Resected Pancreatic Cancer Patients Research Articles

Survival of resected and overall pancreatic cancer patients in Europe and USA in 2003-2014: An international large-scale population-based investigation.

e16251Background: Literature-recorded survival for overall pancreatic cancer (PaC) patients is dismal. This is the first international large-scale population-based study aiming at providing detaile...

Multiple defects in NK cells of surgically resectable pancreatic cancer patients can be reversed by ex-vivo stimulation

Abstract Tumor infiltrating lymphocytes (TILs) are found in advanced pancreatic ductal adenocarcinoma (PDAC) patients and shown to correlate with overall survival (OS) rate. Although majority of TILs consisted of CD8+/CD4+T cells, the presence of NK cells and their role in the pathogenesis of PDAC remains elusive. We performed comprehensive analyses of TIL and PBMC to explore the role of NK cells in the newly developed PDAC patients. Multiple defects in cell migration and effector function were observed in NK cells of patients’ peripheral blood. Extremely low frequencies of NK cells (<0.5%) were found in TILs of PDAC patients which was attributable not to low expression of tumor chemokines, but rather lack of the CXCR2 chemokine receptor. Forced expression of CXCR2 on patients’ NK cells rendered them capable of trafficking PDAC tumors. Furthermore, patients’ NK cells exhibited impaired cell-mediated killing against autologous PDAC tumor cells and failed to proliferate within hypoxic tumor microenvironment. Importantly, these defects can be overcome by ex-vivo activation of NK cells from PDAC patients. When the proliferative capacity of NK cells in vitro was used to stratify patients on the basis of cell expansion, a clear difference in DFS and OS was observed. Patients whose NK cells proliferated <250 fold experienced significantly lower DFS and OS than those expanded ≥250 fold. Multiple defects are observed in NK cells of PDAC patients. Ex-vivo activation of NK cells restores tumor reactivity and provides a therapeutic modality while their fold expansion can be a potentially significant prognostic indicator of OS and DFS in PDAC patients.

Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio as Prognostic Factors for Locally Advanced Pancreatic Cancer Patients

It is well known that locally advanced pancreatic cancer patients have a poor prognosis. Outcomes of these patients are not only determined by tumor characteristics but also by host-related factors. Recently, hematologic markers showing systemic inflammatory status such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have aroused much attention due to its potential to predict patient survival. In this study, we investigated whether pre-treatment NLR and PLR independently and combination of NLR and PLR would be significant prognostic factors for survival in locally advanced pancreatic cancer patients. A total of 497 locally advanced (borderline resectable and unresectable) pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) between January 2005 and December 2015 were included in this study. NLR and PLR prior to the start of treatment within 2 weeks were defined as pre-treatment NLR and PLR. We divided the patients with the median values of pre-treatment NLR and PLR; NLR < 2.44 group (n = 248), NLR ≥ 2.44 group (n = 249), PLR < 149 group (n = 248) and PLR ≥ 149 (n = 249) group. Overall survival (OS) and progression-free survival (PFS) were compared between each group for NLR and PLR. Additionally, we grouped the patients into 3 groups concerning both factors. Patients with NLR < 2.44 and PLR < 149 (n = 175), either NLR ≥ 2.44 or PLR ≥ 149 (n = 146), and NLR ≥ 2.44 and PLR ≥ 149 (n = 176) were evaluated for OS and PFS. Median overall survival was 15.7 months (range, 2.3-128.5 months). For NLR, the OS, PFS rates were significantly lower in the NLR ≥ 2.44 group, with 1-year OS rates of 67.9% and 61.5% (p = 0.003) and 1-year PFS rates of 38.1% and 32.4% (p = 0.003), for NLR < 2.44 and ≥ 2.44 group, respectively. The PLR ≥ 149 group also showed significantly poorer OS and PFS than PLR < 149 group. The 1-year OS rates were 68.1% and 61.3% (p = 0.029) and 1-year PFS rates were 37.9% and 32.5% (p = 0.027), for PLR < 149 and ≥ 149 group, respectively. When multivariate analysis was performed, NLR ≥ 2.44 remained as a significant adverse factor for OS (p=0.007) and PFS (p=0.026). PLR > 149 also proved to be a significant factor for poorer OS (p=0.03) and PFS (0.007). When both NLR and PLR were taken into account, NLR ≥ 2.44 and PLR ≥ 149 group showed the worst OS (p=0.008) and PFS (p=0.002) compared to the other two groups and remained significant after multivariate analysis for both OS (p=0.003) and PFS (p=0.003). Elevated pre-treatment NLR and PLR independently and in combination significantly predicted poor OS and PFS. The NLR or PLR can be easily measured using peripheral blood samples. Pre-treatment NLR and PLR could be useful prognostic factors for OS and PFS in locally advanced pancreatic cancer patients.

