A Case of Chronic Eosinophilic Leukemia in a Patient With Recurrent Cough, Dyspnea, and Eosinophilia

We report the case of a 40-year-old man with no significant past medical history who had been hospitalized multiple times over the course of one year with recurring cough, dyspnea, pruritic rash, and variable degrees of eosinophilia. He was variably diagnosed with asthma and pneumonia. After his last hospitalization with severe symptoms, the patient was referred for pulmonary evaluation where hypereosinophilia (HE) led to a hematologic workup. Fluorescence in situ hybridization revealed the FIP1L1-PDGFRA gene fusion and bone marrow analysis confirmed a diagnosis of chronic eosinophilic leukemia. The patient was treated with daily imatinib and prednisone and he was symptom-free at a four-week follow-up examination

Phase I trial of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy for the treatment of metastatic pancreatic cancer

The safety of oncolytic adenovirus-mediated suicide and interleukin-12 (IL 12) gene therapy was evaluated in metastatic pancreatic cancer patients. In this phase I study, a replication-competent adenovirus (Ad5-yCD/mutTK(SR39) rep-hIL-12) expressing yCD/mutTK(SR39) (yeast cytidine deaminase/mutant S39R HSV-1 thymidine kinase) and human IL-12 (IL 12) was injected into tumors of 12 subjects with metastatic pancreatic cancer (T2N0M1-T4N1M1) at escalating doses (1 × 10(11), 3 × 10(11), or 1 × 10(12) viral particles). Subjects received 5-fluorocytosine (5-FC) therapy for 7 days followed by chemotherapy (FOLFIRINOX or gemcitabine/albumin-bound paclitaxel) starting 21 days after adenovirus injection. The study endpoint was toxicity through day 21. Experimental endpoints included measurements of serum IL 12, interferon gamma (IFNG), and CXCL10 to assess immune system activation. Peripheral blood mononuclear cells and proliferation markers were analyzed by flow cytometry. Twelve patients received Ad5-yCD/mutTK(SR39) rep-hIL-12 and oral 5-FC. Approximately 94% of the 121 adverse events observed were grade 1/2 requiring no medical intervention. Ad5-yCD/mutTK(SR39) rep-hIL-12 DNA was detected in the blood of two patients. Elevated serum IL 12, IFNG, and CXCL10 levels were detected in 42%, 75%, and 92% of subjects, respectively. Analysis of immune cell populations indicated activation after Ad5-yCD/mutTK(SR39) rep-hIL-12 administration. The median survival of patients in the third cohort is 18.1 (range, 3.5-20.0) months. The study maximum tolerated dose (MTD) was not reached

Weekly chemotherapy with radiation versus high‐dose cisplatin with radiation as organ preservation for patients with HPV‐positive and HPV‐negative locally advanced squamous cell carcinoma of the oropharynx

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106948/1/hed23339.pd

Neoadjuvant phase II trial of chemo-radiotherapy (CRT) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDA).

Background: (PDA) is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10e30% of patients are long-term survivors. Micro-metastatic disease has been hypothesized as contributing to recurrence. Emerging data suggest a role for neoadjuvant therapy with (CRT) to target occult micro-metastatic disease. Aim: The aim of the study is to report our institutional experience with a novel neoadjuvant CRT regimen in (R) and (BR) PDA. Methods: Design e Prospective Phase II trial. Eligibility e Patients with (R) and (BR) PDA as defined by the NCCN criteria for resectability. Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with Gemcitabine and Intensity modulated Radiotherapy (IMRT). Gemcitabine was dosed at standard dosing at 1000 mg/m2 on Days 1, 8, 22 and 29 of IMRT. All subjects then received 50.4 Gy to the Gross Tumor Volume. Serial Imaging was performed to determine tumor response and resectability. Results: From April 2014 to June 2017, 24 patients were enrolled. Median age is 63.5 years (range 44 to 80). 23 patients had (BR) disease and 1 patient had (R) disease. 58% of patient had Stage 2 PDA, 29% had Stage I PDA and 12.5% had Stage III PDA. All patients received induction chemotherapy with FOLFOX. 13 patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R 1 resection (15.4%). For patients who underwent resection, the median PFS was 31 m, 1 year PFS rate was 69.2% (95% CI: 0.48e0.99) and 2-year PFS rate was 51.9 % (95% CI: 0.3e0.89). Median OS was 34.8 m (95% CI: 1.045 to infinity), 1 year OS rate was 91.7 % (95% CI: 0.77e1.0) and 2 year OS rate was 75% (95% CI: 0.54e1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range 18e2154), which decreased to 146.9 (range 18e462) after CRT prior to resection. Conclusions: Neo adjuvant therapy for (BR) and (R) PDA with CRT facilitated R0 resection in 84% patients who underwent surgery in a prospective phase II trial. These results warrant further investigation of neoadjuvant CRT in a larger cohort of patients. Disclosures: Authors have no financial interest or relationship to disclose

