bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional survival probability of patients with resected pancreatic adenocarcinoma.
Authors: Mishra Mark Vikas , Champ Colin Eamon , Showalter Timothy Norman , Keith Scott W. , Anne Pramila R. , Bar-Ad Voichita 
Published: February 2017

284 Background: The purpose of this study is to evaluate conditional survival (CS) probabilities for patients with resected pancreatic adenocarcinoma (PC) amongst patients who have survived ≥1 more year(s) after diagnosis. Methods: Patients with resected PC from 1998-2008 were identified from the Surveillance, Epidemiology and End Results Database. Data on patient, tumor and treatment characteristics were extracted. Overall survival (OS) rates were calculated using the Kaplan-Meier method. A multivariate analysis (MVA) at different time points from survival was performed to determine independent prognostic factors associated with all-cause mortality hazard ratios (HRs) using Cox proportional hazards models. Results: A total of 4,883 patients with resected PC were identified. Fourteen percent of patients had Stage IA/B disease, 23% Stage IIA, 53% Stage IIB, and 2% Stage IIIA, and 6% with unknown stage. The 1-, 3-, and 5-year survival estimates for patients at diagnosis were 67%, 29%, and 21%, respectively. One, 3- and 5-year survival probabilities conditional upon number of years already survived are shown in table 1. Prognostic factors significantly correlated with improved OS at the time of diagnosis on MVA include: earlier stage, younger age, later year of diagnosis, white race, female gender, and residence in a high income district (p < 0.05). After already surviving 3 years following diagnosis, younger age was the only prognostic factor correlated with improved OS (p<0.05). Conclusions: CS estimates provide additional prognostic information that may be used to counsel PC patients on how their prognosis may change over time. Further research utilizing prospectively-collected data is warranted to help determine recommended follow-up intervals and benchmarks for future clinical trials. [Table: see text]
A phase II study to evaluate the safety and efficacy of RAD001 plus erlotinib in patients with well-differentiated neuroendocrine tumors (NET).
Authors: Bergsland Emily K. , Watt Lindsey , Ko Andrew H. , Tempero Margaret A. , Korn Wolfgang Michael , Kelley Robin Katie , Weber Thomas , Siah Iche , Hwang Jimmy , Nakakura Eric K. , Venook Alan Paul 
Published: February 2017

285 Background: Building on strong preclinical data, we hypothesized that concomitantly targeting mammalian target of rapamycin (mTOR) and epidermal growth factor receptor (EGFR) signaling pathways will inhibit neuroendocrine tumors (NET) more effectively than targeting either pathway alone (thus improving likelihood of shrinkage). We initiated a prospective, phase II study to assess the safety and efficacy of RAD001 plus erlotinib in patients (pts) with advanced NET. Methods: Pts with well-differentiated NET were enrolled using a Simon 2-stage design with 2 groups: pancreatic NET (PNET) and other low-grade NET/ carcinoid (CARC). Eligibility criteria included histological diagnosis of a well- to moderately-differentiated NET and no prior mTOR- or EGFR-inhibitor. Pts treated with RAD001 5 mg PO QD and erlotinib 100 mg PO QD without scheduled breaks (1 cycle = 28 d). Pts followed for toxicity and radiographic response, with first planned analysis after 8 evaluable pt/group. Results: Since 6/09, 17 pt enrolled: M/F 9/8; PNET/CARC 8/9. Pts on octreotide remained on drug. All pt had PD at enrollment. Median # cycles: 12 in CARC (range 2-20); 5.5 (to date) in PNET (range 0.5-18). Excessive toxicity in first 7 pts prompted reduction in starting erlotinib dose from 150 to 100 mg/d, resulting in improved tolerability: Gr 3 stomatitis in 3/7 initial pts (43%) vs 1/10 (10%) after new starting dose. Overall, the most common side effects include diarrhea, stomatitis, rash, anorexia, and fatigue. Enrollment to CARC cohort stopped after first stage due to insufficient efficacy (7/9 SD, 2/9 PD; 0 PR). Conclusions: RAD001 plus erlotinib appears to be associated with radiographic stability, but not shrinkage, in CARC. Combining the two agents has proven challenging; toxicity precludes administration of either agent at full dose. Interim efficacy analysis for PNET stratum pending. Correlation with expression of mTOR pathway components in archived tissue planned.
Retrospective review of doxorubicin plus sorafenib as second-line therapy in hepatocellular carcinoma (HCC).
Authors: Abou-Alfa Ghassan K. , Ma Jennifer , O'Reilly Eileen Mary , Gansukh Bolorsukh , Chou Joanne F. , Capanu Marinela , Saltz Leonard 
Published: February 2017

