Brenda Ginos

Predictors of Progression in Barrett’s Esophagus with Low-Grade Dysplasia: Results from a Multicenter Prospective BE Registry

Objectives:Low-grade dysplasia (LGD) is a risk factor for progression in Barrett’s esophagus (BE). Progression estimates however vary and predictors of progression are not well established. We aimed to assess predictors of progression in a multicenter BE-LGD cohort.Methods:All subjects with LGD (diagnosed by a GI pathologist) in a prospective BE registry were identified. Progression was defined development of HGD/EAC more than 12 months after index date of LGD diagnosis. Clinical, endoscopic factors and impact of histologic review by an independent panel of two GI pathologists were assessed as predictors of progression. Cox proportional hazard models were used to assess their association with risk of progression.Results:244 BE-LGD subjects met inclusion criteria. Their mean age was 63.2 years. 205 (84%) were males. The median follow up was 4.8 years. Fifty six patients were diagnosed with HGD/EAC in less than 12 months, while 14 progressed to HGD/EAC after 12 months, with an overall annual risk of progression of 1.2%. 29% of LGD subjects were downgraded to non-dysplastic and the remaining re-confirmed as LGD or indefinite dysplasia. The risk of progression in the reconfirmed LGD group was eight fold higher (hazards ratio: 7.6, 95% CI: 1.5–139.4) in a propensity score stratified model.Conclusions:In this large BE-LGD cohort, progression risk increased substantially when an additional panel of two expert GI pathologists re-confirmed a LGD diagnosis. These BE subjects may be candidates for endoscopic therapy. LGD was a marker of prevalent HGD/EAC in 18% of patients.

Persistence of Nondysplastic Barrett’s Esophagus Is Not Protective Against Progression to Adenocarcinoma

© 2017 by the AGA Institute 1542-3565/

Phase II Trial of Nab‐paclitaxel in Patients with Relapsed or Refractory Multiple Myeloma

36.00 http://dx.doi.org/10.1016/j.cgh.2017.02.019 Bfactor for esophageal adenocarcinoma (EAC). Gastrointestinal societies recommend endoscopic surveillance in patients with BE to enable early detection of dysplasia and malignancy. Recently, Gaddam et al have reported that persistence of nondysplastic BE (NBDE) on repeated biopsies predicts lower risk of progression, suggesting that these patients could undergo less intensive surveillance. Conversely, there is also evidence suggesting that the risk of progression in BE continues to increase over time. Therefore, we aimed to investigate if persistence of NBDE in consecutive surveillance biopsies reduces the risk of progression to EAC, providing justification for prolonging surveillance intervals.

Feasibility study of online yoga for symptom management in patients with myeloproliferative neoplasms

between 0.1% and 0.72%. There was a weak significant negative Spearman correlation between the percentage of these cells and age (r 5 20.232 P 5 0.022). We could not detect significant correlations between hematogones and the IPSS-R score, the number of aberrancies in the granulocytic lineage, or percentage of myeloid progenitors, but there were significant negative correlations with the number of monocytic aberrancies (r 5 20.256; P 5 0.012), the number of abnormalities of CD34 cells (r 5 20.206; P 5 0.044), and the total number of aberrancies detected (r 5 20.334; P 5 0.0008). In the univariate Cox regression, the percentage of B-cell precursors was a significant favorable prognostic factor for overall survival (B 5 26.220; P 5 0.011). In the Kaplan–Meier curve, patients with detectable B-cell precursors in BM had a significant better overall survival (log-rank test: P< 0.001) than patients with undetectable CD34/CD19/CD10 cells. After 5 years, 76.7% of the patients presenting BM hematogones at diagnosis were still alive, whereas this value dropped to 51.9% in patients without detectable B-cell precursors (Fig. 1). In a multivariate Cox regression model, the percentage of hematogones (B 5 25.061; P 50.006), of myeloid progenitors (B 5 0.191; P 50.02), and the IPSS-R score (B 5 0.714; P< 0.001) remained in the final model, thus demonstrating that the percentage of B-cell precursors is an independent favorable prognostic factor in MDS patients. In order to estimate the clinical importance of the variable “hematogones” in the model, we calculated the relative Akaike weights (w) for different models according to the Akaike information criteria. The relative weight for the prognostic model based only on IPSS-R was 0.0179 and raised to 0.112 in a model containing IPSS-R and the percentage of myeloid precursors. The weight was even higher in a model based on IPSS-R and the percentage of B-cell precursors (w 5 0.195), but the best model was achieved joining the variables “percentage of B-cell precursors,” “myeloid progenitors,” and the “IPSS-R score” (w 5 0.675). These data indicate that the percentage of hematogones in BM at diagnosis adds important prognostic information independent from already well-known prognostic features for overall survival in MDS patients. This is in keeping with similar results found in the setting of hematological recovery after allogeneic BM transplantation, where the absence of B-cell precursors in BM on day 130 was associated with a higher non-relapse mortality, a higher frequency of acute graft-versus-host disease and infections [6]. In normal individuals, there is a decrease of B-cell precursors, especially after the age 55 years, but these cells are even more decreased in patients with MDS compared to age-matched persons [5]. All these data indicate that the number of B-cell precursors in BM is not only a good marker of a preserved immune function but also for the integrity of the hemopoietic stem cell.

