Multi-institutional Analysis Research Articles

Multi-institutional analysis of extracranial oligometastatic colorectal cancer patients treated with stereotactic body radiation therapy: TROD 02-008 study.

To investigate the treatment outcomes of extracranial oligometastatic colorectal cancer (CRC) patients treated with stereotactic body radiotherapy (SBRT). The clinical data of 388 extra-cranial oligometastatic CRC (≤ 5lesions) patients and 463 lesions treated with SBRT at 19cancer institutions were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local control (LC) were assessed in uni- and multivariable analyses. The median age was 62years (range, 29-92years). The majority of the patients (90.5%) received surgery and systemic treatment for their primary tumor, had ≤ 2 metastasis (83.3%), had single organ involvement (90.3%), and staged using flouro-deoxyglucose positron emission tomography (FDG-PET/CT) (76%). The median fraction and total radiation doses were 10 Gy (range: 6-34 Gy) and 50 Gy (range: 8-64 Gy), respectively, delivered in amedian of 4fractions (range: 1-8). The median follow-up time for the entire cohort was 30.7 months (interquartile range: 27.0-34.3 months). The 3‑year OS, PFS, and LC rates were 64.0%, 42.3%, and 72.7%, respectively. The 3‑year LC rate was significantly higher in patients receiving BED10 ≥ 100 Gy than those receiving BED10 < 100 Gy (76.0% vs.67.3%; p = 0.04). The 3‑year PFS and OS rates were higher in patients receiving BED10 ≥ 100 Gy than those receiving BED10 < 100 Gy (33.2% vs.25.2%; p = 0.03; 53.7% vs. 44.8%; p = 0.02). Single metastasis and complete response after SBRT were independent prognostic factors for survival in multivariable analysis. In this multi-center study, we demonstrated that SBRT is an effective treatment option of metastatic lesions in oligometastatic CRC patients by providing promising LC rates. Higher SBRT doses beyond BED10 ≥ 100 Gy were associated with improved LC and survival. LC of treated lesion and lower tumor burden after SBRT were associated with better outcomes.

Multi-institutional Analysis of Choledocholithiasis in Pediatric vs Adult Patients

BackgroundIn adults, upfront intraoperative cholangiogram with laparoscopic common bile duct exploration (LCBDE) is well accepted for management of choledocholithiasis. Despite recent evidence supporting LCBDE utility in children, there has been hesitation to adopt this surgery first (SF) approach over ERCP first (EF) due to perceived technical challenges. We compared rates of successful stone clearance during LCBDE between adult and pediatric patients to evaluate if pediatric surgeons could anticipate similar rates of successful clearance. MethodsA multicenter, retrospective review of pediatric (<18 years) and adult patients with choledocholithiasis managed from 2018 to 2024 was performed. Demographic and clinical data were obtained. Rate of successful duct clearance with LCBDE was compared. Surgical and endoscopic complications (infections, bleeding, pancreatitis, bile leak) were also compared. Results724 patients, 333 (45.9%) pediatric and 391 (54.0%) adults, were included. The median age of pediatric vs adult patients was 15.2 years [13.1, 16.6] vs 55.5 years [34.1, 70.5], respectively. Of these, 201 (60.4%) pediatric vs 169 (43.2%) adult patients underwent SF, p < 0.001. LCBDE was attempted in 84 (41.7%) pediatric vs 140 (82.8%) adults, p = 0.002. LCBDE success was higher in pediatric vs adult patients (82.1% vs 71.4%, p = 0.004). Complications rates were similar however, pediatric patients who underwent EF had higher endoscopic complications (9.1% vs 3.6%, p = 0.03). ConclusionLCBDE is highly successful in children vs adults with no increased surgical complications. This data, coupled with the limited ERCP access for children, supports that LCBDE is an equally effective tool for managing choledocholithiasis in children as is accepted in adults. Level of EvidenceLevel III.

Commentator Discussion: Long-term outcomes following the Ross procedure in neonates and infants: A multi-institutional analysis

Commentator Discussion: Long-term outcomes following the Ross procedure in neonates and infants: A multi-institutional analysis

PheMIME: an interactive web app and knowledge base for phenome-wide, multi-institutional multimorbidity analysis.

