bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant therapy (Adj) in intraductal papillary mucinous neoplasm cancer (IPMN-Ca) versus pancreatic ductal adenocarcinoma (PDAC): Comparison of survival analyses.
Authors: Krishna Kavya , Krishna Somashekar Gopala , Bloomston Mark , Muscarella Peter , Schmidt Carl Richard , Conwell Darwin , Bekaii-Saab Tanios S.
Published: February 2017

385

Background: Incidence of IPMN-Ca is increasing and due to lack of large prospective trials to evaluate optimal management of IPMN-Ca following resection, benefit of Adj is unknown. Methods: Retrospective review of patients (pts) who underwent pancreatic resection for invasive cancer from 2004 to 2012 at a single institution. Univariate and multivariate Cox regression models were used to determine association between different characteristics and survival. Results: From a total of 225 pancreatic resections (IPMN-Ca = 39, PDAC = 186), data regarding Adj was available in 179 pts (IPMN-Ca = 30, PDAC = 149). As shown in the Table, IPMN-Ca pts were less likely to receive Adj than PDAC (53% vs. 85% p = <0.001). There was no significant difference in tumor stage (stg) (early T vs advanced T) and Nodal stg (N0 vs. N1) distribution between pts who received Adj with IPMN-Ca or PDAC. Univariable survival analysis (SA): In PDAC, Adj improved overall survival (OS) (Hazard ratio [HR]: 0.46, 95% CI 0.28, 0.77), but there was no improvement in OS in IPMN-Ca pts with Adj (HR: 1.6, 95% CI 0.56, 4.64). Multivariable SA adjusting for age, Adj, resection margin, T, N stg: For PDACs, Adj was singularly associated with improved OS (HR 0.50, 95% CI 0.30, 0.82). In contrast, SA for IPMN-Ca did not reveal any significant contributing variable. For all pancreatic cancers, multivariable SA adjusting for IPMN-Ca vs. PDAC, age, Adj, resection margin, T, N stg revealed that a diagnosis of IPMN-Ca (HR: 0.52, 95% CI 0.30, 0.91) and a negative resection margin (HR: 0.65, 95% CI 0.43, 0.96) were significantly associated with better OS. Conclusions: Post resection, although pts with IPMN-Ca have better OS than PDACs, Adj fails to influence OS in IPMN-Ca pts. Larger studies are needed to confirm these findings. [Table: see text]
Octreotide LAR dosage and survival among elderly patients with distant-stage neuroendocrine tumors.
Authors: Shen Chan , Shih Ya-Chen T. , Xu Ying , Yao James C.
Published: February 2017

392

Background: Octreotide long-acting repeatable (LAR) is approved for the management of symptoms due to carcinoid syndrome and may delay tumor progression among patients with neuroendocrine tumors (NETs). It is unknown whether dosage of octreotide LAR has an impact on survival. The current analysis evaluates the impact of initial octreotide LAR dosage on survival of elderly patients with NETs. Methods: Distant stage NET patients diagnosed between 1/1999 and 12/2009 who had received octreotide LAR treatment within 12 months of diagnosis were identified from the SEER-Medicare database. Those under age 65, enrolled in HMOs, or without continuous enrollment in Medicare Parts A and B were excluded. We compared the five-year survival of NET patients based on dose per 28 days averaged over the initial 3 months: Group A, <= 20 mg; B, 21 to 30 mg; C, > 30 mg. Kaplan-Meier estimations and Cox proportional hazard modeling were used to examine the association between octreotide LAR dose and survival. Results: Among 214 distant stage patients (mean and median age at 74 years old) with octreotide LAR treatment, 73 (34%) received <= 20 mg, 82 (38%) received 21 – 30 mg, while 59 (28%) received >30 mg. Median survival for patients who received low, medium and high dosage levels were 20.8 (95% CI: 13.2 – 31.5), 32.6 (95% CI: 20.5 – 51.1), and 36.3 (95% CI: 24.8 – N/A) months respectively. The log rank test had a p-value of 0.006. Multivariate analyses showed that higher octreotide LAR dosage levels were associated with significant survival improvement for distant stage patients. Compared to patients with the low dosage level, patients with medium dosage (HR=0.52, P=0.002) and patients with high dosage (HR=0.48, P=0.004) had better five-year survival. The difference in survival between Groups B and C was not statistically significant. Conclusions: This population-based study suggests potential survival benefits for octreotide LAR 30 mg dosage level among elderly distant stage NET patients.
Quality of life in RCT of pasireotide to reduce pancreatic complications following resection.
Authors: Eaton Anne , Gonen Mithat , Karanicolas Paul Jack , D'Angelica Michael Ian , DeMatteo Ronald P. , Kingham T. Peter , Jarnagin William R. , Allen Peter J.
Published: February 2017

