bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of adjuvant therapies on treatment outcomes for patients with resected gallbladder cancer and changes in treatment patterns in the United States over the past decade: An analysis from the National Cancer Data Base.
Authors: Mitin Timur , Enestvedt C. Kristian , Jemal Ahmedin , Sineshaw Helmneh M. 
Published: March 2017

391 Background: There are no randomized data to guide clinicians treating patients with gallbladder cancer (GBC). Several retrospective studies reported the survival benefits of adjuvant radiotherapy (RT) and chemoradiation (CRT). The aims of this study were to examine whether these publications have impacted the utilization of adjuvant therapies and whether their survival benefits were evident in contemporary cohort of patients. Methods: Using the National Cancer Data Base, we identified 5,029 patients diagnosed with T1-3N0-1 GBC and treated with surgical resection from 2005 to 2013. We described trends in receipt of adjuvant treatments for three time periods (2005-2007, 2008-2010, 2011-2013) and calculated 3-year overall survival (OS) probabilities for 2,989 patients treated in 2005-2010. Results: The percentage of patients who received no adjuvant treatment was unchanged from 2005 to 2013. Adjuvant RT decreased from 4.3% to 1.7% (p < 0.01), adjuvant chemotherapy increased from 8% to 14% (p < 0.01), and adjuvant CRT remained stable at 16% (p = 0.98). Even for locally advanced disease (T3N0 and T1-3N1) or in the setting of positive resection margins, over 50% of patients in US did not receive adjuvant treatments. Adjuvant treatments were associated with improved 3-year overall survival in patients with resected GBC, as listed in Table. Adjuvant CRT was associated with improved survival in all stages, except T1N0, and in patients with negative and positive margins. Conclusions: Over the past decade there was no increase in the utilization of adjuvant therapies in the US for patients with resected GBC. Adjuvant therapy is associated with significantly improved 3-yr OS. In the absence of randomized data, this analysis should form the basis for clinical recommendations and national guidelines should be amended to support adjuvant treatment.[Table: see text]
Outcomes of FOLFIRINOX (FFX) and gemcitabine+nab-paclitaxel (GnP) in initially unresectable locally advanced pancreatic cancer (uLAPC): A population-based study.
Authors: Chan Kelvin K. , Guo Helen , Beca Jaclyn Marie , Redmond-Misner Ruby , Isaranuwatchai Wanrudee , Qiao Lucy , Earle Craig , Berry Scott R. , Biagi James Joseph , Welch Stephen , Meyers Brandon , Mittmann Nicole , Coburn Natalie , Pardhan Aliya , Arias Jessica , Gavura Scott , Kennedy Erin Diane 
Published: March 2017

394 Background: Data regarding the benefits of FFX and GnP in patients (pts) with initially uLAPC is limited. FFX and GnP have been universally publicly funded for first-line uLAPC in Ontario, Canada, since April 2015. The aims of this study are to determine (1) the overall survival (OS) of pts receiving FFX and GnP, (2) the surgical conversion rate of FFX and GnP, and (3) whether resection is associated with better OS in pts with uLAPC in an unselected, real world population. Methods: All pts in Ontario who started first-line FFX, GnP or gemcitabine (G) for uLAPC between April 2015 and March 2016 were identified in Cancer Care Ontario’s New Drug Funding Program database. They were linked to the Ontario Cancer Registry and other population-based databases to ascertain baseline characteristics (age, sex, performance status (PS), locating of tumor, income quintile, and rural residence) and outcomes (pancreatic cancer resection and vital status). Crude and adjusted models of OS were generated using Kaplan-Meier the method and Cox regression. Surgical resection was modelled as a time-dependent variable to examine its association with OS. Results: We identified 147 pts with uLAPC (mean age = 65, 44% female, 31% ECOG PS 0, 61% PS 1, 60% pancreatic head). Ninety (61.2%), 40 (27.2%) and 17 (11.6%) patients were treated with FFX, GnP and G, respectively. With a median follow-up of 7.5 months, median OS was not reached. The 6-month OS rate was 87.8%, 75.1% and 76.4% for FFX, GnP and G, respectively (p = 0.33). Resection occurred in 12 (8.2%) patients, with 10 (11.1%) and 2 (5.0%) treated with FFX and GnP, respectively ( p= 0.34). Surgical resection after initial chemotherapy was not associated with better OS in multivariable analysis (HR 0.26, 95%CI 0.03-1.98, p= 0.19). Conclusions: Pts with uLAPC treated with FFX and GnP appeared to have a reasonable OS in the real world, with > 75% of pts alive at 6 months. Surgical conversion rate in this unselected population appeared to be less than other single institutional studies. The current findings do not appear to show an early surgical benefit, but longer follow-up will be required to assess the potential long-term benefit of surgery.
