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Item Outcomes of COVID-19 in Patients With Cancer: Report From the National COVID Cohort Collaborative (N3C)(ASCO, 2021-06-04) Sharafeldin, Noha; Bates, Benjamin; Song, Qianqian; Madhira, Vithal; Dong, Sharlene; Yan, Yao; Lee, Eileen; Kuhrt, Nathaniel; Shao, Yu Raymond; Liu, Feifan; Bergquist, Timothy; Guinney, Justin; Su, Jing; Topaloglu, Umit; Biostatistics, School of Public HealthPURPOSE Variation in risk of adverse clinical outcomes in patients with cancer and COVID-19 has been reported from relatively small cohorts. The NCATS’ National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multicenter cohort of COVID-19 cases and controls nationwide. We aimed to construct and characterize the cancer cohort within N3C and identify risk factors for all-cause mortality from COVID-19. METHODS We used 4,382,085 patients from 50 US medical centers to construct a cohort of patients with cancer. We restricted analyses to adults ≥ 18 years old with a COVID-19–positive or COVID-19–negative diagnosis between January 1, 2020, and March 25, 2021. We followed N3C selection of an index encounter per patient for analyses. All analyses were performed in the N3C Data Enclave Palantir platform. RESULTS A total of 398,579 adult patients with cancer were identified from the N3C cohort; 63,413 (15.9%) were COVID-19–positive. Most common represented cancers were skin (13.8%), breast (13.7%), prostate (10.6%), hematologic (10.5%), and GI cancers (10%). COVID-19 positivity was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.20; 95% CI, 1.15 to 1.24). Among COVID-19–positive patients, age ≥ 65 years, male gender, Southern or Western US residence, an adjusted Charlson Comorbidity Index score ≥ 4, hematologic malignancy, multitumor sites, and recent cytotoxic therapy were associated with increased risk of all-cause mortality. Patients who received recent immunotherapies or targeted therapies did not have higher risk of overall mortality. CONCLUSION Using N3C, we assembled the largest nationally representative cohort of patients with cancer and COVID-19 to date. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Full characterization of the cohort will provide further insights into the effects of COVID-19 on cancer outcomes and the ability to continue specific cancer treatments.Item Outcomes of COVID-19 in Patients With Cancer: Report From the National COVID Cohort Collaborative (N3C)(American Society of Clinical Oncology, 2021) Sharafeldin, Noha; Bates, Benjamin; Song, Qianqian; Madhira, Vithal; Yan, Yao; Dong, Sharlene; Lee, Eileen; Kuhrt, Nathaniel; Shao, Yu Raymond; Liu, Feifan; Bergquist, Timothy; Guinney, Justin; Su, Jing; Topaloglu, Umit; Biostatistics, School of Public HealthPurpose: Variation in risk of adverse clinical outcomes in patients with cancer and COVID-19 has been reported from relatively small cohorts. The NCATS' National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multicenter cohort of COVID-19 cases and controls nationwide. We aimed to construct and characterize the cancer cohort within N3C and identify risk factors for all-cause mortality from COVID-19. Methods: We used 4,382,085 patients from 50 US medical centers to construct a cohort of patients with cancer. We restricted analyses to adults ≥ 18 years old with a COVID-19-positive or COVID-19-negative diagnosis between January 1, 2020, and March 25, 2021. We followed N3C selection of an index encounter per patient for analyses. All analyses were performed in the N3C Data Enclave Palantir platform. Results: A total of 398,579 adult patients with cancer were identified from the N3C cohort; 63,413 (15.9%) were COVID-19-positive. Most common represented cancers