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ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

Abstract Background Despite multiple randomized trials, the role of perioperative chemotherapy in colorectal cancer liver metastasis (CRLM) is still under debate. In this systematic review and network meta-analysis (NMA), we aim to evaluate the efficacy of perioperative systemic therapies for patients with CRLM. Methods We searched various databases for abstracts and full-text articles published from database inception through May 2021.We included randomized controlled trials (RCTs) comparing the addition of perioperative (post, pre, or both) systemic therapies to surgery alone in patients with CRLM. The outcomes were compared according to the chemotherapy regimen using a random effects model. Outcomes of interest included disease-free survival (DFS) and overall survival (OS). Results Seven RCTs with a total of 1504 patients with CRLM were included. Six studies included post-operative treatment and one evaluated perioperative (pre- and postoperative) therapy. Fluoropyrimidine-based chemotherapy was the most used systemic therapy. NMA showed benefit of adding perioperative therapy to surgery in terms of DFS (HR 0.73, 95% CI 0.63 to 0.84). However, these findings did not translate into a statistically significant OS benefit (HR 0.88, 95% CI 0.74 to 1.05). NMA did not show any advantage of one regimen over another including oxaliplatin or irinotecan. Conclusions This systematic review and NMA of 7 RCTs found that the addition of perioperative systemic treatment for resectable CRLM could improve disease-free survival but not overall survival. Based on the findings, addition of perioperative treatment in resectable CRLM should be individualized weighing the risks and benefits.

PURPOSEThe advancement of natural language processing (NLP) has promoted the use of detailed textual data in electronic health records (EHRs) to support cancer research and to facilitate patient care. In this review, we aim to assess EHR for cancer research and patient care by using the Minimal Common Oncology Data Elements (mCODE), which is a community-driven effort to define a minimal set of data elements for cancer research and practice. Specifically, we aim to assess the alignment of NLP-extracted data elements with mCODE and review existing NLP methodologies for extracting said data elements.METHODSPublished literature studies were searched to retrieve cancer-related NLP articles that were written in English and published between January 2010 and September 2020 from main literature databases. After the retrieval, articles with EHRs as the data source were manually identified. A charting form was developed for relevant study analysis and used to categorize data including four main topics: metadata, EHR data and targeted cancer types, NLP methodology, and oncology data elements and standards.RESULTSA total of 123 publications were selected finally and included in our analysis. We found that cancer research and patient care require some data elements beyond mCODE as expected. Transparency and reproductivity are not sufficient in NLP methods, and inconsistency in NLP evaluation exists.CONCLUSIONWe conducted a comprehensive review of cancer NLP for research and patient care using EHRs data. Issues and barriers for wide adoption of cancer NLP were identified and discussed.

Objective To determine the harms of ezetimibe in people who need lipid-lowering treatment. Design Systematic review and meta-analysis. Data sources Randomised controlled trials and cohort studies. Eligibility criteria for selecting studies Studies comparing ezetimibe with placebo, standard care, or other lipid-lowering agents in people who need lipid-lowering treatment with a follow-up duration of at least six months (or 24 weeks). The relative effects for potential harms of ezetimibe were pooled by use of random effect pairwise meta-analyses for randomised controlled trials and the evidence from observational studies was narratively summarised. The certainty of evidence was assessed using the Grading of Recommendation Assessment, Development, and Evaluation. Results 48 randomised controlled trials with 28 444 participants (median follow-up 34 weeks, range 24-312 weeks) and four observational studies with 1667 participants (median follow-up 282 weeks, range 72-400 weeks) were included. The meta-analyses of randomised trials showed moderate to high certainty that ezetimibe was not associated with cancer (relative risk 1.01; 95% confidence interval 0.92 to 1.11), fractures (0.90; 0.74 to 1.10), discontinuation due to any adverse event (0.87; 0.74 to 1.03), gastrointestinal adverse events leading to discontinuation (1.34; 0.58 to 3.08), myalgia or muscular pain leading to discontinuation (0.82; 0.51 to 1.33), neurocognitive events (1.48; 0.58 to 3.81), or new-onset diabetes (0.88; 0.61 to 1.28). The narrative analysis of observational studies provided consistent findings. No credible subgroup effects were identified for the harm outcomes, including shorter versus longer follow-up duration of trials. Conclusions Ezetimibe results in little to no difference in adverse events or other undesirable effects compared with placebo, usual care or other lipid-lowering agents. Review registration PROSPERO CRD42020187437.

