TPS517 Background: Systemic chemotherapy for pancreatic adenocarcinoma improves survival and cancer related symptoms. Most targeted agents combined with gemcitabine have consistently failed to demonstrate clinical benefits. Src is overexpressed in pancreatic cancer and promotes an aggressive cancer phenotype. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) affecting tumor proliferation through inhibition of Src, Bcr-Abl, CKit and other pathways. Inhibition of Src is associated with biologic modifications favorably modifying the pancreatic cancer phenotype and has synergy with restoring inherent chemosensitivity. Src inhibition can also increase oxaliplatin activity and modulate Tcell responses. The addition of D to the well-established backbone of FOLFOX represents a multifaceted line of scientific investigation. Methods: This is a multicenter phase II trial to determine activity and toxicity of FOLFOX + D in previously untreated metastatic pancreatic adenocarcinoma. Eligible pts must have at least 1 measurable target lesion by RECIST, ECOG PS 0-2, normal QTc and adequate organ function. Pts received standard cycles of mFOLFOX6 repeated q14d with continuous D (150mg PO daily). Tumor assessments occur q8w. Endpoints included progression-free survival (primary; PFS), objective and biochemical response rates, clinical benefit rate, freedom from metastases, overall survival (OS), toxicity, and quality of life. Exploratory tissue, circulating tumor cell and serum analyses to identify predictors of response are planned, particularly in those demonstrating durable disease control or exceptional response. Sample size was based on a 50% improved median PFS from 4 (historical) to 6 months. NCT01652976. Results: Enrollment continues on this prospective phase II study with 38 of 42 evaluable patients. There are no unexpected toxicities noted thus far. Clinical trial information: NCT01652976. [Table: see text]

BACKGROUND:Targeting human epidermal growth factor receptor 2 (HER2) with trastuzumab in metastatic esophagogastric adenocarcinoma (EGA) improves survival. The impact of HER2 inhibition in combination with chemoradiotherapy (CRT) in early stage EGA is under investigation. This study analyzed the pattern of HER2 overexpression in matched-pair tumor samples of patients who underwent neoadjuvant CRT followed by surgery.METHODS:All patients with EGA who underwent standard neoadjuvant CRT followed by esophagectomy at the University of Florida were included. Demographics, risk factors, tumor features, and outcome data were analyzed. Descriptive statistics, Chi-square exact test, uni- and multivariate analyses, and Kaplan Meier method were used. HER2 expression determined by immunohistochemical (IHC) was scored as negative (0, 1+), indeterminate (2+) or positive (3+).RESULTS:Among 49 sequential patients (41 M/8 F) with matched-pair tumor samples, 9/49 patients (18%) had pathologic complete response (pCR), 10/49 had near pCR or not enough tumor (NET) to examine in the post- treatment samples. Patients with initial HER2 negativity demonstrated conversion to HER2 positivity after neoadjuvant CRT (7/30 cases; 23%). Baseline HER2 overexpression was more common in lower stage/node negative patients (67% in stages I, IIA vs. 33% in stages IIB, III) and did not correlate with treatment response or survival.CONCLUSIONS:Although limited by a relatively small sample size, our study failed to demonstrate that baseline HER2 protein over-expression in EGA predicts response to standard CRT. However, our data suggested that HER2 was up regulated by CRT resulting in unreliable concordance between pre-treatment (pre-tx) and post-treatment (post-tx) samples. Pre-therapy HER2 expression may not reliably reflect the HER2 status of persistent or recurrent disease.

Drop-the-losers designs have been discussed extensively in the past decades, mostly focusing on two-stage models. The designs with more than two stages have recently received increasing attention due to their improved efficiency over the corresponding two-stage designs. In this paper, we consider the problem of estimating and testing the effect of selected treatment under the setting of three-stage drop-the-losers designs. A conservative interval estimator is proposed, which is proved to have at least the specified coverage probability using a stochastic ordering approach. The proposed interval estimator is also demonstrated numerically to have narrower interval width but higher coverage rate than the bootstrap method proposed by Bowden and Glimm (Biometrical Journal, vol. 56, pp. 332-349) in most cases. It is also a straightforward derivation from the stochastic ordering result that the family-wise error rate is strongly controlled with the maximum achieved at the global null hypothesis.