were skin (13.8%), breast (13.7%), prostate (10.6%), hematologic (10.5%), and GI cancers (10%). COVID-19 positivity was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.20; 95% CI, 1.15 to 1.24). Among COVID-19-positive patients, age ≥ 65 years, male gender, Southern or Western US residence, an adjusted Charlson Comorbidity Index score ≥ 4, hematologic malignancy, multitumor sites, and recent cytotoxic therapy were associated with increased risk of all-cause mortality. Patients who received recent immunotherapies or targeted therapies did not have higher risk of overall mortality. Conclusion: Using N3C, we assembled the largest nationally representative cohort of patients with cancer and COVID-19 to date. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Full characterization of the cohort will provide further insights into the effects of COVID-19 on cancer outcomes and the ability to continue specific cancer treatments.Item Reply to K. Takada et al(American Society of Clinical Oncology, 2021) Sharafeldin, Noha; Bates, Benjamin; Song, Qianqian; Madhira, Vithal; Shao, Yu Raymond; Liu, Feifan; Bergquist, Timothy; Su, Jing; Topaloglu, Umit; Biostatistics, School of Public HealthSee the letter "Reasons to Consider the COVID-19 Vaccination Status of Patients With Cancer When Analyzing Their COVID-19 Outcomes" in volume 39 on page 3996.Item Risk and Outcome of Breakthrough COVID-19 Infections in Vaccinated Patients With Cancer: Real-World Evidence From the National COVID Cohort Collaborative(American Society of Clinical Oncology, 2022) Song, Qianqian; Bates, Benjamin; Shao, Yu Raymond; Hsu, Fang-Chi; Liu, Feifan; Madhira, Vithal; Mitra, Amit Kumar; Bergquist, Timothy; Kavuluru, Ramakanth; Li, Xiaochun; Sharafeldin, Noha; Su, Jing; Topaloglu, Umit; National COVID Cohort Collaborative Consortium; Biostatistics and Health Data Science, School of MedicinePurpose: To provide real-world evidence on risks and outcomes of breakthrough COVID-19 infections in vaccinated patients with cancer using the largest national cohort of COVID-19 cases and controls. Methods: We used the National COVID Cohort Collaborative (N3C) to identify breakthrough infections between December 1, 2020, and May 31, 2021. We included patients partially or fully vaccinated with mRNA COVID-19 vaccines with no prior SARS-CoV-2 infection record. Risks for breakthrough infection and severe outcomes were analyzed using logistic regression. Results: A total of 6,860 breakthrough cases were identified within the N3C-vaccinated population, among whom 1,460 (21.3%) were patients with cancer. Solid tumors and hematologic malignancies had significantly higher risks for breakthrough infection (odds ratios [ORs] = 1.12, 95% CI, 1.01 to 1.23 and 4.64, 95% CI, 3.98 to 5.38) and severe outcomes (ORs = 1.33, 95% CI, 1.09 to 1.62 and 1.45, 95% CI, 1.08 to 1.95) compared with noncancer patients, adjusting for age, sex, race/ethnicity, smoking status, vaccine type, and vaccination date. Compared with solid tumors, hematologic malignancies were at increased risk for breakthrough infections (adjusted OR ranged from 2.07 for lymphoma to 7.25 for lymphoid leukemia). Breakthrough risk was reduced after the second vaccine dose for all cancers (OR = 0.04; 95% CI, 0.04 to 0.05), and for Moderna's mRNA-1273 compared with Pfizer's BNT162b2 vaccine (OR = 0.66; 95% CI, 0.62 to 0.70), particularly in patients with multiple myeloma (OR = 0.35; 95% CI, 0.15 to 0.72). Medications with major immunosuppressive effects and bone marrow transplantation were strongly associated with breakthrough risk among the vaccinated population. Conclusion: Real-world evidence shows that patients with cancer, especially hematologic malignancies, are at higher