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Pancreatic Neoplasms: HELP
Articles by Richard D. Kim
Based on 18 articles published since 2010
(Why 18 articles?)
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Between 2010 and 2020, Richard Kim wrote the following 18 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Editorial Biomarkers for pancreatic cancer: is it ready for primetime? 2013

Kim, Richard / Mahipal, Amit / Choi, Minsig / Saif, Mohammad Wasif. · ·JOP · Pubmed #23846914.

ABSTRACT: -- No abstract --

2 Review Management of borderline resectable pancreatic cancer. 2015

Mahipal, Amit / Frakes, Jessica / Hoffe, Sarah / Kim, Richard. ·Amit Mahipal, Richard Kim, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States. ·World J Gastrointest Oncol · Pubmed #26483878.

ABSTRACT: Pancreatic cancer is the fourth most common cause of cancer death in the United States. Surgery remains the only curative option; however only 20% of the patients have resectable disease at the time of initial presentation. The definition of borderline resectable pancreatic cancer is not uniform but generally denotes to regional vessel involvement that makes it unlikely to have negative surgical margins. The accurate staging of pancreatic cancer requires triple phase computed tomography or magnetic resonance imaging of the pancreas. Management of patients with borderline resectable pancreatic cancer remains unclear. The data for treatment of these patients is primarily derived from retrospective single institution experience. The prospective trials have been plagued by small numbers and poor accrual. Neoadjuvant therapy is recommended and typically consists of chemotherapy and radiation therapy. The chemotherapeutic regimens continue to evolve along with type and dose of radiation therapy. Gemcitabine or 5-fluorouracil based chemotherapeutic combinations are administered. The type and dose of radiation vary among different institutions. With neoadjuvant treatment, approximately 50% of the patients are able to undergo surgical resections with negative margins obtained in greater than 80% of the patients. Newer trials are attempting to standardize the definition of borderline resectable pancreatic cancer and treatment regimens. In this review, we outline the definition, imaging requirements and management of patients with borderline resectable pancreatic cancer.

3 Review First-line treatment for advanced pancreatic cancer. 2013

Kothari, Nishi / Saif, Muhammad Wasif / Kim, Richard. ·H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA. ·JOP · Pubmed #23474553.

ABSTRACT: Metastatic pancreatic cancer is a rapidly fatal disease with few therapeutic options. The authors summarize four abstracts (#148, #233, #158, #291) presented at the 2013 ASCO Gastrointestinal Cancers Symposium which were focused on novel agents for metastatic pancreatic cancer.

4 Review Systemic therapy of advanced pancreatic cancer: has the landscape changed? 2012

Choi, Minsig / Razzaque, Saqib / Kim, Richard. ·Wayne State University School of Medicine, Detroit, Michigan, USA. ·Clin Adv Hematol Oncol · Pubmed #22895284.

ABSTRACT: Limited progress has been made in the treatment of advanced pancreatic cancer. Gemcitabine was established as a standard of care after a randomized phase III study showed an improvement in clinical benefit response and overall survival over 5-flurouracil. Multiple phase III studies have been conducted to improve upon the response and survival established with single-agent gemcitabine. Combining different cytotoxic chemotherapy with gemcitabine failed to provide any meaningful survival advantage over gemcitabine monotherapy. A modest improvement in overall survival was noted when an epidermal growth factor receptor tyrosine kinase inhibitor (erlotinib) was added to gemcitabine. The landscape for the treatment of advanced pancreatic cancer changed with the introduction of the fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) regimen at the 2010 American Society of Clinical Oncology meeting. The phase III clinical trial showed an overall survival improvement in the gemcitabine group of 6.8 months compared to 11.1 months in the FOLFIRINOX arm (P<.0001). More interestingly, almost half of the patients in the FOLFIRINOX group were alive after 1 year, and the response rate was 31.6%. A new triplet chemotherapy regimen has emerged to replace the use of single-agent gemcitabine in a highly selected patient population. In this article, we will review the published data on first-line chemotherapy, with discussion of targeted agents for advanced pancreatic cancer and potential future directions.

