bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of erlotinib combined with adjuvant chemoradiation and chemotherapy for resectable pancreatic cancer.
Authors: Fan Katherine Y. , Wild Aaron Tyler , Laheru Daniel A. , Pawlik Timothy M. , Zheng Lei , Le Dung Thi , Tran Phuoc T. , Dholakia Avani Satish , Kumar Rachit , Ellsworth Susannah G. , Hacker-Prietz Amy , Rasheed Zeshaan , De Jesus-Acosta Ana , Weiss Matthew , Makary Martin , Cameron John L. , Hruban Ralph H. , Fishman Elliott K. , Wolfgang Christopher Lee , Herman Joseph M. 
Published: February 2017

269 Background: Amplification and overexpression of the EGFR gene and surface protein have been described in up to 80% of pancreatic tumors, making EGFR an attractive target in developing new adjuvant therapy for pancreatic adenocarcinoma (PDAC). Inhibition of EGFR has been suggested to provide additive activity when combined with capecitabine and radiation. Here we evaluate the antitumor activity and toxicity profile of erlotinib combined with adjuvant chemoradiotherapy (CRT) and chemotherapy. Methods: 50 patients with resected stage I/II PDAC were enrolled in a phase II trial of adjuvant erlotinib and capecitabine administered concurrently with IMRT (50.4 Gy), followed by 4 cycles of erlotinib and gemcitabine. Results: Median length of follow-up was 18.2 months (IQR, 13.8-27.1). Seventy-nine percent of tumors were of the pancreatic head, 85% had nodal involvement, and 17% had positive margins. Median RFS was 15.6 months (95% CI, 14.1-17.1), local RFS 21.1 months (95% CI, 17.1-25.1), and OS 24.4 months (95% CI, 17.1-31.6). Local recurrence was only observed in 19% patients and synchronous recurrence in 8%. Patients with maximum tumor diameter of ≤3 cm showed superior RFS (17.9 vs. 14.0 months; P=0.049), as did patients with cutaneous reaction to erlotinib (16.3 vs. 9.3 months, P=0.021). Superior OS was associated with less than median (32.3U/mL) pre-CRT CA19-9 values (28.2 vs. 19.0 months, P=0.012). During CRT, 31% patients experienced grade 3 toxicity and 2% grade 4, while 31% patients required a treatment break/stopped treatment early. During post-CRT chemotherapy, 35% patients experienced grade 3 toxicity and 8% grade 4, while 30% required a dose reduction. Conclusions: Results of this phase II trial suggest erlotinib combined with standard adjuvant CRT and chemotherapy provides excellent local disease control and reasonable tolerability compared with existing adjuvant regimens. Patients with maximum tumor diameter of ≤3 cm, cutaneous reaction to erlotinib, and less than median pre-CRT CA19-9 values appear to especially benefit from this new adjuvant regimen. Clinical trial information: NCT00962520.
Usefulness of FDG-PET in the evaluation of tumor response to proton beam therapy for locally advanced pancreatic ductal adenocarcinoma.
Authors: Shirakawa Sachiyo , Matsumoto Ippei , Terashima Kazuki , Shinzeki Makoto , Asari Sadaki , Goto Tadahiro , Mukubo Hideyo , Tanaka Masaki , Yamashita Hironori , Iwasaki Toshimitsu , Ishida Jun , Okazaki Taro , Kido Masahiro , Takahashi Masanori , Takebe Atsushi , Fukushima Kenji , Ajiki Tetsuo , Fukumoto Takumi , Ku Yonson 
Published: February 2017

