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Abstract BACKGROUND: Our group recently reported on the results of Blood and Marrow Transplant (BMT) Clinical Trials Network (CTN) 1101 a randomized comparison between double umbilical cord blood (dUCB) and haploidentical bone marrow (haplo) with post-transplant cyclophosphamide (ptCy) in the nonmyeloablative setting that showed similar progression free survival (PFS) between the two treatment groups, but lower non-relapse mortality (NRM) and better of overall survival (OS) in the haplo arm. In this secondary analysis we sought to investigate if transplant center experience with haplo and or cord blood HCT had an impact on outcomes. PATIENTS AND METHODS: All patient randomized in BMT CTN 1101 were included. In order to determine the transplant center experience with either haplo or dUCB we queried the Center for International Blood and Marrow Transplant Research (CIBMTR) for number of transplants with each platform in the year prior to initiation of the study. Centers were then grouped as dUCB center (> 10 dUCB, n=117, 10 centers), Haplo center (>10 haplo and ≤10 dUCB, n=110, 2 centers), and ≤10 haplo and ≤10 dUCB HCTs (other center, n=140, 21 centers). Further analysis considered the alternative cut-off for haplo (> 5 vs ≤ 5) experience, and considered the outcomes based on the donor experience vs. others (e.g. dUCB > 10 vs. ≤ 10; haplo > 5 vs. ≤ 5). RESULTS: The effect of center experience on HCT outcomes shown in Figure, below . After adjusting for age, Karnofsky performance score and, disease risk index we found that there was no difference in outcomes between haplo and dUCB for centers that were experienced with dUCB or had limited to no experience with either dUCB or haplo. In contrast, in centers that were primarily experienced with haplo had better outcomes with this donor type, as compared to dUCB. The higher risk of treatment failure (relapse or death) and overall mortality in dUCB in haplo experienced centers was driven by significantly higher risk of relapse. We then considered the transplant experience with each of the donor types separately. In transplant centers that had performed > 10 dUCB, there were similar outcomes for recipients of both dUCB and haplo. Similarly, centers that had ≤ 5 haplo HCTs had no difference in outcomes between donor types suggesting an overlap with centers that had performed > 10 dUCB HCTs. Overall mortality was higher among dUCB recipients in centers that had performed ≤ 10 dUCB. Notably, the hazard ratio of non-relapse mortality favored haplo in all four donor experience type of transplant center, albeit not statistically significant. CONCLUSION: Except for dUCB recipients in centers with < 10 dUCB/year had worse overall mortality, primarily driven by relapse, the transplant center experience in the year prior to the initiation of BMT CTN 1101 had limited impact on the outcomes of this randomized clinical trial. Figure 1 Figure 1. Disclosures Brunstein: NANT: Research Funding; FATE: Research Funding; GamidaCell: Research Funding; BlueRock: Research Funding; AlloVir: Consultancy. Costa: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria. Cutler: Deciphera: Consultancy; Cimeio: Consultancy; Editas: Consultancy; Kadmon: Consultancy; Pfizer: Consultancy; Mallinckrodt: Consultancy; CareDx: Consultancy; Incyte: Consultancy; Omeros: Consultancy; Syndax: Consultancy; Mesoblast: Consultancy; Jazz: Consultancy. Horowitz: Sobi: Research Funding; Regeneron: Research Funding; Orca Biosystems: Research Funding; Tscan: Research Funding; Xenikos: Research Funding; Miltenyi Biotech: Research Funding; Stemcyte: Research Funding; Medac: Research Funding; Vor Biopharma: Research Funding; Kite/Gilead: Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding; Kiadis: Research Funding; Seattle Genetics: Research Funding; Mesoblast: Research Funding; GlaxoSmithKline: Research Funding; Sanofi: Research Funding; Pfizer, Inc: Research Funding; Omeros: Research Funding; Magenta: Consultancy, Research Funding; Jazz Pharmaceuticals: Research Funding; Vertex: Research Funding; Genentech: Research Funding; Takeda: Research Funding; Novartis: Research Funding; Shire: Research Funding; Gamida Cell: Research Funding; Daiicho Sankyo: Research Funding; CSL Behring: Research Funding; Chimerix: Research Funding; Bristol-Myers Squibb: Research Funding; bluebird bio: Research Funding; Astellas: Research Funding; Amgen: Research Funding; Allovir: Consultancy; Actinium: Research Funding. Horwitz: Gamida Cell: Research Funding. McGuirk: Novartis: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; EcoR1 Capital: Consultancy; Pluristem Therapeutics: Research Funding; Novartis: Research Funding; Bellicum Pharmaceuticals: Research Funding; Astelllas Pharma: Research Funding; Gamida Cell: Research Funding; Fresenius Biotech: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau. Rezvani: US Department of Justice: Consultancy; Kaleido: Other: One-time scientific advisory board; Nohla Therapeutics: Other: One-time scientific advisory board; Pharmacyclics-Abbvie: Research Funding. Rybka: Spark Therapeutics: Consultancy; Merck: Consultancy. Vasu: Kiadis, Inc.: Research Funding; Boehringer Ingelheim: Other: Travel support; Seattle Genetics: Other: travel support; Omeros, Inc.: Membership on an entity's Board of Directors or advisory committees.

