bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of bavituximab and sorafenib in advanced hepatocellular carcinoma (HCC).
Authors: Yopp Adam Charles , Singal Amit G , Arriaga Yull Edwin , Verma Udit N. , Shan Joseph , Kallinteris Nikoletta , Beg Muhammad Shaalan , Mansour John C. , Zhu Hao 
Published: February 2017

345 Background: Bavituximab a first-in-class immunomodulator targeting phosphatidylserine (PS), a lipid externalized on tumor and endothelial cells. Preclinical and phase I studies demonstrated that sorafenib upregulates PS externalization and can be given safely with bavituximab. We evaluated the safety and clinical activity of bavituximab plus sorafenib in HCC. Methods: Patients with advanced HCC deemed ineligible for curative therapy with no previous systemic treament, ECOG score ≤ 2, Child Pugh score A or B7 received bavituximab, 3 mg/kg IV weekly, and sorafenib, 400 mg PO BID until disease progression or intolerable toxicity. 38 patients were accrued providing a power of 80% and two-sided significance level of 10% to show an 8.2 month time to progression compared to historical control, 5.5 months. Secondary endpoints included safety and tolerability, 4-month progression free survival, overall survival, and response rates. Correlative studies using pre- and post-treatment tumor biopsies included IHC analysis of regulatory, cytotoxic, and helper T cells in addition to macrophage infiltrates. Results: 38 patients were accrued, 7 still on treatment. Patient characteristics: median age: 60.5 years, male 74%, HCV: 79%, Black: 47%/Hispanic: 29%/White: 21%, previous treatment 37%, and metastases: 24%. Median follow-up is currently 6.1 months with current median TTP of 6.8 months (95% CI 3,10). Four month PFS is 76% and there are no partial or complete responses. Treatment related adverse events were observed in 53% of patients, one grade 3 (GI bleed), four grade 2 (DVT, anorexia, diarrhea, and infusion reaction). Most common grade 1 events were diarrhea (18%), fatigue (16%), and anorexia (16%). Six patients had tissue analyzed pre- and post-treatment, 2 of 6 demonstrated increase tumor infiltration of CD4+, CD8+, and macrophages with a corresponding decrease in Tregs. Conclusions: Bavituximab and sorafenib were well tolerated in patients with advanced HCC. When compared with historical controls, combination therapy demonstrated an improvement in TTP and PFS at four months. Combination therapy increases immune tumor infiltrates. Clinical trial information: NCT01264705.
The effect of bridging locoregional therapies on survival in hepatocellular carcinoma patients undergoing orthotopic liver transplantation: UNOS population study.
Authors: Xing Minzhi , Kim Hyun Sik 
Published: February 2017

346 Background: The effect of bridging locoregional therapies (LRT) on overall survival (OS) in pts with hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT) has not been investigated in large-scale population studies. Methods: TheUnited Network for Organ Sharing (UNOS) database was used to identify pts with HCC who received OLT between 2002 and 2010. Pts within Milan Criteria for whom an HCC Model for End-Stage Liver Disease (MELD) exception was approved were included. OS was compared between pts who received bridging LRT (including transarterial chemoembolization (TACE)) and those who did not. Kaplan-Meier estimation and Cox proportional hazard models were used for OS analysis. Results: Of 11,287 pts with HCC who received OLT, 9,876 pts had LRT data, mean age 56.6 yrs, 77% male; 5,103 received bridging LRT, including 3,676 who received TACE. Comparison groups were similar for age at OLT, waitlist duration, sex, race, BMI and MELD score (p>.05 for all). Significantly prolonged OS with bridging LRT vs. none was observed from both OLT (111.6 vs 106.4 mo, p<.001) and from Listing (176.1 vs 169.4 mo, p=.001). Similarly, significantly prolonged OS with bridging TACE vs. none was observed from both OLT (112.0 vs 107.2 mo, p<.001) and from Listing (177.7 vs 169.9 mo, p=.001). Conclusions: In HCC pts undergoing OLT, both bridging LRT and TACE correlated with prolonged survival from OLT and from Listing in a UNOS population-based study. [Table: see text]
Role of chemoradiation in locally advanced pancreatic cancer: A systematic review and meta-analysis.
Authors: Nagrial Adnan , Chin Venessa T. , O'Connor Chelsie , Sjoquist Katrin Marie , Chantrill Lorraine A. , Biankin Andrew Victor , Yip Desmond 
Published: February 2017