BACKGROUND: Durable clinical gains in surgical care are frequently reliant on well-developed standardization of practices. We hypothesized that the standardization of surgical management would result in improved long-term survival in pancreatic cancer.METHODS: Seventy-seven consecutive, eligible patients representing all patients who underwent pancreaticoduodenectomy and received comprehensive, long-term postoperative care at the University of Florida were analyzed. Patients were divided into prestandardization and poststandardization groups based on the implementation of a pancreatic surgery partnership, or standardization program.RESULTS: Standardization resulted in a reduction in median length of stay (10 vs 12 days; P = .032), as well as significant gains in disease-free survival (17 vs 11 months; P = .017) and overall survival (OS; 26 vs 16 months; P = .004). The improvement in overall survival remained significant on multivariate analysis (hazard ratio 5.46, P = .005).CONCLUSIONS: Standardization of surgical management of pancreatic cancer was associated with significant gains in long-term survival. These results suggest strongly that management of pancreatic head adenocarcinoma be standardized likely by regionalization of care at high performing oncologic surgery programs. (C) 2016 Elsevier Inc. All rights reserved.

Objective: To examine the comparative effectiveness of inhaled long-acting beta-agonist (LABA), inhaled corticosteroid (ICS), and ICS/LABA combinations. Methods: We used a retrospective cohort design of patients older than 12 years with asthma diagnosis in the Clinical Practice Research Datalink to evaluate asthma-related morbidity measured by oral corticosteroid (OCS) initiation within 12 months of initiating LABAs, ICSs, or ICSs/LABAs. Asthma severity 12 months before drug initiation (use of OCSs, asthma-related hospital or emergency department visits, and number of short acting betaagonist prescriptions) and during follow-up (short-acting betaagonist prescriptions and total number of asthma drug classes) was adjusted as a time varying variable via marginal structural models. Results: A total of 51,103 patients with asthma were followed for 12 months after receiving first prescription for study drugs from 1993 to 2010. About 92% initiated ICSs, 1% initiated LABAs, and 7% initiated ICSs/LABAs. Compared with ICSs, LABAs were associated with a 10% increased risk of asthma exacerbations requiring short courses of OCSs (hazard ratio [HA] 1.10; 95% confidence interval [CI] 1.07-1.18). ICS/LABA initiators were 62% less likely than ICS initiators (HR 0.38; 95% Cl 0.12-0.66) and 50% less likely than LABA initiators to receive OCS prescriptions for asthma exacerbations (HR 0.50; 95% CI 0.14-0.78). Conclusions: In concordance with current asthma management guidelines, inhaled LABAs should not be prescribed as monotherapy to patients with asthma. The findings suggest the presence of time dependent confounding by asthma severity, which was accounted for by the marginal structural model.

Abstract Purpose: The relationship between smoking and pancreatic cancer biology, particularly in the context of the heterogeneous microenvironment, remains incompletely defined. We hypothesized that nicotine exposure would lead to the augmentation of paracrine growth factor signaling between tumor-associated stroma (TAS) and pancreatic cancer cells, ultimately resulting in accelerated tumor growth and metastasis. Experimental Design: The effect of tobacco use on overall survival was analyzed using a prospectively maintained database of surgically resected patients with pancreatic cancer. Nicotine exposure was evaluated in vitro using primary patient–derived TAS and pancreatic cancer cells independently and in coculture. Nicotine administration was then assessed in vivo using a patient-derived pancreatic cancer xenograft model. Results: Continued smoking was associated with reduced overall survival after surgical resection. In culture, nicotine-stimulated hepatocyte growth factor (HGF) secretion in primary patient-derived TAS and nicotine stimulation was required for persistent pancreatic cancer cell c-Met activation in a coculture model. c-Met activation in this manner led to the induction of inhibitor of differentiation-1 (Id1) in pancreatic cancer cells, previously established as a mediator of growth, invasion and chemoresistance. HGF-induced Id1 expression was abrogated by both epigenetic and pharmacologic c-Met inhibition. In patient-derived pancreatic cancer xenografts, nicotine treatment augmented tumor growth and metastasis; tumor lysates from nicotine-treated mice demonstrated elevated HGF expression by qRT-PCR and phospho-Met levels by ELISA. Similarly, elevated levels of phospho-Met in surgically resected pancreatic cancer specimens correlated with reduced overall survival. Conclusions: Taken together, these data demonstrate a novel, microenvironment-dependent paracrine signaling mechanism by which nicotine exposure promotes the growth and metastasis of pancreatic cancer. Clin Cancer Res; 22(7); 1787–99. ©2015 AACR.