The SREBP Pathway in Drosophila Regulation by Palmitate, Not Sterols

AbstractIn mammals, synthesis of cholesterol and unsaturated fatty acids is controlled by SREBPs, a family of membrane-bound transcription factors. Here, we show that the Drosophila genome encodes all components of the SREBP pathway, including a single SREBP (dSREBP), SREBP cleavage-activating protein (dSCAP), and the two proteases that process SREBP at sites 1 and 2 to release the nuclear fragment. In cultured Drosophila S2 cells, dSREBP is processed at sites 1 and 2, and the liberated fragment increases mRNAs encoding enzymes of fatty acid biosynthesis, but not sterol or isoprenoid biosynthesis. Processing requires dSCAP, but is not inhibited by sterols as in mammals. Instead, dSREBP processing is blocked by palmitic acid. These findings suggest that the ancestral SREBP pathway functions to maintain membrane integrity rather than to control cholesterol homeostasis

Pathologic response to neoadjuvant chemotherapy and chemoradiation in borderline resectable adenocarcinoma of the pancreas.

Introduction: We sought to investigate the efficacy of neoadjuvant chemotherapy (CT) followed by chemoradiation (CRT) followed by surgery in borderline resectable pancreatic cancer (BRPC). Materials/Methods: Fifteen patients with BRPC were identified. Borderline resectability was determined either radiographically, based on degree of vascular involvement and input from a surgical oncologist; or biochemically, based on CA 19-9 \u3e 150 U/mL, all within a multidisciplinary tumor board setting. All patients had biopsy-proven adenocarcinoma. Staging workup included computed tomography of the chest, abdomen, and pelvis; endoscopic ultrasound, and laboratory studies including baseline CA 19-9. Patients received neoadjuvant CT followed by CRT (50.4 Gy in 28 fractions) given concurrently with capecitabine or gemcitabine. All patients underwent restaging prior to surgery. Pathologic response (PR) was graded by two independent pathologists specializing in GI malignancies according to the Modified Ryan Scheme for Tumor Regression Score. Univariate log-rank analyses were performed to identify predictors of progression-free survival and overall survival. Results: Median age was 60 years (range, 45-77 years). Median CA 19-9 at diagnosis was 469 U/mL (range, \u3c 18-2496 U/mL). All 15 patients successfully completed CRT as prescribed; only 1 patient (6%) experienced grade 2 GI toxicity, with no reported grade 3-4 GI toxicities. Median CA 19-9 following neoadjuvant therapy was 52 U/mL (range, \u3c 18-463 U/ mL). No disease progression was observed prior to surgery. R0 resection was possible in 14 patients (93%). Twelve patients (75%) achieved a partial PR to treatment. Only pretreatment CA 19-9 was associated with PR (p = 0.04). Eleven patients (73%) received adjuvant CT. Median progression-free survival and overall survival were 35 months and 36 months, respectively. Conclusions: Neoadjuvant CT followed by CRT was well-tolerated, and facilitated an R0 resection in 93% of patients with BRPC. Only pretreatment CA 19-9 was associated with PR (p= 0.04). Median overall survival was 36 months. These results warrant further investigation of neoadjuvant therapy in a larger cohort of patients

Pathologic response to neoadjuvant chemotherapy and chemoradiation in borderline resectable adenocarcinoma of the pancreas

