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Introduction: Cancer-associated venous thrombosis (CAT) is a common and serious complication of active malignancies, increasing in frequency during systemic treatment and radiotherapy. Due to a high risk of recurrence and bleeding, the administration of anticoagulants for initial treatment and secondary prevention of CAT is challenging. We conducted a prospective registry study of patients with acute CAT to evaluate the way treatment is given to these patients in routine practice. Methods: From May 2015 to May 2017, all consecutive patients with acute venous thromboembolism (VTE) admitted to specialty or emergency departments of the participating hospitals in Berlin, Germany, were entered into the registry. Patients with cancer underwent extensive baseline evaluation including the type and location of thrombosis and use of anticoagulant therapy. Follow-up assessments were made at discharge and by telephone interviews at 3 and 6 months. Results: A total of 382 patients with acute CAT were enrolled in the study, representing 24.5% of all patients with thrombosis. 70.4% of CAT patients had deep vein thromboses (DVT), 48.2% had pulmonary embolism (PE), and 18.6% had concurrent PE and DVT. A significant proportion of VTE (27%) was asymptomatic and was diagnosed only incidentally. At baseline, 97.9% of the patients received anticoagulant therapy, predominantly with low-molecular-weight heparin (LMWH) (n = 334, 87.4%). Direct oral anticoagulants (DOACs) were given to 5.8% of patients, and vitamin K antagonists were rarely used (Conclusion: In accordance with the guidelines, the majority of CAT patients received anticoagulation therapy for the recommended minimum duration of 3–6 months. LMWH remained the preferred option throughout the study, demonstrating good patient adherence. In deviation from guideline recommendations and available study results during the study period, more than a quarter of CAT patients were treated with DOACs. Only recently, DOACs have been established as another option for anticoagulation in CAT patients.

Background CONKO-006 was designed for patients with pancreatic adenocarcinoma with postsurgical R1 residual status to evaluate the efficacy and safety of the combination of gemcitabine and sorafenib (GemSorafenib) compared with those of gemcitabine + placebo (GemP) for 12 cycles. Patients and methods This randomised, double-blind, placebo-controlled, multicenter study was planned to detect an improvement in recurrence-free survival (RFS) from 42% to 60% after 18 months. Secondary objectives were overall survival (OS), safety and duration of treatment. Results 122 patients were included between 02/2008 and 09/2013; 57 were randomised to GemSorafenib and 65 to GemP. Patient characteristics were wellbalanced (GemSorafenib/GemP) in terms of median age (63/63 years), tumour size (T3/T4: 97/97%), and nodal positivity (86/85%). Grade 3/4 toxicities comprised diarrhoea (GemSorafenib: 12%; GemP: 2%), elevated gamma-glutamyl transferase (GGT) (19%; 9%), fatigue (5%; 2%) and hypertension (5%; 2%), as well as neutropenia (18%; 25%) and thrombocytopenia (9%; 2%). By August 2017, 118 (97%) RFS event had occurred. There were no difference in RFS (median GemSorafenib: 8.5 versus GemP: 9.4 months; p = 0.730) nor OS (median GemSorafenib: 17.6 versus GemP: 17.5 months; p = 0.481). Landmark analyses suggest that patients who received more than six cycles of postoperative chemotherapy had significantly longer OS (p = 0.021). Conclusion CONKO-006 is the first randomised clinical trial to include exclusively patients with PDAC with postsurgical R1 status thus far. Sorafenib added to gemcitabine did neither improve RFS nor OS. However, postoperative treatment exceeding six months seemed to prolong survival and should be further investigated in these high-risk patients. Clinical trial information German Tumor Study Registry (Deutsches Krebsstudienregister), DRKS00000242.

Purpose: We performed next-generation sequencing (NGS) in the CONKO-001 phase III trial to identify clinically relevant prognostic and predictive mutations and conducted a functional validation in The Cancer Genome Atlas (TCGA) sequencing data. Experimental Design: Patients of the CONKO-001 trial received curatively intended surgery for pancreatic adenocarcinoma (PDAC) followed by adjuvant chemotherapy with gemcitabine (Gem) or observation only (Obs). Tissue samples of 101 patients were evaluated by NGS of 37 genes. Cox proportional hazard models were applied for survival analysis. In addition, functional genomic analyses were performed in an NGS and RNA-sequencing dataset of 146 pancreatic tumors from TCGA. Results: The most common mutations in the CONKO cohort were KRAS (75%), TP53 (60%), SMAD4 (10%), CDKNA2 (9%), as well as SWI/SNF (12%) complex alterations. In untreated patients, TP53 mutations were a negative prognostic factor for disease-free survival (DFS; HR mut vs. WT 2.434, P = 0.005). With respect to gemcitabine treatment, TP53 mutations were a positive predictive factor for gemcitabine efficacy [TP53mut: HR for DFS Gem vs. Obs, 0.235 (0.130 – 0.423; P < 0.001); TP53wt: HR for DFS Gem vs. Obs, 0.794 (0.417 – 1.513; P = 0.483)] with a significant test for interaction (P = 0.003). In the TCGA dataset, TP53 mutations were associated with shortened DFS. Conclusions: In CONKO-001, the benefit from adjuvant gemcitabine was confined to the TP53mut patient group. This potentially clinical relevant observation needs to be confirmed in independent prospective studies. The sensitivity of TP53mut PDAC to gemcitabine in CONKO-001 provides a lead for further mechanistic investigations.

