Survival Outcomes of Pancreatic Intraepithelial Neoplasm (PanIN) versus Intraductal Papillary Mucinous Neoplasm (IPMN) Associated Pancreatic Adenocarcinoma

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Pancreatic intraepithelial neoplasms (PanINs) and intraductal papillary mucinous neoplasms (IPMNs) are common pancreatic adenocarcinoma precursor lesions. However, data regarding their respective associations with survival rate and prognosis are lacking. We retrospectively evaluated 72 pancreatic adenocarcinoma tumor resection patients at the University of Kansas Hospital between August 2009 and March 2019. Patients were divided into one of two groups, PanIN or IPMN, based on the results of the surgical pathology report. We compared baseline characteristics, overall survival (OS), and progression free survival (PFS) between the two groups, as well as OS and PFS based on local or distant tumor recurrence for both groups combined. 52 patients had PanINs and 20 patients had IPMNs. Patients who had an IPMN precursor lesion had better median PFS and OS when compared to patients with PanIN precursor lesions. However, the location of tumor recurrence (local or distant) did not show a statistically significant difference in OS

Association between Primary Perioperative CEA Ratio, Tumor Site, and Overall Survival in Patients with Colorectal Cancer

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.There are differences in the incidence, clinical presentation, molecular pathogenesis, and outcome of colorectal cancer (CRC) based on tumor location. Emerging research suggests that the perioperative carcinoembryonic antigen (CEA) ratio (post-op/pre-op CEA) is a prognostic factor for CRC patients. We aimed to determine the association between CEA ratio, tumor location, and overall survival (OS) among patients with CRC. We analyzed 427 patients who underwent resection for CRC at the University of Kansas Medical Center. After excluding those without pre- or post-operative CEA data, 207 patients were classified as either high (≥0.5) or low ( 5 ng/mL at the time of recurrence. The Kaplan–Meier method was used to estimate survival rates. The median age was 62 years (inter-quartile range 51–71), 55% were male, 41% were smokers, 71% had left-sided tumors, the median pre-operative CEA was 3.1 ng/mL (inter-quartile range (IQR) 1.5–9.7), and 57% had a CEA ratio ≥0.5. The OS rates were 65.1% and 86.3% in patients with high versus low CEA ratios, respectively (log-rank p-value = 0.045). The OS rates were 64.4% and 77.3% in patients with right-sided vs. left-sided tumors, respectively (log-rank p-value = 0.5). Among patients with CEA levels greater than 5 at the time of recurrence, the OS rates were 42.9% and 43.4% in patients with right-sided vs. left-sided tumors, respectively (log-rank p-value = 0.7). There was a significantly higher survival among patients with low CEA ratios than among those with high CEA ratios. There was no difference in OS between left- versus right-sided tumors. Among patients with CEA elevation > 5 ng/mL at the time of recurrence, there was no difference in OS between left versus right-sided tumors. These findings warrant validation in a larger cohort as our sample size was limited

Predictive Value of MUC5AC Signature in Pancreatic Ductal Adenocarcinoma: A Hypothesis Based on Preclinical Evidence

Mucin 5AC (MUC5AC) glycoprotein plays a crucial role in carcinogenesis and drug sensitivity in pancreatic ductal adenocarcinoma (PDAC), both individually and in combination with other mucins. Its function and localization are glycoform-specific. The immature isoform (detected by the CLH2 monoclonal antibody, or mab) is usually in the perinuclear (cytoplasmic) region, while the mature (45 M1, 2-11, Nd2) variants are in apical and extracellular regions. There is preclinical evidence suggesting that mature MUC5AC has prognostic and predictive (response to treatment) value. However, these findings were not validated in clinical studies. We propose a MUC5AC signature with three components of MUC5AC—localization, variant composition, and intensity—suggesting a reliable marker in combination of variants than with individual MUC5AC variants alone. We also postulate a theory to explain the occurrence of different MUC5AC variants in abnormal pancreatic lesions (benign, precancerous, and cancerous). We also analyzed the effect of mature MUC5AC on sensitivity to drugs often used in PDAC management, such as gemcitabine, 5-fluorouracil, oxaliplatin, irinotecan, cisplatin, and paclitaxel. We found preliminary evidence of its predictive value, but there is a need for large-scale studies to validate them

RX 3117: Activity of an oral antimetabolite nucleoside in subjects with pancreatic cancer–Preliminary results of stage II of the phase Ia/IIb study

396 Background: RX-3117 is an oral small-molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 2 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 2 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle. Eligible subjects (aged ≥ 18 years) had relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% of evaluable subjects with a partial response rate or better. Results: As of Sep 2017, 44 subjects have been enrolled (22 females, 22 males). The median age was 68 years, ECOG performance statuses were 0 (13 subjects) and 1 (31 subjects) and 6 subjects had received 4 or more prior therapies. One subject had an unconfirmed partial response and 21 subjects met the primary endpoint of stable disease with a duration of 30-224 days. The most frequent adverse events were mild to moderate anemia (19%), mild to moderate fatigue (15%), mild to moderate diarrhea (11%), and severe anemia (9%). Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. The study continues to enroll subjects with advanced pancreatic cancer into stage 2. A phase 2 study with nab-paclitaxel in first-line patients with advanced pancreatic cancer has been started. Clinical trial information: NCT02030067