271 Background: Evaluation of tumor response to radiation therapy in pancreatic ductal adenocarcinoma (PDA) using conventional radiological tests is difficult due to generally small size and inflammatory or fibrotic changes of radiated tissue. Although increasing evidence has shown that 18-F-fluorodeoxyglucose-positoron emission tomography (FDG-PET) can assess functional changes in various tumors, available data in PDA with radiation therapy is scarce. In this study, we investigated the role of FDG-PET in long-term monitoring tumor response to proton beam therapy (PBT) for PDA. Methods: Thirty-four locally advanced PDA patients with pre- and post-PBT FDG-PET data were included in this study. Local tumor responses by computed tomography (CT) and FDG-PET were defined as below: response group in CT (complete response: CR, partial response: PR, stable disease: SD, progressive disease: PD) was defined according to Response Evaluation Criteria in Solid Tumors, but only evaluation of primary tumor; and in FDG-PET, CR was defined as disappearance of FDG uptake, PR as decrease, SD as unchange, and PD as increase, compared to pre-PBT data. We evaluated tumor response at three different time points: 0-3, 3-6, and 6-12 months after PBT. Also serum CA19-9 values were evaluated. Results: Radiation doses were 50.4-70.2 GyE and 28 (82%) patients received concomitant chemotherapy. During the follow-up period (median 19 months), a total of 90 FDG-PET tests were performed. At the first time point, SD was noted in 90% (9/10) of patients by CT, whereas CR or PR in all by FDG-PET. At the second point, 39% (7/18) of patients demonstrated PR by CT, whereas 91% CR or PR by FDG-PET. Two patients with PD by FDG-PET were diagnosed as SD by CT, while one patient with PD by CT was diagnosed as PR by FDG-PET. At the third point, four patients with PD by FDG-PET were diagnosed as PR or SD by CT. Serum CA19-9 values supported FDG-PET findings. In four of 14 patients with serial FDG-PET, the maximum effects were noted at the second point. Conclusions: Serial FDG-PET can detect changes in local tumor response to PBT for PDA earlier and more sensitively than CT. Of note, there is the risk for false positive in early post-PBT FDG-PET.
Effect of the addition of platinum to gemcitabine on outcome in patients with advanced pancreatic cancer who progress on gemcitabine: A comprehensive analysis of published trials.
Authors: Rahma Osama E. , Liewehr David J. , Steinberg Seth M. , Duffy Austin G. , Greten Tim F 
Published: February 2017

275 Background: Pancreatic cancer is one of the deadliest cancers with an estimated 5 years survival rate of 5%. Until recently gemcitabine had been considered the first line treatment for locally advanced or metastatic disease. Although many chemotherapy regimens have been used there is no standard of care for second line therapy. The aim of this analysis was to identify superior regimen in the second line setting. Methods: We conducted a general search on PubMed for “second line therapy in advanced pancreatic cancer”. We limited our search to trials published in English from 2000 through 2012. Studies presented as abstracts in major meetings were also included. Trials that used targeted therapy other than erlotinib were excluded. We compared in an exploratory fashion the RR, PFS and OS of BSC and each of the following regimens to the rest of the treatments: 5FU+platinum, gemcitabine+platinum, taxol, erlotinib. In addition, we compared the combinations of platinum with either 5FU or gemcitabine. Finally, we explored the trend of these treatments outcomes over time. Results: Forty-four trialswere identified, of which 34 trials (T) met the inclusion criteria treating 1503 patients (N). There was a trend toward an improved overall survival with treatments (T: 33; N: 1269) compared to BSC (T: 2; N: 234) only (P= 0.013). The combination of gemcitabine and platinum (T: 5; N: 154) was the only regimen that showed a trend toward superior outcomes compared to the other regimens (T: 28; N: 1115) in terms of RR and PFS (P= 0.006 and 0.059, respectively). However, there was no difference in overall survival (P= 0.10). When compared to 5FU+platinum (T: 12; N: 450) the regimen of gemcitabine+platinum (T: 5; N: 154) showed only a trend toward significance in terms of improved RR (P= 0.030) with no difference in PFS or OS (P= 0.60 and 0.22, respectively). Overall, there was a trend toward a worse RR and PFS with no change in OS over the past 13 years. Conclusions: The combination of gemcitabine and platinum may provide a valid second line option in patients with locally advanced or metastatic pancreatic cancer who progress on gemcitabine.
Ablation for hepatocellular carcinoma: Validating the 3-cm breakpoint.
Authors: Groeschl Ryan Thomas , Gamblin T. Clark , Turaga Kiran 
Published: February 2017