A randomized, double-blind, multicenter phase III study evaluating paclitaxel with and without RAD001 in patients with gastric cancer who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC).
Authors: Al-Batran Salah-Eddin , Riera-Knorrenschild Jorge , Pauligk Claudia , Goetze Thorsten Oliver , Hegewisch-Becker Susanna , Seraphin Jörg , Thuss-Patience Peter C. , Kopp Hans-Georg , Dechow Tobias Nicolaas , Vogel Arndt , Luley Kim Barbara , Pink Daniel , Stahl Michael , Kullmann Frank , Hebart Holger Frithjof , Siveke Jens T. , Egger Matthias , Homann Nils , Probst Stephan , Lorenzen Sylvie 
Published: March 2017

4 Background: There is a need for effective treatments in the second- or further line setting in advanced gastric cancer, especially for new agents. In the current trial we evaluated paclitaxel with RAD001 (everolimus) in patients with gastric carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen. Methods: This is a randomized, double-blind, multi-center phase III study. Patients with gastric carcinoma or adenocarcinoma of the esophagogastric junction which has progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomly assigned to receive Paclitaxel (80 mg/m2) on day 1, 8 and 15 plus placebo (arm A) or RAD001 (10mg daily, arm B) d1-d28, repeated every 28 days as 2nd, 3rd or 4thline therapy. Primary end point was overall survival (OS), secondary endpoints were best overall response, disease control rate, progression free survival (PFS) and toxicity. Results: 300 patients (median age: 62 years; median lines prior therapy: 2) were randomly assigned (Arm A, 150, Arm B, 150). Response rate (complete and partial response) was 8.0% (95%CI: 4.2%-13.6%) in the paclitaxel/RAD001 arm and 7.3% (95% CI: 3.7%-12.7%) in the paclitaxel/placebo arm (p = 0.4).There was no significant difference in median PFS (placebo, 2.07 vs. RAD001, 2.2 months, HR 0.88, p = 0.3) and median OS (placebo, 5.1 vs. RAD001, 6.1 months, HR 0.92, p = 0.48). Combination of paclitaxel and RAD001 was tolerable, but the placebo arm was associated with significantly less (any grade) mucositis (15.8% vs. 37.2%), fever (10.3% vs 20.7%), leukopenia (11.6% vs. 21.4%), neutropenia (13.0% vs. 27.6%) and thrombocytopenia (2.1% vs 14.5%). Conclusions: The addition of RAD001 to paclitaxel/RAD001 did not significantly improve outcomes in pretreated metastatic gastric or esophagogastric junction adenocarcinoma. Additional biomarker studies are planned to look for subgroups that may have a benefit. Clinical trial information: NCT01248403.
Pancreatic neuroendocrine tumors: A population-based analysis of epidemiology and outcomes.
