Clinicopathological features of pancreatic cancer-related diabetes.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 675-675
Author(s):  
Michael Lee ◽  
Hui-Li Wong ◽  
Erica S. Tsang ◽  
Sean McKay Fenlon Addison ◽  
James T. Topham ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Retrospective Chart Review ◽  
Clinicopathological Features ◽  
Initial Diagnosis ◽  
Ductal Adenocarcinoma ◽  
Diabetic Patients ◽  
Diabetes Diagnosis ◽  
Pancreatic Cancer Screening ◽  
Diabetes Status

675 Background: Epidemiological studies suggest pancreatic ductal adenocarcinoma (PDAC) may be strongly interrelated with diabetes. However, little is known about the clinicopathological features of pancreatic cancer related diabetes. Methods: A retrospective chart review was undertaken of all patients with advanced PDAC treated with at least one cycle of palliative chemotherapy at BC Cancer, Vancouver between Jan 2012- Dec 2015. Diagnosis of diabetes was determined by consultation documentation and/or fasting glucose > 7mmol/L or HbA1c > 48mmol/L. Peripancreatic diabetes is defined as diabetes diagnosis < 3 years prior to PDAC diagnosis. Results: 578 patients were identified with median age 66 (49-81), 54.6% male, 39.5% non-smoker and 63.5% ECOG 0/1. 27.3% confirmed diabetics, of which 75.8% (119/157) have peripancreatic diabetes. At initial diagnosis, 11.2% were deemed upfront resectable, 44.0% borderline/locally advanced, and 55.1% metastatic. Median overall survival (OS) for the cohort based on stage of disease at initial diagnosis for borderline, locally advanced and metastatic was 22 months (16.1-27.9), 12 months (10.1-13.9) and 6 months (5.0-7.0) respectively. There was no association with diabetes status and OS noted (p = 0.58). Statistical differences were noted in BMI (24.1 v 26.1, p = 0.003), and proportion of Charlson comorbidity index (CCI) of 2 (2.2 v 88.3%, p < 0.01) between non-diabetic and diabetic patients respectively. Statistical difference between peripancreatic diabetes compared to long-term diabetes were noted in resectable status (18.6 v 7.6%, p = 0.048), weight loss > 2kg (78.6 v 60.5%, p = 0.035), hypertension (25.9 v 59.8%, p = 0.002) and dyslipidemia (18.5 v 42.7%, p = 0.024). Conclusions: The majority of patients diagnosed with advanced PDAC with diabetes appeared to develop diabetes within 3 years prior to diagnosis. Further studies to assess the potential role of pancreatic cancer screening investigations in newly diagnosed diabetics are warranted.

Prognostic impact of chemoradiation-related lymphopenia in patients with locally advanced pancreatic cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 439-439
Author(s):  
Daniel W Kim ◽  
Grace Lee ◽  
Colin D. Weekes ◽  
David P. Ryan ◽  
Aparna Raj Parikh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cox Model ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Pancreatic Head ◽  
Locally Advanced Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Prognostic Impact ◽  
Entire Cohort ◽  
Grade 3