5 Review BRCA and pancreatic cancer: selection of chemotherapy. 2012

Kim, Richard / Byer, Jenifer / Saif, Muhammad Wasif. ·H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA. richard.kim@moffitt.org ·JOP · Pubmed #22406596.

ABSTRACT: Germline mutations in BRCA genes are associated with increased risk of pancreatic cancer. There are pre clinical data which suggests that DNA cross linking agents should be used in pancreatic cancer patients with BRCA mutations. This review is an update from the 2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium regarding recent developments in the treatment of pancreatic cancer with BRCA mutation. Only one study (Abstracts #217) was presented and it is described here.

6 Review What options are available for refractory pancreatic cancer? 2012

Choi, Minsig / Kim, Richard / Saif, Muhammad Wasif. ·Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. ·JOP · Pubmed #22406591.

ABSTRACT: Currently gemcitabine-based regimens and FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) are widely used standard for first-line treatment of patients with advanced pancreatic adenocarcinoma. Refractory patients may receive either FOLFOX (5-fluorouracil and oxaliplatin) or gemcitabine based on the first line regimen. This review is an update from the 2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium regarding recent developments in the treatment of refractory pancreatic cancer, as these were presented in Abstracts #248 and #373 of the meeting.

7 Clinical Trial Phase I study of combination of pasireotide LAR + gemcitabine in locally advanced or metastatic pancreatic cancer. 2015

Suleiman, Yaman / Mahipal, Amit / Shibata, David / Siegel, Erin M / Jump, Helen / Fulp, William J / Springett, Gregory M / Kim, Richard. ·Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA. ·Cancer Chemother Pharmacol · Pubmed #26126727.

ABSTRACT: PURPOSE: Pasireotide LAR (SOM230 LAR) is a cyclohexapeptide engineered to bind to multiple somatostatin receptor subtypes to mimic the action of naturally occurring somatostatin with higher affinity to these receptors than octreotide and is a potent inhibitor of insulin-like growth factor-1 (IGF-1). Somatostatin receptors and IGF receptors are highly expressed in pancreatic cancer, thereby potentially making it a valuable target. This phase I study evaluated safety, tolerability and preliminary tumor response of pasireotide LAR in combination with gemcitabine in locally advanced or metastatic pancreatic cancer. METHODS: Patients with previously untreated metastatic pancreatic cancer were included. A 3 + 3 dose-escalation design was used. Patients received gemcitabine on days 1, 8 and 15 and pasireotide LAR IM monthly in a 28-day cycle. Two dose levels of pasireotide LAR were planned: 40 mg IM and 60 mg. Cohort was expanded by ten more patients at the highest tested dose to further assess the safety and efficacy. RESULTS: Twenty patients were consented on this trial, and 16 patients were evaluable for safety and efficacy. No dose-limiting toxicities were observed. Two out sixteen patients (12%) had partial response, and nine of sixteen (56%) had stable disease as best response. Median progression-free survival was 4.1 months (range 1-16 months), and median overall survival was 6.9 months (range 1-25 months). Most common grade 3 or 4 toxicities were hyperglycemia (n = 5), hyperbilirubinemia (n = 1) and thrombocytopenia (n = 2). Median baseline IGF-1 level was lower in patients with stable disease than in those with progressive disease (63 vs 71 ng/ml). CONCLUSION: Pasireotide in combination with gemcitabine was well tolerated with disease control rate of 68%. Larger trials are needed in the future to establish its efficacy in the treatment of pancreatic cancer. CLINICAL TRIAL: NCT01385956.

8 Clinical Trial FOLFIRINOX: a new standard treatment for advanced pancreatic cancer? 2011

Kim, Richard. ·H Lee Moffitt Cancer Center, Tampa, FL 33612, USA. richard.kim@moffi tt.org ·Lancet Oncol · Pubmed #21050812.

