groups, cancer survivors with loneliness more often reported stress, lack of help, as well as less time talking on the phone and getting together with support persons (Table). In older patients, sequential adjustment for stress, expected help, get-togethers, or church attendance decreased effect of loneliness to cost; among which get-togethers showed the greatest decrease (CC 0.28, -0.03-0.62). Conclusions: Loneliness was associated with higher total medical expenditure in older US cancer survivors. Findings warrant further study of personal or community support to mitigate loneliness, in an effort to reduce healthcare costs and financial burden in older cancer survivors. Age (year) 18-64 (648) ≥65 (1223) Loneliness No (505, 81%) Yes (143, 19%) No (1046, 87%) Yes (177, 13%) Mean Age (years) 56 56 75 74 Female % 64.5 66.4 53.0 59.1 Non-white % 23.1 21.8 15.8 26.4 Federal poverty level &amp;lt; 100%, % 7.4 18.9 8.9 7.2 Comorbidities ≥ 3, % 25.4 44.4 60.4 67.1 Unemployment ≥ 1, % 35.8 45.3 83.3 89.6 &amp;lt; high school % 30.8 33.7 37.7 36.6 Conditional coefficient (95% CI) Ref -0.14 (-0.62-0.36) Ref 0.46 (0.12-0.81) Odds ratio (95% CI) of loneliness to SDHs Stress Ref 8.42 (5.20-13.63) Ref 6.82 (4.72-9.87) Lack of help - family 3.46 (2.32-5.14) 2.61 (1.88-3.60) Lack of help - friends 3.25 (2.00-5.29) 1.92 (1.36-2.72) Lack of help - community 2.45 (1.64-3.66) 2.16 (1.58-2.96) Times of talk on phone 0.55 (0.36-0.85) 0.77 (0.55-1.07) Times of get together 0.34 (0.21-0.55) 0.38 (0.25-0.58) Citation Format: Fangyuan Chen, Ryan Nipp, Xuesong Han, Zhiyuan Zheng, Robin Yabroff, Changchuan Jiang. Effects of loneliness on medical expenditures among US cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2250.

Abstract 6075: Most cancer deaths are unaddressed by current screening paradigms

Abstract Cancer is the leading cause of death at ages ≤80 in the US. To understand the burden of cancer death potentially addressable by new or improved screening approaches, we estimated the proportion of US cancer deaths without recommended guideline-based screening, especially after accounting for lung cancer screening eligibility and adherence. Using 2018-2019 mortality data from the National Center for Health Statistics and published estimates of the proportion of screening-eligible lung cancer patients, we estimated that 31.4% of nearly 600,000 annual cancer deaths were from colorectal, female breast, cervical, and smoking-eligible lung cancers (Table). Further accounting for adherence to lung cancer screening guidelines reduced the estimated proportion of screened cancer deaths to 17.4%; thus, 82.6% of cancer deaths may not be addressed by current guideline-based screening. Among the cancers not covered by guideline-based screening are uncommon cancer types, which (as defined by the National Cancer Institute) comprised 30.4% of cancer deaths. According to incidence-based mortality data from Surveillance, Epidemiology, and End Results registries, 24.7% of all cancer deaths were from stage 4 cancer types without guideline-based screening. These estimates, based on population data without patient-level information on mode of diagnosis, almost certainly underestimate the percentage of cancer deaths missed by currently available screening efforts. The large proportion of cancer deaths unaddressed by guideline-based screening represents a vast opportunity for new cancer screening technologies that are safe, effective, accessible, and affordable to enable earlier detection and successful treatment of the full spectrum of cancer types that contribute to the overall cancer burden. Table. Deaths from cancer by primary type in 2018-2019, US National Center for Health Statistics, with eligibility for and adherence to guideline-based low-dose computed tomography screening for lung cancer All cancer types Lung Colon/rectum Breast (female) Uterine cervix Total screened % of all All cancer deaths 1,198,854 281,681 104,059 84,745 8,290 478,775 39.9% Eligible for screening based on smoking (63.7% of lung)* 179,431 104,059 84,745 8,290 376,525 31.4% Adherent to smoking-guideline-based screening (6.6% of lung)† 11,842 104,059 84,745 8,290 208,936 17.4% *Modeled estimate of proportion of lung cancer patients eligible for screening (Landy et al. 2023). †Lung cancer screening receipt from 2019 American College of Radiology Lung Cancer Screening Registry (Fedewa et al. 2022). Citation Format: Ellen T. Chang, Anuraag Kansal, Earl A. Hubbell, Graham A. Colditz, Allison W. Kurian, Christina A. Clarke. Most cancer deaths are unaddressed by current screening paradigms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6075.

Abstract 843: The burden of Merkel cell carcinoma attributable to immunosuppression, ultraviolet radiation, and Merkel cell polyomavirus in the United States