277 Background: Although many previous studies on ablation outcomes for hepatocellular carcinoma (HCC) have dichotomized tumor size around a 3cm cutoff to determine prognostic significance, a growing number of reports describe excellent outcomes for larger tumors. To address the sensibility of this somewhat arbitrary 3-cm cutoff, we stratified patients by 1cm tumor size intervals and hypothesized that disease-specific survival (DSS) would not vary significantly between adjacent groups. Methods: Patients treated with local ablation for T1 HCC (≤8cm) were identified from the Surveillance, Epidemiology, and End Results database (2004-2008). Log-rank tests were used to compare DSS curves of adjacent study groups, and multivariable Cox proportional hazards models were used adjust for confounding variables. Results: There were 1,093 patients included in the study (26% female, median age: 62 years). The 3-year DSS was significantly lower in patients with 3-4cm tumors compared to 2-3cm tumors (58% vs 72%, p=0.002, Table). In adjusted models, DSS did not vary significantly between any size intervals up to 3cm. Patients with 3-4cm tumors, however, had a poorer prognosis compared to patients with 2-3cm tumors (hazard ratio: 1.60, 95% confidence interval: 1.18-2.18, p=0.002). DSS also fell significantly when tumor size increased from 5-6cm to 6-7cm (53% vs 21%, 0.006). Age and alpha-fetoprotein levels were also independently predictive of DSS in most multivariable models; however, the presence or absence of cirrhosis was not predictive in any models (smallest p=0.382). Conclusions: This study defends the use of a 3cm breakpoint when studying outcomes after ablation for HCC. Although some have advocated that ablation is more successful in cirrhotics, we found no evidence for this in our study. [Table: see text]
Characteristics and outcomes of patients with advanced hepatocellular carcinoma treated on phase I trials.
Authors: Subbiah Ishwaria Mohan , Janku Filip , Tsimberidou Apostolia Maria , Naing Aung , Kaseb Ahmed Omar , Hong David S. , Subbiah Vivek , Hess Kenneth R. , Akmal Owais , Falchook Gerald Steven , Kurzrock Razelle 
Published: February 2017

281 Background: Patients with advanced hepatocellular carcinoma (HCC) have limited effective therapies. With that purpose, we analyzed the outcomes and prognostic factors of such pts treated on phase I trials w an emphasis on locoregional and targeted agents. Methods: We reviewed the records of 100 consecutive pts referred to the Phase I Clinical Trials Program from March 2004 and assessed characteristics, types of clinical trials, progression-free survival (PFS), overall survival (OS) and oncogenic mutations. Results: Of 100 referred pts, 39 were not treated mainly due to poor performance status (n=22). Of 61 treated pts (49 male, 12 female, median age 60yrs), median # of prior therapies was 3 (range, 0-8). There were no treatment-related mortalities. One pt on a sorafenib regimen had g3 hand foot syndrome unresponsive to dose reduction. A 2nd pt developed a L-sided visual blurriness after 5 days on a sunitinib regimen; CT showed a small R parieto-occipital hemorrhage, possibly related to therapy. Of 61 treated pts, 7 (11%) had stable disease (SD) > 6 months, 4 (7%) partial response (PR), on protocols combining bevacizumab+sorafenib, pazopanib+everolimus, or single-agent novel oral multikinase inhibitor of VEGFR2-TIE2, or hepatic arterial infusion (HAI) of paclitaxel or oxaliplatin w IV bevacizumab. Median PFS on Phase I trials was 2.2 months vs. 4.4 months and 4.1 months for their 1st- and 2nd-line FDA-approved therapy (p 0.019). In univariate analysis, the presence of ascites, portal hypertension, cirrhosis, serum sodium, albumin, and poor Royal Marsden Hospital (RMH) prognostic score were associated with shorter PFS and OS (p < 0.05). On multivariate analysis, independent factors of shorter OS were Caucasian race (p = 0.031), cirrhosis (p = 0.016), serum sodium (p = 0.0013), and poor RMH prognostic score (p = 0.0015). Molecular analysis in progress will be updated. Conclusions: Phase I therapy offer a reasonable therapeutic option for patients with advanced HCC. The RMH prognostic score was validated in this population. The SD > 6 months/PR rate of 18% was observed with regimen of multikinase inhibitors with mTOR inhibitors and HAI therapy.
Results of adjuvant chemoradiation for gall bladder carcinoma: An institutional experience.
Authors: Mallick Supriya , Das Sudeep , Gandhi Ajeet , Joshi Nikhil Purushottam , Madan Renu , Mohanti B. K , Sharma Atul , Julka Pramod Kumar , Rath Goura Kishor 
Published: February 2017