10035 Background: COG AALL0331 administered PEG IM in induction (IND) and Delayed intensification (DI) whereas AALL0932 administers the same dose IV. We compared grade 3/4 toxicities resulting from the single doses of PEG given in the IND and DI phases on the standard arms of AALL0331 and AALL0932 that gave only 2 doses of PEG (excluded arms with additional PEG). Methods: AALL0331 and AALL0932 shared a common 3 drug IND: dexamethasone (DEX) 6 mg/m2/day X 28 days, vincristine (VCR) 1.5 mg/m2/dose on days 1, 8, 15, 22, IT methotrexate (age adjusted dosing) on days 8, 29, and PEG 2500 units/m2/dose IM on day 4, 5, or 6 (AALL0331) or IV on day 4 (AALL0932). DI (Days 1-28) for both protocols consisted of: DEX 10 mg/m2/day (days1-7, 15-22), VCR 1.5 mg/m2/dose and Doxorubicin 25 mg/m2/dose IV (days 1, 8, 15), PEG 2500 units/m2on day 4 (AALL03131 IM; AALL0932 IV). Toxicity was graded using CTCAE v4.0, however, AALL0331 collected data using CTCAE v3.0, which was subsequently mapped to v4.0. Results: During IND, the rates of anaphylaxis/allergic reaction were similar between IM and IV PEG (0.2% vs. 0.3%, p = 0.842). The rate of anaphylaxis/allergic reaction in DI was 0.5% (IM) vs 1.8% (IV) (p = 0.007). The rates of pancreatitis, elevated lipase and amylase, and hyperglycemia were similar between IM and IV PEG in both IND and DI. Conclusions: The rates of AEs with PEG administration (IV or IM) are low but more grade 3/4 anaphylaxis/allergic reactions were reported with IV PEG compared to IM PEG during DI. This may be due to more stringent reporting on 0932 or the challenges of determining infusion reactions vs. allergic reactions when PEG is administered IV. Clinical trial information: NCT00103285. Toxicities (%) Grades AALL0331 AALL0932 p-value Allergic reaction/ Anaphylaxis IND DI 3-4 0.2 0.5 0.3 0.8 0.84 0.0007 Pancreatitis IND DI 3-4 0.5 0.4 0.8 0.3 0.07 0.79 Lipase increased IND DI 4 0.6 0.4 0.4 0.3 0.22 0.39 Serum amylase increased IND DI 4 0.3 0.1 0.2 0.1 0.53 1.00 Hyperglycemia IND DI 4 1.1 0.4 1.3 0.1 0.46 0.02 Glucose intolerance IND DI 4 0.02 0 0 0 1.0 ----

319 Background: Triplet drug therapy is now a standard for metastatic pancreatic cancer (mPCa) but limited in use due to toxicity. Src is constitutively active in mPCa and associated with increased chemoresistance. Src inhibition increases oxaliplatin (ox) activity. Inhibition of Src reduces tumor expression of thymidylate synthase with subsequent 5FU chemoresistance reversal. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) capable of inhibiting Src. Demonstrating activity of this triplet combination therapy in mPCa represents a scientifically rational approach to a clinical unmet need. Methods: Eligible pts have biopsy proven, RECIST measurable disease with no prior therapy for met disease and at least 6 months since completing adjuvant therapy, ECOG PS 0-2 and adequate organ function. Pts received standard doses of mFOLFOX6 chemotherapy (5-FU/LV 400mg/m2 bolus and Ox 85 mg/m2 D1; 5-FU 2,400 mg/m2CIVI x 46h D1-2) with continuous D (150 mg PO daily) repeated q14d with tumor assessments q8w. The primary endpoint is progression-free survival (PFS) with secondary endpoints of objective and biochemical response rates, freedom from mets, overall survival (OS), toxicity, and quality of life. Sample size was based on a 50% improved median PFS from 4 (historical) to 6 months (m). Results: 14 of 42 planned pts have received therapy and are included in this report. Baseline pt demographics are in the table. 10 pts (71%) had a grade 3 AE and 1 (7%; sepsis) had a grade 4 AE. There were no grade 5 toxicities. Most common grade 3 AEs included anemia (29%), hyponatremia (29%), neutropenia (21%) and fatigue (21%). Conclusions: Enrollment continues with ongoing toxicity and efficacy monitoring of this targeted combination. Exploratory tissue and serum correlative analyses to identify predictors of response are planned. Clinical trial information: NCT01652976. [Table: see text]

