Iron deficiency anemia (IDA) in pregnancy is associated with poor maternal and childhood outcomes, yet ferritin testing, the standard test for iron deficiency (ID), is not considered part of routine prenatal bloodwork in Canada. We conducted a retrospective cohort study of 44,552 pregnant patients with prenatal testing at community laboratories in Ontario, Canada to determine the prevalence of ferritin testing over five years. Secondary objectives were to determine the prevalence and severity of ID, and to identify clinical and demographic variables that influence the likelihood of ID screening. 59.4% of patients had a ferritin checked during pregnancy; 71.4% were ordered in the first trimester, when the risk of ID is lowest. Excluding patients with abnormally elevated ferritins, 25.2% were iron insufficient (30-44 µg/L) and 52.8% were iron deficient (≤29 µg/L) at least once in pregnancy. 8.3% were anemic (hemoglobin <105 g/L). The proportion of anemic patients with a subsequent ferritin test in pregnancy ranged from 22% to 67% in the lowest and highest anemia severity categories, respectively. Lower annual household income was negatively associated with the odds of a ferritin test; compared to those in the fifth (i.e. highest) income quintile, the odds of ferritin testing for patients in the first, second, and fourth quintiles were 0.83 (95%CI 0.74-0.91), 0.82 (95%CI 0.74-0.91), and 0.86 (95%CI 0.77-0.97), respectively. These data highlight gaps in prenatal care and issues of health equity that warrant harmonization of obstetrical guidelines to recommend routine ferritin testing in pregnancy.

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There are very few xenograft models available for the study of esophageal (E) and gastro-esophageal junction (GEJ) cancer. Using a NOD/SCID model, we implanted 90 primary E and GEJ tumors resected from patients and six endoscopic biopsy specimens. Of 69 resected tumors with histologically confirmed viable adenocarcinoma or squamous cell carcinoma, 22 (32%) was engrafted. One of 11 tumors, considered to have had a complete pathological response to neo-adjuvant chemo-radiation, also engrafted. Of the 23 patients whose tumors were engrafted, 65% were male; 30% were early stage while 70% were late stage; 22% received neo-adjuvant chemo-radiation; 61% were GEJ cancers. Engraftment occurred in 18/54 (33%) adenocarcinomas and 5/16 (31%) squamous cell carcinomas. Small endoscopic biopsy tissue had a 50% (3/6) engraftment rate. Of the factors analyzed, pretreatment with chemo-radiation and well/moderate differentiation showed significantly lower correlation with engraftment (Po0.05). In the subset of patients who did not receive neo-adjuvant chemo-radiation, 18/41 (44%) engrafted compared with those with pretreatment where 5/29 (17%, P ¼ 0.02) engrafted. Primary xenograft lines may be continued through 4-12 passages. Xenografts maintained similar histology and morphological characteristics with only minor variations even after multiple passaging in most instances.

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PurposeBrahma (BRM) is a critical catalytic subunit of the SWI/SNF chromatin remodeling complex; expression of BRM is commonly lost in various cancer types. BRM promoter polymorphisms (BRM-741; BRM-1321) are associated with loss of BRM expression, and with cancer risk/survival. We evaluated these two polymorphisms in the overall survival (OS) of esophageal adenocarcinoma (EAC) patients.ResultsOf 270 patients, 37% were stage IV. Minor allele frequencies were 47−49%; 15% were double-homozygotes. When compared to the wild-type genotype, the homozygous variant of BRM-741 carried an adjusted OS hazard ratio (aHR) of 1.64 (95% CI:1.1−2.4); for BRM-1321, the aHR was 2.09 (95% CI:1.4−3.0). Compared to the double wild-type, carrying homozygous variants of both promoter polymorphisms (double-homozygote) yielded an aHR of 2.21 (95% CI:1.4−3.6). Directions/magnitudes of associations were similar in subsets by age, gender, smoking status, use of platinum agents, and disease stage, and for progression-free survival.Materials and MethodsIn a cohort of EAC patients of all stages (84% male; median age of 64 years), two BRM polymorphisms were genotyped. Cox proportional hazards models, adjusted for known prognostic variables, estimated the association of polymorphisms with OS.ConclusionsBRM polymorphisms were associated with OS in EAC in this study. Validation studies are warranted.