393

Background: A recent trial demonstrated that prophylactic pasireotide reduces pancreatic complication (PC) rates (primary objective). In this secondary analysis, we describe quality of life (QoL) in this population before and after resection using a standard instrument (the EORTC QLQ-C30) and the EORTC pancreatic cancer module (PAN26), which was recently developed to address the unmet need for QoL assessment in this subpopulation. Also of interest is assessing the association between PC and QoL and testing the hypothesis that pasireotide improves QoL. Methods: We conducted a randomized, double-blind, placebo-controlled trial of preoperative subcutaneous pasireotide in 300 patients undergoing pancreaticoduodenectomy or distal pancreatectomy. Participants completed the C30 and PAN26 preoperatively and on postoperative days 14 and 60. Scores were compared using paired t-tests. Results: All patients completed at least one questionnaire and 87% of patients completed all three. No major differences in QoL were seen between treatment groups so pooled results were reported. A significant worsening of function at 14 days was detected on all PAN26 and C30 function scales except hepatic and emotional functioning (EF), and all C30 symptom scales (all p<.01). These effects lessened by 60 days, but scores remained significantly worse than baseline with the exception of the sexuality, cognitive functioning, nausea and vomiting, insomnia and constipation scales, which returned to near baseline, and EF, which was significantly better than baseline (p=0.03). PC occurred in 45 patients and was associated with worse body image, dyspnea, financial difficulties and physical, role, emotional and social functioning at 14 and 60 days (all p<.05). Conclusions: During the first 14 days following resection, patients can be expected to have a significant decline in QoL. Many symptoms abate by 60 days, and EF improves. Although pasireotide effectively reduced PC, its effect did not appear to translate to improved QoL based on this sample of 300 patients. While PC was associated with worse QoL, most patients in both pasireotide and placebo groups did not experience PC, which may explain why no significant difference in QoL was observed. Clinical trial information: NCT00994110.
Characterization of unresectable cholangiocarcinoma patients treated with or without chemoradiation.
Authors: Rogers Jane Elizabeth , Nguyen Van , Nogueras-Gonzalez Graciela M. , Crane Christopher H. , Das Prajnan , Krishnan Sunil , Law Lindsey , Javle Milind M. , Kaseb Ahmed Omar , Shroff Rachna T.
Published: February 2017

403

Background: Curative treatment for cholangiocarcinoma (CC) is surgical resection. Unfortunately, most CC patients (pts) present with unresectable disease in which gemcitabine plus platinum (GEM-P) chemotherapy is the mainstay of treatment (tx). Advanced CC has a dismal prognosis with 5-year survival reported at 5-10 %. Data regarding chemoradiation (CRT) in pts with unresectable CC (uCC) remains limited. Methods: We retrospectively reviewed uCC pts from 1/1/2009 to 7/31/2013. Primary objective: to evaluate the percentage of pts treated with CRT and the median number of chemotherapy cycles given prior to CRT. Secondary objectives: response to first-line tx, progression free survival (PFS) with or without CRT, overall survival (OS) with or without CRT, and duration of CRT control. Inclusion criteria: uCC diagnosis, received tx, and had follow-up at our institution. Exclusion criteria: pts who received liver-directed therapy other than CRT, mixed histology tumors, and a history of other malignancies. Results: 114 pts were included with 62% having intrahepatic CC. Disease control (DC) (response + stable disease) with first-line tx was 75% with 71% receiving GEM-P +/- erlotinib first-line. 65% of pts received CRT with a median of 6 chemotherapy cycles given prior to CRT. DC after CRT was 62% with a median duration of radiation control of 6.4 mths. Median PFS and OS for all pts were 13.4 mths and 27.8 mths, respectively. Median PFS in the CRT group was 14.5 mths versus 11.4 mths in the no CRT group (p = 0.105). Median OS in the CRT cohort was 29.4 mths, while median OS without CRT was 22.4 mths (p = 0.005). Median OS and PFS after CRT for pts with DC on first-line tx were 32.0 months (95% CI = 24-44 mths) and 15.7 mths (95% CI =13.5-18.8 mths), respectively. Pts who progressed on first-line tx and received CRT had a median OS of 23.8 mths (95% CI = 7-30 months) and median PFS of 4.2 mths (95% CI = 2.3-9 mths). Conclusions: Our retrospective review reveals a significant improvement in median OS with CRT in uCC pts. Those with DC on first-line tx showed improvement in PFS and OS with CRT. Patient selection is key with the benefit being highest in pts with DC with first-line tx. Our results warrant further investigation of the role of CRT in uCC.
Factors associated with increased incidence of toxicities following administration of yttrium-90 resin microspheres.
Authors: Roberson John , McDonald Andrew M. , Baden Craig Joseph , Jacob Rojymon , Burnett Omer L.
Published: February 2017

409

Background: To further define factors associated with increased incidences of hepatic, constitutional, and gastrointestinal toxicities following administration of yttrium-90 (90Y) microspheres in a sequential cohort of heterogeneous patients. Methods: Fifty-seven patients who underwent 76 treatments were assessed for toxicity incidence following 90Y administration. Post-treatment clinical and liver function test (LFT) toxicities were assessed using Common Terminology Criteria for Adverse Events version 4.03. Binary logistic regression was used to evaluate the univariate effect of factors on toxicity incidences. A multivariate binary logistic regression model was performed for each toxicity using all factors with a p < 0.10 on univariate analysis. Results: Hepatic toxicities, including LFT toxicities, were present following 46.1% of treatments, while gastrointestinal and constitutional toxicities were present following 57.3% and 55.3%, respectively. Multivariate analyses revealed that colorectal adenocarcinoma, age at time of treatment, intraprocedural stasis, decreased Karnofsky Performance Status, increased body mass index (BMI), and decreased lung shunt were statistically significant (p < 0.05) predictors for increased incidence of toxicities most prevalent among our cohort. Increased pre-treatment laboratory values including albumin, alkaline phosphatase, total bilirubin, and white blood cells were also statistically significant predictors. Conclusions: Colorectal adenocarcinoma, declining functional status, decreased lung shunt, and increased pre-treatment laboratory values should be given more clinical attention when attempting to limit toxicities and improve the quality of life in patients following 90Y treatment. Specific constitutional, gastrointestinal, and hepatic toxicities including weakness, loss of appetite, and laboratory abnormalities are also associated with patients’ age, increased BMI, and intraprocedural stasis.
Predicting early mortality in resectable pancreatic adenocarcinoma: A cohort study.
Authors: Sohal Davendra , Shrotriya Shiva , Glass Katherine , Pelley Robert James , McNamara Michael J. , Estfan Bassam N. , Shapiro Marc A. , Wey Jane , Chalikonda Sricharan , Morris-Stiff Gareth , Walsh Matthew , Khorana Alok A.
Published: February 2017