To address the need for interactive visualization tools and databases in characterizing multimorbidity patterns across different populations, we developed the Phenome-wide Multi-Institutional Multimorbidity Explorer (PheMIME). This tool leverages three large-scale EHR systems to facilitate efficient analysis and visualization of disease multimorbidity, aiming to reveal both robust and novel disease associations that are consistent across different systems and to provide insight for enhancing personalized healthcare strategies. PheMIME integrates summary statistics from phenome-wide analyses of disease multimorbidities, utilizing data from Vanderbilt University Medical Center, Mass General Brigham, and the UK Biobank. It offers interactive and multifaceted visualizations for exploring multimorbidity. Incorporating an enhanced version of associationSubgraphs, PheMIME also enables dynamic analysis and inference of disease clusters, promoting the discovery of complex multimorbidity patterns. A case study on schizophrenia demonstrates its capability for generating interactive visualizations of multimorbidity networks within and across multiple systems. Additionally, PheMIME supports diverse multimorbidity-based discoveries, detailed further in online case studies. The PheMIME is accessible at https://prod.tbilab.org/PheMIME/. A comprehensive tutorial and multiple case studies for demonstration are available at https://prod.tbilab.org/PheMIME_supplementary_materials/. The source code can be downloaded from https://github.com/tbilab/PheMIME. PheMIME represents a significant advancement in medical informatics, offering an efficient solution for accessing, analyzing, and interpreting the complex and noisy real-world patient data in electronic health records. PheMIME provides an extensive multimorbidity knowledge base that consolidates data from three EHR systems, and it is a novel interactive tool designed to analyze and visualize multimorbidities across multiple EHR datasets. It stands out as the first of its kind to offer extensive multimorbidity knowledge integration with substantial support for efficient online analysis and interactive visualization.

Postoperative outcomes in patients with anemia undergoing carotid revascularization

BackgroundPreoperative anemia is associated with worse postoperative morbidity and mortality after major vascular procedures. Limited research has examined the optimal method of carotid revascularization in patients with anemia. Therefore, we aim to compare the postoperative outcomes after carotid endarterectomy (CEA), transfemoral carotid artery stenting (TFCAS), and transcarotid artery revascularization (TCAR) among patients with anemia. Study designThis is a retrospective review of patients with anemia undergoing CEA, TFCAS, and TCAR in the Vascular Quality Initiative database between 2016 and 2023. We defined anemia as a preoperative hemoglobin level of <13 g/dL in men and <12 g/dL in women. The primary outcomes were 30-day mortality and in-hospital major adverse cardiac events (MACE). Logistic regression models were used for multivariate analyses. ResultsOur study included 40,383 CEA (59.3%), 9159 TFCAS (13.5%), and 18,555 TCAR (27.3%) cases in patients with anemia. TCAR patients were older and had more medical comorbidities than CEA and TFCAS patients. TCAR was associated with a decreased 30-day mortality (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.37-0.59; P < .001), in-hospital MACE (aOR, 0.58; 95% CI, 0.46-0.75; P < .001) compared with TFCAS. Additionally, TCAR was associated with a 20% decrease in the risk of 30-day mortality (aOR, 0.80; 95% CI, 0.65-0.98; P = .03) and a similar risk of in-hospital MACE (aOR, 0.86; 95% CI, 0.77-1.01; P = .07) compared with CEA. Furthermore, TFCAS was associated with an increased risk of 30-day mortality (aOR, 2; 95% CI, 1.5-2.68; P < .001) and in-hospital MACE (aOR, 1.7; 95% CI, 1.4-2; P < .001) compared with CEA. ConclusionsIn this multi-institutional national retrospective analysis of a prospectively collected database, TFCAS was associated with a high risk of 30-day mortality and in-hospital MACE compared with CEA and TCAR in patients with anemia. TCAR was associated with a lower risk of 30-day mortality compared with CEA. These findings suggest TCAR as the optimal minimally invasive procedure for carotid revascularization in patients with anemia.

Predictive significance of high neutrophil ratio for thrombosis in myeloproliferative neoplasms: JSH-MPN-R18 subanalysis.

Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch's T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted.

Surgical Outcomes and Sociodemographic Disparities Across All Races: An ACS-NSQIP and NHIS Multi-Institutional Analysis of Over 7.5 Million Patients.

This study aims to fill the gap in large-scale, registry-based assessments by examining postoperative outcomes across diverse races/ethnicities. The focus is on identifying disparities and comparing them with socioeconomic demographics. In a registry-based cohort study using the 2008 to 2020 American College of Surgeons National Surgical Quality Improvement Program, we evaluated 24 postoperative outcomes through multivariable analysis, incorporating 28 preoperative risk factors. In a separate, independent analysis of the 2019 to 2020 National Health Interview Survey (NHIS) database, we examined sociodemographic racial/ethnic normative data. Among 7,504,734 American College of Surgeons National Surgical Improvement Database patients specifying race, 83.8% were White (WT), 11.8% Black or African American (B/AA), 3.3% Asian (AS), 0.7% American Indian or Alaska Native (AI/AN), 0.4% Native Hawaiian or Pacific Islander (NH/PI), 7.3% Hispanic. Reoperation trends reveal favorable outcomes for WT, AS, and NH/PI patients compared with B/AA and AI/AN patients. AI/AN patients exhibit higher rates of wound healing issues, while AS patients experience lower rates. AS and B/AA patients are more prone to transfusions, with B/AA patients showing elevated rates of pulmonary embolism, deep vein thrombosis, renal failure, and insufficiency. Disparities in discharge destinations exist. Hispanic patients fare better than non-WT Hispanic patients, contingent on race. Racial groups (excluding Hispanic patients) with superior surgical outcomes from the NSQIP analysis were found in the NHIS analysis to report higher wealth, better healthcare access, improved food security, greater functional and societal independence, and lower frailty. Our study underscores racial disparities in surgical outcomes. Focused investigations into these complications could reveal underlying causes, informing healthcare policies to enhance surgical care universally.

Abiraterone Acetate Versus Enzalutamide Against Chemo-Naïve Castration-Resistant Prostate Cancer With Full-Dose Induction.

Purpose We recently released the multi-institutional real-world analysis about the difference in survival outcomes between abiraterone acetate and enzalutamide against chemo-naïve castration-resistant prostate cancer (CRPC) in a first-line setting. Although reduced dose induction cases were included in that analysis, induction dose reduction might correlate with reduced efficacy. In this study, we analyzed full-dose induction subgroups from our overall cohort and investigated the true difference in efficacy between these agents. Methods A total of 220 chemotherapy-naïve CRPC cases treated with full-dose induction of first-line androgen receptor signaling inhibitor (ARSI) were analyzed. Outcome measures were prostate-specific antigen (PSA) response, PSA progression-free survival (PSA-PFS), treatment failure-free survival (TFF), cancer-specific survival (CSS), and overall survival (OS). Results Abiraterone acetateand enzalutamide were administered to 58 and 162 patients, respectively. The median PSA response rate (-65.4% (A) and -81.5% (E), p = 0.0252), PSA decline ≥ 90% (22.4% (A) and 37.0% (E), p = 0.0478), PSA-PFS (median four months (A) and seven months (E), p = 0.00833), TFF (median six months (A) and 15 months (E), p<0.0001), CSS (median 45 months (A) and not reached (E), p < 0.0001), and OS (median 34 months (A) and 80 months (E), p<0.001) were significantly better in the E group. Conclusion This study showed that PSA response, PSA-PFS, TTF, CSS, and OS were better with first-line enzalutamide administration. Direct inhibition of androgen receptor signaling by enzalutamide is associated with better clinical outcomes in the full-dose induction cohort.

Long-term consequences of positive surgical margin after partial nephrectomy for renal cell carcinoma: multi-institutional analysis.