348 Background: The role of combined modality therapy in the management of locally advanced pancreatic cancer (LAPC) is uncertain. Current guidelines recommend combined modality therapy for select patients. We sought to review the evidence for combined modality versus single modality therapy in LAPC. We performed a systematic review and meta-analysis of randomised controlled trials (RCT) comparing chemoradiation versus chemotherapy alone as well as chemoradiation versus radiation alone in patients with LAPC. Methods: We searched MEDLINE, EMBASE and CENTRAL from inception to Oct 2013 for RCTs comparing chemotherapy alone versus chemotherapy plus radiation and radiation alone versus chemotherapy plus radiation. We also searched abstracts of major cancer meetings from 1990 to 2013. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), response rate and adverse events. Hazard ratios (HR), confidence intervals (CI) and p-values (p) were estimated with a random-effects model due to the heterogeneity of included studies using Revman 5.3. Results: We included 7 eligible trials including 753 patients. Induction chemotherapy was delivered prior to randomisation in one study. Chemoradiation versus chemotherapy (n= 5 studies) did not improve PFS (HR 1.02, 95% CI 0.87 - 1.20, p = 0.80) or OS (HR 0.91, 95% CI 0.64 - 1.31, p = 0.61). However, chemoradiation versus radiation (n=2 studies) improved PFS (HR 0.63, 95% CI 0.41 - 0.96, p = 0.03) and OS (HR 0.65, 95% CI 0.43 – 0.96, p = 0.03). There was significant statistical heterogeneity in the included studies and subsequently wide confidence intervals in the pooled results. This is most likely due to the small participant numbers in each study. Adverse events were more frequent in the chemoradiation arms. Response rates were assessed in only two studies. Conclusions: Chemoradiation is not superior to chemotherapy alone in LAPC, but may be superior to radiation alone. The studies were small with significant heterogeneity. Combined modality therapy results in increased adverse events. Our results do not provide evidence for a universal standard of care, thus more studies of combined modality therapy in LAPC are needed.
Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma following previous curative intent surgical resection.
Authors: Spolverato Gaya , Kim Yuhree , Alexandrescu Sorin , Marques Hugo , Aldrighetti Luca , Gamblin T. Clark , Pulitano Carlo , Bauer Todd W. , Shen Feng , Sandroussi Charbel , Poultsides George A. , Maithel Shishir Kumar , Pawlik Timothy M. 
Published: February 2017

349 Background: Many patients develop recurrence following resection of intrahepatic cholangiocarcinoma(ICC). Management and outcomes of patients with recurrent ICC following previous curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. Methods: Between 1990-2013, 542 patients who underwent surgery for ICC were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence and recurrence-related management were recorded and analyzed. Results: At initial surgery, treatment was resection only(96.1%) or resection+RFA(3.9%). Overall 5-year survival was 25.9%; 376(69.4%) patients recurred with a median disease-free survival of 11.0 months. Vascular invasion(hazard ratio [HR]=1.43), nodal metastasis(HR=1.40) and poor differentiation(HR=1.30) were predictive of recurrence(all P<0.05). First recurrence site was intrahepatic only (62.0%), extrahepatic only (14.1%), or intra- and extrahepatic(23.9%). Overall 259(68.9%) patients received treatment for recurrent ICC, while 117(31.1%) received best supportive care(BSC). Among patients who received treatment for recurrent disease, therapy consisted of systemic chemotherapy only(49.4%), repeat liver-directed therapy (25.9%), or systemic chemotherapy+liver-directed therapy(24.7%). Repeat liver-directed therapy consisted of repeat hepatic resection±ablation(30.5%), ablation alone (21.4%), and intra-arterial therapy(IAT)(48.1%). Among patients who recurred, median survival from the time of the recurrence was 11.0 months(BSC-7.7 months, systemic chemotherapy only-10.0 months, liver-directed therapy-18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 7.6 months for patients who had IAT(P<0.001). Conclusions: Recurrence following resection of ICC is common, occurring in up to two-thirds of patients. When recurrence occurs, prognosis is poor. In well-selected patients with liver only recurrence, resection+chemotherapy may offer a modest survival benefit.
DocOx (AIO-PK0106): A phase II trial with docetaxel and oxaliplatin as a second-line systemic therapy for patients with advanced and/or metastatic adenocarcinoma of the pancreas—Final results.
Authors: Ettrich Thomas Jens , Perkhofer Lukas , Kaechele Volker , Berger Andreas W. , Guethle Melanie , Muche Rainer , von Wichert Goetz , Gress Thomas M. , Michl Patrick , Geissler Michael , Hebart Holger Frithjof , Buechner-Steudel Petra , Seufferlein Thomas 
Published: February 2017