Portal vein/superior mesenteric vein resection in pancreatic cancer treatment in the elderly.

There is an increased interest in extending surgical criteria for pancreatic cancer by performing pancreaticoduodenectomy (PD) combined with portal vein (PV) or superior mesenteric vein (SMV) resection and reconstruction for borderline resectable patients. However, whether this procedure suitable for elderly patients remains unclear. Here, we studied cases of pancreatic cancer treatment in our medical center to evaluate feasibility and safety of this procedure in the elderly.Eighty-three patients 65 years of age or older who underwent PD from January 2009 to March 2014 were divided into 2 groups: PD only (Group A, 52 cases), and PD combined with PV/SMV resection and reconstruction (Group B, 31 cases). Surgical outcomes and survival rates were compared between groups. Information regarding preoperative, intraoperative and postoperative conditions, and follow-up visits were provided. The outcomes of postoperative complications and survival rates were investigated.No difference in the preoperative data was detected between 2 groups with the exception that the serum albumin level was significantly lower in Group B (P = .013), indicating more deteriorating health conditions in this group. Although intraoperative time and blood loss were higher in Group B (P < .001 and P = .048, respectively), the overall postoperative complications and survival curve showed no statistical differences between 2 groups with one exception in that there was higher incidence of intractable diarrhea in Group B (P = .034). The symptoms, however, resolved later on with conservative treatment. The median survival time for patients in this study was comparable to other reported PD treatments. There was zero postoperative mortality in both groups.PD combined with PV/SMV treatment did not lead to increased morbidity and motility in elderly patients 65 years of age and above. This procedure could provide a promising opportunity for borderline resectable elderly pancreatic cancer patients.

Treatment of resectable pancreatic head cancer

Pancreatic cancer is the highest degree of malignancy in the digestive system tumors, long-term prognosis is poor. Pancreatic head cancer has the highest proportion of pancreatic cancer, so its treatment is the focus of the treatment of pancreatic cancer.Radical pancreaticoduodenectomy is the hope of patients with pancreatic head cancer to be cured, but also is the most important treatment for patients with long-term survival. Choosing the appropriate surgical methods and techniques can improve the rate of radical resection of the tumor and reduce the postoperative complications. Combined with timely and appropriate adjuvant therapy, it may improve the quality of life and prolong the survival of resected pancreatic head cancer patients. Key words: Pancreatic neoplasms; Pancreaticoduodenectomy; Neoadjuvant therapy; Surgical procedures, operative; Pancreatic head carcinoma

P-204 - Skeletal muscle mass as a prognostic indicator in resected pancreatic cancer patients

P-204 - Skeletal muscle mass as a prognostic indicator in resected pancreatic cancer patients

Clinical implications of dihydropyrimidine dehydrogenase expression in patients with pancreatic cancer who undergo curative resection with S-1 adjuvant chemotherapy.

