bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of care and treatment outcomes in older patients with biliary tract cancer.
Authors: Horgan Anne M. , McNamara Mairead G , Aneja Priya , Le Lisa W , McKeever Elizabeth , Knox Jennifer J. 
Published: February 2017

315 Background: Although cancers of the biliary tree (BTC) are more common in older age-groups, treatment approaches and outcomes are understudied in this population. Methods: Data from 913 patients diagnosed with BTC from January 1987 to July 2013 and treated at Princess Margaret Cancer Center, Toronto were analyzed. The impact of age, patient and disease characteristics on survival outcomes were assessed. Results: Five hundred and ninety four patients ≤70 years and 319 patients >70 years were identified. Older patients were less likely to receive active therapy - 154 (26%) patients ≤70 yrs received best supportive care alone compared to 130 (41%) of those >70 yrs; p<0.0001. The characteristics of those receiving active therapy (surgery +/- chemotherapy) are shown (table). For patients receiving active treatment, ECOG PS (p=0.002) and disease stage (p<0.0001) independently predicted overall survival. Adjusting for these variables, median survival did not differ between older and younger patients, median survival 20.1 (95% CI [17.8, 23.3]) and 20.5 (95% CI [18.7, 23]) months respectively; HR 1.064 (95% CI [0.86, 1.32]). Conclusions: In this large retrospective analysis, older patients with BTC are less likely to undergo surgery or chemotherapy. Active therapy results in similar survival benefits, irrespective of age. [Table: see text]
Src inhibition through a phase II study of 5-fluorouracil, oxaliplatin, plus dasatinib (FOLFOX-D) in first-line metastatic pancreatic adenocarcinoma.
Authors: George Thomas J. , Ivey Alison Marguerite , Daily Karen Colleen , Dang Long H. , Watson Scott , Granicz Renee , Tormes Kevin , Lu Xiaomin , Liu Chen , Allegra Carmen Joseph , Behrns Kevin , Hughes Steven J. , Ogunwobi Olorunseun Olatunji , Trevino Jose Gilberto 
Published: February 2017

319 Background: Triplet drug therapy is now a standard for metastatic pancreatic cancer (mPCa) but limited in use due to toxicity. Src is constitutively active in mPCa and associated with increased chemoresistance. Src inhibition increases oxaliplatin (ox) activity. Inhibition of Src reduces tumor expression of thymidylate synthase with subsequent 5FU chemoresistance reversal. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) capable of inhibiting Src. Demonstrating activity of this triplet combination therapy in mPCa represents a scientifically rational approach to a clinical unmet need. Methods: Eligible pts have biopsy proven, RECIST measurable disease with no prior therapy for met disease and at least 6 months since completing adjuvant therapy, ECOG PS 0-2 and adequate organ function. Pts received standard doses of mFOLFOX6 chemotherapy (5-FU/LV 400mg/m2 bolus and Ox 85 mg/m2 D1; 5-FU 2,400 mg/m2CIVI x 46h D1-2) with continuous D (150 mg PO daily) repeated q14d with tumor assessments q8w. The primary endpoint is progression-free survival (PFS) with secondary endpoints of objective and biochemical response rates, freedom from mets, overall survival (OS), toxicity, and quality of life. Sample size was based on a 50% improved median PFS from 4 (historical) to 6 months (m). Results: 14 of 42 planned pts have received therapy and are included in this report. Baseline pt demographics are in the table. 10 pts (71%) had a grade 3 AE and 1 (7%; sepsis) had a grade 4 AE. There were no grade 5 toxicities. Most common grade 3 AEs included anemia (29%), hyponatremia (29%), neutropenia (21%) and fatigue (21%). Conclusions: Enrollment continues with ongoing toxicity and efficacy monitoring of this targeted combination. Exploratory tissue and serum correlative analyses to identify predictors of response are planned. Clinical trial information: NCT01652976. [Table: see text]
Effectiveness study of gemcitabine, oxaliplatin, and capecitabine as first-line treatment for nonresectable biliary tract cancer.