298 Background: Doxorubicin plus sorafenib has yielded an improved overall survival, progression-free-survival, and time-to-progression when compared to doxorubicin plus placebo, in the first line setting in patients with advanced HCC (Abou-Alfa, GK, et al. JAMA 2011). We explored the activity of doxorubicin and sorafenib following sorafenib failure. Methods: An IRB exemption was obtained to identify patients with HCC who were treated with doxorubicin and sorafenib after sorafenib failure. Demographic data, including age, gender, race, stage of disease, and risk factors were collected. Data were collected on treatment doses, duration, response, and adverse events including left ventricular ejection fractions (LVEF). Median progression-free survival (PFS) and overall survival (OS) were calculated from the start of combined therapy. Results: N=14 patients: Median age 60 years (range 43-70), median KPS 80%, 12 males (86%), 4 stage III (29%)/10 stage IV (71%), 8 HBV (57%) /3 HCV (21%). The median number of doxorubicin doses was 3 (range 1-11). Eight patients had grade 3-4 toxicities, including neutropenia, febrile neutropenia, thrombocytopenia, hepatitis B flare, dehydration, nausea, vomiting, mucositis, pain, and seizure. No >20% relative drops in LVEF from baseline were noted. There were no toxicity-related deaths. There were no objective responses. Of 14 evaluable patients, 5 (36%) had SD for ≥ 4 months, and 9 (64%) had POD. Median PFS was 3.4 months (95% CI 2.30-8.36), and OS 10.1 months (95% CI 4.34-11.45). Conclusions: In this small retrospective review of a select group of patients, doxorubicin plus sorafenib was tolerable, albeit with substantial toxicity. Doxorubicin and sorafenib may have activity after sorafenib failure however whether this is due to a synergy between the drugs, or to doxorubicin alone, cannot be determined from this review. A formal evaluation of doxorubicin plus sorafenib versus doxorubicin alone, versus best supportive care in the second line setting is warranted.
Predictive value of KIT immunohistochemical staining for KIT mutations in patients with gastrointestinal stromal tumors (GIST): A systematic review.
Authors: Tun Nay Min , Villani Gina M. 
Published: February 2017

30 Background: Immunohistochemical staining for KIT (CD117) is used as part of diagnostic tool for GIST. Approximately 95% of GIST are known to be positive for CD117. Studies have shown that not all CD117-positive GIST carry KIT mutations nor does CD117 negativity rule out KIT or PDGFRA mutations. We performed a systematic review to investigate the positive and negative predictive values of KIT immunostaining for KIT mutations in GIST. Methods: A Medline search of the MeSH terms “KIT mutation” and “GIST” and “prevalence” yielded 54 articles from year 1999 to 2011. English language studies on GIST with data available for KIT immunostaining as well as KIT gene mutations were included. Studies lacking data on either CD117 positivity or KIT mutations were excluded. Immunostaining was done using Dako polyclonal rabbit antibody or PKCh monoclonal mouse antibody in eligible studies. Denaturing high-pressure liquid chromatography (DHPLC) was used to screen mutations in majority of eligible studies, and ABI Prism Genetic Analyzer to sequence DNA. Results: 6 studies including 708 CD117-positive GIST patients were eligible for analysis of positive predictive value of KIT immunostaining for KIT mutations and 5 studies including 47 CD117-negative GIST patients for negative predictive value. Many studies were excluded due to insufficient data on CD117 positivity or KIT mutational analysis. 72.8% of CD117-positive GIST tumors carried KIT mutations (exon 11 62.2%, exon 9 10.2%, exon 13 1.8% and exon 17 1%), and 4.1% harbored PDGFRA mutations. In contrast, 74.5% of CD117-negative GIST tumors did not have KIT mutations. 25.5% of CD117-negative GIST harbored KIT exon 11 mutations (no mutations in exon 9, 13 or 17 were observed). In addition, 30% of CD117-negative GIST were found to have PDGFRA mutations. Conclusions: PDGFRA mutations were found to be 7 times more common in CD117-negative than in CD117-positive GIST (30% vs. 4.1%). Over half (55.5%) of CD117-negative GIST carried KIT exon 11 or PDGFRA mutations. We recommend mutational analysis in all tumors clinically suspected of GIST and that are CD117-negative for two reasons: 1. in order to make a diagnosis, and 2. to help tailor therapy.
Margin status and neoadjuvant chemoradiation in patients with borderline resectable pancreatic cancer.
Authors: Papavasiliou Pavlos , Piposar Jonathan R , Arrangoiz Rodrigo , Chen Kathryn T , Zhu Fang , Chun Yun Shin , Hoffman John Parker 
Published: February 2017