A phase 2 study of rituximab, cyclophosphamide, bortezomib and dexamethasone (R-CyBorD) in relapsed low grade and mantle cell lymphoma

Myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are clonal, progressive, hematological malignancies resulting in the risk of vascular events, splenomegaly, and significant symptom burden, with a high prevalence of fatigue.[

Feasibility of Implementing the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events in a Multicenter Trial: NCCTG N1048

Abstract In this phase 2 trial, we sought to evaluate the efficacy and safety of rituximab, cyclophosphamide, bortezomib, and dexamethasone (R-CyBorD) in patients with low-grade NHL. The regimen included rituximab on day 1 with weekly cyclophosphamide, dexamethasone, and bortezomib 1.3 mg/m2 IV in a 28-day cycle. Twenty one patients were enrolled on the study. Median age was 69 years (range 51–80) and 17 (81%) patients had two or more prior treatments. Histologies included FL (n = 8), MCL (n = 8), and LPL/WM (n = 5). Hematologic toxicity and peripheral sensory neuropathy were the most common adverse events. With a median follow-up of 38.1 months, ORR was 13/21 (62%), with 4 (19%) CR. The ORR was 7/8 (88%) in FL and was 4/5 (80%) in LPL/WM. Median PFS and OS were 11.6 months and 54.8 months, respectively. R-CyBorD is an effective regimen in relapsed FL and LPL/WM patients with an acceptable safety profile.

A Novel Combination of the mTORC1 Inhibitor Everolimus and the Immunomodulatory Drug Lenalidomide Produces Durable Responses in Patients With Heavily Pretreated Relapsed Lymphoma

Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to enable patient reporting of symptomatic adverse events in oncology clinical research. This study was designed to assess the feasibility and resource requirements associated with implementing PRO-CTCAE in a multicenter trial. Methods Patients with locally advanced rectal cancer enrolled in the National Cancer Institute-sponsored North Central Cancer Treatment Group (Alliance) Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO-CTCAE items weekly from home during preoperative therapy, and every 6 months after surgery, via either the Web or an automated telephone system. If participants did not self-report within 3 days, a central coordinator called them to complete the items. Compliance was defined as the proportion of participants who completed PRO-CTCAE assessments at expected time points. Results The prespecified PRO-CTCAE analysis was conducted after the 500th patient completed the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was reported by participants at 4,491 of 4,882 expected preoperative time points (92.0% compliance), of which 3,771 (77.2%) were self-reported by participants and 720 (14.7%) were collected via central coordinator backup. Compliance at 6-month post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup. Site research associates spent a median of 15 minutes on PRO-CTCAE work for each patient visit. Work by a central coordinator required a 50% time commitment. Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible, with high patient compliance and low site administrative requirements. PRO-CTCAE data capture is improved through centralized backup calls.

