Gad, Mohamed M.

ImportanceStroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies.ObjectiveTo present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location.Design, Setting, and ParticipantsAn in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020.ExposuresIn this study, no particular exposure was specifically targeted.Main Outcomes and MeasuresThe primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals.ResultsIn 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota).Conclusions and RelevanceIn this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

Background The landmark study of durvalumab as consolidation therapy in NSCLC patients (PACIFIC trial) demonstrated significantly longer progression-free survival (PFS) in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) treated with durvalumab (immunotherapy, IO) therapy after chemoradiotherapy (CRT). In clinical practice in the USA, durvalumab continues to be used in patients across all levels of programmed cell death ligand-1 (PD-L1) expression. While immune therapies have shown promise in several cancers, some patients either do not respond to the therapy or have cancer recurrence after an initial response. It is not clear so far who will benefit of this therapy or what the mechanisms behind treatment failure are. Methods A total of 133 patients with unresectable stage III NSCLC who underwent durvalumab after CRT or CRT alone were included. Patients treated with durvalumab IO after CRT were randomly split into training (D1=59) and test (D2=59) sets and the remaining 15 patients treated with CRT alone were grouped in D3. Radiomic textural patterns from within and around the target nodules were extracted. A radiomic risk score (RRS) was built and was used to predict PFS and overall survival (OS). Patients were divided into high-risk and low-risk groups based on median RRS. Results RRS was found to be significantly associated with PFS in D1 (HR=2.67, 95% CI 1.85 to 4.13, p<0.05, C-index=0.78) and D2 (HR=2.56, 95% CI 1.63 to 4, p<0.05, C-index=0.73). Similarly, RRS was associated with OS in D1 (HR=1.89, 95% CI 1.3 to 2.75, p<0.05, C-index=0.67) and D2 (HR=2.14, 95% CI 1.28 to 3.6, p<0.05, C-index=0.69), respectively. RRS was found to be significantly associated with PFS in high PD-L1 (HR=3.01, 95% CI 1.41 to 6.45, p=0.0044) and low PD-L1 (HR=2.74, 95% CI 1.8 to 4.14, p=1.77e-06) groups. Moreover, RRS was not significantly associated with OS in the high PD-L1 group (HR=2.08, 95% CI 0.98 to 4.4, p=0.054) but was significantly associated with OS in the low PD-L1 group (HR=1.61, 95% CI 1.14 to 2.28, p=0.0062). In addition, RRS was significantly associated with PFS (HR=2.77, 95% CI 1.17 to 6.52, p=0.019, C-index=0.77) and OS (HR=2.62, 95% CI 1.25 to 5.51, p=0.01, C-index=0.77) in D3, respectively. Conclusions Tumor radiomics of pretreatment CT images from patients with stage III unresectable NSCLC were prognostic of PFS and OS to CRT followed by durvalumab IO and CRT alone.

Abstract Introduction Because of the improved colorectal cancer (CRC) survival in the U.S., patients may live long enough after CRC diagnosis to the point where non–cancer-related comorbidities may considerably impact their overall survival. In this study, we perform a long-term analysis of causes of death (CODs) following nonmetastatic CRC with respect to different demographic and tumor-related criteria. Materials and Methods We gained access to the Surveillance, Epidemiology, and End Results data to review patients diagnosed with nonmetastatic CRC during 2000–2015. We calculated standardized mortality ratios (SMRs) for each COD following CRC. SMRs represented the change of risk of a specific COD following CRC diagnoses when compared with the risk in the general U.S. population. Results We reviewed 302,345 patients, of whom 112,008 died during the study period. More deaths (68.3%) occurred within 5 years following nonmetastatic CRC diagnosis, with 76,486 deaths. CRC was the most common COD (51.4%) within 5 years of diagnosis followed by heart disease (15.2%) and other cancers (8.4%). As time passed after diagnosis, the number of CRC deaths decreased, and other noncancer causes increased to the point that after 10 years only 10.4% of deaths were attributed to CRC, 15.3% were attributed to other cancers, and 34.2% were secondary to heart disease. Conclusion Following nonmetastatic CRC diagnosis, most deaths remain secondary to CRC. Other causes, including other cancers and cardiovascular disease, represent a significant number of deaths, especially in the 5 years following initial CRC diagnosis. Our findings help guide counseling patients with CRC regarding future health risks. Implications for Practice Most common causes of death following nonmetastatic colorectal cancer (CRC) are heart diseases, other cancers, chronic obstructive pulmonary disease, and cerebrovascular diseases. Physicians should counsel patients regarding survivorship with cancer screening and focus on prevention of noncancer deaths. These findings should be considered by physicians who give care for survivors of nonmetastatic CRC.