7056 Background: Vincristine is associated with CIPN that can impair daily function. Methods: Patients 3.0-9.9 years without neurological disorders, enrolled on ALL0932 at 26 sites, were evaluated ~2 weeks post-induction (vincristine x 4 doses, dexamethasone x 28 days, and pegaspargase) by a physical/occupational therapist for peripheral neuropathy, proximal strength and fitness. Parents reported daily physical function with The Pediatric Outcomes Data Collection Instrument (PODCI). Percentages of measured impairments and limited daily function were calculated and analyzed by multivariable logistic regression. Results: The 149 (80% of eligible) subjects were 48% female, 56% white non-Hispanic (26% Hispanic, 18% other) and a mean of 5.1± 1.7 years. The table summarizes the substantial frequency of measured and reported impairments. Impaired peripheral motor function in the upper (OR=4.6; p=0.01) and lower extremities (OR=3.4; p=0.06) and younger age (OR=1.7; p=0.02) were associated with report of limited physical function. Conclusions: Our data suggest that induction therapy causes significant motor neuropathy predictive of daily physical function in young children with SR ALL. AALL0932 will assess how this neuropathy evolves throughout ALL therapy. Clinical trial information: NCT01190930. % Impaired Peripheral neuropathy Sensory Light touch Protective sensation Vibration Motor (extremity) Upper Lower 21* 11 57* 47* 27* Proximal strength Upper body Core 32* 45* Fitness 48* Upper extremity and physical function core scale (PODCI) 25* * P value from two-sided exact test < 0.001 compared to expected value of 7% for measured impairments and 13.6% for PODCI in healthy norms.

75 Background: The incidence of esophagogastric adenocarcinoma is on the rise. The only targeted therapy that improves patient outcomes is the anti-HER2 antibody, trastuzumab; however, benefit is limited to cases with HER2 overexpression. Inhibition of EGFR in EGA is unsuccessful. cMet overexpression is a proposed resistance pathway for EGFR family inhibition. We sought to characterize the co-expression relationships among the EGFR family and cMet to identify potential dual therapeutic targets. Methods: This study included all sequential patients (pts) with adenocarcinoma of the esophagus and GEJ who underwent primary resection between 2001 to 2011 without neoadjuvant therapy or HER2 inhibition. Demographics, risk factors, tumor features, and outcome data were analyzed. Central blinded immunohistochemistry (IHC) was performed on FFPE tumor specimens with EGFR, HER2, HER3, HER4 and cMet expression scored as low/negative or high/positive expression. Descriptive statistics, Exact chi square test and Cox regression model were used for statistical analyses. Results: 48 pts (39 M/9 F) were eligible (median age 66yr; 37-83). Most (63%) were stage I (T1N0) and 93% had underlying Barrett’s esophagus. High expression of EGFR, HER2, HER3, HER4 and cMet were present in 70%, 43%, 77%, 38% and 56% of tumors respectively. HER3 and HER4 were commonly co-expressed (p=0.003) and moderately differentiated tumors had high expression of HER3 (p=0.01). Stage was the only variable that correlated significantly with survival (p=0.007). Conclusions: This study demonstrated that static baseline cMET expression levels are not associated with EGFR family expression profiles, although HER3/HER4 co-expression is common. No receptors demonstrated prognostic value. Further investigation into dynamic cMET expression changes related to active EGFR inhibition including prognostic and predictive value is warranted.

