Citations

e18790 Background: Patients with SARS-CoV-2 with a diagnosis of cancer have increased risk of severe COVID-19 outcomes compared to patients without cancer. However, little is known regarding outcomes of patients with COVID-19 and cancer in the setting of human immunodeficiency virus (HIV). Given the unique risks of this population, we sought to understand COVID-19 outcomes using registry data. Methods: This is a descriptive research study utilizing the CCC19 registry, an international multi-institutional registry with healthcare provider-reported cases of patients with cancer and COVID-19. Between March 2020-December 2021, 116 persons with HIV (PWH) and 10,642 persons without HIV (PWOH) with laboratory-confirmed SARS-CoV-2 infection were identified as eligible for the analysis. Results: Median follow-up time for both groups was 90 days, with interquartile range (IQR) 30-180 days. Most PWH were actively receiving antiretroviral therapy (ART) at the time of COVID-19 diagnosis, with 71% (n = 82) having named drug information available; bictegravir/emtricitabine/tenofovir was the most common ART (n = 25). PWH were of younger age (median 57.5 yrs [IQR 46.5-63.25] vs 65 yrs [IQR 55-74]), male (81% vs 47%), and either non-Hispanic Black or Hispanic (71% vs 34%) compared to PWOH. 12% of PWH (n = 14) were current smokers compared to 6% of PWOH (n = 638), and more than half in each group were never smokers (51% of PWH and 53% of PWOH). The following comorbidities were identified in PWH vs PWOH: cardiovascular (16% vs 20%), pulmonary (16% vs 20%), renal (15% vs 14%), and diabetes mellitus (18% vs 27%). A higher proportion of PWH had hematologic malignancy compared to PWOH (33% vs 19%). More PWH had active cancer which was progressing at the time of SARS-CoV-2 infection compared to PWOH (24% vs 14%). 44% of PWH (n = 51) had received active systemic anticancer therapy within the 3 months preceding SARS-CoV-2 infection (including cytotoxic, targeted, endocrine therapies, and immunotherapy) compared to 51% of PWOH (n = 5,420). PWH had an increased rate of hospitalization (58% vs 55%) compared to PWOH. Although a lower proportion of PWH required supplemental oxygen during hospitalization compared to PWOH (34% vs 38%) and ICU admission rates were identical between the two groups (16% vs 16%), PWH had an increased rate of mechanical ventilation (14% vs 10%) and death (24% vs 18%) compared to PWOH. Conclusions: This is the first known study describing outcomes of patients with cancer and COVID-19 in the PWH population from a large multinational dataset. PWH have characteristics associated with adverse outcomes in prior analyses (male sex, non-Hispanic Black or Hispanic, hematologic malignancy, progressing cancer) but are notably younger and have fewer comorbidities. HIV infection may portend increased risk of severe COVID-19 and death; however, additional analyses, including multivariable regression, are warranted.

OBJECTIVE The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

BackgroundDespite routine evaluation of cytogenetics in myeloma, little is known regarding the impact of high‐dose therapy (HDT) consolidation on overall survival (OS) or progression‐free survival (PFS) in patients who have high‐risk cytogenetics. The authors performed a meta‐analysis of randomized controlled trials (RCTs) to assess the heterogeneity of HDT efficacy according to cytogenetic risk.MethodsAll RCTs in patients who had newly diagnosed myeloma from 2000 to 2021 that compared upfront HDT versus standard‐dose therapy (SDT) consolidation were included. The primary objective was to assess the difference in HDT efficacy between standard‐risk and high‐risk cytogenetics in terms of the OS or PFS log(hazard ratio) (HR). The pooled OS and PFS HR was calculated according to cytogenetic‐risk subgroup using a random‐effects model, and heterogeneity (I2) (the percentage of total observed variability explained by between‐study differences) was assessed using an interaction test.ResultsAfter screening 3307 citations, 6 RCTs were included for PFS analysis, and 4 were included for OS analysis. The median follow‐up ranged from 3.1 to 7.8 years. The pooled OS HR for HDT versus SDT consolidation in patients with standard‐risk and high‐risk cytogenetics was 0.90 (95% confidence interval [CI], 0.70‐1.17; I2 = 0%) and 0.66 (95% CI, 0.45‐0.97; I2 = 0%), respectively. The difference in HDT efficacy in terms of OS between standard‐risk and high‐risk patients was statistically significant in favor of the high‐risk group (P for interaction = .03). The pooled PFS HR for HDT versus SDT was 0.65 (95% CI 0.56‐0.76; I2 = 0%) versus 0.52 (95% CI, 0.33‐0.83; I2 = 55%), respectively. The difference in HDT efficacy in terms of PFS between standard‐risk and high‐risk patients was not significant (P for interaction = .25).ConclusionsThe magnitude of OS benefit with upfront HDT is cytogenetics‐dependent. Patients with high‐risk cytogenetics should preferably receive upfront rather than delayed HDT consolidation.Lay Summary Upfront autologous stem cell transplantation improves overall survival in patients with newly diagnosed myeloma harboring high‐risk cytogenetics.

Currently, there is no pharmacological treatment targeting defective tissue repair in chronic disease. Here, we used a transcriptomics-guided drug target discovery strategy using gene signatures of smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke, identifying druggable targets expressed in alveolar epithelial progenitors, of which we screened the function in lung organoids. We found several drug targets with regenerative potential, of which EP and IP prostanoid receptor ligands had the most profound therapeutic potential in restoring cigarette smoke–induced defects in alveolar epithelial progenitors in vitro and in vivo. Mechanistically, we found, using single-cell RNA sequencing analysis, that circadian clock and cell cycle/apoptosis signaling pathways were differentially expressed in alveolar epithelial progenitor cells in patients with COPD and in a relevant model of COPD, which was prevented by prostaglandin E2 or prostacyclin mimetics. We conclude that specific targeting of EP and IP receptors offers therapeutic potential for injury to repair in COPD.