414

Background: Overall survival after pancreatic cancer resection remains poor. A subgroup of patients die early (<6 months) and understanding factors associated with early mortality may help identify high-risk patients. The Khorana Score, including baseline hemoglobin, leukocyte and platelet counts, and body mass index [Khorana et al, Blood, 2008], has been shown to be associated with early mortality in solid tumors [Ay et al; Kuderer et al]. We evaluated the role of this score and other prognostic variables in predicting early mortality following resection. Methods: We conducted a cohort study of consecutive patients who underwent surgical resection for pancreatic cancer from January 2006 through June 2013 and were followed at the Cleveland Clinic. Baseline (diagnosis +/- 30 days) parameters were used to define patients as high-risk (Score >=3). Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted hazard ratios (HR) are presented. Results: The study population comprised 334 patients. Median age was 67 years; 50% were female; 86% were Caucasian. Pancreatic head was the primary site for 73%; 67% were T3 and 63% were N1 tumors. Median Khorana score was 2; 152 patients (47%) were high-risk. Adjunctive treatment included chemotherapy (70%) and radiation (40%). Post-operative (30-day) mortality was 0.9%. Six-month mortality for the entire cohort was 9.4%, with significantly higher rates for high-risk patients (13.4% vs. 5.6%, p=0.02). In univariable analyses, Khorana score, low hemoglobin, and elevated blood urea nitrogen (BUN) were associated with early mortality; T- and N-stage, as well as margin status (R0/R1), were not. In multivariable analyses (n=326), Khorana score (HR high-risk = 2.31, p=0.039) and elevated BUN (HR = 4.34, p<0.001) were associated with early mortality. Conclusions: Patients at high risk for early mortality after resection of pancreatic adenocarcinoma can be identified using simple baseline patient-related clinical and laboratory parameters rather than tumor characteristics. Future studies could evaluate the benefit of pre-operative interventions targeting patients at high risk for early mortality.
Surgical resectability after neo-adjuvant FOLFIRINOX for borderline or locally advanced pancreatic adenocarcinoma.
Authors: Alline Mathias , Colombo Pierre Emmanuel , Quenet François , Jarlier Marta , Portales Fabienne , Llacer Carmen , Fabre Jean Michel , Ychou Marc , Rouanet Philippe
Published: February 2017

421

Background: FOLFIRINOX has already demonstrated its efficiency in metastatic pancreatic cancer (PC). This combination need to be assessed in a neoadjuvant situation for locally advanced non metastatic PC. Methods: From 2009 to 2013, 31 patients with borderline or locally advanced PC received a neoadjuvant treatment with FOLFIRINOX so as to get them to a resectable situation. According to the tumoral response, chemoradiotherapy with gemcitabine was done. The primary analysis endpoint was the resecability rate. Pathologic response, chemotherapy’s toxicity and surgical morbidity were also evaluated. Results: Among the 31 PC, 17 were borderline resectable and 14 locally advanced according to NCCN classification. 16 (52%) received complete chemotherapy with a median of 4 cycles. Toxicity lead to treatment modification or interruption for 9 patients (29%). Grade 3-4 toxicity occurred in 7 patients (24%). 22 patients (71%) underwent chemoradiotherapy after FOLFIRINOX chemotherapy. 13 patients (42%) had disease progression under treatment whereas 18 patients with objective radiologic response or at least stable disease were surgically explored with a resection completed in 13 cases (42%). Surgical morbidity was controlled with grade 1-2 complications for 9 patients (69%) and no mortality. 11 patients (35%) demonstrated a significant pathologic response. Resected patients had a global survival median of 36 months. Conclusions: FOLFIRINOX in a neoadjuvant setting seems feasible with limited morbidity in locally advanced PC with encouraging resecability and pathologic response rates. Resected patients’ survival is promising but need to be confirmed in larger series.
The oncologic impact of pancreatic fistula after pancreatectomy in patients with pancreatic cancer.
Authors: Kawai Manabu , Murakami Yoshiaki , Hirono Seiko , Okada Ken-Ichi , Motoi Fuyuhiko , Unno Michiaki , Sho Masayuki , Nakajima Yoshiyuki , Uemura Kenichiro , Satoi Sohei , Kwon A-Hon , Matsumoto Ippei , Asari Sadaki , Honda Goro , Kurata Masanao , Yamaue Hiroki
Published: February 2017