288 Background: Adjuvant chemoradiation for gall bladder carcinoma is not a well established treatment modality. Methods: We retrospectively analysed our database between 2000 and 2011. All patients underwent surgery followed by adjuvant chemoradiation. The radiation dose was 45 Gy in 25 fractions planned by either conventional (2D) or 3 dimensional conformal radiation therapy (3D). Adjuvant chemotherapy was either Gemcitabine or 5 FU/leucovorin based. Log-rank test was used to compare survival distribution. The data was analysed using SPSS 16. Results: 75 patients were analysed. The median age was 48 years (range: 22 to 75 years). 16 males & 59 females were noted. 37 had well differentiated carcinoma while 38 had moderately differentiated carcinoma. The stage was IIIA or less in 45 patients and IIIB or more in 25 patients while it was unknown in 5. No patient had metastatic disease at presentation. 17 patients had a simple cholecystectomy, 57 had a radical cholecystectomy while status was unknown for 1. 25 patients had node negative disease while 50 had node positive disease. All patients received the prescribed radiation. 18 patients had 2D while 57 patients had 3D radiation. 13 patients had Gemcitabine based chemotherapy while 36 patients had 5 FU/leucovorin based chemotherapy. The status of chemotherapy was unknown for 26 patients. The median follow up was 12.7 months (range: 0 to 99 months). 22 patients relapsed. 2 patients had locoregional failure, 18 had distant failure while 2 had both locoregional & distant failure. The relapse free survival at 2 years was 57% and at the end of 6 years was 34%. Relapse free survival was significantly better for radical cholecystectomy vs. simple cholecystectomy (relapse free survival at 2 years 59.2% vs. 30.2 %; p = 0.054 on univariate analysis and relapse free survival at 2 years, 60% vs. 30%; p = 0.035 on multivariate analysis). Gender, tumor differentiation, nodal status, radiation technique and type of chemotherapy did not correlate with relapse free survival. Conclusions: Adjuvant chemoradiation resulted in excellent locoregional control. Radical surgery is an important factor for relapse free survival.
A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin in cancer patients.
Authors: Kanai Masashi , Otsuka Yoshihiko , Otsuka Kazunori , Nishimura Takafumi , Mori Yukiko , Matsumoto Shigemi , Kodama Yuzo , Kawaguchi MIchiya , Hatano Etsuro , Murakami Yoshiki , Imaizumi Atsushi , Chiba Tsutomu , Nishihira Jun , Shibata Hiroyuki 
Published: February 2017

290 Background: Curcumin is a natural polyphenol derived from turmeric (Curcuma longa). Growing preclinical data suggests that curcumin could be a promising anticancer drug, however, poor bioavailability has been a challenging problem for its clinical application. To overcome this problem, a new form of curcumin (Theracurmin) was developed using a microparticle and surface-controlled drug delivery system. We evaluated the safety and pharmacokinetics of Theracurmin in combination with gemcitabine-based chemotherapy in cancer patients. Methods: Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible. Planned Theracurmin doses comprised Level 0: 100 mg/body/day; Level 1: 200 mg/body/day; and Level 2: 400 mg/body/day. Level 1 was selected as a starting dose, and daily oral Theracurmin was added to standard gemcitabine-based chemotherapy. In addition to plasma curcumin levels, quality of life (QOL) score scaled according to the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30), NF-κB activity, cytokine levels (interleukin-6 and tumor necrosis factor–α), and efficacy were investigated. Results: We enrolled 16 patients between February 2011 and January 2012. Peak plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL (range: 47–1,029) at Level 1 and 440 ng/mL (range: 179–1,380) at Level 2. These values were significantly higher than those in our previous data achieved using 8 g of conventional curcumin. Long systemic exposure to high concentrations of curcumin did not increase the incidence of adverse events. Interestingly, fatigue- and functioning-associated QOL scores significantly improved after Theracurmin administration (p< 0.01). Conclusions: Up to 400 mg/body/day of Theracurmin could safely increase plasma curcumin levels in cancer patients receiving gemcitabine-based chemotherapy. Clinical trial information: 000002950.
Circulating biomarkers of sorafenib efficacy in advanced HCC.
Authors: Chelis Leonidas , Anagnostopoulos Kostantinos , Trypsianis Grigorios , Hamalidou Eleni Kyrillos , Xenidis Nikolaos , Amarantidis Kiriakos , Deftereos Savas , Pitsiava Dimitra , Michailidis Prodromos , Christakidis Evagelos , Michailidis Dimitrios , Matthaios Dimitrios , Koukaki Filio , Kortsaris Alexandros H. , Kakolyris Stylianos 
Published: February 2017