439 Background: Chemoradiation (CRT) induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. The objective of this study was to evaluate the prognostic impact of lymphopenia in patients with nonmetastatic, unresectable pancreatic ductal adenocarcinoma (PDAC) treated by neoadjuvant FOLFIRINOX (5-fluorouracil [5FU]/leucovorin/irinotecan/oxaliplatin) followed by CRT. We hypothesized that severe lymphopenia would correlate with worse survival. Methods: The inclusion criteria for this single-institution retrospective study were: 1) biopsy-proven diagnosis of unresectable PDAC, 2) absence of distant metastasis, 3) receipt of neoadjuvant FOLFIRINOX followed by CRT, and 4) absolute lymphocyte count (ALC) available prior to and two months after initiating CRT. In general, CRT consisted of 5FU or capecitabine and RT with 58.8 Gy over 28 fractions. Lymphopenia was graded according to CTCAE v5.0. The primary variable of interest was lymphopenia at two months, dichotomized by ALC of < 0.5/μl (Grade 3 lymphopenia). The primary endpoint was overall survival (OS). Cox modeling and Kaplan-Meier methods were used to perform survival analyses. Results: A total of 138 patients were identified. Median follow-up for the entire cohort was 16 months. Median age was 65. Fifty-six percent were female, 86% were Caucasian, and 97% had ECOG ≤1. Median tumor size was 3.8 cm. Tumor location was pancreatic head in 63%, body in 22%, tail in 8%, and neck in 7%. Median baseline ALC for the entire cohort was 1.5 k/ul. Two months after initiating CRT, 106 (77%) had severe (Grade 3 or worse) lymphopenia. While there were no significant differences in baseline patient or disease characteristics, patients with severe lymphopenia received higher doses of RT with longer duration of treatment compared to those without severe lymphopenia. On multivariable Cox model, severe lymphopenia at two months was significantly associated with increased hazards of death (HR = 4.00 [95% CI 2.03-7.89], p < 0.001). Greater number of neoadjuvant FOLFIRINOX cycles received prior to CRT was associated with lower hazards of death (HR = 0.84 [95% CI 0.77-0.92], p < 0.001). The 12-month OS was 73% vs. 90% in the cohort with vs. without severe lymphopenia, respectively (log-rank p < 0.001). Conclusions: Treatment-related lymphopenia is common and severe lymphopenia may be a prognostic marker of poorer survival in locally advanced pancreatic cancer. Closer observation in high-risk patients and minimization of RT dose and duration are potential approaches to mitigating CRT-related lymphopenia. Our findings also suggest an important role of the host immunity in pancreatic cancer outcomes, supporting the ongoing efforts of immunotherapy trials in pancreatic cancer.

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 

scholarly journals Conversion Surgery for Advanced Pancreatic Cancer

2019 ◽  
Vol 8 (11) ◽  
pp. 1945
Author(s):  
Thomas Hank ◽  
Oliver Strobel
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Palliative Therapy ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Conversion Surgery ◽  
Radiological Criteria ◽  
Intention To Treat ◽  
Conversion Rates

While primarily unresectable locally advanced pancreatic cancer (LAPC) used to be an indication for palliative therapy, a strategy of neoadjuvant therapy (NAT) and conversion surgery is being increasingly used after more effective chemotherapy regimens have become available for pancreatic ductal adenocarcinoma. While high-level evidence from prospective studies is still sparse, several large retrospective studies have recently reported their experience with NAT and conversion surgery for LAPC. This review aims to provide a current overview about different NAT regimens, conversion rates, survival outcomes and determinants of post-resection outcomes, as well as surgical strategies in the context of conversion surgery after NAT. FOLFIRINOX is the predominant regimen used and associated with the highest reported conversion rates. Conversion rates considerably vary between less than 5% and more than half of the study population with heterogeneous long-term outcomes, owing to a lack of intention-to-treat analyses in most studies and a high heterogeneity in resectability criteria, treatment strategies, and reporting among studies. Since radiological criteria of local resectability are no longer applicable after NAT, patients without progressive disease should undergo surgical exploration. Surgery after NAT has to be aimed at local radicality around the peripancreatic vessels and should be performed in expert centers. Future studies in this rapidly evolving field need to be prospective, analyze intention-to-treat populations, report stringent and objective inclusion criteria and criteria for resection. Innovative regimens for NAT in combination with a radical surgical approach hold high promise for patients with LAPC in the future.