Authors: Jensen Lars Henrik , Mellergaard Anne Haahr , Hoegdall Dan , Larsen Ole 
Published: February 2017

334 Background: Since 2010, the doublet gemcitabine and cisplatin has been standard first-line systemic treatment for non-resectable biliary tract cancer. In a phase I-II trial of the well-tolerated triplet of gemcitabine, oxaliplatin, and capecitabine, the median progression free survival (PFS) and overall survival (OS) were 6.9 and 12.5 months, respectively. Overall response rate was 34%. Since 2005 the regimen has been used in Denmark. We wanted to investigate the effectiveness of the triplet regimen given in daily clinic. Methods: We included 192 patients from two institutions. Patients had to have non-resectable biliary tract cancer and to be suitable for combination chemotherapy on doctor’s discretion. Gemcitabine 1000 mg/m2 and oxaliplatin 60 mg/m2 were given every two weeks followed by capecitabine 1000 mg/m2 b.i.d. for one week. At one institution the oxaliplatin dose was 50 mg/m2 and capecitabine dose 650 mg/m2 b.i.d. continuously. One cycle included two treatments and was typically administered for up to six cycles/months, but was allowed for longer time until progression. Results: At institution A, 117 patients were included and 73 (62%) were women. Median age was 66 years (range 25-80). Median treatment duration was six cycles/months (range 1-12). Thirty-five, 69, 12, and one patient(s) were in performance status 0, 1, 2, and 3, respectively. Ninety patients were evaluable for response and 6 (7%) had complete response, 18 (20%) partial response, 53 (59%) stable disease, and 13 (14%) progression as best response. Median PFS was 9.7 months (95% CI 8.5-11.7) and median OS 11.7 months (9.8-14.0). The results were comparable to institution B, where the response rate in 56 patients with measurable disease was 30%. In 75 patients evaluable for survival analysis, PFS was 8.1 months and OS 12.0 months for performance status 0-1 (n=55). Patients in performance status 2 (n=25) had a PFS and OS of only 1.7 and 2.8 months, respectively. Conclusions: A triplet of gemcitabine, oxaliplatin, and capecitabine given in daily clinic was well tolerated and has effectiveness comparable to results from a phase II trial and the pivotal phase III trial of gemcitabine and cisplatin.
Effects of the sequential administration of GEMOX followed by FOLFIRI in cholangiocarcinoma.
Authors: Sebbagh Sihem , Dreyer Chantal , De Gramont Armand , Hentic Olivia , Hammel Pascal , Raymond Eric , Faivre Sandrine J. 
Published: February 2017

348 Background: Advanced cholangiocarcinoma are benefiting from platinum-based therapy (Valle et al, NEJM) but no validated option is available as second line systemic therapy. Methods: Objective : Explore the effect of 2 consecutive lines of chemotherapy in patients with cholangiocarcinoma fitted to receive sequential administration of received gemcitabine and oxaliplatin (GEMOX) followed by FOLFIRI. A retrospective study was conducted among patients who received GEMOX in first line followed by FOLFIRI in second line from January 2005 and September 2013 at Beaujon hospital (France). Overall survival, progression free survival and prognostic factors were determined by the Kaplan-Meier method and univariate analysis. Results: Thirty-four patients were included in the cohort. Eighteen patients (53%) presented intrahepatic cholangiocarcinoma (ICC) and 16 (47%) presented extrahepatic cholangiocarcinoma (ECC). At diagnosis, tumors were localized in 4 patients (12%), locally advanced in 13 patients (38%) and metastatic in 17 patients (50%). Among 10 patients with prior surgery, 7 received GEMOX adjuvant chemotherapy. The median overall survival time was 20.6 months in all patients and 17.1 months in patients who received GEMOX followed by FOLFIRI in the advanced setting. The median first line progression-free survival (PFS) was 5.7 months with a median number of 8 cycles of GEMOX. The median second line PFS was 2.9 months with a median number of 5 cycles of FOLFIRI. Patients who received >8 cycles of GEMOX in first line survived longer than those who received ≤ 8 cycles (23.1 vs 15.1 months; hazard ratio (HR) 5.22, P=0.009). The PFS of second line FOLFIRI was not different in patients who received more than 8 cycles of GEMOX (HR=1.72 P=0.26). Univariate analysis showed no correlation between age, sex, localization of primary, stage, and surgery with overall survival. No severe toxicity was reported related to GEMOX-FOLFIRI sequential combination in this study. Conclusions: Sequential administration of GEMOX followed by FOLFIRI is feasible for fitted patients with cholangiocarcinomas, yielding overall survival over 1 year.