Abstract Background The incidence of young-onset colorectal cancer (yoCRC) is increasing. It is unknown if there are survival differences between young and older patients with metastatic colorectal cancer (mCRC). Methods We studied the association of age with survival in 2326 mCRC patients enrolled in the Cancer and Leukemia Group B and SWOG 80405 trial, a multicenter, randomized trial of first-line chemotherapy plus biologics. The primary and secondary outcomes of this study were overall survival (OS) and progression-free survival (PFS), respectively, which were assessed by Kaplan-Meier method and compared among younger vs older patients with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards modeling, adjusting for known prognostic variables. All statistical tests were 2-sided. Results Of 2326 eligible subjects, 514 (22.1%) were younger than age 50 years at study entry (yoCRC cohort). The median age of yoCRC patients was 44.3 vs 62.5 years in patients aged 50 years and older. There was no statistically significant difference in OS between yoCRC vs older-onset patients (median = 27.07 vs 26.12 months; adjusted HR = 0.98, 95% CI = 0.88 to 1.10; P = .78). The median PFS was also similar in yoCRC vs older patients (10.87 vs 10.55 months) with an adjusted hazard ratio of 1.02 (95% CI = 0.92 to 1.13; P = .67). Patients younger than age 35 years had the shortest OS with median OS of 21.95 vs 26.12 months in older-onset patients with an adjusted hazard ratio of 1.08 (95% CI = 0.81 to 1.44; Ptrend = .93). Conclusion In this large study of mCRC patients, there were no statistically significant differences in survival between patients with yoCRC and CRC patients aged 50 years and older.

Purpose: The purpose of this study is to quantify cancer risk in patients with Fuchs endothelial corneal dystrophy (FECD). Methods: Using the 2014 to 2016 Medicare Limited 5% Data Sets—Carrier Line File, US Medicare fee-for-service beneficiaries (aged 65 years or older) with FECD and cancer were identified through International Classification of Diseases, ninth and 10th Revision diagnostic codes from January 1, 2014, to December 31, 2016. The main outcome measures were odds ratios (ORs) of cancer at various anatomic locations in patients with versus without FECD. Results: Of the 1,462,740 Medicare beneficiaries, 15,534 patients (1.1%) had an International Classification of Disease code for FECD. Compared with US Medicare beneficiaries without FECD, patients with FECD were at increased risk for the following malignancies: breast [OR: 1.32; 95% confidence interval (CI): 1.22–1.43; P < 0.001], cutaneous basal cell (OR: 1.42; 95% CI: 1.35–1.49; P < 0.001), cutaneous melanoma (OR: 1.20; 95% CI: 1.03–1.40; P = 0.02), cutaneous squamous cell (OR: 1.45; 95% CI: 1.38–1.53; P < 0.001), ovarian (OR: 1.84; 95% CI: 1.48–2.30; P < 0.001), and thyroid (OR: 1.32; 95% CI: 1.04–1.68; P = 0.02). By contrast, FECD cases were at lower odds of having lung (OR: 0.81; 95% CI: 0.71–0.93; P = 0.003) and prostate cancer diagnoses (OR: 0.88; 95% CI: 0.81–0.96; P = 0.002). Conclusions: Patients with FECD aged 65 years or older may be at increased risk for cancer at several anatomic locations. Follow-up studies are needed to further explore the association of FECD and malignancy, elucidate potential disease mechanisms, and identify genetic and/or environmental risk factors.

Background Women with cardiomyopathy (CM) are often advised against pregnancy due to risk for major adverse cardiovascular events (MACE). However, the impact of CM subtype on maternal MACE is not understood, and so we sought to evaluate the influence of CM phenotype on maternal outcomes, as well as the effect on immediate and late left ventricular function. Methods We evaluated all pregnant women in our high-risk maternal cardiovascular programme (2009–2019). Composite maternal MACE included: death, inotrope use, left ventricular assist device, orthotopic heart transplant and/or escalation in transplant listing status, acute decompensated heart failure and sustained ventricular arrhythmia. Results Among 875 women followed, 32 had CM (29±7 years old, left ventricular ejection fraction (LVEF) 41%±12%): 3 ischaemic CM (ICM), 10 peripartum CM (PPCM) and 19 non-ICM (NICM). MACE events occurred in 6 (18%) women (PPCM: 2 (33%), NICM: 4 (67%)). There was no difference in LVEF at baseline, however, women with MACE had significantly lower LVEF both early (LVEF: 27±5% vs . 41±2%, p<0.05) and late post partum (LVEF: 28±5% vs . 44±2%, p<0.01). Conclusions In this contemporary cohort of women with CM, maternal MACE rates were lower than previously reported, and were less common in PPCM as compared with ICM and NICM. Heart function in women with MACE was negatively impacted immediately after delivery and in late postpartum follow-up, suggesting that pregnancy itself likely has influence on future left ventricular function in women with underlying CM.