426

Background: There is a few reports that evaluates the association between pancreatic and long-term survival after pancreatectomy in patients with pancreatic cancer. The aim of this study was to elucidate the oncological impact of pancreatic fistula (PF) on long-term survival after pancreatectomy in patients with pancreatic cancer by performing a survey of high volume centers for pancreatic resection in Japan. Methods: Between January 2001 and December 2012, 1,369 patients who underwent pancreatectomy for pancreatic cancer at 7 high-volume centers in Japan were retrospectively reviewed. Results: Pancreatic fistula(PF) occurred in 320 of 1,369 patients (23.5%), and these were classified based ISGPF as follows; grade A in 10.2%, grade B in 10.7%, and grade C in 2.6% of the patients. Median survival time (MST) in no fistula/grade A, grade B and grade C were 24.0, 26.3 and 11.0 months, respectively. MST in grade B PF was similar with that in no fistula/grade A. However, patients with grade C PF had a significantly poorer survival than those without (P<0.001). In the multivariate cox proportional hazard analysis, grade C PF was detected as an independent prognostic factor after pancreatectomy for pancreatic cancer (hazard ratio (HR) 2.15; 95% confidence interval (CI) 1.40-3.29; P< 0.001). Conclusions: Grade C PF adversely affects long-term survival of patients with pancreatic cancer undergoing pancreatectomy, although patients with grade B PF have similar prognosis with no fistula/grade A. Postoperative management to prevent grade C PF is important to improve prognosis in patients with pancreatic cancer undergoing pancreatectomy.
Efficacy trend of hepatic resection for hepatocellular carcinoma with large multinodular tumor or macrovascular invasion.
Authors: Zhong Jian-Hong , Li Le-Qun , Ye Xin-Ping , Ke Yang , Wang Lin , Wu Fei-Xiang , Xiang Bang-De , Ma Liang , You Xue-Mei , Chen Jie
Published: February 2017

427

Background: Official guidelines and retrospective studies have different view on the role of hepatic resection (HR) for patients with large (≥5 cm) multinodular (≥2) hepatocellular carcinoma (HCC) and those involving macrovascular invasion (MVI). We aim to evaluate the efficacy and its variation trend and the safety of HR for these patients in three tertiary care settings. Methods: A consecutive sample of 1,824 patients with Child-Pugh A liver function and large/multinodular HCC or involving MVI and who underwent initial HR were divided into four groups: large/multinodular HCC of the previous (2000-2004, n = 496) and recent five years (2005-2010, n = 765), involving MVI of the previous (n = 242) and recent five years (n = 321). Results: Among our patient sample, the hospital mortality was less than 5% and had a downward trend. Moreover, patients in recent five years have statistically significant longer survival time. Among patients with large/multinodular HCC, patients in recent five years showed a significantly better overall survival than those in previous five years at 1-year (92% vs. 84%), 3-year (69% vs. 61%), and 5-year (45% vs. 40%) (P = 0.004). Moreover, among patients involving MVI, overall survival in recent five years was significantly higher at 1-year (83% vs. 78%), 3-year (50% vs. 41%), and 5-year (25% vs. 17%) (P= 0.033). However, the disease-free survival of recent five years was only slightly higher than that of the previous five years in the two subgroups. Conclusions: HR offers good overall survival for patients with resectable large/multinodular HCC or those involving MVI and with preserved liver function. Outcomes have tended to improve in recent decade.
Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic cancer: Implications for adjuvant radiotherapy.
Authors: Osipov Arsen , Naziri Jason , Hendifar Andrew Eugene , Dhall Deepti , Rutgers Joanne K , Chopra Shefali , Li Quanlin , Annamalai Alagappan , Tighiouart Mourad , Nissen Nicholas N. , Tuli Richard
Published: February 2017

429

Background: Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assess the impact of these variables on clinical outcomes to identify the subset of patients who may benefit from adjuvant CRT. Methods: We identified 106 patients with resected stage 1-3 PDA from 2007-13. Resection margins were categorized as positive (tumor at ink), ≤ 1 mm, or > 1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), and presence of periportal adenopathy. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling. Actuarial estimates for DFS and OS were calculated using Kaplan-Meier methods. Results: Margin status was highly correlated with NP (p=0.012). Margin status adjusted for NP was a significant predictor of DFS in patients receiving adjuvant chemotherapy (CT) alone with greater margin clearance leading to improved DFS for all 3 groups (p=0.0412, HR = 0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (p=0.005). A median NR of 0.11 was associated with inferior DFS (p=0.0043; HR=4.04), but was not associated with OS. Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, p=0.0052; OS, p=0.023). The use of adjuvant CRT was associated with improved OS (p=0.049; HR=0.29). Conclusions: In patients receiving adjuvant CT alone, there was a clinically significant benefit in clearing the surgical margin beyond tumor at ink. Higher NR, having 5 or more NP and presence of periportal adenopathy clearly led to worse clinical outcomes. A more comprehensive evaluation of margins and LN parameters may identify an increasing number of patients at risk for locoregional failure who may benefit from adjuvant CRT.
Risks of severe adverse events of docetaxel, cisplatin, and 5-fluorouracil (DCF) combination chemotherapy of esophageal cancer.
Authors: Yuda Sayako , Kato Ken , Sasaki Yusuke , Takahashi Naoki , Shoji Hirokazu , Takashima Atsuo , Okita Natsuko T. , Honma Yoshitaka , Iwasa Satoru , Hamaguchi Tetsuya , Yamada Yasuhide , Nagashina Kengo , Boku Narikazu
Published: February 2017

