Citations

73 Background: This study evaluated the impact of diabetes mellitus (DM) on survival in gastric and esophageal cancer patients, and examined the impact of these cancers on glycemic control in DM. Methods: Patients with newly diagnosed gastric and esophageal cancers with DM (n = 92) were identified from the Institutional Cancer Registry and matched to 92 gastric and esophageal cancer patients without DM according to age, gender and year of cancer diagnosis (2006 to 2016). The electronic medical record provided information on DM and cancer therapies and laboratory results. Overall survival (OS) was estimated with the Kaplan-Meier method and compared by Cox regression analysis using stratification for matched pairs. Mixed models were used to compare hemoglobin A1c (HbA1c) and glucose during the year following cancer diagnosis. Results: Mean age of the entire cohort was 68 years, 91% were white, 78% were men, and 53% had stage III/IV disease. Adenocarcinoma (79%) was the most common histologic type. BMI was significantly different between DM and non-DM patients (p = 0.006). Alcohol use at time of cancer diagnosis was more prevalent in non-DM patients vs. DM (p = 0.018). Among those with DM, mean HbA1c during the year following cancer diagnosis was 6.8%. Mean glucose was significantly different between DM and non-DM patients (149 mg/dL vs. 116 mg/dL, p < 0.001). For glucose, there was a significant interaction effect (p = 0.005) as DM patients demonstrated a decrease in glucose values over time compared to non-DM patients. Median follow-up time was 35 months. Three year OS was estimated at 46% (95% CI: 36-58%) for DM patients versus 52.0% (95% CI: 41-64%) in non-DM (p = 0.25). Hazard ratio (stratification for matched pairs) was 1.95 (95% CI: 1.14 – 3.43; p = 0.02). Three year PFS was estimated at 40% (95% CI: 31-53%) for DM patients versus 50% (95% CI: 40-63%) for non-DM patients (p = 0.12). Hazard ratio (stratification for matched pairs) was 1.74 (95% CI: 1.04-2.90; p = 0.03). Conclusions: Gastric and esophageal cancer and its treatment did not affect glycemic control. Risks of death and progression are greater in DM patients as compared to non-DM.

239 Background: The aim of this case-control study was to determine the impact of DM on survival in pancreatic cancer patients, and to examine the impact of pancreatic cancer on glycemic control in DM. Methods: Ninety-two patients with newly diagnosed pancreatic cancer from 2007 to 2015 with DM were identified from the institutional Cancer Registry and matched to ninety-two pancreatic cancer patients without DM according to age, gender, and year of pancreatic cancer diagnosis. The file was linked to the electronic medical record to obtain information on DM and pancreatic cancer therapies, and laboratory results. Overall survival (OS) was estimated with the Kaplan-Meier method and compared by Cox regression analysis. Mixed models were used to compare hemoglobin A1c (HbA1c) and glucose over time. Results: Mean age of the entire pancreatic cancer cohort was 70 years, most (92%) were white, most common (88%) histology was adenocarcinoma, and majority (41%) were stage IV. No differences in age, race/ethnicity, histology, or tumor stage were detected between patients with and without DM, although DM patients had higher body mass index (P = 0.014). Mean ca 19-9 (U/ml) was 804 for diabetics, and 395 for non-diabetics. Among those with DM the mean HbA1c during the year following cancer diagnosis was 7.3%. Time (days since diagnosis) was significant in DM patients (p = 0.014) as HbA1c decreased over time. Mean glucose during the year following diagnosis among DM patients was significantly higher compared to non-DM patients [160.6 (SD = 38.0) versus 117.2 (SD = 19.0); p < 0.001]. Both groups had a decline in glucose over time (p = 0.008). In Kaplan-Meier survival analysis (median follow-up time of 11.9 months), 2 year overall survival was estimated at 15% [95% CI: 8-24%] for DM patients versus 26% [95% CI: 17-36%] in non-DM patients. Hazard ratio (for matched pairs) was 1.15 (95% CI: 0.75-1.77; p = 0.51). Conclusions: DM did not adversely impact survival in patients with pancreatic cancer. Pancreatic cancer did not affect glycemic control. Elevated ca 19-9 in diabetic patients may be an unreliable marker for gauging disease progression.