ABSTRACT: -- No abstract --

9 Article Phase 1 trial of enzalutamide in combination with gemcitabine and nab-paclitaxel for the treatment of advanced pancreatic cancer. 2019

Mahipal, Amit / Tella, Sri Harsha / Kommalapati, Anuhya / Goyal, Gaurav / Soares, Heloisa / Neuger, Anthony / Copolla, Domenico / Kim, Jongphil / Kim, Richard. ·Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA. Mahipal.amit@mayo.edu. · Department of Oncology, Mayo Clinic, 200 1st street SW, Rochester, MN, 55906, USA. Mahipal.amit@mayo.edu. · Department of Internal Medicine, University of South Carolina School of Medicine, Columbia, SC, USA. · Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA. · Department of Oncology, University of New Mexico, Albuquerque, NM, USA. · Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. · Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. · Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, FL, USA. ·Invest New Drugs · Pubmed #30298303.

ABSTRACT: Background Androgens were shown to play a key role in the growth and progression of pancreatic cancer. We evaluated the safety and tolerability of the combination of enzalutamide, a novel androgen receptor (AR) antagonist with gemcitabine and nab-paclitaxel as a first-line treatment in advanced pancreatic cancer. Methods We used the standard 3 + 3 dose escalation design with cohort expansion to evaluate 2 dose levels of enzalutamide: 80 mg and 160 mg/day orally (phase 1a) in combination with gemcitabine and nab-paclitaxel in metastatic pancreatic cancer patients. In the expansion phase (phase 1b), AR+ was a pre-requisite criterion. We also evaluated the full pharmacokinetic (PK) profile for nab-paclitaxel and enzalutamide. Results We enrolled 24 patients, 12 patients in phase 1a and 12 patients in phase 1b. The median age was 68 (range, 32-84) years. No DLTs were observed. Grade 3/4 treatment related adverse events included neutropenia (44%), anemia (40%), leukopenia (24%), nausea and vomiting (20%), diarrhea (16%), infections (12%), thrombocytopenia (8%), thromboembolic event (8%), hypertension (8%), hypokalemia (8%), hyponatremia (8%), and ALT elevation (8%). Median overall survival and progression-free survival was 9.73 [95%CI:9.73-13.5] and 7.53 (95%CI:6.05-12.8) months, respectively. PK analysis suggests that the combination therapy does not impact the kinetics of either drug evaluated. Enzalutamide reached steady-state levels between day 22 and 29 and the mean half-life of nab-paclitaxel was 19.6 ± 4.7 h. Conclusions Enzalutamide 160 mg daily in combination with gemcitabine and nab-paclitaxel can be safely administered with no unexpected toxicities. We also noticed preliminary signals of efficacy with this combination.

10 Article Use of Radiation Therapy in Locally Advanced Pancreatic Cancer Improves Survival: A SEER Database Analysis. 2018

Sajjad, Monique / Batra, Sachin / Hoffe, Sarah / Kim, Richard / Springett, Gregory / Mahipal, Amit. ·Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. · Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX. ·Am J Clin Oncol · Pubmed #26796313.

ABSTRACT: OBJECTIVES: Although both radiation therapy and chemotherapy are frequently used to treat locally advanced pancreatic cancer (LAPC) patients, the role of radiation therapy remains controversial with data evaluating its efficacy mostly derived from small randomized trials. In this study, we evaluate the survival benefit of radiation therapy using SEER dataset in patients with LAPC. MATERIALS AND METHODS: The SEER Registry dataset from 2004 to 2011 was queried to identify LAPC (TNM stage III) patients. Patients with survival <2 months, unknown radiation status, or who received postoperative radiation were excluded. Multivariate analyses of prognostic factors related to survival were performed using a Cox proportional hazard-regression model. Propensity scores were estimated using probit regression. RESULTS: Our search identified 4460 patients; 59% who received radiation and 41% who did not. Radiation group patients were younger (below 65 y old: 49% vs. 38%), had smaller tumor size (largest dimension <4.5 cm: 80% vs. 75%), less lymph node involvement (33% vs. 36%), and lower rate of surgical resection (4% vs. 9%). Patients who received radiation therapy had better survival (HR=0.773; 95% CI, 0.687-0.782). The 12-month overall survival in the radiation group and nonradiation group was 43% versus 29%, respectively (P<0.001). On multivariate analyses, radiation was independently associated with improved outcomes. The survival benefit with radiation was observed in propensity score-matched cohort. CONCLUSIONS: Radiation therapy was associated with improved survival. Prospective randomized trials are needed to confirm these findings. The optimal schedule and radiation type remain undetermined.