Introduction: We sought to investigate the efficacy of neoadjuvant chemotherapy (CT) followed by chemoradiation (CRT) followed by surgery in borderline resectable pancreatic cancer (BRPC). Materials/Methods: Fifteen patients with BRPC were identified. Borderline resectability was determined either radiographically, based on degree of vascular involvement and input from a surgical oncologist; or biochemically, based on CA 19-9 \u3e 150 U/mL, all within a multidisciplinary tumor board setting. All patients had biopsy-proven adenocarcinoma. Staging workup included computed tomography of the chest, abdomen, and pelvis; endoscopic ultrasound, and laboratory studies including baseline CA 19-9. Patients received neoadjuvant CT followed by CRT (50.4 Gy in 28 fractions) given concurrently with capecitabine or gemcitabine. All patients underwent restaging prior to surgery. Pathologic response (PR) was graded by two independent pathologists specializing in GI malignancies according to the Modified Ryan Scheme for Tumor Regression Score. Univariate log-rank analyses were performed to identify predictors of progression-free survival and overall survival. Results: Median age was 60 years (range, 45-77 years). Median CA 19-9 at diagnosis was 469 U/mL (range, \u3c 18-2496 U/mL). All 15 patients successfully completed CRT as prescribed; only 1 patient (6%) experienced grade 2 GI toxicity, with no reported grade 3-4 GI toxicities. Median CA 19-9 following neoadjuvant therapy was 52 U/mL (range, \u3c 18-463 U/ mL). No disease progression was observed prior to surgery. R0 resection was possible in 14 patients (93%). Twelve patients (75%) achieved a partial PR to treatment. Only pretreatment CA 19-9 was associated with PR (p = 0.04). Eleven patients (73%) received adjuvant CT. Median progression-free survival and overall survival were 35 months and 36 months, respectively. Conclusions: Neoadjuvant CT followed by CRT was well-tolerated, and facilitated an R0 resection in 93% of patients with BRPC. Only pretreatment CA 19-9 was associated with PR (p= 0.04). Median overall survival was 36 months. These results warrant further investigation of neoadjuvant therapy in a larger cohort of patients

Neoadjuvant Phase II Trial of Chemoradiotherapy in Patients With Resectable and Borderline Resectable Pancreatic Cancer

BACKGROUND: Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease. AIM: To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer. MATERIALS AND METHODS: Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT). RESULTS: From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval [CI], 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection. CONCLUSION: Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery

Racial Disparities Among Pancreatic Adenocarcinoma Patients: A Retrospective Survival Analysis of Non-Metastatic Pancreatic Cancer Patients

Purpose/Objective(s): It is predicted that in 2020, approximately 57,600 individuals will be diagnosed with pancreatic cancer (PaC). Based on SEER database analysis, there are conflicting opinions in literature about the overall treatment and outcomes in African-American patients with PaC. The purpose of this study was to determine if there was a racial disparity in overall survival rates between African Americans (AAs) and non-African Americans (non-AAs) diagnosed with PaC who received neoadjuvant radiation therapy (RT) in a tertiary-care cancer center with an established multi-disciplinary PaC tumor board and clinic. Materials/Methods: An IRB-approved retrospective chart analysis was completed on 100 patients who were diagnosed with pancreatic adenocarcinoma and treated with neoadjuvant RT between 2017-2019. Patients who were deemed resectable, borderline resectable (BR), or locally advanced/unresectable (LA) at initial diagnosis were included in the analysis. The following baseline characteristics were collected for each patient: staging, gender, age and ECOG score at initial diagnosis, tumor site and size, clinical T and N stage, CA19-9, and treatment variables (i.e., surgery, chemotherapy, and RT type). Overall survival was calculated from the RT start date. In order to identify any baseline differences among the AA group and the non-AA group, a two-sample t-test and Chi-square were employed. A log-rank test and Kaplan-Meier were used to determine any differences in overall survival among the two groups. Results: Of the 100 patients included in the analysis, 25 were AA and 58 were female. There were 17 (68%) BR and 8 (32%) LA patients in the AA group. In the non-AA group, there were 2 (3%) resectable, 47 (63%) BR, and 26 (35%) LA patients. There were no statistically significant differences detected in any of the baseline characteristics except a trend for increased CA19-9 values of 399.8 U/mL for AAs and 229 U/mL for non-AAs. There was no statistically significant difference in receipt of chemotherapy and RT between the two groups. The estimated median survival rates were 11.5 months for non-AAs and 8.4 months for AAs. One-year overall survival was 45% for AAs versus 48% for non-AAs (p = 0.57). Conclusion: There was no difference in overall survival among AAs and non-AAs who received neoadjuvant RT+/- chemotherapy for PaC at our institution between 2017-2019. Contrary to previous publications based on large SEER database analysis, there does not appear to be any difference in overall survival based on race if patients receive treatment in a comprehensive multi-disciplinary collaborative center