304 Background: The objective of this study was to examine the effect of margin status and neoadjuvant therapy in determining outcomes for borderline resectable (BLR) pancreatic cancer and how neoadjuvant chemoradiation impacts margin of resection. Methods: A retrospective chart review was conducted to identify patients who underwent resection for BLR pancreatic cancer based on the AHPBA/SSO/SSAT consensus definition. Outcomes including overall survival (OS) and disease free survival (DFS) were determined based on margin status, location of positive margin (artery, vein, or pancreas), and receipt of neoadjuvant chemoradiation. Results: One hundred and three patients who met the definition of BLR pancreatic cancer and underwent resection between April 1993 and July 2010 were reviewed. Mean age at diagnosis was 65 with a median follow up time of 19.7 months. Neoadjuvant chemoradiation was administered in 49.5% of patients. Twenty-five percent of patients underwent portal and/or superior mesenteric vein resection, and 7% hepatic artery resection. Microscopic positive margin rate was 54%. Median OS was 17.2 months for patients with positive margins versus 24.9 months for patients with negative margins (p=0.003). Median DFS was 13.1 months for patients with positive margins versus 18.6 months for patients with negative margins (p=0.001). There was no difference in OS or DFS for patients with positive margins based on location or number of positive margins. Of the patients who received neoadjuvant chemoradiation, 61.7% had a negative margin of resection versus a 38.3% negative margin of resection rate for patients who did not receive neoadjuvant chemoradiation (p=0.02). Among patients with a positive margin, there was no difference in OS or DFS with or without neoadjuvant chemoradiation. Conclusions: A positive margin of resection, irrespective of location or number, is associated with worse outcome in patients with BLR pancreatic cancer. The use of neoadjuvant chemoradiation is associated with higher rates of margin free resection.
FOLFIRINOX in locally advanced or metastatic pancreatic cancer.
Authors: Faris Jason Edward , Hong Theodore S. , McDermott Shaunagh , Guimaraes Alexander R , Sahani Dushyant , Clark Jeffrey W. , Ryan David P. , Blaszkowsky Lawrence Scott 
Published: February 2017