Abstract BACKGROUND Relapsed childhood B-ALL has a poor prognosis, with time to and site of relapse being the best clinical predictors of outcome. The role of allogeneic SCT is unclear for patients with late bone marrow (BM) or isolated extramedullary (IEM) relapse. We recently reported initial results from the AALL0433 trial for intermediate-risk relapse of childhood B-ALL, which established a 0.1% end-induction minimal residual disease (MRD) threshold as the best predictor of outcome (Lew, ASCO 2014). We now report an updated analysis, including outcomes for patients receiving SCT vs. continued chemotherapy. METHODS AALL0433 included patients with early CNS/testicular (IEM) relapse (<18 mo. from diagnosis), or late BM/combined relapse (≥36 mo. from diagnosis) of B-ALL, enrolling 271 eligible patients between 3/2007 and 10/2013. Therapy was based upon the earlier COG AALL01P2 / P9412 platforms. BM MRD was measured by flow cytometry at the end of Induction block 1, and for this analysis was considered positive (MRD+) if ≥0.1%, or negative (MRD-) if <0.1%. MRD testing was performed centrally by a COG reference lab, with results blinded to local investigators. 48 patients underwent matched family donor SCT per protocol after 3 induction blocks. An additional 31 patients were removed from protocol therapy to pursue off-study alternative donor SCT. Donor sources for these patients were 21 unrelated BM, 9 unrelated cord blood, and 1 haploidentical BM. The remaining 192 patients received chemotherapy (plus irradiation for those with EM involvement at relapse). Event free and overall survival (EFS/OS) comparisons for patients receiving chemotherapy vs. SCT were adjusted to start from median time to SCT (138 days) or the actual time of SCT if <138d. Patients who had events or dropped out before the adjusted starting time were excluded from the survival analyses. RESULTS The 3-yr. EFS/OS for the entire cohort of 271 patients were 61.4 ± 4.3% and 72.9 ± 3.9% respectively. Focusing on patients with BM/combined relapse, the 3-yr EFS/OS for the 175 patients with available MRD data showed EFS/OS of 80.4 ± 4.7% and 88.3 ± 3.8% respectively for MRD- patients, compared to 45.1 ± 8.4% and 60.1% ± 8.3% for those who were MRD+ (p<0.01) (FIGURE 1). Because outcomes for patients who received matched family donor or alternative donor SCT were highly similar, these were pooled in all analyses of chemotherapy vs. SCT. There was no significant difference in survival for MRD- patients; 3-yr EFS and OS for the chemotherapy group were 75.4 ± 6.7% / 91.8 ± 4.3%, vs. 80.1 ± 8.9% / 84.0 ± 8.1% in the SCT group (p>0.5). In MRD+ patients the 3-yr EFS was 42.2 ± 13.1% vs 62.8 ± 13.5% (p=0.30) for the chemotherapy and SCT groups respectively, corresponding to a 3-yr OS of and 57.6 ± 12.5% vs 78.1 ± 12.9% (p=0.14), with a trend toward improved survival after 3 years with SCT (FIGURE 2). Although numbers were small, there was a clear trend toward improved outcomes in IEM patients receiving SCT over chemotherapy (FIGURE 3). 3-yr EFS for the chemotherapy vs. SCT groups were 31.3% ± 25.9% vs. 71.4% ± 22% (p=0.16), with OS of 31.3% ± 25.9% vs. 77.8% ± 21.2% (p=0.08). No IEM relapse patients were MRD+ at end induction. CONCLUSIONS Patients with late BM relapse of B-ALL who are MRD- after induction have a relatively good outcome (3-yr EFS of 80.4 ± 4.7%) on COG AALL0433. While additional follow-up is needed, there was no obvious benefit of SCT over chemotherapy for these patients. Outcomes were worse for BM relapse patients who remained MRD+ after induction (3-yr EFS 45.1 ± 8.4%). There was a trend toward benefit for SCT over chemotherapy for MRD+ patients. In the small number with early IEM, there was also a clear trend toward superiority of SCT over chemotherapy + radiotherapy. These data support the approach of reserving SCT for patients with late BM relapse of childhood B-ALL who remain MRD+, and also for patients with early IEM relapse. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Rheingold: Novartis: Consultancy. Whitlock:Glaxo-Smith-Kline: Research Funding. Borowitz:Becton Dickinson Biosciences: Research Funding. Hunger:Sigma Tau Pharmaceuticals: Honoraria; Jazz Pharmaceuticals: Honoraria.