Background: Benchmarking international cancer survival differences is necessary to evaluate and improve healthcare systems. Our aim was to assess the potential regional differences in outcomes among patients with metastatic colorectal cancer (mCRC) participating in international randomized clinical trials (RCTs). Design: Countries were grouped into 11 regions according to the World Health Organization and the EUROCARE model. Meta-analyses based on individual patient data were used to synthesize data across studies and regions and to conduct comparisons for outcomes in a two-stage random-effects model after adjusting for age, sex, performance status, and time period. We used mCRC patients enrolled in the first-line RCTs from the ARCAD database, which provided enrolling country information. There were 21,509 patients in 27 RCTs included across the 11 regions. Results: Main outcomes were overall survival (OS) and progression-free survival (PFS). Compared with other regions, patients from the United Kingdom (UK) and Ireland were proportionaly over-represented, older, with higher performance status, more frequently male, and more commonly not treated with biological therapies. Cohorts from central Europe and the United States (USA) had significantly longer OS compared with those from UK and Ireland ( p = 0.0034 and p < 0.001, respectively), with median difference of 3–4 months. The survival deficits in the UK and Ireland cohorts were, at most, 15% at 1 year. No evidence of a regional disparity was observed for PFS. Among those treated without biological therapies, patients from the UK and Ireland had shorter OS than central Europe patients ( p < 0.001). Conclusions: Significant international disparities in the OS of cohorts of mCRC patients enrolled in RCTs were found. Survival of mCRC patients included in RCTs was consistently lower in the UK and Ireland regions than in central Europe, southern Europe, and the USA, potentially attributed to greater overall population representation, delayed diagnosis, and reduced availability of therapies.

Objective To compare the prevalence and patterns of anomalous coronary artery origin from the opposite sinus (ACAOS) in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). Methods Retrospective review of consecutive patients with surgically excised BAV and TAV was performed from 1994 to 2015. Clinical notes, echocardiograms, coronary angiograms, CT angiographies, and pathology reports were reviewed. ACAOS included right coronary artery from the left cusp, left circumflex artery from the right cusp and left main or left anterior descending artery from the right cusp. Results 2371 (years 1994–2015) and 1679 (years 2009–2015) consecutive patients with pathology-confirmed BAV and TAV, respectively, and defined preoperative coronary anatomy were identified. A left dominant coronary circulation was present in 386 (18%) patients with BAV and 179 (11%) patients with TAV (p<0.001). ACAOS was identified in 43 (1.8%) patients with BAV and 15 (0.9%) patients with TAV, p=0.02. Among patients with BAV and ACAOS, the most common phenotype was right-left fusion (n=34, 79%) with present raphe (n=36, 84%), with no association between BAV phenotype and ACAOS type. On multivariate analysis, BAV status and size of the mid-ascending aorta were independently associated with ACAOS (OR 3.29; CI 1.26 to 8.6; p=0.02; OR 0.93; CI 0.87 to 0.98; p=0.01; respectively). Only two patients with ACAOS, one with BAV and one with TAV, had a perioperative coronary ischaemic event. Conclusions The prevalence of the potentially malignant ACAOS is significantly higher (threefold higher odds) in patients with BAV as compared with TAV, yet remains uncommon in absolute terms. Most patients with BAV and ACAOS had right-left cusp fusion and present raphe. Perioperative coronary events are rare in patients with ACAOS.

There is a lack of pharmacogenetic predictors of outcome in gastric cancer patients. The aim of this study was to assess previously identified candidate genes associated with 5-fluorouracil (5-FU), cisplatin, or epirubicin toxicity or response in a cohort of resected gastric cancer patients treated on CALGB (Alliance) 80101. Gastric or gastroesophageal cancer patients randomized to adjuvant 5-FU/leucovorin or epirubicin/cisplatin/5-FU before and after 5-FU chemoradiation were genotyped for single nucleotide polymorphisms (SNPs) in GSTP1 (rs1695), ERCC1 (rs11615 and rs3212986), XRCC1 (rs25487), UGT2B7 (rs7439366) and the 28 base-pair tandem repeats in TYMS (rs34743033). Logistic regression and log rank tests were used to assess the association between each SNP and incidence of grade 3/4 neutropenia and leukopenia, overall (OS) and progression-free survival (PFS), respectively. Toxicity endpoint analyses were adjusted for the treatment arm, while OS and PFS were also adjusted for performance status, sex, age, lymph node involvement, and primary tumor site and size. Of 281 subjects with successful genotyping results and available clinical (toxicity and efficacy) data, 166 self-reported non-Hispanic White patients were included in the final analysis. There was a lack of evidence of an association among any SNPs tested with grade 3/4 neutropenia and leukopenia or OS and PFS. Age, lymph node involvement, and primary tumor size were significantly associated with OS and PFS. This study failed to confirm results of previous gastric cancer pharmacogenetic studies.