43

Background: Although adding docetaxel to cisplatin plus 5-fluorouracil (i.e. the DCF regimen) for esophageal cancer treatment may improve outcomes, this regimen has increased toxicity. However, the risk factors for severe non-hematological toxicities remain unknown. Methods: We analyzed data on esophageal cancer patients given at least one cycle of DCF between July 2009 and April 2014 at the National Cancer Center Hospital, Japan. DCF consisted of docetaxel 70 mg/m2/day (day 1), cisplatin 70 mg/m2/day (day 1), and continuous infusion of 5-fluorouracil 750 mg/m2/day (days 1–5), repeated every 3 weeks. Data on adverse events developing within three cycles were collected from medical records. Risk factors for severe adverse events were analyzed. Results: One hundred patients were enrolled, with a median age of 63 (range, 37 to 76); 81 male and 19 female; 96 squamous cell carcinomas and 4 adenocarcinomas; clinical situation neoadjuvant/induction/palliative: 69/23/8/1; clinical stage I/II/III/IV: 1/12/64/23; and performance status (PS) 0/1/2: 44/55/1. Forty patients (40%) developed grade 3 or more non-hematological adverse events, including anorexia (12%), mucositis (6%), and esophagitis (2%); 45 developed grade 4 hematological adverse events. Seventeen experienced febrile neutropenia (FN). There was one case of treatment-related death from serious infection. In multivariate analysis, age≥63 was at significantly increased risk of FN (P=0.013). Conclusions: DCF chemotherapy was safe in most patients and its toxicity was controllable. However, elderly patients may suffer from intense toxicity during DCF therapy.
A phase II study of 5-FU/l-LV/oxaliplatin (mFOLFOX6) in patients with metastatic or unresectable small bowel adenocarcinoma: A post hoc analysis.
Authors: Funakoshi Taro , Horimatsu Takahiro , Nakayama Norisuke , Moriwaki Toshikazu , Hirashima Yoshinori , Fujita Mikio , Asayama Masako , Moriyama Ichiro , Nakajima Koji , Baba Eishi , Kitamura Hiroshi , Tamura Takao , Hosokawa Ayumu , Muto Manabu
Published: February 2017

430

Background: Small bowel adenocarcinoma (SBA) is a rare disease. Previous studies suggested several prognostic factors of unresectable SBA, including age, performance status (PS), primary site, resection of primary tumor, histology, and tumor marker (CEA and CA19–9) levels. However, prognostic factors of the patients treated with oxaliplatin–fluoropyrimidine combination therapy were unknown, while these drugs were reported as a promising chemotherapy regimen for SBA. Methods: Previously untreated SBA patients were treated with an mFOLFOX6 regimen, and a post hoc analyses for prognostic factors were performed. Results: Between April 2010 and November 2012, 24 patients were included in this study. The overall response rate was 45% (9/20). The median progression-free survival and overall survival (OS) were 5.4 months (95% CI, 4.8–6.0) and 17.3 months (95% CI, 11.7–19.0), respectively. Univariate analysis revealed that lower PS (HR= 0.27; 95% CI, 0.10–0.77; p= 0.014), primary disease of the jejunum (HR= 0.35; 95% CI, 0.11–1.12; p=0.077), and serum CEA in the normal range (HR= 0.40; 95% CI, 0.14–1.11; p= 0.079) were potential prognostic factors of longer OS (threshold, p< 0.10). Although resection of the primary tumor was not a predictive factor of survival in this study, 54% and 21% of the patients needed surgery (primary resection or bypass) because of stenosis before and during chemotherapy, respectively. It is considered that bowel obstruction should be addressed before and during treatment. Conclusions: PS, primary site, and serum CEA levels are potential prognostic factors of unresectable SBA. There is a higher incidence of bowel stenosis or obstruction caused by the primary tumor before and during the treatment of SBA.
Risk factors associated with overall survival (OS) in recurrent pancreatic adenocarcinoma (PAC) following curative resection (CR).
Authors: Ahn Daniel H. , Ahn Chul , Krishna Kavya , Krishna Somashekar , Muscarella Peter , Bloomston Mark , Bekaii-Saab Tanios S.
Published: February 2017

437

Background: Patients (pts) with localized pancreas cancer (LPAC) undergo CR with curative intent. Despite improvements in adjuvant treatment (trmt) and surgical techniques, the majority of pts succumb to recurrent disease (dx). The purpose of this study is to identify risk factors associated with OS in pts with recurrent PAC. Methods: Pt clinical and dx data was obtained by a retrospective review of patients with LPAC who underwent CR from 2004-2012 and had recurrent dx. Pts were subdivided into two groups, time to recurrence less/equal or greater than 6 months. Univariate and multivariate Cox regression models were used to determine the association between pt characteristics and OS. Results: 93 pts were identified with recurrent PAC. Select pt characteristics are listed in the Table. In univariate Cox models, only lymph node (LN) status is significantly associated with OS (HR 01.67; p=0.043). OS was 25.6 months (95% CI, 19.4-25.6) for LN positive tumors and 10.6 months (95% CI, 10.6-20.1) for LN negative tumors. In a multivariate Cox model adjusted for pt characteristics, LN status remained significant for OS (HR=1.67; p=0.043). Pts with early recurrent PAC (≤6 month) seem to follow patterns of distant metastatic dx while pts with later recurrence that of locoregional dx. Conclusions: LN involvement is associated with patterns of early recurrence with predominantly metastatic disease and decreased OS in pts with recurrent PAC. LN status may act as a surrogate marker for pattern of recurrence and merit consideration in the selection, stratification and trmt of patients in clinical trials. After CR, LN involvement may influence choice trmt and warrant more aggressive therapy. [Table: see text]
The significance of ascites in patients with pancreatic cancer: A case-control study.
Authors: Pulluri Bhargavi , Kathait Anjaneya , Tsai Hua-Ling , Blackford Amanda L. , Herman Joseph M. , Laheru Daniel A. , Zheng Lei , Le Dung T. , Rasheed Zeshaan , De Jesus-Acosta Ana
Published: February 2017