352 Background: Pancreatic ductal adenocarcinoma still remains a major cause of cancer related deaths in the western world. The current study was conducted to confirm the activity and feasibility of docetaxel/ oxaliplatin combination in second line treatment of advanced pancreatic ductal adenocarcinoma. Methods: Prospective single arm, non-randomized, multi-center, Simon’s two stage phase II trial using docetaxel (75 mg/m2, 60 min, d 1) and oxaliplatin (80 mg/m2, 120 min, d 2) in 21-day cycles. Duration of the trial was scheduled up two 8 cycles. Primary endpoint was tumor response according to RECIST 1.0. Secondary endpoints were progression free survival, overall survival, safety/toxicity, quality of life and clinical benefit. Results: Data represents the intention to treat analysis of 44 patients included between 2008 and 2012. The majority of patients received a gemcitabine based first-line chemotherapy (95.5%). The primary endpoint of tumor response was achieved in 15.9% (7 partial remissions, no complete remission), with a disease control rate of 48% after the first two treatment cycles. Median progression free survival was 7 weeks (CI 6-15.9 weeks) and overall survival 40 weeks (CI 20.4-56.4 weeks). No unexpected adverse events occured. The recorded AEs were mainly hematologic (neutropenia grade 3/4 63.6%, febrile neutropenia 4.6%), gastrointestinal (29.6% grade 3/4 AEs) and infectious (18.2% grade 3/4 AEs). Conclusions: In this single-arm second line trial for the treatment of advanced PDAC, the combination of docetaxel and oxaliplatin shows promising results comparable with other second line protocols such as OFF (oxaliplatin, 5-FU, leucovorin) or liposomal irinotecan (MM-398) plus 5-FU/leucovorin (NAPOLI 1-trial). Some patients seem to benefit particularly as indicated by long periods of treatment in this setting. Even after 8 cycles of treatment with DocOx, partial response was observed in 2 patients and stable disease in another 6 patients corresponding to a disease control rate of 18%. The toxicity profile was quite tolerable and comparable to other second line studies. Clinical trial information: NCT00690300.
Curative treatments and survival benefit in elderly patients with hepatocellular carcinoma: A SEER population-based analysis.
Authors: Makarova-Rusher Oxana V. , Ulahannan Susanna Varkey , Duffy Austin G. , Greten Tim F. , Altekruse Sean 
Published: February 2017

355 Background: Transplant, resection, and ablation are potentially curative treatments for hepatocellular carcinoma (HCC) with limited outcome data in young-old (65-74) and older (≥75) patients. Methods: We evaluated curative treatment and relative survival (RS) outcomes in patients with HCC in 3 age groups (<65 years, 65-74 years, and ≥75 years). Patients with HCC diagnostic codes (histology 8,170-8,175, morphology C22) were identified in the SEER 18 database from 2000 to 2011. Treatments included curative (transplant, resection, radiofrequency ablation (RFA), and other ablations) and palliative therapies. Primary outcome was 5 year RS. Statistical analysis was performed using Kaplan-Meier and Chi-Square tests. Results: We identified 29,654 cases. The mean age was 62 years with almost 40% of HCC cases in patients over 65 years old. Potentially curable, localized stage rates were similar in all age groups, 46%, 48% and 46%, respectively. As a result of less resection and rare transplant use, fewer cases underwent curative treatments in the group 75 years and older in comparison to all other age groups (15% vs. 27%, p = 0.001). Five-year RS in all 3 age groups (<65 years, 65-74 years, and ≥75 years) was better after resection relative to RFA (47% vs. 35% p<0.0001, 44% vs. 37%, p=0.0093, and 43% vs. 28% p=0.0002). The highest survival was seen after liver transplant. Interestingly, among transplanted patients with HCC, 13% were 65-75 years old. Five-year RS was similar in transplanted patients 65-75 vs. those under 65 (76% vs 74% p=0.65). Conclusions: The use of curative treatments for HCC significantly decreases with age, yet there are clear survival benefits in elderly patients receiving such. Even when considering transplant, the data shows that outcome is as good in elderly patients as in younger patients. The benefit of hepatic resection appears to be superior compared to RFA in all age groups, in our analysis. [Table: see text]
Outcomes of liver-directed therapy for metastatic carcinoid tumors.
Authors: Hamner John Blair , White Michael , Iruarte Philip HG , Singh Gagandeep 
Published: February 2017