The predictive roles of dihydropyrimidine dehydrogenase (DPD) in patients who undergo curative resection and adjuvant chemotherapy with S-1, which is the oral 5-fluorouracil prodrug tegafur combined with oteracil and gimeracil, remain unclear. In the present study, the clinical data from 66 consecutive patients who underwent curative resection and received adjuvant chemotherapy with S-1 for the treatment of pancreatic cancer at Kanagawa Cancer Center (Yokohama City, Japan) from April 2005 to March 2014 were retrospectively analyzed. The association between the DPD status and the survival and clinicopathological features were investigated. Of the 66 patients, 34 patients exhibited positive DPD expression (51.5%). Although a significant increase in DPD expression in male patients was observed, no significant differences were identified for other clinicopathological parameters, including tumor factor or node factor, between the DPD-positive expression group and the DPD-negative expression group. The median follow-up period of the present study was 29.2 months. There was no significant difference in the 3-year overall survival (OS) rates following surgery, which were 12.6 and 14.5% in the DPD-positive and DPD-negative expression groups, respectively (P=0.352). However, in a subgroup analysis, a significant difference in the 3-year OS rates following surgery was noted, which were 58.9 and 14.5% in the DPD-high and DPD-low expression groups, respectively (P=0.019). The intratumoral DPD expression in curatively resected pancreatic cancer patients treated with S-1 adjuvant chemotherapy was identified to not be useful as a predictive marker, whereas the level of DPD expression is a potential predictive marker. The results of the present study require confirmation in another cohort or in a prospective multicenter study.

Outcomes of resectable and borderline resectable pancreatic cancer patients in rural practice.

e15712 Background: Accurate selection of patients based on radiological and biological variables is crucial to avoid over treatment and unnecessary R1 resection in pancreatic cancer (PC). Methods: We retrospectively investigated 73 patients diagnosed with PC treated between January 1998 to October 2015. We applied NCCN definitions for Resectable (RD), borderline resectable (BRD) and unresectable disease(URD). Logistic regression was used to identify significant indicators of R0 resection. Odds ratios were used to compare differences of overall survivability by R0 and No surgery. Fisher’s Exact Test was used for significance on all tabulated data. Wilcoxon Rank-Sum was used for the comparison of two medians and Kruskal-Wallis to compare more than two medians, and log-rank test was used to compare Kaplan-Meyer Curves. Results: Radiologically RD comprised 21% (15/73) of total cases, 80% (12/15) of these underwent R0 resection. URD comprised 79% (58/73). Patients presenting with abdominal pain were 2.5 times (Odds Ratio; p = 0.0275) more likely to be URD. The mean tumor size for R0 resectability was 2.28 cm (n = 12). The median CA 19-9 for URD was 1473 vs 162 for RD (p = 0.0124). Stage at presentation and resectability were statistically associated. (p = 0.0002): 100% of Stage 1 (n = 4) and, 27% of Stage 2, (11/41) were resectable. Twenty-three cases were identified as BRD, 21/23 received neoadjuvant chemotherapy, 47.83% had radiological PR, 28.26% had SD and 23.91% PD. There was no association between type of Neoadjuvant treatment (Chemo XRT vs Chemotherapy) and radiological response (p = 0.8798). None of the 21 BRD patients underwent surgery. Median Overall Survival for R0 resection was 22.3 months (95% CI 15.23, 36.50) vs. 5.1 who did not have surgery (95% CI 3.55, 7.57) (p = 0.0010). Conclusions: Nearly 80% patients identified as resectable on imaging underwent R0 resection. Although there were partial responses seen in BRD patients that underwent neoadjuvant treatment eventually none underwent R0 resection. Patients presenting with abdominal pain and high CA19-9 ( &gt; 1400 U/ml) are likely to URD. Early stage and R0 resection were associated with positive outcomes.

Survival of borderline resectable pancreatic cancer patients receiving neoadjuvant therapy and surgery

Survival of borderline resectable pancreatic cancer patients receiving neoadjuvant therapy and surgery

Real-world evidence (RWE) to show improved time to progression among resected pancreatic cancer (RPC) patients receiving adjuvant chemotherapy (adjch).