445

Background: Malignant ascites confers a poor prognosis in patients with metastatic pancreatic cancer (PC). It is unknown if radiographic ascites in patients with localized disease is a poor prognostic factor and if this finding should be sufficient to avoid upfront local therapies. We aimed to evaluate the survival outcomes of patients with PC and ascites. Methods: Retrospective case control study with overall survival as primary outcome. Eighty newly diagnosed PC patients with ascites (case group) and 80 similar controls without ascites were collected.Cases and controls were matched on age, gender, stage, ECOG performance, surgical treatment, lymph node status and margin status. Overall survival was compared between groups with Cox proportional hazards models by stages, and with a gamma frailty term to account for the correlation between matched pairs on entire cohort. Results: The 80 matched cases included 19 with resectable disease, 9 borderline resectable, 22 locally advanced and 31 with metastatic disease. 29 patients underwent pancreaticoduodenectomy. Table 1 summarizes the overall survival. Ascites patients had higher risk of death compared to patients without ascites (conditional hazard ratio = 1.58 (95% CI: 1.11-2.27), p=0.01). Conclusions: PC patients with ascites have poor overall survival compared to patients without ascites. Even in the setting of resectable disease, survival is similar to patients with advanced disease. This data suggest that all patients with ascites regardless of disease stage should be considered for systemic chemotherapy prior to attempting local treatments. [Table: see text]
Beneficial effects of perioperative chemotherapy for pancreatic cancer.
Authors: Kitago Minoru , Itano Osamu , Shinoda Masahiro , Yagi Hiroshi , Abe Yuta , Hibi Taizo , Kitagawa Yuko
Published: February 2017

448

Background: We retrospectively assessed the benefits of 5-fluorouracil (5-FU)- and heparin-based portal infusion chemotherapy (PI) combined with systemic administration of mitomycin C (MMC) and cisplatin (CDDP) for 4 weeks following surgery (PI4W). The goal was to determine if this treatment prevented liver metastasis and improved survival for patients with potentially curative resection of pancreatic cancer. Methods: 263 patients who underwent pancreatectomy from January 1985 to December 2013 were treated. Of these cases, 50 patients received portal infusion with 5-FU (250 mg/day) for 2 weeks (PI2W) following surgery (1985 `2001 Group A), while 94 patients received PI4W therapy (250 mg/day of 5-FU with 2,000 IU/day of heparin for 4 weeks, 4 mg MMC on days 6, 13, 20, 27, and 10 mg CDDP on days 7, 14, 21, 28)(2001 `2013 Group B). The remaining 119 patients (Ct) without adjuvant therapy during the perioperative period divided Group A (n=58) and Group B (n=61). Results: The cumulative overall survival rate in the PI2W was significantly higher than those in Ct of Group A. The cumulative overall survival rate in the PI4W also was significantly higher than those in Ct of Group B. Furthermore, in the PI4W group, the rate of liver metastasis is lower than Ct. Conclusions: PI therapy after surgery, especially PI4W, could become a promising adjuvant therapy in patients with potentially curative resection of pancreatic cancer. Clinical trial information: 000002976.
Significance as a recurrence predictor of postoperative neutrophil-lymphocyte ratio in patients with stage II/III gastric cancer: A retrospective study.
Authors: Tanaka Hiroaki , Muguruma Kazuya , Sakurai Katsunobu , Toyokawa Takahiro , Kubo Naoshi , Ohira Masaichi , Hirakawa Kosei
Published: February 2017

45

Background: Tumor markers such as carcinoembryonic antigen (CEA) and CA 19-9 are both widely used in the follow up of patients with gastric cancer. However, there are no definitive predictive markers for postopetrative recurrence. It has been reported that preoperative neutrophil lymphocyte ratio (NLR) was associated with prognosis of patients with gastrointestinal cancer. The aim of this study was to examine the impact of postoperative NLR on prediction for postoperative recurrence of gastric cancer. Methods: We retrospective reviewed data from 318 patients with Stage II/III gastric cancer who underwent curative surgical resection followed by adjuvant chemotherapy for between 2006 and 2013. Patients treated with preoperative chemotherapy or multiple cancers were excluded. Results: We found 118 recurrent diseases which mainly included 47 cases with peritoneal dissemination, 27 with distant lymph node metastasis and 24 with liver metastasis. Postoperative NLR was calculated every 6 months and the data at the time of recurrence or last survival were used for analysis. In univariate analysis, histological diffuse type, mascroscopical type 4 cancer, regional lymph node metastasis, lymphatic invasion in primary tumor, tumor diameter, elevated CEA or CA19-9, and elevated NLR were associated with poor prognosis. In multivariate analysis, we found that elevated CA19-9 and NLR were independent predictive markers. Increased NLR was associated with diffuse type, peritoneal dissemination, elevated CEA and preoperative NLR but not with adverse effect of adjuvant chemotherapy. Conclusions: The postoperative NLR might be one of the surrogate markers for recurrence after curative surgery for patients with Stage II/III gastric cancer.
Identifying factors impacting subsequent gemcitabine dose intensity in patients undergoing chemoradiation for locally advanced pancreatic cancer.
Authors: Shaikh Talha , Burki Meher , Wang Lora S , Egleston Brian , Hoffman John Parker , Cohen Steven J. , Meyer Joshua E.
Published: February 2017