Prognostic factors in advanced biliary tract cancer treated with first-line chemotherapy with cisplatin and gemcitabine.
Authors: Peixoto Renata D'Alpino , Renouf Daniel John , Lim Howard John 
Published: February 2017

350 Background: Data regarding prognostic factors in advanced biliary tract cancer (ABTC) remains scarce. The aim of this study was to review our experience in ABTC as well as to evaluate potential prognostic factors for overall survival (OS) as defined in the ABC-02 trial. Methods: 106 consecutive patients with ABTC who initiated palliative chemotherapy with Cisplatin and Gemcitabine from 2009 to 2012 at the BC Cancer Agency were identified using our pharmacy database. Clinicopathologic variables and treatment outcome were retrospectively collected. Potential prognostic factors were assessed by univariate (Kaplan-Meier curves and log-rank test) and multivariate analyses (Cox proportional hazards model). Results: 106 patients (46 males) with a median age of 64 years (range 43 – 88) were included. Median progression free-survival (PFS) was 6.2 months (95%CI: 5.4-7.0). Median OS from diagnosis of advanced disease to death was 12.9 months (95%CI: 10.0-15.7), while median OS from initiation of chemotherapy to death was 10.0 months (95%CI: 7.3-12.6). 34.9% of the patients received 2nd line chemotherapy, with single-agent 5-fluorouracil being the most used drug. On univariate analysis, ECOG performance status (PS) at diagnosis, primary tumor location (gallbladder, intra-hepatic cholangiocarcinoma, extra-hepatic cholangiocarcinoma, ampulla of Vater, unkown), and sites of advanced disease (unresectable locally advanced, regional lymph nodes, liver-limited metastases, extra-hepatic metastases) were significantly associated with worse OS (p < 0.001, 0.003 and 0.009, respectively). Age, gender, CA19-9, CEA, hemoglobin, neutrophil count, prior stent and prior surgery were not significantly associated with OS. On multivariate analysis, predictors of poorer OS were ECOG PS (p<0.001), primary location (p=0.009), site of advanced disease (p=0.006) and CEA (p=0.002). Conclusions: In this population based analysis, outcomes for patients with ABTC were comparable to those noted in the ABC-02 trial. ECOG PS, primary tumor location, site of advanced disease and CEA were all found to be significantly prognostic.
Correlation between overall survival and other efficacy endpoints in advanced biliary tract cancer: Literature-based analysis from 13 randomized trials of first-line chemotherapy.