242 Background: Two recent clinical trials (IMPRESS and APACT) suggest the overall survival (OS) of patients with resected pancreatic cancer (RPC) is far longer than previously believed. Improvements in patient selection, intra/post-operative surgical care adjch are suggested as explanations for the improved OS. RWE of time to progression (TTP) from surgery were calculated to assess if the results of these trials are generalizable. Methods: RPC patients (ICD-9=157.x, excluding 157.4; CPT=48140, 48146, 48150, 48152-5) diagnosed between 03/2012-06/2015 were selected from the Inovalon More2 administrative claims database. Adjch was defined as initiating chemotherapy within 90 days of surgery. TTP was the time from surgery until the first claim for metastatic disease (ICD-9 =196.0-.3, .5-.6, 197.0-.8, 198.0-.8) using the Kaplan-Meier method. Patients without a metastatic diagnosis during their follow-up were censored at 12 months to adjust for underreporting of metastatic disease codes in claims. Results: 1,014 RPC patients selected. Mean follow-up time was 12.9 months (SD = 10.8). Mean age at diagnosis was 62.7 years (SD = 13.0) and 39.7% (n=403) had commercial insurance, 40.9% (n=415) Medicare and 18.5% (n=188) Medicaid. Of all RPC patients, 54.4% (n=552) received any chemotherapy of which 59.8% (n=330) was adjch; 37.4% (n=379) were diagnosed with metastatic disease at the time of or following resection. The rate of progression events was 40.5% (n=277) without adjch and 30.9% (n=102) with adjch (p&lt;0.01). Among all resected patients, median TTP was 15.7 months (95% CI: 13.8-26.0) with 93.7% (n=355) of progression events by 12 months. Median TTP was 20.4 months (95% CI: 15.5-NR) in patients receiving adjch vs 17.7 months (95% CI: 17.7-31.5) without adjch (p=&lt;0.0001). Conclusions: This analysis demonstrated a 2.7 month longer TTP for patients who received adjch compared to those who did not (p&lt;0.0001). The median TTP in both adjch and non-adjch groups was longer than the observed in the ESPAC-1 trial for adjch patients TTP (15.3 months) and OS (20.1 months). These data support a new baseline for efficacy in adjch trials and are in line with more recent RCT estimates.

Propensity score matched analysis of neoadjuvant therapy for resectable pancreatic cancer.

381 Background: Neoadjuvant therapy (NT) for resectable pancreatic cancer continues to be debated. There is little data to demonstrate survival benefit over patients who were treated with up front surgery (UFS) vs NT. We sought to examine the impact of neoadjuvant chemotherapy (NCT), neoadjuvant chemoradiation (NCRT), and UFS on survival in pancreatic cancer patients. Methods: The NCDB was accessed to identify patients with pancreatic adenocarcinoma. Propensity score matching (PSM) was performed against age, tumor size, margin status, and institutional surgery volume. Patient characteristics (continuous and categorical variables) were compared using Mann-Whitney U, Kruskal Wallis and Pearson’s Chi-square test as appropriate. Survival analyses were performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) were developed to identify predictors of survival. All statistical tests were two-sided and α &lt; 0.05 was considered significant. Results: After PSM, 5,034 patients (UFS 2,517; NT 2,517: 1,143 NCT and 1,374 NCRT) were included in the analysis. There was no difference in age, tumor size, or grade among cohorts. The mean nodes positive were 1.6 ± 2.6 in NT and 2 ± 3.3 in UFS, p = 0.02. In the pre-matched cohort R0 resections were performed in 75.9% UFS, 82.9% NCRT, and 79.6% NCT, p &lt; 0.001. The median and 5 year survival for NCT, NCRT and UFS was 28.6 months and 25.2%, 25.7 months and 22.2%, and 21.3 months and 21.7%, p &lt; 0.001. Adjuvant therapy (chemotherapy (CT) or CRT) in the UFS did demonstrate a survival benefit 22.5 months vs 18.6 months, p &lt; 0.001, however this did not benefit NCT or NCRT, p = 0.8 and p = 0.8 respectively. Additionally survival in the UFS with adjuvant therapy either CT or CRT was still decreased compared to either NCT or NCRT, p &lt; 0.001 and p = 0.001 respectively. MVA demonstrated that age, T-stage, lymph nodes positive, R0 resection, grade, NCT and NCRT were predictors of survival. Conclusions: Neoadjuvant therapy improves survival in resectable pancreatic cancer patients. NCT and NCRT demonstrated survival benefit compared to UFS even with adjuvant therapy. Patients with resectable pancreatic cancer should be considered for neoadjuvant therapy.