The aim of the study was to determine the impact of positive surgical margins (PSM) after PN on very long-term recurrence in a contemporary cohort. Patients who underwent PN for a localized renal tumour were included. Patients were stratified according to the presence of PSM. Data on patients' characteristics, the tumour, the peri- and postoperative events were collected. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method and compared by the log-rank test. Sensitivity analyses using weighted propensity score analysis was performed to account for potential selection biases arising from the nonrandom allocation of patients to different groups. A total of 1115 patients were included in the study. The incidence of PSM was 5.4% (n = 61). The median follow-up time was 51months for the PSM group and 61months for the NSM group (p = 0.31). Recurrence rates were significantly higher in the PSM group (13%, n = 8) compared to the NSM group (7%, n = 73) (p = 0.05). This resulted in a significant reduction in DFS in the PSM group (p = 0.004), particularly pronounced in patients with clear cell renal cell carcinoma. Additionally, OS was significantly lower in the PSM group (p < 0.01). Propensity score analysis confirmed a decrease in DFS for the PSM group (p = 0.05), while there was no significant difference in OS between the two groups (p = 0.49). In this retrospective multicenter study, PSM impact on oncological outcomes, increasing recurrence, but no difference in OS was observed post-adjustment for biases.

Outcomes of Concomitant Cardiac Surgical Procedures Performed During Pediatric Lung Transplantation in the United States.

Data on concomitant cardiac surgery (CCS) performed during pediatric lung transplantation (LTx) is limited. Therefore, we conducted a multi-institutional analysis to identify the incidence and outcomes of CCS in pediatric (< 18 years) LTx recipients by merging data (2004-2023) from the United Network for Organ Sharing (UNOS) and Pediatric Health Information System (PHIS) databases. Of the total of 596 pediatric LTx recipients, 87 (15%) underwent CCS. The majority of these cardiac surgeries were atrial septal defect (ASD) closure (90%) followed by aortic arch/descending aortic repair (3%), atrial repair (3%), ventricular septal defect closure (2%), patent ductus arteriosus ligation (2%), and tricuspid valve repair (2%). The median age at LTx was 3years (IQR: 0-12). Pulmonary hypertension (PHT) was the predominant indication for LTx (54%). Survival to discharge was 94% and 5-years survival was 64%. Our findings indicate CCS in children undergoing LTx has acceptable outcomes.

Long-term outcomes following the Ross procedure in neonates and infants: A multi-institutional analysis

ObjectivesFor neonates and infants with aortic valve pathology, the Ross procedure historically has been associated with high rates of morbidity and mortality. Data regarding long-term durability are lacking. MethodsThe international, multi-institutional Ross Collaborative included 6 tertiary care centers. Infants who underwent a Ross operation between 1996 and 2016 (allowing a minimum 5 years of follow-up) were retrospectively identified. Serial echocardiograms were examined to study evolution in neoaortic size and function. ResultsPrimary diagnoses for the 133 patients (n = 30 neonates) included isolated aortic stenosis (14%, n = 19), Shone complex (14%, n = 19), and aortic stenosis plus other (excluding Shone complex; n = 95, 71%), including arch obstruction (n = 55), left ventricular hypoplasia (n = 9), and mitral disease (moderate or greater stenosis or regurgitation, n = 31). At the time of the Ross procedure, median age was 96 days (interquartile range, 36-186), and median weight was 4.4 kg (3.6-6.5). In-hospital mortality occurred in 13 of 133 patients (10%) (4/30 [13%] neonates). Postdischarge mortality occurred in 10 of 120 patients (8%) at a median of 298 days post-Ross. Post-Ross neoaortic dilatation occurred, peaking at 4 to 5 SDs above normal at 2 to 3 years before returning to near-baseline z-score at a median follow-up of 11.5 [6.4-17.4] years. Autograft/left ventricular outflow tract reintervention was required in 5 of 120 patients (4%) at a median of 10.3 [4.1-12.8] years. Freedom from moderate or greater neoaortic regurgitation was 86% at 15 years. ConclusionsNeonates and infants experience excellent postdischarge survival and long-term freedom from autograft reintervention and aortic regurgitation after the Ross. Neoaortic dilatation normalizes in this population in the long-term. Increased consideration should be given to Ross in neonates and infants with aortic valve disease.

Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis

PurposeDespite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT.MethodsA propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test.ResultsMedian follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2α/β=1.5 Gy) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis.ConclusionsOverall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.