Authors: Moriwaki Toshikazu , Endo Shinji , Yamamoto Yoshiyuki , Yamada Takeshi , Sugaya Akinori , Kobayashi Mariko , Hyodo Ichinosuke 
Published: February 2017

352 Background: Chemotherapy for advanced biliary tract cancer (ABC) has progressed. Now gemcitabine plus cisplatin combination is considered the standard 1st-line treatment based on the results of many randomized studies. However, the impact of various efficacy parameters on overall survival (OS) remains unclear. Methods: We searched PubMed database with the key words of (“biliary tract neoplasms” or “bile duct neoplasms” or “gallbladder neoplasms” or “cholangiocarcinoma” [All fields]) AND (“chemotherapy”[All fields]) AND Clinical trial [ptyp] between Apr 1984 to Jun 2013 and abstracts presented at the meetings of ASCO/Gastrointestinal Cancers Symposium (2004–2013) and ESMO/WCGC (2002–2013). Then we identified randomized trials of 1st-line chemotherapy for ABC, and analyzed the relations between the results of OS and those of progression-free survival (PFS) or time to progression (TTP), response rate (RR), disease control rate (DCR), post-progression survival (PPS = median OS − median PFS/TTP), and the proportion of patients who received 2nd-line chemotherapy (%2nd). Results: Among 329 papers/abstracts retrieved, 13 randomized trials, 26 treatment arms of first-line chemotherapy for ABC were identified. Number of trials with information on median OS, median PFS/TTP, hazard ratio (HR) for OS and PFS/TTP, RR, DCR, and %2nd were 13, 13, 6, 13, 12, and 7, respectively. The analysis of all these trials demonstrated the median values (range) of OS, PFS/TTP, HR of OS, HR of PFS/TTP, RR, DCR, PPS, and %2nd were 9.4 (4.6–13) months, 5.3 (2.7–8.5) months, 0.71 (0.39–0.93), 0.65 (0.44–0.85), 20 (7.1–36) %, 67 (21–87) %, 4.0 (1.0–7.6) months, and 41 (15–79) %, respectively. Spearman rank correlation coefficient of differences (Δ) OS with ΔPFS/TTP, ΔRR, ΔDCR, and ΔPPS were 0.66, − 0.07, 0.66, and 0.34, respectively. The correlation coefficient between HRs for PFS/TTP and OS was 0.60. The correlation coefficient between ΔPPS and Δ%2nd was − 0.15. Conclusions: OS was moderately associated with PFS/TTP and DCR.
Oxaliplatin, irinotecan, and PK-adjusted 5-fluorouracil within a multidisciplinary approach in patients with locally advanced pancreatic cancer (LAPC): Preliminary results.
Authors: Martin Romano Patricia , Aldaz Azucena , Chopitea Ana , Pardo Fernando , Arbea Leire , Subtil Jose Carlos , Rotellar Fernando , Garzon Carlos , Zufia Laura , Sola Iosu , Solorzano Jose Luis , Castanon Eduardo , Rodriguez Javier 
Published: February 2017

356 Background: Neoadjuvant therapy is an increasingly used approach in LAPC patients (pts) but the optimal sequence remains to be defined. We evaluated the feasibility and efficacy of induction chemotherapy (ICT) with pharmacokinetic (PK) monitoring, chemo-radiotherapy (CRT) and surgery. Methods: Borderline resectable and unresectable LAPC pts with EUS stages T3-4/N+ were included. Pts were planned to receive 4 cycles of biweekly ICT with Oxalipatin (85mg/m²), Leucovorin (400mg/m²), Irinotecan (150mg/m²) and 5-FU (initial dose of 3200mg/m² in 46h and then tailored according to PK monitoring to reach an area under the curve (AUC) between 25-30 mg·h·L-1.) After ICT, pts with no progressive disease received CRT (50.4 Gy, daily concurrent Capecitabine and weekly Oxaliplatin). Surgery was planned 4 to 6 weeks after the completion of CRT. Pathological response was graded according to the CAP classification. Toxicity was recorded according to the NCI-CTCAE 4.0. Results: From November 2011 to February 2013, 13 LAPC treatment-naïve (M/F: 11/2) pts were enrolled (T4; 30.8%, N+; 61.5%, 8 borderline resectable, 5 unresectable due to celiac abutment (2 pts), SMA and celiac encasement (1 pt), unreconstructible SMV and portal occlusion (2 pts). Median age was 63. During ICT, 5- FU dose had to be increased from baseline in 30.7% pts. Grade 3-4 ICT-related toxicities were neutropenia (6 pts) and diarrhea (1 pt). During CRT, grade 3 toxicity included neutropenia (2 pts), thrombocytopenia (1 pt), diarrhea (1 pt), asthenia (1 pt) and mucositis (1 pt); three pts required hospital admission in hospital. Twelve pts completed the whole neoadjuvant program. Ten pts proceeded to surgery with an R0 resection rate of 76.9%. Pathological response was CAP 0 (no viable cells) and CAP 1 (small groups of cancer cells) in 20% and 50% of pts, respectively; ypT0 and ypN0 rates were 20 and 60%. After a median follow-up of 12 months, the 12-month actuarial median PFS and OS were 80% and 75%, respectively. Conclusions: This neoadjuvant strategy seems feasible and promising although a longer follow-up is required. 5-FU PK modulation may contribute to a better therapeutic index.