The relationship between SPARC expression in primary tumor and metastatic lymph node of resected pancreatic cancer patients and patients' survival

Previous researches in pancreatic cancer demonstrated a negative correlation between secreted protein acidic and rich in cysteine (SPARC) expression in primary tumor and survival, but not for SPARC expression in lymph node. In the present study, we aimed to evaluate the SPARC expression in various types of tissues and its impact on patients' prognosis. The expression of SPARC was examined by immunohistochemistry in resected pancreatic cancer specimens. Kaplan-Meier analyses and Cox proportional hazards regression were applied to assess the mortality risk. A total of 222 tissue samples from 73 patients were collected to evaluate the SPARC expression, which included 73 paired primary tumor and adjacent normal tissues, 38 paired metastatic and normal lymph nodes. The proportion of positive SPARC expression in metastatic lymph node was high (32/38), whereas in normal lymph node it was negative (0/38). Positive SPARC expression in primary tumor cells was associated with a significantly decreased overall survival (P=0.007) and disease-free survival (P=0.003), whereas in other types of tissues it did not show a predictive role for prognosis. Univariate and multivariate analyses both confirmed this significance. SPARC can serve a dual function role as both predictor for prognosis and potentially biomarker for lymph node metastasis in resected pancreatic cancer patients.

The impact of SPARC expression in survival of pancreatic ductal adenocarcinoma patients after curative resection.

321 Background: The predictive roles of secreted protein acidic and rich in cysteine (SPARC) in resected pancreatic ductal adenocarcinoma (PDAC) patients have not been clarified. We investigated the correlations between the SPARC expression and the postoperative prognosis. Methods: We retrospectively analyzed the clinical data from consecutive patients who underwent curative resection for pancreatic cancer in our institution from 2005 to 2014. Stromal SPARC expression was analyzed by immunohistochemistry on tumor tissue microarrays (TMAs) from the patients. Results: 179 patients were enrolled to this study. The median follow-up period of the present study was 62.1 months. 70 patients had positive SPARC expression (39.1%). There were no significant difference between the positive SPARC expression group and negative group. In survival analysis, there was significant difference in the 5-year overall survival (OS) rates after surgery, which were 8.1% and 19.8% between the SPARC positive and negative groups, respectively (p = 0.0316). Univariate analysis showed SPARC expression, size of tumor, lymph node metastasis, and residual tumor as the possible prognostic factors. Multivariate analysis revealed SPARC expression (hazard ratio (HR) = 1.44 95%CI; 1.017-2.051), lymph node metastasis (HR = 2.019 95%CI; 1.318-3.091), and residual tumor (HR = 1.648 95%CI; 1.132-2.401)as the independent prognostic factor. Conclusions: Stromal SPARC expression in resectable pancreatic cancer patients might be useful as the predictive survival marker. The prognostic value of SPARC expression should be confirmed in another cohort or in a prospective multicenter-study.

Clinical implication of inflammation-based prognostic score and perioperative nutrition control in pancreatic cancer.