Abstract Myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to evolve into accelerated and blast-phase disease (MPN-AP/BP), carrying a dismal prognosis. Conventional antileukemia therapy has limited efficacy in this setting. Thus, MPN-AP/BP is an urgent unmet clinical need. Modest responses to hypomethylating agents and single-agent ruxolitinib have been reported. More recently, combination of ruxolitinib and decitabine has demonstrated synergistic in vitro activity in human and murine systems. These observations led us to conduct a phase 1 study to explore the safety of combined decitabine and dose-escalated ruxolitinib in patients with MPN-AP/BP. A total of 21 patients were accrued to this multicenter study. Ruxolitinib was administered at doses of 10, 15, 25, or 50 mg twice daily in combination with decitabine (20 mg/m2 per day for 5 days) in 28-day cycles. The maximum tolerated dose was not reached. The most common reasons for study discontinuation were toxicity/adverse events (37%) and disease progression (21%). Fourteen patients died during study treatment period or follow-up. The median overall survival for patients on study was 7.9 months (95% confidence interval, 4.1-not reached). Among evaluable patients, the overall response rate by protocol-defined criteria (complete remission with incomplete count recovery + partial remission) was 9/17 (53%) and by intention-to-treat analysis was 9/21 (42.9%). The combination of decitabine and ruxolitinib was generally well tolerated by patients with MPN-AP/BP and demonstrates potentially promising clinical activity. A phase 2 trial evaluating the efficacy of this combination regimen is ongoing within the Myeloproliferative Disorder Research Consortium.

Abstract The Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (PMF), frequently progress to more overt forms of MF and a type of acute leukemia termed MPN-accelerated phase/blast phase (MPN-AP/BP). Recent evidence indicates that dysregulation of the tumor suppressor tumor protein p53 (TP53) commonly occurs in the MPNs. The proteins MDM2 and MDM4 alter the cellular levels of TP53. We investigated in 1,294 patients whether abnormalities involving chromosomes 1 and 12, which harbor the genes for MDM4 and MDM2, respectively, and chromosome 17, where the gene for TP53 is located, are associated with MPN disease progression. Gain of 1q occurred not only in individuals with MPN-BP but also in patients with PV and ET, who, with further follow-up, eventually evolve to either MF and/or MPN-BP. These gains of 1q were most prevalent in patients with a history of PV and those who possessed the JAK2V617F driver mutation. The gains of 1q were accompanied by increased transcript levels of MDM4. In contrast, 12q chromosomal abnormalities were exclusively detected in patients who presented with MF or MPN-BP, but were not accompanied by further increases in MDM2/MDM4 transcript levels. Furthermore, all patients with a loss of 17p13, which leads to a deletion of TP53, had either MF or MPN-AP/BP. These findings suggest that gain of 1q, as well as deletions of 17p, are associated with perturbations of the TP53 pathway, which contribute to MPN disease progression.

AbstractBackgroundFluconazole is the most commonly used antifungal treatment for various forms of coccidioidomycosis. Although we had anecdotally observed a high proportion of patients reporting cutaneous adverse effects associated with fluconazole treatment, this observation was not well described in the medical literature, and we were unsure of the additional effect of the arid desert environment of Arizona.MethodsWe performed a one‐time, voluntary survey of patients with coccidioidomycosis and compared the responses of patients treated with fluconazole with those of untreated patients.ResultsFrom January 1, 2015, to August 22, 2017, 62 fluconazole‐treated and 35 untreated patients with coccidioidomycosis provided consent and were enrolled in the study; demographics were similar between the two groups. Among the 62 fluconazole‐treated patients, daily dosages ranged from 200 mg to 800 mg. However, most (44/62, 71%) took 400 mg daily, the typical dose for the treatment of coccidioidomycosis. The median fluconazole treatment duration at the time of study participation was 6 months. When compared with untreated patients, those taking fluconazole had more moderate to severe dry lips (74.2% [46/62] vs. 23.5% [8/34]; P < 0.001), dry skin (45.8% [27/59] vs. 22.9% [8/35]; P = 0.03), and alopecia (31.1% [19/61] vs. 11.4% [4/35]; P = 0.004).ConclusionsFor the treatment of coccidioidomycosis, patients receiving fluconazole reported significantly more severe cutaneous effects, including dry lips, dry skin, and alopecia, than untreated patients. Our findings identify an association but do not prove causality.