356 Background: Patients with liver metastases from carcinoid tumors can have a variable and often indolent disease course. That said, left untreated, these tumors will often lead to the death of the patient secondary to the effects of tumor burden within the liver and the sequelae of carcinoid syndrome. In this study, we evaluate the effects of liver directed therapy on disease-specific survival in patients with liver metastases from carcinoid tumors. Methods: The California Cancer Registry was queried for patients with liver metastases from a primary carcinoid tumor. Demographic data was recorded. Patients were subdivided into six groups: those who received 1) no liver directed therapy, 2) surgical resection only, 3) trans-arterial chemoembolization (TACE) only, 4) radioembolization (RE) only, 5) surgical resection plus TACE, or 6) surgical resection plus RE. Kaplan-Meier curves were applied to estimate 10 year disease-specific survival. Results: 4,566 patients were identified with liver metastases from a primary carcinoid tumor, and 4,277 patients with complete clinical information included in the analysis. A slight majority of cases were male (51.4%), 183 (4%) were less than 40 years of age, 2,006 (44%) were between 40 and 65 years, and 2,363 (52%) were over 65. The 10 year median disease-specific survival was 66 months for those treated with TACE only, 80 months for those who received no liver directed therapy and 111 months for those who received liver resection plus TACE. The 10 year median survival has not yet been reached for the other groups. When compared directly, surgery plus RE had a trend toward better disease specific survival than surgery plus TACE, though statistical significance was not reached. Conclusions: While patients with liver metastases from carcinoid tumors often have an indolent disease course, liver directed therapy may help improve disease-specific survival. Surgical treatment, when completely resectable, remains the best treatment, although many patients will not have disease that is amenable to complete resection. In these cases, resection with the addition of RE appears to be more effective in improving disease-specific survival than other forms of liver directed therapy alone or in combination.
Next-generation sequencing (NGS) to identify potential therapeutic targets in advanced pancreatic cancer.
Authors: Kundranda Madappa N. , Braun Donald Peter , Kramer Kim , Ai Jizhou , Tan Bradford A. , Kilmant Eiko , River George L. , Markman Maurie 
Published: February 2017

357 Background: Even with the advent of newer systemic therapies; long term survival in advanced PDAC is dismal. Hence there is an urgent need to use technologies such as NGS to identify potential therapeutic targets. Methods: A retrospective analysis was performed of all advanced PDAC patients (pts) evaluated with NGS through Foundation One (Foundation Medicine Inc., MA). DNA was extracted from biopsy specimens and sequencing was performed of 315 cancer-related genes plus select introns. Statistical analysis including Kaplan Meier survival analysis along with the log-rank test was used to compare the differences between groups. Results: 53pts were analyzed between Nov 2012 - Sep 2014; 25 (47%) were females; median age was 59 yrs (range: 33-77). 178 genomic alterations (GAs) were identified in 52 pts (average 3.43 GAs/pt). The GAs included mutations 140 (78%), amplifications 25 (14%), loss/deletions 13 (7%) and 1 pt had no GAs. Most frequent GAs and associated survival are listed in Table 1. There was no statistically significant difference in median overall survival (mOS) between the groups with or without KRAS (22.1 vs. 21 months; p=0.95) and with or without TP53 (21 vs. 23.4 months; p=0.76). 6/52 pts (12%) who had received at least 3 prior lines of therapy (range 3-4) and had an ECOG performance status <2; were treated off label with trametinib. The median PFS on the last therapy prior was 5 months (range 1.6-7). On trametinib, the median PFS was 1.9 months (range 1.1-7.1) with mOS of 5.1 months. Conclusions: Our data demonstrate that there are a range of GAs that are eligible for investigational targeted therapies. Secondly, the choice of agents (eg. Trametinib - targets downstream RAS effectors ) based on individual genomic profile can be considered when an appropriate clinical trial is not available or inaccessible even in heavily pretreated patients with a good performance status. Tumor profiling should be utilized in drug development to personalize treatment options in patients with advanced PDAC. [Table: see text]
Phase II trial of veliparib (V) in patients (pts) with previously treated BRCA or PALB2-mutated (mut) pancreas adenocarcinoma (PC).
Authors: Lowery Maeve Aine , Kelsen David Paul , Smith Sloane C. , Moore Malcolm , Kindler Hedy Lee , Golan Talia , Segal Amiel , Hollywood Ellen , Maynard Hannah , Capanu Marinela , Moynahan Mary Ellen , Fusco Anne , Stadler Zsofia Kinga , Do Kinh G , Chen Alice P. , Yu Kenneth H. , Tang Laura H. , O'Reilly Eileen Mary 
Published: February 2017