390 Background: Systemic inflammation and nutrition status are considered to influence survival in cancer patients. A variety of systemic inflammation-based prognostic scores have been explored; however, there has been no study to clarify which score could best reflect survival in resected pancreatic cancer patients. Methods: Between 2002 and 2016, 422 consecutive patients who underwent curative resection of pancreatic cancer were enrolled. The Glasgow Prognostic Score (GPS), modified GPS (mGPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic index (PI), and prognostic nutritional index (PNI) scores for each patients were calculated. Survival of each score was evaluated, and correlations between the score selected on the basis of the prognostic significance and various clinicopathological factors were analyzed. On the other hand, the nutrition markers (pre-albumin, transferrin, and retinol-binding protein) of 30 patients who received the enteral nutrition during the perioperative period were also evaluated. Results: In the analysis of the GPS, the median survival time (MST) was 29.4 months for score 0, 25.5 for score 1, and 17.7 for score 2 ( p&lt; 0.001), and mGPS was also found to be significant ( p= 0.003). On the contrary, there were no significance in MST between other scores (NLR, PLR, PI, or PNI). Multivariate analysis revealed that lymph node metastasis, positive peritoneal washing cytology, and a GPS score of 2 were significant prognostic factors. There was also statistically significant correlation between the GPS score and tumor location (head), tumor size ( &gt; 2.0cm), bile duct invasion, and duodenal invasion. In terms of nutrition status, the postoperative nutrition markers of 30 patients managed by enteral nutrition tended to recover earlier than 79 patients managed by intravenous nutrition. Conclusions: Our results demonstrated that the GPS could be an independent predictive marker and was superior to other inflammation-based prognostic scores in patients with resected pancreatic cancer. The results also suggested that perioperative nutrition support and infection control would improve survival of pancreatic cancer patients.

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors for locally advanced pancreatic cancer patients.

326 Background: It is well known that locally advanced pancreatic cancer patients have a poor prognosis. Recently, hematologic markers showing systemic inflammatory status such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have aroused much attention due to its potential to predict patient survival. In this study, we investigated whether pre-treatment NLR and PLR independently and in combination would be significant prognostic factors for survival in locally advanced pancreatic cancer patients. Methods: A total of 497 locally advanced (borderline resectable and unresectable) pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) between January 2005 and December 2015 were included in this study. NLR and PLR prior to the start of treatment within 2 weeks were defined as pre-treatment NLR and PLR. We divided the patients with the median values of pre-treatment NLR and PLR; NLR &lt; 2.44 group (n = 248), NLR ≥ 2.44 group (n = 249), PLR &lt; 149 group (n = 248) and PLR ≥ 149 (n = 249) group. Overall survival (OS) and progression-free survival (PFS) were compared between each group for NLR and PLR. Results: Median overall survival was 15.7 months (range, 2.3-128.5 months). For NLR, the OS, PFS rates were significantly lower in the NLR ≥ 2.44 group, with 1-year OS rates of 67.9% and 61.5% (p = 0.003) and 1-year PFS rates of 38.1% and 32.4% (p = 0.003), for NLR &lt; 2.44 and ≥ 2.44 group, respectively. The PLR ≥ 149 group also showed significantly poorer OS and PFS than PLR &lt; 149 group. The 1-year OS rates were 68.1% and 61.3% (p = 0.029) and 1-year PFS rates were 37.9% and 32.5% (p = 0.027), for PLR &lt; 149 and ≥ 149 group, respectively. When multivariate analysis was performed, NLR ≥ 2.44 remained as a significant adverse factor for OS (p = 0.011) and PFS (p = 0.026). PLR &gt; 149 also proved to be a significant factor for poorer OS (p = 0.003) and PFS (p = 0.021). Conclusions: Elevated pre-treatment NLR and PLR independently and in combination significantly predicted poor OS and PFS. Pre-treatment NLR and PLR are useful prognostic factors for OS and PFS in locally advanced pancreatic cancer patients.

Gemcitabine/taxane adjuvant therapy in resected pancreatic cancer: A signal of improved survival?