Value of Early Check-Up of Carbohydrate Antigen 19-9 Levels for Pancreatic Cancer Screening in Asymptomatic New-Onset Diabetic Patients

Pancreas ◽  
2016 ◽  
Vol 45 (5) ◽  
pp. 730-734 ◽  
Author(s):  
Jung Wan Choe ◽  
Jae Seon Kim ◽  
Hyo Jung Kim ◽  
Soon Young Hwang ◽  
Moon Kyung Joo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Screening ◽  
Carbohydrate Antigen ◽  
Diabetic Patients ◽  
Pancreatic Cancer Screening ◽  
New Onset

Sequential neoadjuvant chemotherpy with nab-paclitaxel plus gemcitabine and FOLFIRINOX in locally advanced pancreatic cancer (LAPC): A PILOT study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15193-e15193 ◽  
Author(s):  
Volker Kunzmann ◽  
Ingo Hartlapp ◽  
Michael Scheurlen ◽  
Hermann Einsele ◽  
Justus Mueller ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pilot Study ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Sensory Neuropathy ◽  
Disease Stage ◽  
Ductal Adenocarcinoma ◽  
Hematological Toxicity ◽  
Highly Active

e15193 Background: Nab-Paclitaxel (nab-P) + Gemcitabin (G) and FOLFIRINOX have both shown promising activity in metastatic pancreatic cancer (mPC). Our group has developed sequential usage of both regimens in order to exploit the stromal depletion effects of nab-P and increase global efficacy of chemotherapy in the neoadjuvant setting of LAPC. Methods: This pilot study evaluated patients with cytological/histological confirmed diagnosis of locally advanced pancreatic ductal adenocarcinoma without evidence of metastatic disease (stage III). nab-P+G was administered for 2 cycles (nab-P 125 mg/m2, G 1000 mg/ 2; on days 1, 8, 15; every 28 days) followed by 2 cycles of FOLFIRINOX (as reported by Conroy et al., NEJM 2011). Results: We report the preliminary analysis of 8 pts treated in our institution. Patients characteristics were M/F: 5/3; median age 63 (46-79); PS 0/1: 6/2. 3 pts (37%) had a biliary stent before starting treatment. All pts received the planned 4 cycles of neoadjuvant chemotherapy without dose reductions. There were no treatment-related deaths and none of pts stopped treatment due to toxicity. Grade 3-4 toxicities were neutropenia (50 %), nausea (12%), diarrhea (12%) and thrombopenia (25%). Grade 2-3 sensory neuropathy occured in 25% of pts. Prior nab-P+G did not result in increased hematological or non-hematological toxicity of FOLFIRINOX. Among the 8 patients evaluable so far, 5 partial responses (63%) and 3 stable disease (37%) have been observed, resulting in a disease control rate of 100%. After sequential chemotherapy 3 pts (37%) underwent radical surgical resection. Of note, all resected patients pts showed regression of the tumor (Evans Regression Score 2-4) with 1 patient fullfilling the criteria of a complete pathological remission (pCR). 4 pts received concomitant chemo-radiotherapy and 1 pt underwent an explorative laparotomy with evidence of occult (micronodular) peritoneal metastasis. Conclusions: Sequential neoadjuvant chemotherapy with nab-P+G and FOLFIRINOX seems to be highly active with manageable toxicity profile and may allow to achieve pCR in LAPC. These results are encouraging to test this approach in a prospective phase II trial.

scholarly journals Mitochondrial DNA and MitomiR Variations in Pancreatic Cancer: Potential Diagnostic and Prognostic Biomarkers

2021 ◽  
Vol 22 (18) ◽  
pp. 9692
Author(s):  
Loredana Moro
Keyword(s):  
Pancreatic Cancer ◽  
Current Knowledge ◽  
Locally Advanced ◽  
Prognostic Biomarkers ◽  
Mitochondrial Proteins ◽  
Ductal Adenocarcinoma ◽  
Metastatic Progression ◽  
Response To Chemotherapy ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