11 Article Metabolic Activity by 18F-FDG-PET/CT Is Prognostic for Stage I and II Pancreatic Cancer. 2016

Pimiento, Jose M / Davis-Yadley, Ashley H / Kim, Richard D / Chen, Dung-Tsa / Eikman, Edward A / Berman, Claudia G / Malafa, Mokenge P. ·From the *Surgical Oncology, H. Lee Moffitt Cancer Center and Research Institute; and †Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, FL. ·Clin Nucl Med · Pubmed #26673243.

ABSTRACT: PURPOSE: Metabolic activity, as defined by F-FDG uptake on PET, is a prognostic marker for multiple malignancies; however, no study has examined the prognostic value of imaging with FDG PET in stage I and II pancreatic cancer. We examined the value of PET FDG uptake in early-stage pancreatic cancer patients. METHODS: We identified patients with early-stage pancreatic cancer (I-II) who had FDG PET scan performed as part of their preoperative evaluation. The patients were divided into either high or low FDG uptake according to the median primary tumor standard uptake value (SUVmax). Our primary end points were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier estimate was used for survival analysis. Pathologic data were compared using the Fisher exact and χ tests. RESULTS: One hundred five patients were identified: 51 patients with low FDG uptake and 54 patients with high FDG uptake. Eighty-five patients (81%) had PET avid tumors, whereas 20 (19%) patients did not. High FDG uptake correlated with pathologic stage (P = 0.012). Patients with low FDG uptake had significantly better median OS than patients with high FDG uptake (28 vs. 16 months; P = 0.036). Patients with low-FDG uptake had significantly longer median RFS than patients with high FDG uptake (14 vs. 12 months; P = 0.049). CONCLUSIONS: Low FDG uptake in PET scans in patients with stage I and II pancreatic cancer correlates with improved OS and RFS. This supports the concept that glucose metabolic pathways are important in pancreatic cancer biology and that PET scan activity can be used as a prognostic biomarker after pancreatectomy.

12 Article Triciribine Phosphate Monohydrate, an AKT Inhibitor, Enhances Gemcitabine Activity in Pancreatic Cancer Cells. 2015

Kim, Richard / Yamauchi, Teruo / Husain, Kazim / Sebti, Said / Malafa, Mokenge. ·Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. Richard.Kim@moffitt.org. · Division of Medical Oncology, Department of Internal Medicine, St. Luke's International Hospital, Tokyo, Japan. · Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. Department of Oncologic Sciences, University of South Florida, Tampa, FL, U.S.A. Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A. · Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. ·Anticancer Res · Pubmed #26254348.

ABSTRACT: BACKGROUND: Pancreatic cancer is a highly lethal cancer due to early metastasis and resistance to current chemotherapeutic agents. Abnormal protein kinase B (AKT) activation is an important mechanism of chemoresistance to gemcitabine, the most widely used agent in pancreatic cancer. MATERIAL AND METHODS: In the study, we tested the hypothesis that combining an AKT inhibitor with gemcitabine would augment anti-tumor activity. We treated human pancreatic cancer MiaPaCa-2 cells with gemcitabine and the AKT inhibitor triciribine, alone and in combination, and evaluated treatment effects using trypan blue assay, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium (MTT) assay, and cell death enzyme-linked immunosorbant assay. Colorimetric data of MTT assay were computationally analyzed for synergism of the combination therapy by CalcuSyn2 (Biosoft, Great Shelford, Cambridge, UK). RESULTS: Both gemcitabine and triciribine inhibited cell growth in a dose-dependent manner. Triciribine synergistically enhanced the cytotoxic activity of gemcitabine. The combination index (CI) provides the synergistic, additive, or antagonistic effects of the two-drug combination. CI at the 50% effective dose at 1:500 ratio of gemcitabine to triciribine was 0.74, indicating the synergistic effect of the drugs. The combination treatment with the non-apoptotic dose of each agent distinctly induced apoptosis, with gemcitabine in combination with triciribine, synergistically inhibiting pancreatic cancer cell growth and inducing apoptosis. CONCLUSION: These findings support the use of triciribine to overcome activated AKT-mediated resistance of pancreatic cancer to gemcitabine.