Authors: Alsidawi Samer , Westin Gustavo Figueiredo Marcondes , Hobday Timothy J. , Halfdanarson Thorvardur Ragnar 
Published: March 2017

401 Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms comprising less than 2% of pancreatic tumors. Outcomes of PNETs vary by stage, grade, and clinical presentation. New therapies may have improved outcomes. We present an analysis of the epidemiology and prognosis of patients (pts) with PNETs evaluating a more recent period than previously reported. Methods: Using data from the SEER registry, we identified adults with PNETs between 2000 and 2013. Cases were identified using a combination of ICD-O-3 site and histology codes. The JMP and SEER*STAT 8.3.2 were used for statistical analysis. Overall survival (OS) was analyzed using the Kaplan–Meier method. The prognostic effect of variables was studied using multivariate Cox proportional hazards models. Results: We identified 5993 pts with PNETs. Over the study duration, there was an increase in the annual incidence from 0.3 to 1.2 per 100.000. This was largely explained by the increase in number of pts with localized disease. The OS for the entire cohort was 54 months (95%; CI 50-58) and 5-year OS rates in localized, locally advanced and metastatic disease were 81.7%, 62% and 26% respectively. New therapies were increasingly implemented after 2008 such as sunitinib, everolimus and capecitabine/temozolomide. OS was better for pts diagnosed after 2008 (HR 0.73; 95% CI, 0.69-0.79; P < 0.0001) and this remained significant after excluding pts with localized disease (HR 0.85; 95% CI, 0.78-0.92; P = 0.0002). Factors found to favorably affect OS included younger age, female sex, early stage, low grade, and surgery. In metastatic disease, pts who had surgery had better OS and this was significant after adjusting for possible confounders (HR 0.36; 95% CI, 0.3-0.45). Conclusions: In this large population-based study, we saw an increase in the annual incidence of PNETs mainly due to an increased number of pts with localized disease. The OS has improved over the study duration likely due to both stage migration and new therapies used in advanced disease. Younger age, female gender, low histologic grade, early stage and surgery were found to be factors that favorably affected survival. Surgery was found to be a predictor of better outcomes in metastatic disease.
A phase I/II study combining tosedostat with capecitabine in patients with metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: Wang-Gillam Andrea , Du Lingling , Teague Andrea S. , Suresh Rama , Lim Kian-Huat , Amin Manik A. , Pedersen Katrina , Tan Benjamin R. , Huffman Jess , Lockhart Albert C. 
Published: March 2017

410 Background: Recent advances in front-line therapy have improved survival in patients with advanced PDAC. A fluorouracil-based regimen is recommended for patients who progress on a gemcitabine-based therapy. Tosedostat is an oral aminopeptidase inhibitor that disrupts the cleavage of amino acids from peptides downstream of proteasomal degradation. It prevents the recycling of free amino acids, leads to intracellular depletion of amino acids, and triggers an amino acid deprivation response that subsequently results in apoptosis. Because PDAC cells frequently upregulate expression of these aminopeptidases, tosedostat offers therapeutic promise, particularly in combination with fluoropyrimidines. Methods: This is a single institution phase I/II trial to evaluate the safety and toxicity of tosedostat plus capecitabine in patients with metastatic PDAC progressed on a gemcitabine-based therapy. The phase I portion is being conducted in a dose de-escalation fashion, with two dose levels of tosedostat (120 mg or 60 mg) p.o. daily on days 1 to 21 with capecitabine 1000 mg/m2 p.o. BID on days 1 to 14 of a 21-day cycle. If more than one out of 6 patients in the tosedostat (120 mg) cohort experience a dose limiting toxicity (DLT), then 6 more will be enrolled to the tosedostat (60 mg) cohort. The primary objective of the phase I portion is to determine the optimal phase II dose. The primary objective of the phase II portion is to determine the progression-free survival at 3 months. Secondary objectives include the overall response rate, overall survival and CA 19-9 response. To avoid futility, interim analysis is planned after 10 evaluable patients enrolled. Results: Up to date, a total of 11 patients have been enrolled in the study, and 10 patients are evaluable. No DLT have been observed. Tosedostat at a dose of 120 mg with capecitabine is extremely well tolerated. Prolonged stable disease has been observed in 4 (40%) patients with a time on treatment of 10 months, 7.5 months, 5.5 months and 4 months, and 3 of the 4 patients remain on the trial. Conclusions: The combination of tosedostat and capecitabine is a well-tolerated regimen with impressive clinical activity in the subset of patients studied thus far. Clinical trial information: NCT02352831.