Pancreatic cancer is an aggressive disease with poor prognosis. Only about 15–20% of patients diagnosed with pancreatic cancer can undergo surgical resection, while the remaining 80% are diagnosed with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). In these cases, chemotherapy and radiotherapy only confer marginal survival benefit. Recent progress has been made in understanding the pathobiology of pancreatic cancer, with a particular effort in discovering new diagnostic and prognostic biomarkers, novel therapeutic targets, and biomarkers that can predict response to chemo- and/or radiotherapy. Mitochondria have become a focus in pancreatic cancer research due to their roles as powerhouses of the cell, important subcellular biosynthetic factories, and crucial determinants of cell survival and response to chemotherapy. Changes in the mitochondrial genome (mtDNA) have been implicated in chemoresistance and metastatic progression in some cancer types. There is also growing evidence that changes in microRNAs that regulate the expression of mtDNA-encoded mitochondrial proteins (mitomiRs) or nuclear-encoded mitochondrial proteins (mitochondria-related miRs) could serve as diagnostic and prognostic cancer biomarkers. This review discusses the current knowledge on the clinical significance of changes of mtDNA, mitomiRs, and mitochondria-related miRs in pancreatic cancer and their potential role as predictors of cancer risk, as diagnostic and prognostic biomarkers, and as molecular targets for personalized cancer therapy.

scholarly journals Primary Thromboprophylaxis in Pancreatic Cancer Patients: Why Clinical Practice Guidelines Should Be Implemented

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 618 ◽  
Author(s):  
Dominique Farge ◽  
Barbara Bournet ◽  
Thierry Conroy ◽  
Eric Vicaut ◽  
Janusz Rak ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Practice ◽  
Cancer Patients ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Randomized Trials ◽  
Treatment Options ◽  
Locally Advanced ◽  
Ductal Adenocarcinoma ◽  
Recent Advances

Exocrine pancreatic ductal adenocarcinoma, simply referred to as pancreatic cancer (PC) has the worst prognosis of any malignancy. Despite recent advances in the use of adjuvant chemotherapy in PC, the prognosis remains poor, with fewer than 8% of patients being alive at 5 years after diagnosis. The prevalence of PC has steadily increased over the past decades, and it is projected to become the second-leading cause of cancer-related death by 2030. In this context, optimizing and integrating supportive care is important to improve quality of life and survival. Venous thromboembolism (VTE) is a common but preventable complication in PC patients. VTE occurs in one out of five PC patients and is associated with significantly reduced progression-free survival and overall survival. The appropriate use of primary thromboprophylaxis can drastically and safely reduce the rates of VTE in PC patients as shown from subgroup analysis of non-PC targeted placebo-controlled randomized trials of cancer patients and from two dedicated controlled randomized trials in locally advanced PC patients receiving chemotherapy. Therefore, primary thromboprophylaxis with a Grade 1B evidence level is recommended in locally advanced PC patients receiving chemotherapy by the International Initiative on Cancer and Thrombosis clinical practice guidelines since 2013. However, its use and potential significant clinical benefit continues to be underrecognized worldwide. This narrative review aims to summarize the main recent advances in the field including on the use of individualized risk assessment models to stratify the risk of VTE in each patient with individual available treatment options.

The effects of pioglitazone treatment on pancreatic cancer-related insulin resistance.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 329-329
Author(s):  
Jennifer Stern ◽  
Yull Edwin Arriaga ◽  
Arjun Gupta ◽  
Udit Verma ◽  
Sirisha Karri ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Pancreatic Cancer ◽  
Insulin Sensitivity ◽  
Ppar Gamma ◽  
Post Treatment ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Fasting Insulin ◽  
Diabetes Status ◽  
Pioglitazone Treatment