313 Background: The recently published Phase III trial of 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) demonstrated improved survival compared to gemcitabine in good performance status (PS) patients with metastatic pancreatic cancer (Conroy et al, NEJM 2011). Less is known about the efficacy and tolerability with FOLFIRINOX in the non-clinical trial setting. In this retrospective analysis, we report our institutional experience with FOLFIRINOX. Methods: 29 patients with locally advanced or metastatic pancreatic cancer treated with FOLFIRINOX between July 2010 and April 2011 were used for this analysis. Clinical characteristics, and gradeable toxicities were tabulated, and formal radiographic review performed to determine best overall response rates (ORR). Results: 17 patients received FOLFIRINOX for metastatic disease and 12 patients for locally advanced disease. The median age of patients was 60 (range 39-76). 22/29 patients were men. 18/29 patients had received no prior chemotherapy. There was one patient with PS 2; all others had PS 0 or 1. 8/29 patients had biliary stents. Overall, 11 partial responses (PR) were observed (ORR 38%); 10/11 partial responses were in chemo-naïve patients, who had an ORR of 56%. In the metastatic setting, there were 6 PR, for an ORR of 35%, and 7 patients with stable disease (SD). In the locally advanced setting, there were 5 PR (ORR 42%), and 7 patients with SD. Following treatment with FOLFIRINOX, one patient with locally advanced disease has subsequently undergone R0 resection. The median number of cycles performed was 8 in both the locally advanced and metastatic settings. 12/29 patients required an ED visit or hospitalization during treatment. Grade 3/4 neutropenia was observed in 10 patients; 7/10 had not received prophylactic growth factor treatment from the start of FOLFIRINOX. 4 patients developed febrile neutropenia, 4 patients developed grade 3/4 thrombocytopenia, and 1 patient developed grade 4 anemia. Conclusions: In a non-clinical trial setting, FOLFIRINOX demonstrated activity in both the metastatic and locally-advanced settings. FOLFIRINOX appears to be associated with manageable, but significant toxicities, with over 40% of patients requiring hospitalization.
Helical tomotherapy and concurrent gemcitabine-based chemotherapy for locally advanced pancreatic cancer.
Authors: Seong Jinsil , Chang Jisuk , Song Siyoung , Keum Woong 
Published: February 2017

318 Background: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between May 2006 and May 2009. Radiotherapy was directed to the primary tumor with a 0.5 cm margin without prophylactic nodal coverage. Twenty nine patients (79%) received full-dose (1000 mg/m2) gemcitabine based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range 3.4-43.9) for the entire cohort, and 22.5 months (range 12.0-43.9) for surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (20%) were converted to resectable status, including one with a pathologic complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than grade 3. Severe late GI toxicity (≥ Grade 3) occurred in 10 patients (26%); one treatment related death due to GI bleeding was observed. Conclusions: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.
Multiple utilities of portal vein embolization for patients with hepatocellular carcinoma.
Authors: Beppu Toru , Okabe Hirohisa , Okabe Kazutoshi , Masuda Toshiro , Mima Kosuke , Imai Katsunori , Hayashi Hiromitsu , Doi, Koichi , Chikamoto Akira , Ishiko Takatoshi , Takamori Hiroshi , Baba Hideo 
Published: February 2017

319 Background: Portal vein embolization (PVE) is a multi-potential treatment for hepatocellular carcinoma (HCC). The aim of this study is to identify the efficacies of PVE for resectable and unresectable HCC patients. Methods: Until 2011, 668 HCC patients underwent hepatic resection and 102 HCC patients treated with PVE. PVE was performed with percutaneous and ipsilateral approach using ethanolamine oleate iopamidol. Preoperative future remnant liver volume (%LV) and functional liver volume (%FLV ) were assessed with our developed combined 99mTc- galactosyl human serum albumin (GSA) scintigraphy (SPECT)/CT system. In unresectable cases chemoembolization (TACE) was repeated after PVE. Results: 1. Comparison of %LV and %FLV after right-PVE (n=40). %FLV before PVE was significantly lower in PVE group (38%) compared to non-PVE group (58%), but increased remarkably after PVE (from 38% to 55%, P < 0.0001). Right hepatectomy was successfully completed in 10 patients based on %FLV, instead of conventional %LV. 2. Long-term prognosis after right-hepatectomy with /without PVE (n=60). The 3- and 5-year disease-free survival (DFS) rates in the PVE group were significantly greater than those in the non-PVE group (78% and 78% versus 20% and 0%, P = 0.01). The 3- and 5-year overall survival (OS) rates in the PVE group were also higher than those in the non-PVE group (72% and 72% versus 57% and 12%, P <0.05). By multivariate analysis, independent prognostic factors for DFS were application of PVE (HR3.59), Multiple tumor (HR3.57), Fibrosis stage F3–4 (HR2.81), and protein induced by vitamin K absence or antagonists-II (PIVKA-II) ≥678AU/ml (HR2.69). 3. Prevention of intrahepatic metastases in unresectable HCCs in hemi-liver (n=40). The 3-year intrahepatic recurrence rates in the non-portal-embolized area was 58.8% and 81.8%, and the 5-year OS was 38.2% and 8.5%, in the PVE/TACE group and TACE group, respectively. The former rates were sinificantly higher (P<0.05). Conclusions: PVE can improve resectability, and might improve disease-free and overall survival for patients with both resectable and unresectable HCC.
Accelerated fraction radiotherapy with concomitant capecitabine as neoadjuvant therapy of borderline resectable pancreatic cancer.
Authors: Chakraborty Samhita , Bauer Todd W. , Morris Monica M , Yarde Erin , Parsons J Thomas , Adams Reid B , Sanoff Hanna Kelly 
Published: February 2017