392 Background: Gemcitabine-taxane combination chemotherapy has demonstrated a survival benefit in metastatic pancreatic cancer (PC). We present our experience with gemcitabine/docetaxel (gem/tax) based adjuvant treatment (Rx) following curative intent surgery. Methods: Patients with upfront resectable PC from January 1, 2010 to December 31, 2015 were identified from our institutional database and tumor registry. We included resected patients who received gem/tax as initial Rx administered exclusively at our institution with or without chemoradiation (CRTx). Patients were excluded if they died or recurred prior to Rx or received neoadjuvant Rx. Survival was estimated by Kaplan-Meier methods and prognostic factors identified by Cox regression. Results: Of 185 eligible patients, 58 met study criteria. Characteristics included: median age of diagnosis 64.9 years, female gender 56.9%, Whipple procedure 69% and R1 resection in 55.2%%. Tumour characteristics included: median size 28.0mm, poor differentiation 53.5% and AJCC stage 2A/2B 27.6%/67.2%. Patients completing ≥ 80% of 24 week Rx was 89.7% (n = 52). Of those patients, 71.2% received post gem/tax CRTx. With a 51.2 month median follow-up (95%CI: 37.1-55.7), median disease-free survival (DFS) and overall survival (OS) were 35 months (95%CI: 20.7-NR) and 52.3 months (95%CI: 27.4-NR), respectively. Five year OS was 49.5% (95%CI: 33.7-63.4). Patients receiving CRTx (n = 37) had a superior OS compared to patients who only completed gem/tax Rx (n = 15)(61.5 vs. 26.7 months, p = 0.04). Prognostic variables impacting OS on multivariate analysis (HR, 95%CI) included: margin status (4.55, 1.46-14.2, p = 0.01), AJCC stage (10.9, 2.46-47.9, p = 0.002) and administration of CRTx (0.08, 0.03-0.24, p &lt; 0.000). Variables impacting DFS included: AJCC stage (3.29, 1.15-9.41, p = 0.03), tumour size (2.59, 1.11-6.04, p = 0.03) and administration of CRTx (0.23, 0.09-0.56, p = 0.001). Conclusions: In this select cohort of resected PC patients with adverse pathologic features, adjuvant gem/tax with or without CRTx is feasible with favorable DFS and OS. These findings support further prospective studies of gem/taxane-based adjuvant Rx in PC.

Frailty: A major consideration for short- and long-term outcomes in resected pancreatic cancer.

418 Background: Frailty has been associated with adverse postoperative outcomes. However, little is known about its correlation with survival in resected pancreatic cancer. This study examined the correlation of frailty with postoperative outcomes and survival after pancreatectomy for cancer. Methods: Data from National Surgical Quality Improvement Program (NSQIP) patients (n = 7400) who underwent pancreatectomy between 2011 to 2013. A modified frailty index (mFI) validated for use in NSQIP was used to examine correlations between frailty and postoperative outcomes. California Cancer Registry (CCR) data for patients (n = 4959) who underwent pancreatectomy for cancer between 2000 to 2012 was used to assess the association between the Charlson Comorbidity Index (CCI), as a surrogate for frailty, and overall survival. Results: The distribution of NSQIP patients according to the mFI was 0, 1, 2, 3, 4 in 2797 (37.8%), 3422 (46.2), 1074 (14.5), 104 (1.4) and 3 (0.04) respectively. The patients were divided to non frail (mFI = 0), mildly frail (mFI = 1-2), or severely frail (mFI3 ≥ 3). Overall, 8.7% of patients experienced a grade 4 Clavien complication and 3.1% experienced postoperative mortality. Worsening frailty correlated with an increase in grade 4 Clavien complications (non-frail: 6.3% vs. mildly frail: 9.7% vs. severely frail: 26.2%; p &lt; 0.001) and mortality (1.9% vs. 3.8% vs. 4.7% respectively; p &lt; 0.001). The majority of CCR patients had similarly few comorbidities: CCI: 0, 1, ≥ 2 in 3869 (77.8%), 861 (17.31%) and 243 (4.89%) respectively. Median survival decreased as CCI increased (for CCI 0, 1 and ≥ 2 was 23 vs. 19 vs. 15 months respectively; p &lt; 0.001). Conclusions: Frailty is a powerful correlate of postoperative outcome and survival for resected pancreatic cancer patients and is an important consideration in planning for surgical intervention.