The survival benefit of adjuvant trastuzumab with or without chemotherapy in the management of small (T1mic, T1a, T1b, T1c), node negative HER2+ breast cancer

There is limited data regarding the added benefit of adjuvant systemic therapy in the management of small, node-negative, HER2+ breast cancer. In a multi-institutional retrospective analysis using the American Society of Clinical Oncology CancerLinQ database, we compared survival outcomes among T1a-c N0 HER2+ patients diagnosed between 2010 to 2021 who received locoregional therapy alone or in combination with adjuvant trastuzumab (+/− chemotherapy). Primary outcomes were invasive disease-free survival (iDFS) and overall survival (OS). Of the 1,184 patients, 436 received locoregional therapy alone. We found a statistically significant improvement in iDFS (HR 0.73, P = 0.003) and OS (HR 0.63, P = 0.023) on univariate analysis with adjuvant trastuzumab with or without chemotherapy which remained statistically significant on multivariate analysis. Three-arm univariate analysis found that iDFS was significantly improved with trastuzumab monotherapy (P = 0.003) and combination therapy (P = 0.027) compared to observation. Subgroup data suggests that T1b/c tumors derive the greatest benefit.

GCT-05. UPDATED REPORT ON TREATMENT MODALITIES IN METASTATIC GERMINOMA IN CHILDREN: A MULTI-INSTITUTIONAL ANALYSIS

Abstract BACKGROUND Primary intracranial germ cell tumors (GCTs) are rare heterogeneous tumors; germinoma accounts for two-thirds of cases. While neoadjuvant chemotherapy followed by response-based reduced radiotherapy dose and field is the established approach for managing localized CNS germinomas, controversy persists regarding the treatment of primary metastatic disease. Additionally, limited research exists on the utilization of neoadjuvant chemotherapy in primary metastatic germinoma. METHODS A retrospective multi-institutional analysis was conducted to assess overall survival (OS) and event-free survival (EFS) among patients diagnosed with metastatic germinoma who were treated with various modalities. RESULTS We identified 88 patients, including 63 males and 25 females. The median age at presentation was 13.5 years. All patients, who had undergone both brain and spine MRIs, had their diagnoses confirmed through a biopsy, positive CSF cytology, and/or positive CSF tumor markers at presentation. Primary Tumor location was pineal (n=37), suprasellar (n=27), bifocal (n=14) and others (n=9). Eight patients underwent subtotal resection. Craniospinal irradiation (CSI; 21-24 Gy) was administered to 71 patients (81%), while eight patients (9%) received whole ventricular irradiation (WVI; 23.4-30 Gy). Whole brain radiation was given to four patients (5%; 24 Gy), and two patients (2%) had unknown fields. Boosts to primary and/or metastatic sites were administered in all but seven patients. Notably, thirty patients (34%) received CSI without neoadjuvant chemotherapy. At the end of therapy, 69 patients had complete response, 10 partial response and the response was unknown in six. Three patients did not receive irradiation, all died of disease progression. The median follow-up was 64 months (range 6-159 months), yielding an OS of 96.6%. Ongoing multi-institutional data collection and analysis will be presented at the meeting. CONCLUSION Our study is one of the largest studies to date in metastatic germinoma and may provide insight into the role of neoadjuvant chemotherapy with lower CSI doses.

Purely Off-Clamp Sutureless Robotic Partial Nephrectomy for Novice Robotic Surgeons: A Multi-Institutional Propensity Score-Matched Analysis.