101 Background: Colorectal cancer (CRC) incidence and mortality have decreased since the 1970s, but the incidence in young adults (20-49 years, named early-onset CRC, eoCRC) has been increasing. eoCRC patients with metastatic disease are treated with the same standard regimens as late-onset CRC (loCRC, age ≥ 50 years) although detailed response data for eoCRC are largely missing. Methods: Individual patient data on 7,604 subjects with metastatic eoCRC from 11 first line randomized bevacizumab studies between 2000 and 2012 in the ARCAD advanced colorectal cancer database were pooled. The distributions of demographics, clinicopathological features, biomarkers, and outcome data were summarized by age groups. Progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for potential confounders. Predictive value of age group was evaluated by testing interaction effect between treatment and age variables. Results: Female eoCRC are more commonly seen compared to loCRC (46.8% vs. 38.7%, p<0.0001). Patients with eoCRC (n=1,289) were significantly more likely to have had prior metastasectomy (17.5% vs. 13.5%, p=0.043) and lung metastatic disease (67% vs. 59.8%, p<0.001), but less likely to have distant lymph node metastatic disease (58.8 vs. 62.9%, p=0.036) or KRAS mutation (29.2% vs. 34.4%, p=0.042) compared to those with loCRC (n=6,315). eoCRC and loCRC patients had similar distributions according to PS, primary tumor sidedness, prior primary tumor resection, liver involvement, peritoneal involvement, number of metastatic sites, NRAS and BRAF. Age of disease onset was not a statistically significant prognostic factor for PFS in univariate and multivariate analysis (seen in table). Bevacizumab in addition to chemo improved PFS in eoCRC population (9.9 vs. 6.8 months, HR = 0.66, p<0.001), which was similar to the findings in loCRC population (9.4 vs. 7.3 months, HR= 0.73, p<0.001, interaction p=0.54). By multivariate analysis, a greater improvement in PFS was noted for the addition of bevacizumab in eoCRC relative to LoCRC patients (HR = 0.62 vs. HR = 0.82). Conclusions: Treatment naive eoCRC patients with metastatic disease derive similar benefit from bevacizumab relative to their average age counterparts.[Table: see text]

80 Background: Higher baseline body mass index is associated with improved survival in metastatic CRC (mCRC). Whether weight gain or loss after mCRC diagnosis is associated with survival remains largely unknown. Methods: We analyzed individual patient data from 3504 patients with previously untreated mCRC enrolled in five phase III randomized trials (AVF2017g, AVF2192g, CRYSTAL, N9741, OPUS) conducted between 2000 and 2006. Weight measurements were prospectively collected at 3 months after diagnosis and then up to 5 years. Patients were categorized into three groups based on the percent weight change at 3 months: stable weight or gain, weight loss up to 5% of baseline weight, and ≥5% weight loss of baseline weight. Cox models were used to assess the prognostic associations of weight change at 3 months with overall survival (OS) and progression-free survival (PFS), adjusting for baseline BMI, age, sex, performance score, chemotherapy backbone (oxaliplatin vs. irinotecan), and biologics type (cetuximab vs. bevacizumab). Sub-analyses included Cox models adjusted for additional clinical-pathological factors (primary tumor sidedness [right colon vs. left colon-rectum], and BRAF status; N=1,511). Results: Median percent weight change at 3 months was -0.5% (IQR -4.0 to+1.6%). OS was better in patients with weight stability or gain than in those with weight loss (up to 5% or ≥5%; (Table). Results were consistent for PFS for patients with ≥5% weight loss of baseline weight, as well as for sub-analyses. Conclusions: Patients losing weight during the first 3 months of systemic therapy for metastatic colorectal cancer have significantly shorter overall survival than those with stable or increasing weight. Degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight and obese individuals. Further studies examining possible usefulness of on-treatment early weight loss as a novel intermediary end-point are needed.[Table: see text]

Background and Purpose: The CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) consists of 2 parallel randomized stroke prevention trials in patients with asymptomatic high-grade stenosis of the cervical carotid artery. The purpose of this report is to detail the outcomes of a health screening effort to increase trial enrollment of women and minorities. Methods: Life Line screening (LLS) conducts nationwide screening for vascular disease. Screenings within a 50-mile radius of each CREST-2 center were identified for participation in a joint CREST-LLS program over the course of one year (November 2018 to October 2019) whereby patients with an abnormal carotid ultrasound were referred to the local CREST-2 center for further workup, management, and potential consideration for trial enrollment. Results: LLS completed the screening of 588 198 individuals in 29 732 zip codes across the United States. Of those, 230 021 individuals were screened at events occurring near a CREST-2 clinical center and 646 (0.3%) were found to have abnormal carotid ultrasound findings. Each of the 646 individuals was contacted by CREST-LLS program staff for permission to be referred to their local CREST-2 center; 200 (31%) consented to be contacted by CREST-2. Of those, 39 (19.5%) agreed to be, and were, evaluated at their local CREST-2 center. High-grade stenosis was confirmed in 27 patients. A total of 3 patients were eligible for the trial and were enrolled, one woman but no racial/ethnic minorities. Conclusions: The LLS program appears to identify community-living individuals with high-grade carotid stenosis through ultrasonography. However, the prevalence of abnormal carotid findings was low. In addition, screening and offering participation into the CREST-2 trial had no substantial impact on the proportion of women and minorities enrolled in the trial. Additional innovative strategies are needed to promote enrollment of diverse patients with carotid stenosis into stroke prevention trials.