10014 Background: Relapsed childhood B-ALL has a poor prognosis. Few risk factors beyond immunophenotype, timing, and site of relapse are known to affect outcome. MRD is a powerful predictor of outcome in newly diagnosed ALL, but its significance after relapse is less clear. We report an analysis of MRD and outcome from the AALL0433 protocol for childhood B-ALL with intermediate-risk relapse. Methods: AALL0433 is a Phase 3 study of intermediate-risk relapsed childhood B-ALL, defined as CNS/testicular relapse <18 mo. or bone marrow (BM)/combined relapse >36 mo. from diagnosis. Therapy is based upon the AALL01P2 / 9412 platforms. BM MRD was measured by flow cytometry at end-induction; results were blinded to investigators. Only matched family donor SCT was allowed on protocol. 271 eligible patients were enrolled. Outcome by treatment received remains blinded at this time. Results: The 3-yr. EFS/OS for the entire cohort of 271 patients were 60.7 ± 4.6% and 71.3 ± 4.3%, respectively. All 29 patients with isolated extramedullary relapse had MRD <0.01% at end-induction. Further analyses focused on patients with BM/combined relapse (n=242). The 3-yr. EFS/OS for this group of patients was 62.8 ± 4.8% and 73.6 ± 4.4%, respectively. 175 patients had available end-induction MRD data: 84 patients had MRD levels <0.01%, 28 were between 0.01-0.1%, and 63 had MRD > 0.1%. These three groups had 3-yr. EFS of 83.4 ± 5.4%, 70.4 ± 12.8%, and 40.9 ± 8.4% respectively (p=0.001), and 3-yr. OS of 88.5 ± 4.6%, 83.0 ± 10.3%, and 56.2 ± 9.0%, respectively (p = 0.0019). An MRD cutoff of 0.1% provided the best discriminator of outcome, with 3-yr. EFS 80.2 ± 5.2% vs. 40.9 ± 8.4%, and 3-yr. OS of 87.1 ± 4.3% vs. 56.2 ± 9.0% for those below (n=112) or above (n=63) this cutoff. Conclusions: Preliminary efficacy of the AALL0433 platform for intermediate-risk relapse of childhood B-ALL is encouraging. An end-induction MRD cutoff of 0.1% was the best predictor of outcome for patients with late BM/combined relapse. Because of the major survival difference at the 0.1% MRD cutoff, it will be used to stratify late BM relapse patients to receive chemotherapy vs. SCT in the next COG relapsed ALL trial. Clinical trial information: NCT00381680.

With the new treatments for multiple myeloma (MM), increasing numbers of patients fail to mobilize sufficient peripheral blood stem cells (PBSC) for autologous stem cell transplant (ASCT). Multiple studies have identified clinical and laboratory factors, such as age, number of lines of chemotherapy, radiation exposure, bone marrow involvement, and low PLT count as risks for poor mobilization. However, there are fewer studies that analyze only the effect of multiple clinical risk factors on mobilization outcomes. We retrospectively analyzed 259 MM patients who underwent first apheresis after GCSF mobilization between December 2000 and December 2012. Clinical risk factors analyzed include age, number of lines of chemotherapy, number of cycles of chemotherapy, number of doses of cyclophosphamide, number of doses of lenalidomide, and prior external beam radiation. The standard dose of GCSF was 10 mcg/kg/day, however the exact dose for a significant number of patients was not known. Patients were assessed as to whether optimal (≥8x106 CD34+ cells/kg) or minimal (≥4x106 CD34+ cells/kg) number of stem cells for two ASCTs were collected. The median age of the entire cohort was 59.7 years (27.9-76.0). Overall 10.8% and 32.6% failed to collect the minimal and optimal number of stem cells after one round of apheresis. Of the twenty patients who underwent a second round of apheresis, 9 (45%) collected minimal and 7 (35%) collected optimal total number of stem cells, with an overall failure rate of 4.6% and 29.8%, respectively. The effect of the number of clinical risk factors on the mobilization failure during first apheresis is summarized in Table 1. For each additional clinical risk factor, the likelihood of collecting the minimal and optimal number of CD34+ cells is reduced by 34% (CI=0.484-0.893, p=0.0072) and 32% (CI=0.538–0.860, p=0.0013) respectively. On univariate analysis, all risk factors were analyzed as continuous variables, except for prior radiation which was analyzed as a categorical variable. Prior lenalidomide exposure (odds ratio=0.502, CI=0.297–0.845, p=0.0096), and prior radiation therapy (odds ratio=0.502, CI=0.293–0.861, p=0.0123) had the greatest negative predictive value. Of the 38 patients who were exposed to lenalomide (median 4 cycles; range 1-24 cycles), 13% and 42% failed to collect minimal and optimal number of stem cells in the first apheresis cycle, respectively. An association was seen between number of days required to collect target number of stem cells and number of risk factors (p≤0.001). Median number of days required to collect target number of stem cells for 0, 1 or 2+ clinical risk factors was 2, 2, and 4 days, respectively. When the effect of clinical risk factors were analyzed according to number of CD34+ cells/kg collected on each day of apheresis, statistically significant differences in collection efficiency were seen on the first 3 days of apheresis (Figure 1). In summary, clinical characteristics of patients with MM can potentially be used to predict mobilization failure. The presence of 2 or greater clinical risk factors adversely affect the ability to successfully collect the target stem cell dose. These risk factors may help in identifying high-risk MM patients who may benefit from alternative mobilization regimens that can be tested in prospective clinical trials.Number of Clinical Risk Factors012+N1128561% Patients not collecting optimal # of cells on 1st apheresis cycle23.231.850.895% CI15.8-32.122.1-42.833.7-63.9p-value0.19710.0003% Patients not collecting minimal # of cells on 1st apheresis cycle5.411.818.095% CI2.0-11.35.8-20.69.4-30.0p-value0.11950.0096Median number of days of collection224Range1-81-91-10p-value0.4233<0.0001 Disclosures: No relevant conflicts of interest to declare.