13 Article PET/CT Fusion Scan Prevents Futile Laparotomy in Early Stage Pancreatic Cancer. 2015

Kim, Richard / Prithviraj, Gopi / Kothari, Nishi / Springett, Greg / Malafa, Mokenge / Hodul, Pamela / Kim, Jongphil / Yue, Binglin / Morse, Brian / Mahipal, Amit. ·From the *Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; †Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; ‡Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. ·Clin Nucl Med · Pubmed #26053713.

ABSTRACT: BACKGROUND: Surgical resection with negative margins is the only curative approach for pancreatic cancer. A paucity of data exists in using PET/CT scan as staging workup in resectable pancreatic cancer. The aim of this study is to determine if PET/CT prevents futile laparotomy by detecting occult metastatic disease in patients with resectable or borderline resectable pancreatic cancer. METHODS: Patients were included using institutional PET/CT data base incorporating National Oncologic PET Registry with diagnosis of resectable or borderline resectable pancreatic cancer from 2005 to 2012. Clinical, radiographic, and pathologic characteristics were evaluated. The impact of PET/CT on patient management was estimated by calculating the percentage of patients whose treatment plan was altered secondary to PET/CT. RESULTS: We identified 285 patients with early stage pancreatic cancer who received PET/CT as part of initial staging workup. Upon initial workup (CT + EUS), 62% of patients were considered resectable, and 38% were borderline resectable. Addition of PET/CT scan changed the management in 10.9% (n = 31) of the patients (95% CI, 8%-15%). Metastatic lesions were confirmed with biopsy in 19 patients (61%). The proportion of change in treatment plan was significantly higher in patients who were initially considered to have borderline resectable compared with resectable malignancy (17% vs 7%, P = 0.019). In 199 patients who underwent surgery, 18.1% (n = 36) were found to have metastatic disease intraoperatively. CONCLUSIONS: PET/CT helped improve detection of occult metastases, ultimately sparing these patients a potentially unnecessary surgery. The role of PET/CT scan should be validated in prospective study.

14 Article Predictive and prognostic roles of ribonucleotide reductase M1 in resectable pancreatic adenocarcinoma. 2013

Xie, Hao / Jiang, Wei / Jiang, John / Wang, Yixin / Kim, Richard / Liu, Xiaobo / Liu, Xiuli. ·Department of Anatomic Pathology, The Cleveland Clinic, Ohio, USA. ·Cancer · Pubmed #22736490.

ABSTRACT: BACKGROUND: Ribonucleotide reductase M1 (RRM1) is an important molecule in different types of cancer. The objective of this study was to evaluate the predictive roles of RRM1 in the survival of patients with resectable pancreatic adenocarcinoma who received treatment with gemcitabine or nongemcitabine adjuvant therapy. METHODS: In total, 122 patients underwent tumor resection for pancreatic adenocarcinoma at the authors' institution from October 1999 to December 2007. Total RNA was isolated from microdissected, paraffin-embedded tumors. RRM1 expression levels were measured using quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and were dichotomized using recursive partitioning analysis. The Kaplan-Meier method was used to estimate overall survival and progression-free survival, and the predictive value of RRM1 expression on survival was examined using Cox proportional hazards regression. RESULTS: RRM1 expression did not have significant prognostic value in the entire cohort regarding overall survival (P = .2) or progression-free survival (P = .7). In the subgroup of 44 patients who received adjuvant gemcitabine, patients who had low RRM1 expression had longer overall survival (median, 47.8 months vs 14.1 months; P = .005) and a trend toward longer progression-free survival (median not reached vs 12.9 months; P = .06). In contrast, in the subgroup of 35 patients who received nongemcitabine adjuvant therapy, patients who had high RRM1 expression had significantly longer overall survival (median, 41.9 months vs 19.8 months; P = .01) and progression-free survival (median, 70.0 months vs 11.8 months; P = .04). These results were confirmed in Cox proportional hazards multivariable analysis. CONCLUSIONS: In patients with resectable pancreatic adenocarcinoma, low RRM1 expression in the tumor predicted an overall survival benefit of adjuvant gemcitabine; and high RRM1 expression predicted the survival benefit of nongemcitabine adjuvant therapy.