e24070 Background: We have maintained a living interactive systematic review (LISR) on the treatment of CAT ( CAT LISR ). Recent publications of CASTA-DIVA and CANVAS trials prompted this report of updated analysis. Methods: The approach to creating LISRs has been previously published and is available on our website. ( LIvE synthesis framework ). Patient important outcomes included venous thromboembolism (VTE) recurrence, major bleeding (MB), clinically relevant non-major bleeding (CRNMB), net clinical benefit (NCB) and all-cause mortality. Mantel-Haenszel method was used to pool treatment effect estimates. A Paul-Mendel random-effects meta-analysis was conducted to compare DOACs with LMWH. Mixed-treatment comparisons were computed using fixed-effect model within a Bayesian framework owing to a sparse and open network. Effect estimates were expressed as odds ratio (OR) with 95% confidence intervals (CI). Surface under the cumulative ranking curve (SUCRA) was used to assess relative treatment rankings. Results: This systematic review currently includes six RCTs with a total of 3690 patients and four unique treatment choices. Apixaban was assessed in two trials (ADAM-VTE, CARAVAGGIO), rivaroxaban in two (SELECT-D, CASTA-DIVA) and edoxaban in one (HOKUSAI-VTE). CANVAS trial reported efficacy of DOACs as a class and hence, was only included in direct comparisons with LMWH. Direct comparisons showed that DOACs as a class significantly decreased the odds of VTE recurrence (OR 0.63, 95% CI: 0.49-0.82) without significantly increasing major bleeding (OR 1.23, 95% CI: 0.84-1.79) when compared to LMWH. However, higher odds of CRNMB (OR 1.65, 95% CI: 1.18-2.31) was observed with DOACs when compared to LMWH. Mortality rates were not different between the two groups (OR: 1.03, 95% CI: 0.87-1.21). Mixed treatment comparisons showed decreased VTE recurrences with rivaroxaban (rank 1; OR 0.49, 95% CI: 0.23-0.99) and apixaban (rank 2; OR 0.58, 95% CI: 0.36-0.90) relative to LMWH (rank 4). No significant differences were observed between edoxaban (rank 3) and LMWH in terms of VTE risk reduction. Edoxaban (rank 4) increased the risk of major bleeding (OR 1.77, 95% CI: 1.05-3.15) compared to LMWH (rank 2); there were no significant differences among rivaroxaban (rank 3) apixaban (rank 1), and LMWH. Rivaroxaban (rank 4; OR 3.16; 95% CI: 1.61-6.68) and apixaban (rank 3; OR 1.51, 95% CI: 1.01-2.28) increased the risk of CRNMB compared to LMWH (rank 1). Significant net clinical benefit was observed with apixaban (rank 1; OR 0.66; 95% CI: 0.46-0.94) when compared to LMWH (rank 4). No significant differences were observed among other mixed treatment comparisons. Conclusions: Patients treated with DOACs have 31 fewer VTE events per 1000 CAT patients compared to LMWH. Amongst DOACs, apixaban offers the greatest net clinical benefit with 39 fewer VTE and MB events per 1000 patients compared to LMWH.

e19502 Background: Inconsistent results observed in recent trials (ZUMA-7, TRANSFORM, BELINDA) assessing chimeric antigenic receptor T (CAR-T) cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the available evidence and to compare the effectiveness of different CAR-T products. Methods: MEDLINE and EMBASE were searched to identify full-text or abstract publications of phase 3 randomized controlled trials (RCTs) assessing CAR-T in patients with R/R DLBCL compared to standard of care (SOC). Efficacy outcomes included event-free survival (EFS), progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and complete response (CR). CR rates were also compared between CAR-T and patients in SOC arm who received autologous stem-cell transplantation (ASCT). Safety outcomes included grade > 3 any adverse events (AE), cytokine release syndrome (CRS) and neurological toxicity (NT). A DerSimonian-Laird random-effects meta-analysis was conducted to pool effect estimates. Freeman-Tukey transformation method was used to estimate pooled proportion (PP) of safety events specific to CAR-T. Mixed treatment comparisons were computed using a frequentist network meta-analysis approach. Results: Of 1803 studies identified, three RCTs with 865 patients were included. Meta-analysis showed significant improvement in EFS (HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), PFS (HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T compared to SOC. OS was not significantly different between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Higher objective response (RR: 1.49; 95% CI: 1.13-1.97; I2: 81%), and CR rates (RR: 1.55; 95% CI: 1.07-2.24; I2: 79%) were observed with CAR-T compared to SOC. However, CAR-T was associated with lower CR when compared to patients who underwent ASCT (RR: 0.65; 95% CI: 0.46-0.90; I2: 89%). The safety profile was not different between CAR-T and SOC. The incidences of grade ≥3 CRS (PP: 4.19; 95% CI: 1.60-7.80; I2: 57%) and grade ≥3 NT (PP: 7.57; 95% CI: 0.20-22.6; I2: 95%) were low. Mixed treatment comparisons showed significant EFS benefit with liso-cel (rank 1: HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (rank 2: HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel (rank 3). No significant differences were observed among different CAR-T products for PFS or OS improvement. The safety profile of CAR-T products was comparable with tisa-cel (rank 1) being the safest. Conclusions: CAR-T therapy, as a second line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL. However, given lack of OS benefit coupled with lower response rates when compared to patients who received ASCT, we should exercise caution in adopting CAR-T as second line therapy for all patients with R/R DLBCL.