OBJECTIVETo examine the effects of a greens alkalizing dietary supplement on urinary pH levels in individuals with lower-than-average pH levels.METHODSThe present study investigated the effects of an alkalizing formula (Reserveage Wholeganic Greens(TM)) on four individuals who had average urinary pH levels below 6.0 for three consecutive days. Following the three-day, baseline period, participants received Reserveage Wholeganic Greens(TM) for four consecutive days and were instructed to continue to measure their urine pH levels. Paired samples t-tests were used to examine pH levels before and after a four-day treatment period with Reserveage Wholeganic Greens(TM).RESULTSCompared to baseline, mean urine pH levels in all volunteers were significantly higher following the supplementation with Reserveage Wholeganic Greens(TM) (5.89 ± 0.20 vs 5.56 ± 0.23; P<0.01). Participants' pH levels were also significantly higher than baseline on days 5, 6, and 7 of the treatment period (P < 0.05). Noteworthy, on day 7, participants' mean pH levels were significantly higher than at the beginning of the treatment period (6.03 ± 0.15 at day 7 vs 5.65 ± 0.24 at day 4; P < 0.01).CONCLUSIONThe findings of this study suggest that supplementation with Reserveage Wholeganic Greens(TM) has an alkalizing effect on the body and can increase the urine pH levels in individuals with lower-than-average pH levels.

BACKGROUND:Targeted therapy with anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody in patients with HER2 overexpressed esophagogastric adenocarcinoma (EGA) improves survival; however, the effect is transient due to the development of resistance. Some studies suggest that cMet overexpression provides cross talk for epidermal growth factor receptor (EGFR) and HER2 inhibition. We sought to characterize the expression profile of the EGFR family and cMet receptors in untreated, resected EGA.METHODS:This retrospective analysis included all sequential patients with esophageal or gastroesophageal junction (GEJ) adenocarcinoma who underwent primary resection, without neoadjuvant therapy or HER2 inhibition, with adequate tissue, at the University of Florida from 2001 to 2011. Central blinded immunohistochemistry (IHC) was performed on tumor specimens with EGFR, HER2, HER3, HER4 and cMet expression scored as low (0, 1+) or high (2+, 3+). Demographic and tumor characteristics were compared using Fisher exact test. Kaplan-Meier curves and univariate analysis compared survival among different receptors.RESULTS:Total 52 patients were included in the study with median age 66 years. High expression of EGFR (73%), HER2 (40%), HER3 (75%), HER4 (35%) and cMet (69%) was detected among the study group. HER3 and HER4 co-expression was found in 18 (35%) cases. Pan expression of all four EGFR family members with cMet was noted in only 17% of cases. On univariate analysis, tumor stage and depth correlated with survival, while cMet + HER3 +/- EGFR receptor co-expression trended towards a worse survival.CONCLUSIONS:EGFR family and cMet are frequently co-expressed in treatment naïve resected EGA or GEJ tumors. Although our data do not significantly show receptor status as a prognostic factor, the co-expression profiles support for further investigation to improve targeting of this signal transduction axis.

Adaptive design is widely used in clinical trials. In this paper, we consider the problem of estimating the mean of the selected normal population in two-stage adaptive designs. Under the LINEX and L2 loss functions, admissibility and minimax results are derived for some location invariant estimators of the selected normal mean. The naive sample mean estimator is shown to be inadmissible under the LINEX loss function and to be not minimax under both loss functions.