329 Background: Surgical therapy remains the only curative modality for pancreatic cancer, though survival remains quite poor even for patients with resected early stage disease. Better (neo) adjuvant therapies are needed to improve resectability rates for patients with borderline resectable pancreatic cancer and to prevent recurrence following resection. We undertook this pilot study to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in such patients. Methods: Eligible patients have histologically confirmed borderline resectable adenocarcinoma of the pancreas as defined by the MD Anderson categories of vascular involvement, indeterminate metastatic disease, borderline performance status; normal organ function; and no prior therapy for pancreatic cancer. Radiation is given as external beam radiation therapy to a dose of 50 Gy delivered in 20, 2.5 Gy fractions Mon-Fri using IMRT. If insurance denied IMRT, 3D conformal techniques with daily image guidance is permitted. Capecitabine is delivered as 825mg/m2 BID on radiation days. The primary outcome is to determine the frequency of treatment-related adverse events (AE). Planned enrollment is 40 pts. Results: 10 pts have enrolled to date. 8/10 received IMRT. This regimen has been exceedingly tolerable. Lymphopenia is the most common AE (n=10), grade 3-4 n=6. Other common toxicities were hyponatremia (n=6), fatigue (n=5). Grade 3 AE occurred in 8 pts, grade 4 in 3 patients. One pt had hemorrhage from a radiation induced gastric ulcer complicated by an MI. 5/10 pts had stable disease and were resected and 4/5 had an R0 resection. In the remaining 5/10 patients, disease progressed outside the pancreas and they are receiving palliative therapy. Conclusions: The combination of AFRT and capecitabine was well tolerated. Xenograft models derived from these patients’ tumors are being used to study molecular mechanisms of treatment resistance that could be targeted in a follow up phase II study building on this platform.
A prospective randomized controlled trial comparing 4-weekly versus 3-weekly adjuvant chemotherapy with gemcitabine after curative resection of biliary tract cancer.
Authors: Nakahira Shin , Kobayashi Shogo , Miyamoto Atsushi , Shimizu Junzo , Kashiwazaki Masaki , Ueshima Shigeyuki , Kim Yong-Kook, , Kitagawa Toru , Dono Keizo , Mori Masaki , Doki Yuichiro , Nagano Hiroaki 
Published: February 2017

345 Background: Resection of biliary tract cancer, employing pancreatoduodenectomy and major hepatectomy, is highly aggressive. Thus, postoperative gemcitabine cannot be administered employing a routine dosage protocol. We theorized that a 3-weekly protocol (days 1 and 8, every 3 weeks) of gemcitabine as adjuvant chemotherapy would be superior to the usually administered 4-weekly protocol (days 1, 8, and 15 every 4 weeks). Methods: The outcomes of 6 cycles of the 4-weekly protocol and 9 cycles of the 3-weekly protocol were compared in a prospective randomized clinical setting. The primary endpoint was the treatment completion rate, while secondary endpoints were adverse events and recurrence-free survival. Results: We enrolled a total of 27 patients. Only two patients (14%) on the 4-weekly protocol and three (23%) on the 3-weekly protocol (p=0.8099) completed treatment with no omissions and/or dose modifications. Most of the remaining patients (70%) experienced grade 3/4 neutropenia. Relative dose intensities were 72% and 78%, respectively, with the 4-weekly and 3-weekly protocols. Recurrence-free survival rates did not differ significantly between the two protocols. Conclusions: Contrary to our hypothesis, the 3-weekly protocol did not produce superior results in terms of completion, adverse events or recurrence-free survival rates as compared to the standard 4-week protocol.