Sa1067 Rates and Predictors of Progression in Barrett's Esophagus With Low Grade Dysplasia: Results From a Prospective U.S. Registry

Micro‐Abstract: Relapsed and refractory lymphoproliferative neoplasms have a significant need for novel therapeutic options. A phase I/II trial using a combination therapy of everolimus and lenalidomide in 58 patients with relapsed or refractory Hodgkin and non‐Hodgkin lymphomas demonstrated a modest overall response of 27% and tolerability in a heavily pretreated patient population. Background: Treatment outcomes have improved in lymphoid malignancies but relapse remains inevitable for most patients. Everolimus and lenalidomide have shown clinical activity as single agents in patients with relapsed and refractory Hodgkin and non‐Hodgkin lymphomas. Patients and Methods: The present phase I/II trial for patients with relapsed and refractory lymphoid malignancy opened at Mayo Clinic from January 2011 to May 2013. The trial used a standard cohort 3 + 3 design to determine the maximum tolerated dose for the combination. Stem cell transplantation had failed in 27 of the patients (49%), 63% had stage IV disease, and ≥ 3 previous therapies had failed in 78%. Results: Of the 58 patients, enrolled, 55 were evaluable for analysis. The maximum tolerated dose was 5 mg/d for everolimus plus 10 mg/d for 21 days for lenalidomide. The most common grade ≥ 3 toxicities were hematologic and included neutropenia (56%), leukopenia (38%), and thrombocytopenia (33%). Seven patients discontinued the study because of adverse events. One patient died of disease progression. The overall response rate was 27% (15 of 55), with 38% (21 of 55) having stable disease. Conclusion: The present phase I/II trial of everolimus and lenalidomide for R/R lymphoma has shown the combination to be tolerable, with neutropenia as the main dose‐limiting toxicity. Encouraging responses were seen in this heavily pretreated group, and the patients with a response had meaningful duration of response.

Online-Streamed Yoga As a Non-Pharmacologic Symptom Management Approach in Myeloproliferative Neoplasms

BACKGROUND Estimates of progression in BE-LGD are limited by heterogeneity in pathological diagnoses. While recent data show that ablation in BE-LGD reduces risk of progression to HGD/EAC, they are limited by high rates of progression not seen in most studies. Identification of risk factors for progression in BE-LGD may help in selecting subjects for endoscopic therapy. We aimed to assess the rates and predictors of progression in a cohort of BE-LGD subjects who were part of a large prospective BE-EAC registry in a tertiary care center. METHODS Subjects with a histologic diagnosis of LGD (made by expert GI pathologists) were identified from a prospective BE registry at our institution. The registry database has records of demographic details, endoscopic findings and histologic data from esophageal biopsies. Index date was defined as the first date of LGD diagnosis. Progressors were defined as BE-LGD subjects who developed HGD / EAC more than 12 months after the index date. Risk factors assessed included demographic variables, family history of BE/ EAC, GERD symptoms, duration of BE, medication use, endoscopic findings and histological findings (multifocal vs unifocal LGD, H pylori status in gastric biopsy). Univariate and multivariable analyses were performed to identify predictors of progression using Cox Proportional Hazards models. RESULTS 353 BE-LGD subjects were identified, of which 337 were included after excluding those with missing data. The mean (SD) age of these subjects was 63.2 (11.2) years. 283 (84 %) were males. Baseline characteristics are summarized in table 1. Of the 337 BE-LGD patients, 21 (6.2 %) subjects progressed to HGD / EAC. The mean (SD) follow up of subjects was 7 (5) years. The annual incidence of HGD/EAC in subjects with BE-LGD was 0.8%. Univariate and multivariable predictors of progression to HGD/ EAC are presented in table 2. On univariate analysis, longer BE segment length and presence of nodularity increased risk of progression, while a longer follow up duration after LGD diagnosis reduced the risk of progression. Multifocal dysplasia (dysplasia at multiple levels) approached statistical significance as a predictor of progression. On multivariable analysis, increased BE segment length remained a predictor of progression while older age and longer LGD follow up (likely reflecting persistent LGD) reduced the risk of progression. CONCLUSIONS: In this well-defined cohort of BE-LGD patients with all histology confirmed by expert GI pathologists, progression rates for LGD subjects were substantially lower than those reported in some European studies. Longer BE segment length and younger age at LGD diagnosis predicted a higher risk of progression. These subjects may be candidates for intensive surveillance or endoscopic therapy.