Objectives: To compare perioperative outcomes of patients treated with sutureless off-clamp robotic partial nephrectomy (sl-oc RAPN) by either a novice or an expert robotic surgeon at two different institutions. Methods: Data concerning two continuous series of patients with cT1-2N0M0 renal tumors treated with sl-oc RAPN either by a novice or an expert surgeon were extracted from prospectively populated institutional databases over the last 4 years. Perioperative outcomes as well as the baseline characteristics of patients and tumors were compared by using χ2 and Mann-Whitney tests for categorical and continuous variables, respectively. A 1:1 propensity match score analysis (PMSa) generated two homogeneous cohorts. Logistic regression analysis was performed to assess predictors of trifecta outcomes, defined as negative surgical margins, no Clavien-Dindo ≧ 3 grade complications, and no ≧ 30% postoperative eGFR reduction. Results: Overall, 328 patients were treated by an expert surgeon, while 40 were treated by a novice surgeon. After PMSa analysis, two cohorts of 23 patients each were generated, homogeneous for all baseline variables (p ≥ 0.07). Hospital stay was the only significantly different outcome observed between the two groups (5 days vs. 2 days; p < 0.001). No statistically significant differences were recorded when comparing trifecta outcomes (expert: 100% vs. novice: 87%; p = 0.07). In the logistic regression analysis, no statistically significant predictors of trifecta outcomes were recorded. Conclusions: sl-oc RAPN is a feasible and safe nephron sparing technique, even when performed by a novice robotic surgeon.

Malnutrition and the Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Multi-Institutional Population-Based Propensity Score-Matched Analysis.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global health crisis, exacerbating issues like malnutrition due to increased metabolic demands and reduced intake during illness. Malnutrition, a significant risk factor, is linked to worse outcomes in patients with COVID-19, such as increased mortality and extended hospital stays. This retrospective cohort study investigated the relationship between malnutrition and clinical outcomes within 90-180 days using data obtained from the TriNetX database. Patients aged >18 years diagnosed with COVID-19 between 1 January 2022, and 31 March 2024 were enrolled in the study. The propensity score-matching (PSM) method was used to match patients with malnutrition (malnutrition group) and those without malnutrition (control group). The primary composite outcome was the cumulative hazard ratio (HR) for post-COVID-19 condition, all-cause hospitalization, and all-cause mortality between 90 days and 180 days after COVID-19 diagnosis. The secondary outcomes were the individual components of the primary outcomes. Two cohorts, each consisting of 15,004 patients with balanced baseline characteristics, were identified using PSM. During the 90-180-day follow-up period, the malnutrition group exhibited a higher incidence of all-cause hospitalization, mortality, or post-COVID-19 condition (HR = 2.315, 95% confidence interval: 2.170-2.471, p < 0.0001). Compared with patients with COVID-19 without malnutrition, those with malnutrition may be associated with a higher risk of adverse clinical outcomes.

Real-world safety and efficacy of concurrent immunotherapy and thoracic chemoradiotherapy: A multi-institutional analysis.

e23262 Background: Despite the success of Immune checkpoint inhibitors (ICIs) as consolidation following concurrent chemoradiotherapy (CCRT), 22% to 30% of patients still cannot be treated with durvalumab due to progression or adverse events (AEs) during or after CCRT. Concurrent ICIs with CCRT would offer the opportunity to receive ICIs and may provide treatment benefit to a greater proportion of patients. In this study, we performed a multicenter investigation to evaluate the safety and efficacy of ICIs and chemotherapy with concurrent thoracic radiotherapy. Methods: All patients from three institutions who underwent ICIs and concurrent thoracic radiotherapy were included. The rate of 12-month progression-free survival (PFS) was estimated using the Kaplan-Meier method and evaluated with 95% CIs calculated using the Greenwood formula. Therapy-related pneumonitis (TRP) and esophagitis (TRE) were defined per CTCAE v5.0. Statistics utilized logistic regression modeling and receiver operating characteristic (ROC) analysis. Results: 69 patients (median [range] age, 62 [52-76]; 61 [88.4%] male; median follow-up 30.4 months) were collected, including 18 (26.1 %) cases of non-small cell lung cancer (NSCLC), 26 (37.7 %) cases of small cell lung cancer (SCLC), and 25 (36.2 %) cases of esophageal cancer (EC). The 12-month PFS rates in NSCLC, SCLC and EC were 72.2%, 69.2% and 72.0%, respectively. The median PFS in NSCLC and SCLC was 24.3 and 13.1 months, and not reached (mean 29 months) for EC. The incidences of all-grade TRP and TRE were 60.7% and 57.7%, respectively. Grades 1-5 TRP occurred in 15.9%, 30.4%, 8.6%, 1.4%, and 0, respectively. Grades 1-5 TRE occurred in 20.2%, 28.9%, 8.6%, 0, and 0, respectively. On multivariable analysis, age and MLD significantly predicted for any-grade and grade ≥2 TRP. Only age significantly predicted for grade ≥3 TRP. ROC analysis was able to pictorially model RP risk probabilities for a variety of MLD and age thresholds. Conclusions: This real-world study can be helpful for understanding the true efficacy and toxicity of ICIs and chemotherapy with concurrent thoracic radiotherapy given the lack of robust clinical data. Close monitoring should be recommended in this patient population during RT and follow-up.