Pancreaticoduodenectomy (PD) for periampullary tumors: Results from Tata Memorial Centre (TMC) over two decades.
Authors: Shrikhande Shailesh V. , Mitra Abhishek , Sirohi Bhawna , Bal Munita , Goel Mahesh 
Published: February 2017

366 Background: There is scarcity of short and long term data regarding results of pancreaticoduodenectomy done for periampullary tumours. Contrary to the western data, ampulla of Vater is the commonest site of involvement in Indian patients. Methods: A retrospective analysis PD was done for periampullary tumors from 1991 to July 2013 at TMC. The time period was divided into 4 spans A (1991 to 2001), B (2003 to July 2009), C (Aug 2009 to Dec 2012) and D (Jan 2013 to July 2013) based on the increasing surgical volumes and changing practice trends. Survival outcomes were analysed. Data was prospectively maintained from 2006 onwards. Results: 626 pts underwent PD for periampullary tumors over this time period. 144, 206, 150 and 126 pts were operated during span A, B, C and D respectively. Sites involved were ampulla (67.5%), head of pancreas (16.6%), duodenum (9.9%) and bile duct (6.9%). Adenocarcinoma was the most common histology (81.5%). The morbidity and mortality was 31.7% and 4.3%. Postoperative pancreatic fistula, delayed gastric emptying (DGE), post-pancreatectomy haemorrhage (PPH) and bile leaks were 12.4%, 2.8%, 4.8% and 2.7% respectively for the whole group. Morbidity, mortality, DGE, PPH and bile leak rates have declined over subsequent time periods. Majority of pts in span C and D received adjuvant chemotherapy with gemcitabine 1000mg/m2 on day 1,8 and 15 of a 28 day cycle. 2 year disease free survival (DFS) for periampullary adenocarcinoma-ampulla, bile duct & pancreas from April 2006 for 294 pts was 79.3%, 68.6% and 41.8% respectively. Overall 2 year DFS was 74%. Conclusions: These data represent the largest single centre experience with PD from Indian subcontinent. The improvement of results over the 2 decades can be due to increasing volume of pts, standardisation of surgical technique and gradually increasing experience of the operating team. The impressive 2 year DFS can be attributed to a large number of good prognosis ampullary tumors.
Chemoradiation for locally advanced perihilar cholangiocarcinoma.