Preoperative predictors for early recurrence of resectable pancreatic cancer

BackgroundThe first-line treatment for resectable pancreatic cancer (RPC) is surgical resection. However, our patients have often experienced early recurrence after curative resection for RPC, with desperately poor prognosis. Some reports indicated that minimally distant metastasis not detected at operation might cause early recurrence. The present study aimed to identify preoperative clinicopathological features of early recurrence after curative resection of RPC.MethodsNinety RPC patients who underwent curative resection between 2000 and 2014 at our institution were retrospectively analyzed.ResultsOf the 90 patients, 32 had recurrence within 1 year. Univariate analysis demonstrated that preoperative serum carbohydrate antigen (CA19-9) ≥529 U/mL (P = 0.0011), preoperative serum s-pancreas-1 antigen (SPan-1) ≥37 U/mL (P = 0.0038), and histological grades G2–G4 (P = 0.0158) were significantly associated with recurrence within 1 year after curative resection. Multivariate analysis demonstrated that preoperative serum CA19-9 ≥ 529 U/mL (P = 0.0477) and histological grade G2–G4 (P = 0.0129) were independent predictors of recurrence within 1 year. Recurrent cases within 1 year postoperatively had significantly more distant metastasis than cases with no recurrence within 1 year (P < 0.001).ConclusionsPreoperative serum CA19-9 ≥ 529 U/mL and histological grades G2–G4 were independent predictive factors for recurrence within 1 year after pancreatectomy for RPC. Furthermore, recurrent cases within 1 year had more frequent distant metastasis than cases with no recurrence within 1 year. These results suggest that RPC patients with preoperative serum CA19-9 ≥ 529 U/mL should receive preoperative therapy rather than surgery.

Association between metformin use and mortality in patients with type 2 diabetes mellitus and localized resectable pancreatic cancer: a nationwide population-based study in korea.

BackgroundPreclinical studies support an antitumor effect of metformin. However, clinical studies have conflicting results and metformin's effect remains controversial. The aim of this study was to evaluate metformin's effect on clinical outcomes in diabetic patients with pancreatic cancer treated with curative resection.ResultsA total of 764 patients underwent curative resection, met none of the exclusion criteria, and were prescribed oral hypoglycemic agents. The cancer-specific survival (5-year, 31.9% vs. 22.2%, p < 0.001) was significantly higher in the 530 metformin users than in the 234 diabetic metformin non-users. After multivariable adjustments, metformin users had significantly lower cancer-specific mortality as compared with metformin non-users (hazard ratio, 0.727; 95% confidence interval, 0.611–0.868). Cubic spline regression analysis demonstrated significantly decreased cancer-specific mortality with increasing dose of metformin (p = 0.0047).Materials and MethodsData were provided from the Korea Central Cancer Registry and the National Health Insurance Service in the Republic of Korea. The study cohort consisted of 28,862 patients newly diagnosed with pancreatic cancer between 2005 and 2011. Metformin exposure was determined from prescription information from 6 months before the first diagnosis of pancreatic cancer to last follow-up. The main outcome was cancer-specific survival.ConclusionsThis large study indicates that metformin might decrease cancer-specific mortality rates in localized resectable pancreatic cancer patients with pre-existing diabetes, independently of other factors, with a dose-response relationship.

The Significance of the Prognostic Nutritional Index for All Stages of Pancreatic Cancer

ABSTRACTNutritional status affects the prognosis of various tumors. The prognostic nutritional index (PNI) is the known predictor of postoperative outcome in resectable pancreatic cancer patients. This study aimed to validate the prognostic value of PNI in all stages of pancreatic cancer. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed at Severance Hospital between January 2006 and December 2011. The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm3) at initial diagnosis. The median patient age was 62 yr, and 289 were men. The study group comprised resectable disease (n = 121), locally advanced disease (n = 118), and metastatic disease (n = 260). Univariate and multivariate analysis revealed that PNI ≤ 49.5 at initial diagnosis, together with performance status, platelet count, and clinical stage, was significantly associated with overall survival (hazard ratio, 1.562; all P < 0.05). Patients with PNI ≤ 49.5 (n = 208) had shorter median overall survival compared to patients with high PNI (9.8 vs. 14.2 mo; log rank, P < 0.001). In clinical stage subgroup analysis, initial PNI ≤49.5 independently predicted shorter overall survival, especially in resectable and metastatic disease (P = 0.041, P = 0.002, respectively).