6589 Background: Real-world utilization and comparative effectiveness of direct oral anticoagulants (DOACs), low molecular weight heparin (LMWH) and warfarin for cancer-associated venous thromboembolism (VTE) treatment remains largely unexplored. Methods: De-identified administrative claims data (OptumLabs - Data Warehouse) for adult active cancer patients with acute VTE (1/1/2012-9/30/2019) were assessed for utilization patterns, recurrent VTE, and major bleeding differences between DOACs, LMWH, and warfarin. Patients were followed up till the end of treatment. Patients who crossed over to other anti-coagulants within the follow up period were excluded. Multinomial logistic regression was used to assess predictors of anticoagulant administration. Kaplan-Meier curves were used to evaluate the differences in time to medication discontinuation among the three groups. Propensity score (PS) and inverse probability of treatment weighting were used to balance baseline differences between groups. Standardized difference (SD) was used to assess the balance of covariates after weighting and SD < 10% was considered acceptable. Weighted Cox proportional hazards regression with a robust variance estimator was then used to assess outcomes in PS weighted groups. Results: A total of 5100 patients met the inclusion criteria; 49.3% filled DOACs (n = 2512), 29.2% LMWH (n = 1488), and 28.6% warfarin (n = 1460). Median treatment duration was around 3.2 months for DOACs and warfarin, and 1.8 months for LWMH ( P-value < 0.01). Multinomial regression analysis showed that younger patients were more likely to be prescribed LMWH (OR 0.97 95% CI: 0.97-0.98) as compared to DOACs. Patients with lung (OR 2.07 95% CI: 1.12-3.65; OR 1.87 95% CI: 1.04-3.37), urological (OR: 1.94 95% CI:1.08-3.49; OR: 2.04 95% CI: 1.12-3.73), gynecological (OR 4.25, 95% CI: 2.31-7.82; OR 2.31 95% CI: 1.22-4.39) and colorectal cancer (OR 2.26 95% CI: 1.20-4.32; OR 2.51; 95% CI: 1.32-4.79) were more likely to be prescribed LMWH or warfarin respectively, compared to DOACs. VTE recurrences were more frequent for patients receiving LMWH (HR: 1.47; 95% CI: 1.14-1.90) or warfarin (HR: 1.46; 95% CI: 1.13-1.87) compared to DOACs. LMWH, but not warfarin, was associated with greater major bleeding rates compared to DOACs (HR: 2.27; 95% CI: 1.62-3.20). All-cause mortality rates were also significantly higher for patients receiving LMWH, but not warfarin compared to DOACs (HR: 1.61; 95% CI: 1.15-2.25). Conclusions: Patients with cancer associated VTE remain on anti-coagulation for a remarkably short duration in real-world clinical practice. DOACs and warfarin may offer better compliance than LMWH. Patients receiving DOACs have a lower risk of VTE recurrence, less major bleeding, and improved mortality. Warfarin may still be considered for patients with contraindications to DOACs and non-compliant to LMWH.