Preoperative COVID-19 Infection Increases Risk for 60-Day Complications Following Total Shoulder Arthroplasty: A Propensity-Matched Analysis

Total shoulder arthroplasty (TSA) is an effective treatment for a wide range of shoulder pathologies. Literature investigating the impact of COVID-19 diagnosis on outcomes following TSA is limited. The objective of this study was to perform a retrospective multi-institutional database analysis to investigate the association between preoperative COVID-19 diagnosis and 60-day complications following TSA. We queried the TriNetX database using Current Procedural Terminology and the International Classification of Diseases, Tenth Revision codes for patients who underwent a TSA from January 1, 2018 to July 1, 2023. Patients were categorized by those who had and those who did not have a diagnosis of COVID-19 within 30days prior to surgery. The cohorts were matched based on age, gender, ethnicity, race, and past medical history. Chi-square analysis was performed to determine the relationship between COVID-19 diagnosis and 60-day postoperative complications including pneumonia, sepsis, emergency department (ED) visit, hospital admission, mortality, periprosthetic fracture, superficial wound infection, deep vein thrombosis (DVT), pulmonary embolism (PE), acute myocardial infarction, and revision surgery. The search results identified a total 63,768 patients who met study criteria. Of these patients, 7118 (11.08%) were diagnosed with COVID-19 within 30days prior to their TSA procedure. Propensity score matching resulted in 6982 patients in each of the 2 cohorts. Patients with a recent COVID-19 diagnosis prior to surgery had 1.96 (P=.0005) times the odds of sepsis, 1.42 (P=.0032) times the odds of superficial wound infections, 1.42 (P<.0001) times the odds of DVT, 1.52 (P=.0001) times the odds of PE, 1.10 (P=.0249) and 1.79 (P<.0001) times the odds of ED visits and hospital admissions, respectively, and 3.10 (P<.0001) and 2.87 (P<.0001) times the odds of periprosthetic fracture and revision surgery within 60days of TSA. Our study suggests an increased risk of sepsis, ED visits, hospital admissions, periprosthetic fracture, superficial wound infection, DVT, PE, and revision surgery in TSA patients with a recent COVID-19 diagnosis. There may be significant benefit to closer monitoring and greater preventive measures to reduce the occurrence of postoperative complications in this setting. In addition, patients may benefit from postponing elective TSA procedures in the setting of a recent COVID-19 infection.

Prognostic factors and long-term survivors in EGFR-mutated lung cancer: A multi-institutional retrospective analysis.

e20594 Background: Evolution of tyrosine kinase inhibitors (TKIs) shapes the treatment paradigm of EGFR-mutated lung cancer, but resistance eventually develops. It is important to dissect the prognostic factors and to know the differences between long-term responders (LTR) and non-responders (NR). Methods: Electronic medical records were retrieved from Chang-Gung Medical Foundation from 2011 to 2020. Kaplan-Meier method was used to estimate survival, such as progression-free survival (PFS), and overall survival (OS). Multivariate Cox proportional hazard models was adopted to estimate adjusted hazard ratios and 95% confidence intervals. P &lt; 0.05 was set to be statistical significance. Results: Totally, there are 3,551 patients receiving frontline TKIs, of which 825 (23.2%) are LTR with OS &gt; 36 months, and 1,036 (29.2%) are NR with OS &lt; 12 months. Besides, there are 1,200 (33.8%) LTRs with PFS &gt; 18 months and 882 (24.8%) NR with PFS &lt; 6 months. LTR tend to be younger, female, non-smoker, clinical stage 3b, no baseline brain metastasis, exon 19 deletions subtype, subsequent T790M development, bevacizumab usage, and osimertinib exposure (p all &lt; 0.05). The median PFS of all enrolled patients is 12.3 months and median OS is 22.3 months. By multivariate analysis, age older than 65 years (Hazard ratio, [HR]:1.25 [1.15-1.36]), male (HR: 1.24 [1.13-1.36]), clinical stage 4 (2.19 [1.78-2.69]), baseline brain metastasis (1.25 [1.12-1.37]) are poor prognostic factors (p &lt; 0.05). Also, T790M is not only predictive to osimertinib but also prognostic factor to OS (p &lt; 0.05), and patients who developed subsequent T790M tend to have better PFS (18.1 v.s. 11.8 months). In patients without detected T790M along their disease course, exposure to osimertinib is related to better OS (33.1 v.s. 18.3 month, log-rank p &lt; 0.05). Conclusions: LTR and NR are of distinctive characteristics, and T790M is prognostic and predictive to osimertinib. Further study is warranted for choosing the optimal treatment by clinical factors and T790M status.