455

Background: Systemic therapy is a critical part of the management of locally advanced pancreatic cancer (LAPC) due to the risk of distant failure. In the clinic, anecdotal evidence suggests that maintaining dose intensity of chemotherapy is more challenging after prior chemoradiotherapy (CRT). We thus evaluated whether treatment or patient factors limit the amount of systemic therapy received in LAPC patients receiving CRT. Methods: Following IRB approval, we retrospectively reviewed all patients diagnosed with LAPC undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of non-gemcitabine chemotherapy or chemotherapy prior to CRT. Patient and treatment factors were evaluated for their relationship to total gemcitabine dose received during CRT and within the first three months post-CRT. Statistical analysis was performed using regression models. Results: A total of 76 patients met the inclusion criteria with a median age of 69 (range 44-89) and a median follow-up of 13.2 months (range 3-68). The median gemcitabine dose received during CRT was 3,000 mg/m2 of a planned 3,600 mg/m2 and post-CRT was 5000 mg/m2 of a planned 9,000 mg/m2. Patients receiving a higher percentage of the desired chemotherapy dose during CRT received a lower percentage of desired chemotherapy dose post-CRT (p<0.01). Patients who underwent subsequent surgical resection (p<0.01) or received a higher radiation dose (p=0.03) were more likely to have received a higher total post-CRT chemotherapy dose. There were no variables correlated to chemotherapy dose received during CRT. Conclusions: Our analysis suggests that chemotherapy dosing during CRT rather than radiation dose impacts subsequent gemcitabine dose intensity. As a number of different CRT regimens are utilized in practice, this finding warrants further confirmation in a larger database.
The value of tissue protein expression as a predictor of efficacy for first- or second-line therapy (tx) in metastatic ductal pancreas cancer (PDAC) in patients (pts) receiving either gemcitabine (G)-based tx or 5FU (F)-based tx.
Authors: Carcas Lauren , Macintyre Jessica , Merchan Jaime R. , Hosein Peter Joel , Akunyili Ikechukwu Immanuel , Restrepo Maria , Garcia Monica T. , Portelance Lorraine , Sleeman Danny , Levi Joe U , Rocha Lima Caio Max S.
Published: February 2017

460

Background: No validated biomarkers exist to direct treatment decisions in PDAC. Decisions regarding tx choices are based on age, organ function, and performance status. Defining predictors of efficacy to F (alone or in combination) or G (alone or in combination) in PDAC are urgently needed. Histologic subtype by immunohistochemistry (IHC); pancreatobiliary type (PB), intestinal type (I), gastric type (Ga) and intestinal/gastric type (I/G); may predict benefit to G or F. Methods: Charts of PDAC pts from 2 institutions from 2007 to 2013 having both pathology specimen and a qualifying tx (FOLFIRINOX, FOLFOX, FOLFIRI, Capecitabine or G or G and nab-paclitaxel) were reviewed. IHC phenotypes were defined by staining >25% CDX2 = I, >25% MUC5 = Ga, >25% CDX2 and MUC5 = I/G, >25% MUC1 = PB. Results: 51 pts were identified. 4 cases had Stage II disease without recurrence after adjuvant tx and were excluded. 5 tumors were PB, 1 I, 3 I/G, 38 Ga. 41 (87%) had Ga or I/G type. Due to lack of statistical power for the other histologic subtypes, response to F or G was only analyzed in the 35 metastatic pts with the Ga subtype. 14 were metastatic at diagnosis. 24 males. Median age 57. 21 Hispanic, 14 Non-Hisp. The PFS for Ga treated with F based tx (>12 m) versus G (~9 m) based tx in the 1st line approached statistical significance (p=0.050). In multivariable analysis with adjustments for clinical stage, ECOG, age at dx, there was a significant lower risk of progression in pts treated with F based tx versus G based tx (HR=0.278, p=0.0315). Conclusions: There was near statistical significance favoring F based tx over G based tx in PDAC Ga subtype (p=0.05). Historically, G has proven superior to F as a single agent but our findings suggest F in combination may be superior to G in combination, at least for the treatment of Ga subtype.
Treatment of hepatocellular carcinoma using hypofractionated stereotactic radiosurgery.
Authors: Lederman Ariel Joseph , Loksen Mordecha , Lowinger Thomas , Izon Daniel , Lederman Gilbert S.
Published: February 2017

461

Background: Hypofractionated stereotactic Radiosugery (HFSR) is a non-invasive focused radiation treatment that delivers high dose therapy to cancer. HFSR for treatment of HepatocellularCarcinoma is analyzed in this prospective study. Methods: Twenty-three Hepatocellular Carcinomas (HCCs) were treated in 19 patients. All patients were prospectively evaluated before and after treatment. Age at treatment ranged from 11 to 84 years (mean 57) with 12 males and 6 females. Twenty-two percent of patients had prior chemotherapy, 17% had prior surgery and one patient had embolization. Tumor volumes ranged from 3 to 1,684cc (mean 312). The HCCs were treated with 500-800 cGy per fraction (median 600), in 5 or 6 fractions (median 5). For a total of 2,500-4,000 cGy (median 3,000). Cancers were followed with contrast CT and/or MRI scans and reviewed independently by radiologists. Control of the treated cancer is defined as cessation of growth, shrinkage or disappearance of the cancer after treatment. Results: Follow up ranged from 2 to 52 months. There was a 95.6% control rate at 14 months. By dose, volume, age, sex and prior treatment, there was no statistically significant difference in outcome. Conclusions: HFSR for HCCs is a generally well tolerated, non-invasive treatment modality with a high rate of local tumor control. Patients continue to be evaluated for longer follow up, progression free survival and overall survival. HFSR remains an attractive option for those in whom standard approaches have not produced desired results and for patients seeking an alternative to surgical or chemotherapeutic treatment.
Effect of metformin use on the survival outcomes in diabetic patients with resectable pancreatic cancer: A single-institutional experience and meta-analysis.
Authors: Ambe Chenwi , Mahipal Amit , Fulp William J. , Chen Dung-Tsa , Malafa Mokenge Peter
Published: February 2017