5083 Background: ARASENS and PEACE-1 trials suggests treatment intensification with novel hormonal therapy (NHT) in addition to androgen deprivation therapy (ADT) and docetaxel (DOC) provides survival benefit as compared to DOC+ADT in patients with metastatic castration sensitive prostate cancer (mCSPC). However, the performance of triplet therapy as compared to NHT+ADT remains unexplored. Methods: MEDLINE, EMBASE and recent conference proceedings were searched to include phase III trials evaluating triplet therapy in patients with mCSPC and reporting treatment effects in subgroup of patients with and without docetaxel. Outcomes included overall survival (OS) and radiographic progression free survival (rPFS). Precomputed hazard ratios (HRs) and confidence intervals (CIs) from non-randomized subgroup comparisons were pooled after logarithmic transformation using inverse-variance weighting approach. A DerSimonian-Laird random-effects meta-analysis was then performed to assess subgroup differences. Interaction between subgroups was assessed using P-value of heterogeneity. Mixed treatment comparisons were computed using a fixed-effect model within the frequentist framework using subgroup effect estimates from eligible trials. Results: This meta-analysis included five clinical trials (ARASENS, PEACE-1, ENZAMET, ARCHES and TITAN) with a total of 5804 patients (docetaxel: 2836; no docetaxel: 2836). Subgroup analysis showed statistically significant difference between treatment effects in patients who received docetaxel (NHT + DOC + ADT; HR: 0.74; 95% CI: 0.66-0.84; I2: 0%) and those who did not (NHT + ADT; HR: 0.61; 95% CI: 0.53-0.70; I2: 0%) for OS (p-value of interaction: 0.04). However, no statistically significant interaction was observed in terms of rPFS (p-value: 0.46). Mixed treatment comparisons showed improved OS with NHT + DOC + ADT (HR: 0.74; 95% CI: 0.66-0.84) as compared to DOC + ADT, but not when compared to NHT + ADT (HR: 0.97; 95% CI: 0.78-1.20). NHT + ADT significantly improved OS compared to DOC + ADT (HR: 0.77; 95% CI: 0.64-0.92). Consistently, significant rPFS improvement was observed with NHT + DOC + ADT when compared DOC + ADT (HR: 0.49; 95% CI: 0.42-0.57) but not when compared to NHT + ADT (HR: 0.82; 0.65-1.04). NHT + ADT was observed to improve rPFS compared to DOC + ADT (HR: 0.60; 95% CI: 0.50-0.72). Conclusions: This exploratory and hypothesis generating analysis suggests that addition of docetaxel (triplet therapy) may not delay progression or prolong survival compared to NHT-based doublets. These findings provide direction for future clinical trials in this space and suggest an equipoise to the question of how triplet regimens compare with NHT-doublets. The results should be interpreted with caution as this analysis does not account for potential confounding relationships such as volume of disease.

e16550 Background: Improved computational power and modern algorithms have generated significant interest in radiomics for cancer diagnosis and staging. Here we assess the performance of deep learning (DL) models as a means for feature extraction in combination with supervised machine learning (ML) algorithms for accurate staging and chemotherapy response assessment of bladder cancer. Methods: Deidentified grayscale CT images from bladder cancer patients scheduled to undergo radical cystectomy were included in this retrospective study. These images were manually annotated with two regional masks (normal region and cancer region). Five DL models- namely, AlexNet, GoogleNet, InceptionV3, ResNet-50, and XceptionNet pre-trained on the ImageNet dataset, a public dataset, were then fine-tuned on our bladder CT scan data to extract features. Through feature selection process, the subset of the features was used to build ML classifiers for classification. The classification was performed using five different ML classifiers, namely k-Nearest Neighbor (KNN), Naïve-Bayes (NB), Support Vector Machine (SVM), Linear Discriminant Analysis (LDA), and Decision Tree (DT). The classification task was performed with 10-fold cross-validation, and each of the experiments contained a different but not mutually exclusive subset of samples. The evaluation metrics include accuracy, sensitivity, specificity, precision, and F1-score. Results: A total of 200 deidentified grayscale CT images of 100 patients with histologically proven bladder cancer, were included in this study. For experiment (1) normal vs. cancer, the LDA classifier on XceptionNet based features provides the best performance with an accuracy of 86.07%, sensitivity of 96.75%, specificity of 69.65%, precision of 83.07%, and F1-score of 89.39%. For experiment (2) non-muscle invasive Cancer (NMIBC) vs. muscle invasive bladder cancer (MIBC), the LDA classifier on XceptionNet based features provided the best performance with an accuracy of 79.72%, sensitivity of 66.62%, specificity of 87.39%, precision of 75.58%, and F1-score of 70.81%. For experiment (3) T0 lesion vs. MIBC, the LDA classifier on XceptionNet based features provides the best performance with an accuracy of 74.96%, sensitivity of 80.51%, specificity of 70.22%, precision of 69.78%, and F1-score of 74.73%. Conclusions: Our proposed model has shown good results in differentiating normal vs cancer and promising performance in differentiating T0 vs MIBC after chemotherapy treatment. We are expanding our dataset to further improve the performance in differentiating T0 vs MIBC. In addition, we will investigate the applicability of GAN for data augmentation to address data limit. We believe the hybrid DL and ML framework may facilitates radiologists' decisions and clinical decision-making in patients with bladder cancer.