risk for developing breakthrough infections and severe outcomes. Patients with vaccination were at markedly decreased risk for breakthrough infections. Further work is needed to assess boosters and new SARS-CoV-2 variants.Item Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma(Springer Nature, 2023-12-07) Mitra, Amit Kumar; Mukherjee, Ujjal Kumar; Mazumder, Suman; Madhira, Vithal; Bergquist, Timothy; Shao, Yu Raymond; Liu, Feifan; Song, Qianqian; Su, Jing; Kumar, Shaji; Bates, Benjamin A.; Sharafeldin, Noha; Topaloglu, Umit; National COVID Cohort Collaborative Consortium; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthPatients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.Item The Brain Tumor Segmentation (BraTS-METS) Challenge 2023: Brain Metastasis Segmentation on Pre-treatment MRI(ArXiv, 2023-06-01) Moawad, Ahmed W.; Janas, Anastasia; Baid, Ujjwal; Ramakrishnan, Divya; Jekel, Leon; Krantchev, Kiril; Moy, Harrison; Saluja, Rachit; Osenberg, Klara; Wilms, Klara; Kaur, Manpreet; Avesta, Arman; Cassinelli Pedersen, Gabriel; Maleki, Nazanin; Salimi, Mahdi; Merkaj, Sarah; von Reppert, Marc; Tillmans, Niklas; Lost, Jan; Bousabarah, Khaled; Holler, Wolfgang; Lin, MingDe; Westerhoff, Malte; Maresca, Ryan; Link, Katherine E.; Tahon, Nourel Hoda; Marcus, Daniel; Sotiras, Aristeidis; LaMontagne, Pamela; Chakrabarty, Strajit; Teytelboym, Oleg; Youssef, Ayda; Nada, Ayaman; Velichko, Yuri S.; Gennaro, Nicolo; Connectome Students; Group of Annotators; Cramer, Justin; Johnson, Derek R.; Kwan, Benjamin Y. M.; Petrovic, Boyan; Patro, Satya N.; Wu, Lei; So, Tiffany; Thompson, Gerry; Kam, Anthony; Guzman Perez-Carrillo, Gloria; Lall, Neil; Group of Approvers; Albrecht, Jake; Anazodo, Udunna; Lingaru, Marius George; Menze, Bjoern H.; Wiestler, Benedikt; Adewole, Maruf; Anwar, Syed Muhammad; Labella, Dominic; Li, Hongwei Bran; Iglesias, Juan Eugenio; Farahani, Keyvan; Eddy, James; Bergquist, Timothy; Chung, Verena; Shinohara, Russel Takeshi; Dako, Farouk; Wiggins, Walter; Reitman, Zachary; Wang, Chunhao; Liu, Xinyang; Jiang, Zhifan; Van Leemput, Koen; Piraud, Marie; Ezhov, Ivan; Johanson, Elaine; Meier, Zeke; Familiar, Ariana; Kazerooni, Anahita Fathi; Kofler, Florian; Calabrese, Evan; Aneja, Sanjay; Chiang, Veronica; Ikuta, Ichiro; Shafique, Umber; Memon, Fatima; Conte, Gian Marco; Bakas, Spyridon; Rudie, Jeffrey; Aboian, Mariam; Radiology and Imaging Sciences, School of MedicineClinical monitoring of metastatic disease to the brain can be a laborious and timeconsuming process, especially in cases involving multiple metastases when the assessment is performed manually. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) guideline, which utilizes the unidimensional longest diameter, is commonly used in clinical and research settings to evaluate response to therapy in patients with brain metastases. However, accurate volumetric assessment of the lesion and surrounding peri-lesional edema holds significant importance in clinical decision-making and can greatly enhance outcome prediction. The unique challenge in performing segmentations of brain metastases lies in their common occurrence as small lesions. Detection and segmentation of lesions that are smaller than 10 mm in size has not demonstrated high accuracy in prior publications. The brain metastases challenge sets itself apart from previously conducted MICCAI challenges on glioma segmentation due to the significant variability in lesion size. Unlike gliomas, which tend to be larger on presentation scans, brain metastases exhibit a wide range of sizes and tend to include small lesions. We hope that the BraTS-METS dataset and challenge will advance the field of automated brain metastasis detection and segmentation.