302 Background: Sorafenib represents the only drug with proven efficacy as first-line treatment of hepatocellular carcinoma (HCC). We analyzed 12 cytokines and growth factors related to angiogenesis, inflammation and cell proliferation and evaluated their possible utility as biomarkers of sorafenib efficacy in HCC. Methods: Our study population consisted of 62 HCC patients who received first-line sorafenib and 20 healthy controls. Material was collected at 3 different snapshots: (A) at baseline, (B) after 4 weeks on treatment, (C) at disease progression. Using commercially available ELISA kits we measured the serum levels of: VEGF-A, b FGF, sVEGFR2, Ang2, SDF1, VEGF-C, IL-6, IL-8, AFP, HGF, TSP1, BMP9 (bone morphogenetic protein 9). BMP9, a vascular quiescence factor, was explored for first time in HCC. Results: Patients had significant: (a) higher levels of Ang2, IL-6, IL-8, AFP, HGF, VEGF-A, FGFb , (b) lower levels of SDF1 than controls. At snapshot (B) we found a significant decrease of BMP9 and sVEGFR2 while a trend for significant increase was observed for VEGF-A, bFGF and IL-6. All statistically significant correlations for baseline levels of examined cytokines and their median change at week 4 with overall survival (OS) and progression free survival (PFS) are listed (Table). At disease progression (snapshot C) in comparison with baseline we found statistical significant: (a) increase for AFP, VEGF-A, bFGF, IL-6, (b) decrease for BMP9 and sVEGFR2. Conclusions: The values of circulating cytokines and growth factors examined in the present study showed frequent and statistically significant alterations during the disease course. Whether these factors could serve as potential biomarkers of sorafenib efficacy in HCC is something warranting further exploration and confirmation in bigger studies. [Table: see text]
A single-center experience of modified FOLFOX-6 in locally advanced and metastatic pancreatic adenocarcinomas.
Authors: Sumrall Bradley Thomas , Son Chang O , Fuloria Jyotsna , Satti Suma 
Published: February 2017

303 Background: Pancreatic adenocarcinoma has historically been as a disease with a poor prognosis with a 5 year survival rate of about 6%. The recently published ACCORD 11 trial demonstrated an improved overall survival utilizing FOLFIRINOX versus gemcitabine which has been the standard of care. However, FOLFIRINOX was associated with a significantly higher incidence of both hematologic and nonhematologic toxicities at the expense of increased toxicity. At our institution, FOLFIRINOX has been found to have a very similar toxicity profile with a significant impact on quality of life. For that reason, many patients at our institution have been treated with mFOLFOX6 with better tolerability instead of FOLFIRINOX in the palliative setting. Methods: We performed a retrospective chart review to analyze overall survival in patients withof unresectable pancreatic cancer (locally advanced and metastatic). Institutional tumor registry database was used to identify patients with unresectable pancreatic adenocarcinoma from January 2009 to March 2012. Medical records were reviewed to identify patients who were treated with at least 1 cycle of modified FOLFOX-6 as a line of treatment during their disease course. Overall survival was calculated for this cohort of patients. Results: 26 patients (15 male, 11 female) with unresectable pancreatic adenocarcinoma were identified. Mean age was 65.3 years. 19 patients had metastatic disease whereas 7 patients had locally advanced disease at diagnoses. Modified FOLFOX6 as a 1st line, 2nd line and 3rd line therapy was given in 17, 6 and 3 patients respectively. The median overall survival was 9 month while the mean survival was 10.6 months. 7 patients were treated with FOLFIRI as 2nd or 3rd line treatment. Nine patients are still alive. Conclusions: Modified FOLFOX-6 is an acceptable treatment for metastatic and locally advanced pancreatic adenocarcinoma. Even though our sample size is small, overall survival is comparable to that of FOLFIRINOX. A multi-institutional, randomized trial evaluating sequencing of mFOLFOX6 and FOLFIRI and comparing it with FOLFIRINOX would be useful.