15 Article Harnessing gemcitabine metabolism: a step towards personalized medicine for pancreatic cancer. 2012

Saif, Muhammad Wasif / Lee, Yoomi / Kim, Richard. ·Director, GI Oncology Program, Tufts University School of Medicine, 800 Washington Street, Box 295, Boston, MA 02111, USA. ·Ther Adv Med Oncol · Pubmed #23118809.

ABSTRACT: Pancreatic cancer is a lethal malignancy with a 5-year survival rate of only 6%. Surgical resection remains the only cure, yet even after resection the 5-year survival is only 20% due to a high recurrence rate. Thus, a high proportion of patients with this disease will ultimately require systemic chemotherapy for advanced pancreatic cancer (APC). While the advent of personalized medicine has resulted in significant advances in the management of many cancer types, the standard of care for pancreatic cancer remains gemcitabine based, with very few exceptions. This article first aims to provide an overview of the benefits and limitations of gemcitabine alone, gemcitabine combinations, and different modes of administration of gemcitabine in APC. It then discusses research, suggesting that pharmacogenomic differences in enzymes that affect gemcitabine transport and metabolism can predict benefit from this drug in pancreatic cancer. Finally, the article outlines novel therapies and combinations that exploit these interindividual variations in gemcitabine metabolism to improve the efficacy of this drug in the management of APC.

16 Article Prognostic roles of human equilibrative transporter 1 (hENT-1) and ribonucleoside reductase subunit M1 (RRM1) in resected pancreatic cancer. 2011

Kim, Richard / Tan, Ann / Lai, Kevin K / Jiang, John / Wang, Yixen / Rybicki, Lisa A / Liu, Xiulu. ·Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA. Richard.kim@moffitt.org ·Cancer · Pubmed #21264835.

ABSTRACT: BACKGROUND: Pancreatic adenocarcinoma is a malignancy with a dismal prognosis. Previous studies have suggested that in pancreatic cancer, human equilibrative nucleoside transporter 1 (hENT-1) and ribonucleoside reductase subunit M1 (RRM1) expression may have prognostic value as well as predictive value with sensitivity to gemcitabine. This study investigated the prognostic value of hENT-1 and RRM1 expression in resected pancreatic cancer. METHODS: Eighty-four patients who underwent pancreaticoduodenectomy from 2000 to 2005 were included in this study. Patients were followed for a median of 60 months (range, 44-110). Total RNA was isolated from macrodissected paraffin-embedded tumors. hENT-1 and RRM1 expression levels in tumors were evaluated by quantitative reverse transcription-polymerase chain reaction (QRT-PCR), normalized to 2 reference genes, and expressed as ΔCt (low ΔCt means high expression). Univariate and multivariable prognostic factors for overall survival (OS) and progression-free survival (PFS) were identified via Cox proportional hazards analysis. RESULTS: Univariate analysis identified hENT-1, overall stage, lymphovascular invasion, perineural invasion, and adjuvant therapy as prognostic factors for both PFS and OS. Multivariate analysis confirmed the association of low expression of hENT-1 (ΔCt > 0.2027) (P = .007), perineural invasion (P = .021), and lack of adjuvant treatment (P < 0.001) with worse OS. Multivariate analysis also confirmed the association of low expression of hENT-1 (ΔCt > 0.5391) with worse PFS (P = .016) in addition to overall stage (P = .013), perineural invasion (P = .042), and lack of adjuvant treatment (hazard ratio 2.31, P = .029). RRM1 expression was not associated with OS or PFS in the current cohort. CONCLUSIONS: Low expression of hENT-1 was associated with worse OS and PFS in patients with resected pancreatic adenocarcinoma independent of gemcitabine therapy.