329 Background: Insulin resistance (IR) in pancreatic cancer (PC) patients is associated with cachexia and poor outcome. Pioglitazone (PIO) improves insulin sensitivity via activation of peroxisome proliferator-activated receptor (PPAR gamma). Effects of PIO on insulin sensitivity, glucose homeostasis, and circulating adipokine levels in PC have not been examined. Methods: Patients with metastatic PC were administered PIO 45mg/day orally for 8 weeks concurrent with chemotherapy. Patients with known DM at enrollment were identified Fasting plasma was collected at baseline, weeks 2, 4, 6, 8 of pioglitazone treatment and at 2 weeks-post treatment. The primary objective was to describe changes in indicators of IR, including glucoregulatory hormone levels, glucose tolerance, and inflammatory cytokines. Results: Fourteen patients (age 64y), with a mean BMI of 28 were enrolled. Mean adiponectin increased from baseline to week 8 of treatment (14.2± 3.3 and 46.9±11.4µg/ml, respectively, P ≤ 0.01), and returned to baseline levels at 2 weeks post-treatment (15.1±1.9 µg/ml). Markers of IR (serum glucose, insulin, glucagon, and response to an oral glucose bolus) did not correlate with tumor size, inflammatory cytokine levels, GM-CSF, or CA19-9. A dichotomous response to PIO treatment was observed between non-diabetic and T2DM patients. Fasting insulin increased 70.6±31.3% from baseline to treatment week 8 in patients with T2DM. In contrast, treatment of non-diabetic patients decreased fasting insulin by 40.2±6.3%, demonstrating a significant, P ≤ 0.01, difference in treatment response between PC patients with or without T2DM. Conclusions: We have demonstrated that PC patients respond to 8 weeks of PIO treatment with a significant rise in the insulin sensitizing adipokine, Adiponectin, with a complete wash-out after 2 weeks of cessation. PIO results in opposing fasting insulin responses in non-diabetic and DM patients suggests that diabetes status plays a significant role in the glucoregulatory effects of PIO treatment in PC patients. Clinical trial information: NCT01838317.

Results of conversion surgery after the triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 366-366
Author(s):  
Naoya Ikeda ◽  
Takahiro Akahori ◽  
Sohei Satoi ◽  
Hiroaki Yanagimoto ◽  
Minako Nagai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Clinical Impact ◽  
Ductal Adenocarcinoma ◽  
Unresectable Pancreatic Cancer ◽  
Conversion Surgery ◽  
Open Label ◽  
Grade 3 ◽  
Medical University

366 Background: Recent improvements in chemotherapy for initially unresectable pancreatic ductal adenocarcinoma (UPDAC) occasionally show remarkable antitumor effect and lead to conversion surgery (CS). However, the optimal indication and clinical impact of CS remains unknown. We have recently developed a new regimen consisted of biweekly S-1, oxaliplatin, and irinotecan (SOXIRI). In this regimen, we used S-1 in alternate-day administration instead of 5-FU, that can be more feasible than FOLFIRINOX. The aim of this study was to evaluate the clinical impact of CS after SOXILI treatment for initially UPDAC. Methods: We conducted an open-label, single-arm, phase II study that was carried out at Nara Medical University and Kansai Medical University in Japan. Patients with untreated metastatic and locally advanced PDAC were enrolled. They received 80 mg/m2 twice a day of S-1 for 2 weeks in alternate-day administration, 150 mg/m2 of irinotecan on day 1, and 85 mg/m2 of oxaliplatin on day 1 of a 2-week cycle. Results: The 35 enrolled patients received a median of six (range: 2-15) treatment cycles. The RR was 22.8%; median OS, 17.7 months; and median PFS, 7.4 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). Twenty-three out of 35 patients of UR-PDAC were unresectable locally advanced pancreatic cancer (UR-LAPA). Seven out of 23 patients with UR-LAPA underwent CS. Distal pancreatectomy with celiac axis resection was performed in three patients, central pancreatectomy was performed in one patient. Pancreatoduodenectomy (PD) was performed in two patients, and PD with portal vein resection in one patient. Two out of seven patients had postoperative complications. One case had grade B pancreatic fistula, and the other case underwent cholecystectomy due to acute cholecystitis. The median OS in patients who received CS was 31.4 months. Conclusions: SOXIRI regimen has shown promising clinical efficacy with acceptable tolerability in patients with unresectable pancreatic cancer. Furthermore, it may be a potent first-line treatment when considering conversion surgery. Clinical trial information: UMIN000014339.

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