The high morbidity and mortality of patients with esophageal (E) and gastro-esophageal junction (GEJ) cancers, warrants new pre-clinical models for drug testing. The utility of primary tumor xenografts (PTXGs) as pre-clinical models was assessed. Clinicopathological, immunohistochemical markers (p53, p16, Ki-67, Her-2/neu and EGFR), and global mRNA abundance profiles were evaluated to determine selection biases of samples implanted or engrafted, compared with the underlying population. Nine primary E/GEJ adenocarcinoma xenograft lines were further characterized for the spectrum and stability of gene/protein expression over passages. Seven primary esophageal adenocarcinoma xenograft lines were treated with individual or combination chemotherapy. Tumors that were implanted (n=55) in NOD/SCID mice had features suggestive of more aggressive biology than tumors that were never implanted (n=32). Of those implanted, 21/55 engrafted; engraftment was associated with poorly differentiated tumors (p=0.04) and older patients (p=0.01). Expression of immunohistochemical markers were similar between patient sample and corresponding xenograft. mRNA differences observed between patient tumors and first passage xenografts were largely due to loss of human stroma in xenografts. mRNA patterns of early vs late passage xenografts and of small vs large tumors of the same passage were similar. Complete resistance was present in 2/7 xenografts while the remaining tumors showed varying degrees of sensitivity, that remained constant across passages. Because of their ability to recapitulate primary tumor characteristics during engraftment and across serial passaging, PTXGs can be useful clinical systems for assessment of drug sensitivity of human E/GEJ cancers.

BackgroundThe Hedgehog (Hh) signaling pathway is active in esophageal adenocarcinoma (EAC). We used a patient-derived murine xenograft (PDX) model of EAC to evaluate tumour response to conventional treatment with radiation/chemoradiation with or without Hh inhibition. Our goal was to determine the potential radioresistance effects of Hh signaling and radiosensitization by Hh inhibitors.MethodsPDX models were treated with radiation, chemotherapy or combined chemoradiation. Tumour response was measured by growth delay. Hh transcript levels (qRT-PCR) were compared among frozen tumours from treated and control mice. 5E1, a monoclonal SHH antibody, or LDE225, a clinical SMO inhibitor (Novartis®) inhibited Hh signaling.ResultsPrecision irradiation significantly delayed xenograft tumour growth in all 7 PDX models. Combined chemoradiation further delayed growth relative to either modality alone in three of six PDX models. Following irradiation, two of three PDX models demonstrated sustained up-regulation of Hh transcripts. Combined LDE225 and radiation, and 5E1 alone delayed growth relative to either treatment alone in a Hh-responsive PDX model, but not in a non-responsive model.ConclusionHh signaling mediates the radiation response in some EAC PDX models, and inhibition of this pathway may augment the efficacy of radiation in tumours that are Hh dependent.

Introduction: Systems to quantify and incentivize quality of care (QoC) have been developed in multiple healthcare settings. In pediatric oncology, lists of QoC metrics or recommendations have been procured through consensus methodologies such as the Delphi process. To date, no QoC metrics have been developed for outpatient pediatric oncology. Objectives: The aim of this study was to develop a list of QoC metrics for the leukeumia-lymphoma (LL) clinic at the Hospital for Sick Children in Toronto, using a consensus process that could be adapted to other clinic settings. Methods: A modified Delphi process following the American Society of Clinical Oncology (ASCO) guidelines was used to generate consensus on a list of QoC metrics (Loblaw et al., 2012). A Medline-Ovid search was conducted for quality indicators, metrics and recommendations relevant to pediatric oncology. Results were screened for (a) system-level metrics that could be translated to a clinic level and (b) clinic-level recommendations that could be converted to measurable quantities. Additional metrics outside the literature search were considered. A provisional list was compiled and circulated electronically to local stakeholders, including medical and nursing staff (n=10). Stakeholders ranked each metric on a 5-point Likert scale based on importance and feasibility of measurement (round 1). Stakeholders provided feedback on the metrics and suggested additional metrics. Median, interquartile range and full ranges were calculated for each metric. A metric was considered to reach consensus if the percent of respondents ranking within two consecutive scores was ≥70%. Results and comments from round 1 were re-circulated to stakeholders in personalized reports. This allowed each stakeholder to compare his or her previous scores with overall scores for each metric. Stakeholders were asked to re-rank each metric (round 2). Results: The literature search yielded 2 relevant publications from which a provisional list of 27 metrics was generated. Metrics were grouped into 7 categories (Table 1). In round 1, 19/27 (70%) metrics reached consensus. Stakeholders’ comments resulted in 4 new metrics and edits to 8 original metrics. All metrics were included in round 2 for a total of 31. Twenty-four of 31 (77%) metrics reached consensus after round 2 (Table 1). Thirteen were chosen for the final list based on highest consensus scores, highest interquartile and full ranges, and minimizing redundancy. Conclusion: This study demonstrates the feasibility of using a modified Delphi process to generate QoC metrics for a pediatric hematology oncology clinic, and provides a model other clinics may employ for local use. The final metrics will be used to evaluate the quality of care in the LL clinic, and to identify areas for improvement in clinic function. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.