17 Article A single institution review of adjuvant therapy outcomes for resectable pancreatic adenocarcinoma: outcome and prognostic indicators. 2010

Kim, Richard / Tsao, Raymond / Tan, Ann / Byrne, Mike / Almhanna, Khaldoun / Lazaryan, Aleksander / Elson, Paul / Pelley, Robert J. ·Taussig Cancer Center, Cleveland Clinic, R35 9500 Euclid Ave, Cleveland, OH 44195, USA. KimR3@ccf.org ·J Gastrointest Surg · Pubmed #20446118.

ABSTRACT: INTRODUCTION: A large single-institution series of patients who recently underwent pancreaticoduodenectomy for resectable pancreatic cancer was analyzed to determine prognostic factors for overall survival, including the impact of adjuvant radiation and chemotherapy. METHODS: Medical records were reviewed for 179 consecutive patients treated at The Cleveland Clinic with pancreaticoduodenectomy for resectable pancreatic adenocarcinoma from 1999 to 2006. Clinical data were collected, and Kaplan-Meier method was used to estimate overall survival. Univariate and multivariate analysis was performed. RESULTS: One hundred seventy-nine patients with pT1-3N0-1M0 pancreatic cancer met the above criteria. But analysis was available for 158 patients. Median age at diagnosis was 67 (range 35-93). Peri-operative mortality rate was 0.6%. On univariate analysis, poor prognostic factors for overall survival were poorly differentiated histology, lymph node positive disease, elevated alkaline phosphatase, elevated total bilirubin, elevated AST, age at diagnosis >70, and high T stage. On multivariate analysis, poorly differentiated histology (p = .001), age >70 (p = .007), lymph node involvement (> or = 3 positive vs <3, p = .03), and elevated LFTs (alkaline phosphatase and/or bilirubin and/or AST; p = .002) were independent predictors of survival. Median survival for patients treated with adjuvant chemo-XRT was 28.4 months (vs. 11.8 months for patients receiving no adjuvant therapy (p < .001) in both univariate analysis and in multivariate analysis after adjusting for the independent prognostic factors described above). Median survival for patients treated with adjuvant chemotherapy alone had not yet been reached (p < .001 compared to no adjuvant therapy, in both univariate and multivariate analysis). CONCLUSION: In the twenty-first century, curative-intent surgery for pancreatic cancer at large academic institutions can have very low mortality rates. Pathology findings are valuable prognostic markers in resected pancreatic cancer. Few studies have examined the prognostic value of preoperative LFTs or lymph node ratio, and our analysis indicates they may have prognostic value-this should be confirmed in other series. Pts who receive adjuvant therapy (chemo-XRT or chemotherapy) appear to live longer than patients who receive no adjuvant therapy in this retrospective analysis.

18 Unspecified Is there a role for second line therapy in advanced pancreatic cancer? 2014

Choi, Minsig / Saif, Muhammad Wasif / Kim, Richard. ·Wayne State University, Karmonos Cancer Center. Detroit, FL, USA. choim@karmanos.org. ·JOP · Pubmed #24618429.

ABSTRACT: FOLFIRINOX (5-FU, oxaliplatin and irinotecan) and gemcitabine based regimens are widely used for the first-line treatment for patients with advanced pancreatic adenocarcinoma. Nab-paclitaxel and gemcitabine has replaced the use of many single agent gemcitabine in these patients population. In patients who progress on the first line therapy use of either 5-FU, leucovorin and oxaliplatin (FOLFOX) or gemcitabine and nab-paclitaxel combination has become a de facto standard depending on the chemotherapy they received in first line. Progress made in first line chemotherapy has lead to more interest in refractory pancreatic cancer. This article examines the 2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium regarding recent developments in the treatment of refractory pancreatic cancer, as these were presented in Abstracts #296, #297, #337, #344, and #381 of the meeting.