Health care costs and treatment patterns among metastatic pancreatic cancer (MPC) patients (pts) initiating first-line (1L) on nab-paclitaxel/gemcitabine (nab-P+G) or FOLFIRINOX (FFX).
Authors: McBride Ali , Bonafede Machaon , Cai Qian , Princic Nicole , Tran Oth , Pelletier Corey , Patel Manish 
Published: March 2017

415 Background: The economic burden of MPC is substantial while treatment options are limited. This study aimed to compare healthcare costs and treatment patterns in MPC patients who initiated nab-P+G or FFX in a large insured US population. Methods: A retrospective study was conducted using the Truven Health MarketScan administrative claims databases. Adults who had ≥2 claims for pancreatic cancer, ≥1 claim with a secondary malignancy, completed ≥ 1 cycle of nab-P+G or FFX as 1L during 1/1/2013 and 3/31/2015, and had continuous enrollment in health plans for ≥6 months prior to and 3 months following the start of 1L were selected. Total healthcare costs and MPC-related treatment costs were measured per patient per month (PPPM) during 1L. Kaplan-Meier curve was used to describe time to treatment discontinuation (TTD) between groups. Results: 550 MPC patients met selection criteria ( nab-P+G, n=294; FFX, n=256). Patients on nab-P+G were significantly older (mean age: 63.6 vs 58.8 years; p<0.001) and had higher counts of unique diagnostic categories (21.2 vs 19.0, p<0.001) vs FFX. There was no significant difference in median TTD of 1L (3.8 vs 4 months; log-rank test p=0.602) between nab-P+G and FFX. Compared with FFX, nab-P+G pts had higher chemotherapy drug costs but incurred lower total healthcare, supportive care, and treatment administration costs (Table). Conclusions: This claims analysis suggests patients treated with FFX had similar treatment duration and higher total healthcare costs driven by treatment administration and supportive care. Table: Mean Healthcare and Select MPC-related Treatment Costs During 1L (PPPM) [Table: see text]
Escalated dose somatostatin analogues (SSAs) in management of neuroendocrine tumors (NETs): A systematic review.
Authors: Chan David , Ferone Diego , Albertelli Manuela , Segelov Eva , Singh Simron 
Published: March 2017

422 Background: SSAs are effective in controlling NET symptoms and more recently have been shown to have anti-proliferative properties. PROMID and CLARINET have established “standard” doses of octreotide and lanreotide, but dose escalation is often employed both for symptom relief and tumor control. Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL and abstracts of major conferences. Studies investigating patients treated with doses of octreotide higher than 30mg/28d or lanreotide higher than 120mg/28d were eligible for inclusion. Data extracted included patient population, interventions and prior SSA use. The primary endpoint was disease control rate; secondary endpoints included response rate, symptom control, biochemical response, progression-free survival and toxicity. Results: 19 studies (12 prospective; 981 patients) were identified from 609 search results. Of the 13 studies that mandated prior treatment, the reasons for dose escalation were tumor progression (5), symptoms (3), either (2) and not listed (3). SSAs used were octreotide LAR (10), lanreotide ATG (1), short-acting octreotide (3), short-acting lanreotide (3), and mixtures (2). Significant heterogeneity existed in dosing schedules as well as reporting of efficacy data. Disease control rates ranged from 40-100% (pooled rate 248/396) with response rates from 0-42% (pooled rate 24/396). Dose escalation was associated with improvement in carcinoid symptoms in at least 50% of patients. Biochemical response was variably defined but reported rates ranged from 33% to 100% (pooled rate 55/78). Median PFS ranged from 6 months to 30 months. Dose escalation was generally well tolerated with side effect profile and frequency comparable to normal dose SSA. Conclusions: Escalated dose SSA is well tolerated and results in significant rates of disease control and symptomatic improvement. Compared to a prior systematic review (Broder WJG 2015), this review includes studies of lanreotide, includes 721 additional patients, and restricts inclusion to clinical studies. Prospective randomized trials of escalated SSA therapy are warranted.