465

Background: Observational studies have shown that metformin use in diabetic patients decreases both cancer incidence and mortality. The aim of this study was to determine whether metformin use had a survival benefit in patients with resected pancreatic cancer. Methods: All patients with diabetes who underwent pancreatic resections for adenocarcinoma between 12/1/1986 and 4/30/2013 at our institution were identified. Patients were categorized by metformin use. Survival analysis was done using the Kaplan Meier method, with log rank test, and Cox proportional hazards multivariable regression models. The comprehensive Meta-Analysis version 2.2 was used to perform a meta-analysis using data from our study and the only other published study. Results: The study from our institution was comprised of 19 patients receiving treatment with metformin, and 25 patients not receiving metformin. There were no significant differences in major clinical and demographic characteristics between metformin and non-metformin users. The estimated median survival for metformin users was 35.3 months (95% CI 10.7 - not estimable) vs. 20.2 months (95% CI 14.4-58.6) for nonusers. The estimated 2, 3 and 5 year survival rates for non-metformin users were 42% (95% CI 22-62%), 28% (95% CI 7-55%) and 14% (95% CI 1-43%) respectively. Metformin users fared better with corresponding rates of 68% (95% CI 41-84%), 34% (95% CI 12-59%) and 34% (95% CI 12-59%) respectively. Metformin users had a 46% lower risk of death; hazard ratio 0.54 (95% CI 0.16-1.86) in a multivariate analysis, p = 0.3275. For the meta-analysis, there were a total of 111 patients from both studies. There were 46 metformin users and 65 nonusers. Metformin users had a 33% lower risk of death; the HR 0.668 (95 % CI 0.397-1.125), in a multivariate analysis p= 0.129. Conclusions: Although the findings of the current study suggests that metformin use does not significantly impact survival outcomes in diabetic patients with resected pancreatic cancer, there appears to be a clinically meaningful improvement in survival. The potential benefit of metformin should be investigated in adequately powered prospective studies.
Long-term survivors after sorafenib therapy in unresectable hepatocellular carcinoma.
Authors: Imura Satoru , Shimada Mitsuo , Morine Yuji , Ikemoto Tetsuya , Arakawa Yusuke , Iwahashi Shuichi , Saito Yu , Yamada Shinichiro , Shibata Hiroshi , Miyake Hidenori
Published: February 2017

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Background: Sorafenib is one of the standard therapies for unresectable HCC. Recently, so-called “conversion” cases, who had received curative resection after sorafenib therapy, have been reported sporadically. Here, we investigated outcome of sorafenib treatment and characteristics of long-term survivors. Methods: 1) Thirty-five patients with advanced HCC underwent sorafenib therapy were enrolled. 2) The data of 59 patients from main three hospitals in Tokushima were reviewed to study the characteristics of long-term survivors. Results: 1.) The median treatment period was 3.7mo. The 1-year survival rate was 58%. The rate of partial response was 9% and the rate of stable disease was 34%. These two patients were converted to the surgical resection after sorafenib therapy. Conversion case: 50-year old male with huge unresectable HCC underwent sorafenib therapy as initial treatment. Three months after sorafenib induction, main tumor was shrunken and some intrahepatic metastase were disappeared. Right lobectomy as curative resection could be performed. He has no recurrence for 2 years after surgery. 2.) Of 59 patients, over three-years survivors were four patients (L-group) and twenty-three patients were dead within 1 year after sorafenib induction (S-group). Between the two groups, there was no significant difference in age, gender, liver function, and tumor markers. Only the response to sorafenib was significant factors for long-term survival. Sorafenib administration was continued for more than 3 years in two patients of L-group, but withdrawn in two patients. However, other treatments such as TACE or radiation were done soon after withdrawal. Conclusions: Sorafenib combined with surgical treatment may contribute to improve prognosis of patients with initially unresectable HCC.
Risk factors for 6-month continuation of S-1 adjuvant chemotherapy for resected pancreatic cancer.
Authors: Katayama Yusuke , Aoyama Toru , Asari Masahiro , Murakawa Masaaki , Yamaoku Koichiro , Kanazawa Amane , Higuchi Akio , Shiozawa Manabu , Akaike Makoto , Ueno Makoto , Morimoto Manabu , Yamamoto Naoto , Yoshikawa Takaki , Rino Yasushi , Masuda Munetaka , Morinaga Soichiro
Published: February 2017

471

Background: The factors which affect the six-month continuation of adjuvant chemotherapy with S-1 have not been fully evaluated in pancreatic cancer. The objective of this retrospective study was to clarify the risk factors for the discontinuation of S-1 adjuvant chemotherapy after six months of treatment. Methods: The study included patients who underwent curative surgery for pancreatic cancer, were diagnosed with stage II or III disease, had a serum creatinine level < 1.2 mg/dl and received adjuvant S-1 between June 2007 and March 2014. Results: Forty patients were eligible for the present study. A comparison of the six-month continuation stratified by each clinical factor using the log-rank test revealed a significant difference in the creatinine clearance (CCr) between the patients who continued and discontinued the treatment. A CCr of 60 ml/min was regarded as a critical point. The uni- and multivariate Cox’s proportional hazard analyses demonstrated that the CCr was the only significant independent predictive factor. The six-month continuation rate was 70.8% in the patients with a CCr > 60 ml/min, and was 25.0% in patients with a CCr < 60 ml/min (P=0.008). The patients with a CCr < 60 ml/min developed adverse events more frequently and earlier than those with a CCr > 60 ml/min. Conclusions: A CCr < 60 ml/min was a significant risk factor for the six-month discontinuation of S-1 adjuvant chemotherapy in pancreatic cancer patients, even though the renal function was judged to be normal based on the serum creatinine level. Careful attention is therefore required to improve the S-1 continuation in patients with a CCr < 60 ml/min.