358 Background: BRCA1, BRCA2, and PALB2 germline mutations are associated with an increased risk of PC. Other BRCA-associated cancers have demonstrated increased sensitivity to PARP inhibitors (PARPi) and early trials have shown activity of PARPi in untreated BRCAmut PC. We evaluated theactivity of V in patients with previously treated BRCA/PALB2mutPC. Methods: Eligibility: BRCA1/2, or PALB2mutPC, at least 1 and up to 2 prior treatment regimens, measurable stage III/IVPC; ECOG 0-1. Treatment Plan: V 300mg BID (N= 3 pts), then V 400mg BID day1- 28. Primary endpoint: RECIST 1.1 response rate (RR). Statistical plan: Single-arm, non-randomized, open-label, phase II, two-stage design, unacceptable RR 10%, promising 28%, type I, II error rates 10%. Secondary endpoints: progression-free survival (PFS), duration of response, overall survival, safety, tolerability and archival tumor analyses. Results: Between 05/12 and 12/13, N= 16 enrolled. Male= 8, Female= 8. Median age= 52 years (range 43- 77). BRCA1 mut=5. BRCA2 mut=11. N= 1AJCC stage III PC, N= 15 AJCC stage IV PC. N= 8 and N= 8 (50%) had 1 and 2 prior lines of therapy respectively. N= 13 (81%) received prior platinum therapy. Response: N= 1 unconfirmed PR (PR at 4 months (mo), POD at 6 mo), N= 4 stable disease (SD), N= 10 progressive disease (PD); N= 1 inevaluable (12 days of V only due to disease-related complications). Median PFS was 52 days (range 12 to 423). Three pts treated at 400mg V were dose-reduced for toxicity. Six pts had V related grade 3 toxicity including fatigue (N=3), hematologic (N=2) and nausea (N=1). No therapy-related grade 4-5 toxicities were observed. Conclusions: V was well tolerated. While no confirmed partial responses were observed, single-agent activity of V in previously treated PC was noted, and N= 4 (25%) remained on study with SD for ≥ 4mo (4, 6, 6, 9 mo). A randomized phase II trial evaluating cisplatin,gemcitabine +/- V is underway in untreated BRCA/PALB2mutPC (NCT01585805). Results of correlative studies will be presented. Acknowledgements: Lustgarten Foundation. NCI.AbbVie. Clinical trial information: NCT01585805.
Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma.
Authors: Mellon Eric Albert , Hoffe Sarah E. , Springett Gregory M. , Hodul Pamela Joy , Malafa Mokenge Peter , Frakes Jessica M. , Chuong Michael D. , Strom Tobin Joel Crill , Shridhar Ravi 
Published: February 2017

360 Background: Limited data is available for neoadjuvant treatment of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. We update our institutional outcomes with a neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT) approach. Methods: We performed an IRB-approved analysis of all BRPC and LAPC patients treated with our departmental treatment protocol. After staging, medically fit patients underwent chemotherapy for 2-3 months, with regimen at the discretion of the treating medical oncologist (FOLFIRINOX, GTX, gem/abraxane, or gemcitabine alone). Patients then received SBRT delivered in 5 consecutive daily fractions with median radiation doses of 30 Gy to tumor and 40 Gy dose painted to tumor-vessel interfaces. This was followed by restaging imaging for possible resection. Overall survival (OS), event free survival (EFS), and locoregional control (LRC) rates were estimated and compared by Kaplan-Meier and log-rank methods. Results: We identified 159 patients, 110 BRPC and 49 LAPC, with 14.0 months median overall follow-up. The resection and margin negative (R0) rate for BRPC patients who completed neoadjuvant therapy was 50.9% and 96.4%, respectively. Estimated median OS was 14.4 months for BRPC patients and 11.3 months for LAPC patients (p=0.402). Median OS was 34.2 months for surgically resected patients vs 14.0 months for unresected patients (p<0.001). Five of 21 (23.8%) LAPC patients receiving FOLFIRINOX chemotherapy underwent R0 resection. In LAPC, FOLFIRINOX recipients underwent R0 resection more often than other chemotherapy recipients (5 of 21 vs. 0 of 28, p=0.011). There was a trend for improved survival in those resected LAPC patients (p=0.09). For those not undergoing resection, one year LRC was 78.4%. Grade ≥3 potentially radiation related toxicity rate was 6.9%. Conclusions: This data underscores the feasibility, safety, and effectiveness of neoadjuvant SBRT and chemotherapy for BRPC and LAPC. Compared with other chemotherapies, FOLFIRINOX induced greater tumor response in LAPC, permitting for R0 resection in a subset of LAPC patients and trend towards improved OS.