Sequential treatment in patients with metastatic pancreatic neuroendocrine tumors after progression on first-line therapy.
Authors: Tsang Erica S , Speers Caroline , Cheung Winson Y. , Kennecke Hagen F. 
Published: March 2017

426 Background: Pancreatic neuroendocrine tumors (pNETs) are rare malignancies with an age-adjusted annual incidence of 0.32/100,000, with metastatic disease at diagnosis occurring in 64%. Patients with advanced disease are considered for surgery/ablative therapy (SG) or systemic therapy (ST), including chemo- and targeted therapy, somatostatin analogues, and peptide receptor radiotherapy (PRRT). Optimal sequence of therapy is unknown and we sought to characterize sequential treatment patterns in patients with metastatic pNETs and overall survival (OS). Methods: Patients diagnosed with metastatic pNETs referred to the BC Cancer Agency between 2000-2013 and received more than one line of therapy were reviewed. Results: Of 151 patients, 81 received one line of therapy while 45 patients received >1 treatment. Median age was 55.1 years (IQR 47.4-64.8) and 23 (51%) were male. Sites of metastases included liver (n=33), lymph nodes (n=5), lung (n=1), peritoneum (n=2), and bone (n=5). Median time to start of therapy was 1.5 months (IQR 0.4-3.0). First-line SG was associated with increased OS compared to first-line ST (88.9 vs. 38.2 months; p=0.004). There was no difference in OS between patients receiving second-line SG or ST, measured from start of second-line therapy. Second-line chemotherapy was associated with decreased PFS compared to alternate treatments, both after first-line chemotherapy (0.7 vs. 5.8 months; p=0.002) and after other treatments (4.8 vs. 16.7 months; p=0.002). Median length of follow-up was 48.3 months. Conclusions: We present the sequential treatment patterns of patients with metastatic pNETs. Results confirm the primary role of SG, reserving ST for secondary therapy. Upon progression, choice of second-line therapy was not prognostic and may be chosen based on disease and patient characteristics. [Table: see text]
A UGT1A1 genotype-guided dosing study of modified FOLFIRINOX (mFOLFIRINOX) in previously untreated patients (pts) with advanced gastrointestinal malignancies.
Authors: Sharma Manish , Catenacci Daniel V.T. , Karrison Theodore , Ganjoo Anubha , Allen Kenisha , Suh Grace K. , Phillips Brooke Elizabeth , Marsh Robert de Wilton , Kozloff Mark , Polite Blase N. , Kindler Hedy L. 