OBJECTIVE Scoliosis is common in patients with Chiari malformation type I (CM-I)–associated syringomyelia. While it is known that treatment with posterior fossa decompression (PFD) may reduce the progression of scoliosis, it is unknown if decompression with duraplasty is superior to extradural decompression. METHODS A large multicenter retrospective and prospective registry of 1257 pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for patients with scoliosis who underwent PFD with or without duraplasty. RESULTS In total, 422 patients who underwent PFD had a clinical diagnosis of scoliosis. Of these patients, 346 underwent duraplasty, 51 received extradural decompression alone, and 25 were excluded because no data were available on the type of PFD. The mean clinical follow-up was 2.6 years. Overall, there was no difference in subsequent occurrence of fusion or proportion of patients with curve progression between those with and those without a duraplasty. However, after controlling for age, sex, preoperative curve magnitude, syrinx length, syrinx width, and holocord syrinx, extradural decompression was associated with curve progression > 10°, but not increased occurrence of fusion. Older age at PFD and larger preoperative curve magnitude were independently associated with subsequent occurrence of fusion. Greater syrinx reduction after PFD of either type was associated with decreased occurrence of fusion. CONCLUSIONS In patients with CM-I, syrinx, and scoliosis undergoing PFD, there was no difference in subsequent occurrence of surgical correction of scoliosis between those receiving a duraplasty and those with an extradural decompression. However, after controlling for preoperative factors including age, syrinx characteristics, and curve magnitude, patients treated with duraplasty were less likely to have curve progression than patients treated with extradural decompression. Further study is needed to evaluate the role of duraplasty in curve stabilization after PFD.

Abstract: Corneal tomography has an emerging role in the assessment of Fuchs endothelial corneal dystrophy (FECD) in clinical practice and potentially for future clinical trials. Posterior elevation and pachymetry maps derived from elevation based Scheimpflug tomography can detect early corneal edema, even at a subclinical stage, enabling clinicians to better counsel patients about their vision and the risk of disease progression with and without cataract surgery. Tomographic imaging provides a functional assessment of corneal endothelial health, and could enable objective assessment of FECD progression, or regression, in response to novel therapeutic interventions. Clinicians and investigators should adopt Scheimpflug imaging for the assessment of FECD over traditional morphologic imaging modalities.

3588 Background: Growing data suggest dietary factors are associated with survival among pts with non-metastatic CRC. However, data on diet and survival among pts with advanced or metastatic disease are very limited. Methods: We prospectively examined dietary fat intake assessed at initiation of treatment for advanced or metastatic CRC in relation to OS and PFS. This analysis was conducted among 1,149 pts in the CALGB 80405 randomized controlled trial who completed a validated food frequency questionnaire. We examined intakes of saturated, monounsaturated, and polyunsaturated (total n-3, long-chain n-3, and total n-6) fats as well as animal and vegetable fats. Based on data from non-metastatic CRC and other cancers, we hypothesized that higher intakes of long-chain n-3 fatty acids and vegetable fats would be associated with longer OS and PFS and higher intakes of saturated fat and animal fat would be associated with shorter OS and PFS. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: Over a median follow-up of 6.1 years [y; interquartile range (IQR): 5.3, 7.2 y], we observed 974 deaths and 103 events of progression without death during follow-up. Participants in this analysis had a median age of 59 y (IQR: 51 to 67 y); 41% were female and 86% identified as white. We observed no statistically significant associations between any type of dietary fat and OS. However, vegetable fat was non-linearly associated with longer PFS (HR comparing 4th to 1st quartile: 0.78; 95% CI: 0.64, 0.96; p-trend: 0.10). We also observed a linear association between continuous saturated fat and PFS (HR per 5% kcal/d: 1.21; 95% CI: 1.03, 1.42; p-value: 0.02), perhaps driven by pts with high saturated fat intake. Conclusions: We observed no statistically significant associations between types of dietary fat and OS among pts with advanced or metastatic CRC. However, a healthy diet that includes vegetable fat and is modest in saturated fat may be associated with longer PFS. Future studies to replicate these findings and examine diet in relation to cancer survival in racially/ethnically diverse populations are needed. Support: K07CA197077, U10CA180821, U10CA180882, https://acknowledgments.alliancefound.org . Clinical trial information: NCT00265850.