e16662 Background: Cholangiocarcinoma (CCA) is a relatively rare malignancy accounting for 3% of gastrointestinal cancers in the US. While multiple risk factors for CCA are established and well-studied, other potential risk factors are still controversial and not well established. Herein, we used a large national database to investigate possible risk factors and associations. Methods: We used the National Inpatient Sample (NIS) database to review all admissions between 2011 and 2015. We grouped patients based on the presence and absence of CCA using the appropriate ICD-9 codes. We used multivariate logistic regression to assess the association between obesity, alcohol abuse, smoking, diabetes mellitus (DM), and non-alcoholic fatty liver disease (NAFLD). Results: We reviewed 30,955,295 admissions of which 20,030 had CCA. CCA Patients were older compared to the rest of the patients (mean age 67 years ±12.8 vs. 57±20.6, P < .001) and had less female patients (48% vs 59%, P < .001). Patients’ characteristics are shown in the table. After adjusting for viral hepatitis B (HBV), viral hepatitis C (HCV), liver cirrhosis, inflammatory bowel disease (IBD), primary sclerosing cholangitis (PSC), and bile duct stones, logistic regression showed DM to be proportionately associated with CCA (OR = 1.04, 95%CI[1.01-1.08], P < .001), whereas alcohol, smoking and obesity were all inversely associated with CCA; OR = 0.75, 95%CI [0.69-0.81], P < .001, OR = 0.75, 95%CI [0.71-0.79], P < .001 and OR = 0.71, 95%CI [0.67-0.75], P < .001, respectively. In addition, compared to whites, Hispanic and Asian/Pacific Islander races were proportionally associated with CCA; OR = 1.27, 95%CI [1.21-1.34], P < .001, and OR = 1.79, 95%CI, [1.67-1.92], P < .001, respectively, while black race was inversely associated with CCA (OR = 0.85, 95%CI [0.81-0.89], P < .001). Conclusions: In our large database study, we found that patients with diagnosis of DM or being from certain minority ethnic groups are associated with increased incidence of CCA. Other factors like alcohol and smoking were associated with decreased incidence of CCA, but those factors may be under reported. This raises the need for further evaluation for these factors and their effect on CCA incidence and outcomes in those specific groups. [Table: see text]

e16059 Background: Anal cancer is an uncommon malignancy accounting for less than 3% of gastrointestinal malignancies in the US. In this large database study, we aimed to re-evaluate the difference in the incidence and mortality trend in both genders. Methods: We used SEER 18 database to study anal cancer cases in the US during 2000-2016. Incidence and mortality rates of anal cancer were calculated by gender and were expressed by 1,000,000 person-years. Annual percent change (APC) was calculated using join point regression software. Results: We reviewed 25,418 patients with anal cancer, of which 61.4% were females. Incidence of anal cancers was 14.375 and 19.427 per 1,000,000 person-years, in males and females, respectively. Incidence rates of anal cancer significantly increased over the study period, but this increase was sharper in females (APC = 2.220%, 95%CI [1.924-2.517], P < .001) when compared to males (APC = 0.915%, 95%CI [0.303-1.531], P = .006). Mortality rates from anal cancer over the study period were 7.425 and 7.532 per 1,000,000 person-years, in males and females, respectively. Overall anal cancer mortality rates did not change between 2000-2009 but started to decrease starting from 2010 and this decrease became sharpest between 2014-2016; APC = -44.905%, 95%CI [-57.572- -28.457], P = .001). Mortality rates followed the same trend in both genders. Conclusions: Anal cancer incidence is increasing with significant increase in the incidence trend is noticed in females compared to males which is a change from the previous trend that was seen from 1973-2000. On the other hand, anal cancer mortality has started to decrease for the first time starting from 2010 with no difference in the mortality trend between males and females. This improvement in mortality rate can be explained by the improvement in early detection rate and possibly improvement in the treatment approach for these high-risk patients.

Background: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. Methods: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. Results: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700–107 900) and 35 700 (95% UI, 30 500–42 500) deaths, and 12.6 million (95% UI, 11.4 million–13.8 million) and 18.1 million (95% UI, 17.6 million–18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million–2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%–0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%–117%) and 35% (95% UI, 23%–47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. Conclusions: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

604 Background: Renal cell carcinoma (RCC) is the third most common urologic malignancy worldwide, with clear cell subtype being the most common. In this study, we sought to investigate RCC incidence and mortality trends by demographic and tumor characteristics using data from the surveillance, epidemiology and end results (SEER) database. Methods: We used SEER database to study RCC cases between 1973 and 2014. Incidence and mortality rates were calculated by sex, age, race, state, stage, size, and histological subtype of RCC. Annual percent change (APC) was calculated using joinpoint regression software. Results: A total of 96,058 RCC cases were identified, with 54,000 RCC deaths between 1973 and 2014. Overall incidence was 9.712 per 100,000 persons-years, being highest among males (13.698), blacks (11.886), and people older than 65 years (38.693). Incidence rates of localized cases (5.845) and tumors smaller than 7 cm (6.550) were higher than other tumor subgroups with distant disease incidence of 1.773 per 100,000 persons-years. Overall incidence rates increased by 2.709% (95% CI, 2.544-2.875, p < .001) per year over the study period, but rates became stable since 2007 with only an increase in the incidence of clear-cell subtype (2.538%; 95% CI, 1.300-3.791, p < .001). Overall RCC mortality rates have been declining since 2000, and distant disease mortality have been decreasing since 2008 with most profound decline in the period between 2012 and 2014 with APC of -22.635% (-37.419- -4.359, P = .019) Conclusions: Despite overall increase in rates over the last 40 years, recent years have shown stable incidence and decrease in mortality rates of RCC. The significant decline in mortality over the last 10 years since the approval of the first Vascular Endothelial Growth Factor ‘VEGF’ inhibitor highlights the impact of this class of medications along with other subsequent agents such as mTOR inhibitors and checkpoint inhibitors on the prognosis of renal cell carcinoma.