Published: March 2017

427 Background: FOLFIRINOX improves survival compared with gemcitabine in advanced pancreatic cancer (PC), but with significant toxicity (Conroy, NEJM 2011). UGT1A1 clears SN-38, the active metabolite of irinotecan (IRI); UGT1A1*28 polymorphism reduces enzymatic activity and predisposes to severe IRI toxicity. We hypothesized that dosing mFOLFIRINOX based on UGT1A1 genotype would improve tolerability. The primary objective of this study (NCT01643499) was to determine whether genotype-guided dosing of IRI in mFOLFIRINOX is tolerable. A secondary objective was to describe objective response rates (ORR) in PC and biliary tract cancers (BTC). Methods: mFOLFIRINOX was given every 14 days. CT scans were obtained every 8 weeks. UGT1A1 *1/*1, *1/*28, and *28/*28 pts received initial IRI doses of 180, 135, and 90 mg/m2, respectively. 5-FU dose was 2400 mg/m2 over 46 hours (no bolus); leucovorin 400 mg/m2; oxaliplatin 85 mg/m2. In cohort 1 (tolerability cohort by genotype), prophylactic pegfilgrastim was not allowed in cycle 1 (28 days) unless clinically indicated. In cohort 2 (expansion tolerability cohort in PC and BTC), prophylactic pegfilgrastim was given. DLT during cycle 1 was defined as Grade (Gr) 3/4 neutropenia with fever; Gr 4 neutropenia lasting ≥ 5 days; Gr 4 thrombocytopenia, or Gr 3/4 non-hematologic toxicity despite optimal medical management. Doses were tolerable if the DLT rate during cycle 1 was ≤ 33% with 70-80% statistical confidence. Results: In cohort 1, DLTs were observed in 2/15 (13%) *1/*1 pts; 2/16 (13%) *1/*28 pts; 3/9 (33%) *28/*28 pts. In cohort 2, DLTs were observed in 6/19 (32%) PC pts and 4/19 (21%) BTC pts. DLTs in cohort 1 (some pts with multiple): neutropenic fever (5); Gr 3 fatigue (4); Gr 3 diarrhea (2). DLTs in cohort 2: Gr 3 fatigue (3); Gr 3 diarrhea (3); Gr 3 nausea/vomiting (2); Gr 5 sepsis without neutropenia (1); Gr 5 multi-organ failure (1); neutropenic fever (1); Gr 3 anorexia (1). To date, ORR is 13/39 (33%) in PC and 6/28 (21%) in BTC. Conclusions: mFOLFIRINOX is not tolerable in PC and BTC, even with UGT1A1 genotype-guided dosing of IRI and prophylactic pegfilgrastim. More needs to be done to improve the tolerability of this regimen. Clinical trial information: NCT01643499.
Short-term outcomes of laparoscopic D2 gastrectomy with complete mesogastrium excision (D2+CME) for advanced gastric cancer.
Authors: Xie Daxing , Gong Jianping 
Published: March 2017

43 Background: D2 lymphadenectomy has been widely accepted as a standard procedure of surgical treatment for local advanced gastric cancer [1,2]. However, neither the dissection boundary nor the extent of the excision for perigastric soft tissues has been described [3-7]. Our previous researches demonstrate the existence of disseminated cancer cells in the mesogastrium [8, 9] and present an understandable mesogastrium model for gastrectomy [10]. Hence, the D2 lymphadenectomy plus complete mesogastrium excision (D2+CME) is firstly proposed in this study, aiming to assess the safety, feasibility and corresponding short-term surgical outcomes. Methods: All of these patients underwent laparoscopy assisted D2+CME radical gastrectomy with a curative R0 resection, and all the operation was performed by Prof. Jianping Gong, chief of GI surgery of Tongji Hospital, Huazhong University of Science and Technology. All participants provided informed written consent to participate in the study. This study was approved by the Tongji Hospital Ethics Committee. The standard surgical procedures in the video are described as follows. Reconstruction of the alimentary tract was done by extracorporeal anastomosis. Standard recovery protocols were followed in postoperative treatments. Results: 68 patients between September 2014 and March 2016 have been recruited with informed consent and underwent laparoscopic D2+CME by a single surgeon. The mean number of retrieved regional lymph nodes was 33.62±11.40 (ranges 14-55). The mean volume of blood loss was 12.44±22.89 ml (ranges 5-100). The mean laparoscopic surgery time was 127.82±17.63 mins (ranges 110-165). The mean hospitalization time was 16.5±3.3 days (ranges 8-28). No operative complication was observed during the hospitalization. Conclusions: The anatomical boundary of mesogastrium is well described and dissected within D2+CME surgical process. It proves to be safely feasible and repeatable with less blood lost, qualified lymph nodes, retrieval results, and other improved short-term surgical outcomes in advanced gastric cancer. Meanwhile, potential disseminated cancer cells fall into the mesogastrium can be eradicated by D2+CME. Clinical trial information: NCT01978444.