Comparison of chemotherapy to chemo-immunotherapy as first-line treatment in patients with advanced large cell neuroendocrine carcinomas (LCNECs) of mixed histology: A multi-institutional international retrospective study.

8602 Background: LCNECs are a rare subtype of lung cancer, with limited clinical trial data and an unclear consensus on first-line treatment. Even less is known about the optimal treatment approach for pts with mixed LCNECs, a pathologic subtype where tumors contain both LCNEC histology as well as features of adenocarcinoma, squamous cell, or small cell lung cancer. Methods: We conducted an international multi-institutional retrospective analysis (n=13 institutions) of pts with advanced or metastatic mixed LCNECs who received 1st-line systemic therapy with either chemotherapy alone (chemo) or chemo-immunotherapy (chemoIO) between 2010-2023. Clinical outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events (trAEs). Survival comparisons were made via the log-rank test. Results: Seventy-three pts with mixed LCNECs received either chemo (n=42, 57.5%) or chemoIO (n=31, 42.5%). The most common chemo regimens were carboplatin/etoposide (n=27) and cisplatin/etoposide (n=8), while the most common chemoIO was carboplatin/etoposide/atezolizumab (n=19). Median age at 1st-line therapy initiation was 65 (IQR: 60-72). 64% of pts were male (n=47). The majority were former smokers (n=41, 56.2%), with 22 current smokers (30.1%), and 10 non-smokers (13.7%). Mixed histologies included LCNEC/NSCLC (n=45, 56.2%), LCNEC/SCLC (n=17), LCNEC/carcinoid (n=1), and unspecified mixed LCNEC (n=10). Median PFS for chemo was 5 months (95% CI 2.7-9.2) vs. 6 months (95% CI 4.4-8.3) for chemoIO ( p=0.86). Median OS for chemo was 14.2 months (95% CI 10.4-22.5) vs. 17.2 months (95% CI 9.4-27.2) for chemoIO ( p=0.66). The ORR did not differ between chemo (n=18, 45%) and chemoIO (n=15, 48.4%) ( p=0.81). In the chemo group, 60% (n=25) experienced trAEs of any grade, with 23.8% (n=10) experiencing grade 3+ events and four requiring hospitalizations. For chemoIO pts, 61% (n=19) experienced trAEs, with 25.8% (n=8) experiencing grade 3+ events and six requiring hospitalizations. Neutropenia was the most common grade 3+ trAE for both chemo (n=5) and chemoIO (n=4). Overall, there were no significant differences between chemo or chemoIO groups for ORR ( p=0.81), all-grade trAEs ( p=0.88), grade 3+ trAEs ( p=0.84), PFS ( p=0.86), or median OS ( p=0.66). There were no significant differences in median PFS ( p=0.46) or OS ( p=0.99) for pts with mixed LCNEC/NSCLC vs. LCNEC/SCLC. Conclusions: For mixed LCNECs, there was no significant difference in PFS or OS between first-line treatment with chemo vs. chemoIO, suggesting limited benefit from immunotherapy for these pts. Additionally, survival outcomes did not differ between mixed LCNEC/NSCLC and LCNEC/SCLC, suggesting a biology primarily driven by their neuroendocrine component.