Abstract Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. No published study has estimated the contribution of the major potentially modifiable risk factors, such as immunosuppression, ultraviolet radiation (UVR) and infection with Merkel cell polyomavirus (MCPyV), to the burden of MCC in the US. We estimated the population attributable fractions (PAFs) for MCC associated with immunosuppression (HIV and organ transplantation), MCPyV, and UVR in the US during 2001-2020. Methods: We calculated PAFs for immunosuppression and UVR using the formula: prevalence in cases (Pc)*[(Relative risk, RR-1)/RR]. The proportion of MCC cases among organ recipients and people with HIV (Pc) were derived from US cancer registries in the HIV/AIDS Cancer Match Study, Transplant Cancer Match Study, and the Surveillance Epidemiology and End Results (SEER) Program data. To approximate the RRs, we calculated standardized incidence ratios (SIRs) comparing MCC incidence in people with HIV and organ recipients to the general population. We merged SEER data on MCC cases by county with data on ambient UVR levels in order to create population quintiles of UVR exposure. Since only non-Hispanic White individuals showed elevated IRRs for increased ambient UVR exposure, we estimated the PAF of UVR by calculating incidence rate ratios (IRR ≈ RR) comparing MCC incidence in non-Hispanic White individuals to all other races/ethnicities (at any UVR level) as the reference; here, Pc was the proportion of non-Hispanic White patients in each quintile. To estimate the PAF of MCPyV, we meta-analyzed US studies reporting on MCPyV prevalence in MCC tissues (here PAF ≈ Pc). Results: Over the study period (2001-2020), 40,571 MCCs were diagnosed in the US. Compared to the general population, organ recipients had 13 times higher (SIR=12.7, CI: 11.3-14.2) and people with HIV had three times higher (SIR=2.78, CI: 2.01-3.75) risk of MCC. Due to the rarity of these exposures (HIV Pc = 0.4%; Transplant Pc = 1.9%), only 0.2% of MCC cases were attributable to HIV and 1.7% were attributable to organ transplantation. Compared with people in other racial/ethnic groups, the IRRs of non-Hispanic White individuals at the various levels of ambient UVR for MCC arising on the head and neck ranged from 4.24 to 5.03 and for other primary sites ranged from 2.81 to 3.36. After combining the PAFs for these sites, the overall PAF for UVR was 65.8%. Meta-analyzing 20 studies with 984 MCC cases combined, we found that 66.1% (CI: 58.0-72.2%) of MCCs were attributable to MCPyV. Conclusions: While a small proportion of MCCs were due to immunosuppression from HIV infection and organ transplantation, UVR and MCPyV played a major role in MCC burden. Future research is required to assess the combined impact of these risk factors on MCC incidence. Citation Format: Jacob T. Tribble, Karena Volesky-Avellaneda, Qianlai Luo, Michael R. Sargen, Isaac Brownell, Elizabeth K. Cahoon, Meredith Shiels, Ruth Pfeiffer, Adrianne Moreno, Brenda Y. Hernandez, Eric Engels. The burden of Merkel cell carcinoma attributable to immunosuppression, ultraviolet radiation, and Merkel cell polyomavirus in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 843.

Abstract 4675: Reduction in NSCLC tumorigenesis by targeting sphingosine kinase 2

Abstract Lung cancer will account for 21% of US cancer deaths in 2023 with 238,340 cases and 127,070 deaths. Treatment with EGFR-TKI (epidermal growth factor receptor tyrosine kinase) inhibitors initially decrease tumor growth, but often leads to TKI resistance. According to studies, non-small cell lung cancer (NSCLC) tumors express more SphK2 (Sphingosine kinase 2) than normal lung tissue and patients with overexpression have worse survival chances. However, SphK2's role in TKI resistance is unclear. We hypothesize that inhibiting/downregulating SphK2 could reduce tumorigenicity and overcome ER (Erlotinib) and OR (Osimertinib) resistance. We studied the expression of SphK2 in both drug-resistant (OR/ER) and drug sensitive (parental) H358, H2170, H3255, and PC9 NSCLC cell lines using Western blotting, qRT-PCR, and immunofluorescence. H3255OR cells were also bioprinted with GelMA hydrogel using an R-Gen 200 bioprinter to mimic the physiological tumor environment and treated with SphK2 siRNA or ABC294640 (SphK2i). Immunoblotting was done to analyze changes in the expression of SphK2 in H358 (WT-EGFR) and H3255 (mutant EGFR- L858R) parental and OR-resistant cell lines. Results indicated a 1.5-1.8-fold upregulation of SphK2. Increased SphK2 gene expression was observed using qPCR in TKI-resistant H3255OR (4.3-fold), PC9ER/OR with mutant EGFR (E746-A750del) (1.8-3.3-fold), and H2170ER/OR with WT EGFR (1.3-1.5-fold) compared to parental cells. Immunofluorescence studies showed increased fluorescence of SphK2 in H3255OR (2.6-fold), H358 ER (2.4-fold) and OR cells (2.3-fold) compared to parental cells. Spheroids formed from single cancer cells can "re-create" the growth of a tumor. The spheroid count of H3255OR was reduced by 73.98% and 56%, respectively, when SphK2i was added to the 3D-cell culture with Matrigel, compared to the diluent and OR alone (p≤0.01). We used 3D bioprinting to precisely stack cells on biological scaffolds to recreate lung tumors from patients and boost the therapeutic efficacy of these findings. When bioprinted spheroids of H3255OR were treated with SphK2i in combination with OR, the number of spheroids per microscopic field were reduced by 87.3% compared to OR alone. Bioprinted H3255OR spheroids treated with SphK2 siRNA and OR revealed a 75.8% and 84% reduction of spheroid count, respectively, compared to treatments with siRNA alone or OR alone (p≤0.05). This data supports the hypothesis that SphK2 suppression or downregulation can assist in mitigating oncogenesis. We also used H3255OR transwell migration assays to examine how SphK2 inhibition affects cell migration. Combining OR with SphK2i resulted in a 94.7% and 91.4% decrease in cell migration compared to diluent and OR alone (p≤0.01). In H358OR-resistant cells, combining OR with SphK2i resulted in a 94.97% inhibition compared to diluent (p≤0.01). These results suggest that targeting SphK2 could be a valuable approach for treating lung cancer. Citation Format: Ayesha Khan, Bamby Dieng, Namrata Dube, Mohammad Fazle Alam, Neelu Puri. Reduction in NSCLC tumorigenesis by targeting sphingosine kinase 2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4675.