Authors: Lim Seungtaek , Choi Hye Jin , Seong Jinsil 
Published: February 2017

372 Background: Locally advanced perihilar cholangio-carcinoma (LA-PHC) is a rare malignancy with dismal prognosis, and chemoradiation (CRT) is used to palliate symptoms and extend survival. However, its role has not been established due to the rarity of these tumors. We intended to investigate the efficacy of chemo-concurrent radiotherapy (CRT) for patients with LA-PHC. Methods: This study included 52 patients who received CRT for LAPHC in a single institue. Patients received external beam radiotherapy with a median dose of 50.4Gy (range, 720-5400) with gemcitabine or 5-FU (or its analogues). The objective response rate (ORR), disease control rate (DCR), and overall survival (OS) were evaluated. All statistical analysis were performed by SPSS program version 18.0. Results: The median OS was 14.2 months (95% CI, 8.9~19.5). The ORR and DCR was 12% and 85%, respectively. Thirteen patients (19%) whose disease were converted to resectable after CRT had a significant survival advantage compared to patients who underwent CRT alone (29.2 vs. 10.8 months, P=0.005). CA 19-9 response (defined as more than 30% decrease in the CA 19-9 level compared to baseline) at 1month after CRT predicted prolonged survival (Table). CRT was generally well tolerated. Although gemcitabine-based CRT had a higher ORR, DCR, and CA 19-9 response at 1 month than 5FU-based CRT, the difference was not statistically different, and there was no difference in OS between two regimens. Moreover, patients treated with gemcitabine based CRT suffered more severe hematologic toxicity (grade 3 or 4 neutropenia, 20% vs. 4%). Conclusions: This study suggested that CRT is a good therapeutic option in the treatment of LA-PHC. Also, CA 19-9 response 1 month after completion of CRT was identified as a predictive marker of survival in patients who underwent CRT. Further research is warranted regarding optimal chemotherapy regimen, and schedule of radiation. [Table: see text]
Neoadjuvant therapy in Indian patients with locally advanced gall bladder cancer: Tata Memorial Centre (TMC) experience.
Authors: Sirohi Bhawna , Sheth Vipul , Singh Ashish , Engineer Reena , Ramadvar Mukta , Goel Mahesh , Shrikhande Shailesh V. 
Published: February 2017

379 Background: Gemcitabine/platinum (Gem-P) is currently the standard of care for patients with advanced biliary tract cancers based on the ABC02 study. Pts usually present in locally advanced (LA) stage in India and as surgery remains the only curative option- neoadjuvant (NA) strategy needs to be explored. Methods: This is retrospective analysis of the prospectively maintained database of 38 patients with LA GB cancer treated at TMC between Feb 2009 to May 2013. Aim of the study was to assess resectability rate in patients with LA GB cancer (defined as GB mass invading liver > 2cm without porta hepatis / vascular invasion, GB mass adherent to duodenum and hepatic flexure, coeliac/gastrohepatic adenopathy/portocaval and peripancreatic nodes). Pts received cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on D1 and D8 of 21d cycle, for gem-oxaliplatin, pts received gemcitabine 1000mg/m2 D1 and oxaliplatin 100mg/m2 D2 every 14 days. Response was assessed after 3-4 cycles. Results: Of the 38 pts (median age 54 y,30-71; 11M, 29F, median CA19.9 19 (<2-74605), 33patients were treated with Gem-P (25 oxaliplatin, 8 cisplatin; 1cetuximab-Gem-P) based therapy and 5 pts received chemoradiotherapy (CTRT) with wkly gemcitabine 300mg/m2. Site of disease was liver in 22 pts, nodal in 12, adjacent organ in 9 & other in 3 pts. Median number of chemotherapy cycles given were 4 (1-12). Response rate to NA therapy was 5 (13%) complete response (CR), 17(45%) partial response (PR), 9 stable disease (SD), 5 (13%) progressive disease and not assessed in 2 patients (1 pt died post CTRT and 1 was inoperable at surgery). Overall clinical benefit rate (CR+PR+SD) was 82%. Of the 24 pts who underwent surgery, 21 (87%) had curative resection and 3 were inoperable. Of 9 pts with SD, 6 received 2nd –line NA therapy as they were not downstaged enough to undergo surgery– 4 CTRT, 1 gemcitabine-cape, 1 cape-Ox. Perioperative morbidity (biliary leak) was higher post CTRT. Overall, 7 pts have relapsed. Conclusions: This is the first report of the use of neoadjuvant chemotherapy in patients with LA GB cancer. We conclude that preoperative chemotherapy is feasible with acceptable toxicity and perioperative morbidity.