Automated vehicles are entering the roads and automation is applied to cars, trucks, buses, and even motorcycles today. High automation foresees transitions during driving in both directions. The driver and rider state become a critical parameter since reliable automation allows safe intervention and transit control to the automation when manual driving is not performed safely anymore. When the control transits from automation to manual an appropriate driver state needs to be identified before releasing the automated control. The detection of driver states during manual and automated driving and an appropriate design of the human-machine interaction (HMI) are crucial steps to support these transitions. State‐of‐the‐art systems do not take the driver state, personal preferences, and predictions of road conditions into account. The ADAS&ME project, funded by the H2020 Programme of the European Commission, proposes an innovative and fully adaptive HMI framework, able to support driver/rider state monitoring‐based transitions in automated driving. The HMI framework is applied in the target vehicles: passenger car, truck, bus, and motorcycle, and in seven different use cases.

The issue of driving performance after sleeping becomes highly interesting when introducing automated driving in Level 4 (SAE). It is known that fatigue as well as hypovigilance are severe risk factors for traffic accidents while an effective countermeasure is sleeping. In Level 4 automation sleeping while driving becomes a possible scenario, including the issues of transitions. Several seconds for take-over as known from distraction studies are not enough to adjust the seat, regain control and recover after sleeping. Furthermore, when analyzing human performance after sleeping, the phenomenon of sleep inertia may affect reaction time and quality of performance.Take-over time and the effect of sleep inertia are investigated in a driving simulator study with 44 participants. As independent variable, the time after waking-up until taking over is varied: The participants had to take-over the driving task one minute, seven minutes or 15 min after waking up. A control group completed the task without sleeping. Lane keeping, deviation of line during the lane change task, braking time and mental workload served as dependent variables. There were no significant differences in driving performance between the groups when looking at driving performance, safety aspects and mental workload, hence no effect of sleep inertia was measured here. Further studies should investigate individual performance of more outliers and apply even more controlled measures to understand better if and how sleep inertia can become a problem for driving and what countermeasures should be applied. The study also shows, that take-over time of one minute leads to successful, but hectic take-overs, whereas a take-over time of 15 min induces fatigue in some drivers. We conclude that powernaps have a good chance to become a safe reality in Level 4 automation with a suitable take-over time between one and seven minutes. Keywords: Autonomous driving, Sleep inertia, Take-over, Driving performance, Driving simulation

Background: high recurrence rates of up to 75% within 2 years in pancreatic ductal adenocarcinoma (PDAC) patients resected for cure indicate a high medical need for clinical prediction tools and patient specific treat-ment approaches. Addition of the EGFR inhibitor erlotinib to adjuvant chemotherapy failed to improve out-come but its efficacy in some patients warrants predictors of responsiveness.Patients and Methods: we analysed tumour samples from 293 R0-resected patients from the randomized, multicentre phase III CONKO-005 trial (gemcitabine +/- erlotinib) with targeted sequencing, copy number, and RNA expression analyses.Findings: a total of 1086 mutations and 4157 copy-number aberrations (CNAs) with a mean of 17.9 /tumour were identified. Main pathways affected by genetic aberrations were the MAPK-pathway (99%), cell cycle control (92%), TGFb signalling (77%), chromatin remodelling (71%), and the PI3K/AKT pathway (65%). Based on genetic signatures extracted with non-negative matrix factorization we could define five patient clusters, which differed in mutation patterns, gene expression profiles, and survival. In multivariable Cox regression analysis, SMAD4 aberrations were identified as a negative prognostic marker in the gemcitabine arm, an effect that was counteracted when treated with erlotinib (DFS: HR=1.59, p = 0.016, and OS: HR = 1.67, p = 0.014). Integration of differential gene expression analysis established SMAD4 alterations with low MAPK9 expression (n = 91) as a predictive biomarker for longer DFS (HR=0.49; test for interaction, p = 0.02) and OS (HR = 0.32; test for interaction, p = 0.001).Interpretation: this study identified five biologically distinct patient clusters with different actionable lesions and unravelled a previously unappreciated association of SMAD4 alteration status with erlotinib effective-ness. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that SMAD4 status might guide addition of erlotinib treatment in early-stage PDAC patients. (C) 2021 The Author(s). Published by Elsevier B.V.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most fatal malignancies worldwide. It is suggested that survival in PDAC depends, among other things, on pattern of disease recurrence.We performed a pooled analysis of the adjuvant therapy studies CONKO-001, CONKO-005, and CONKO-006, including a total of 912 patients with regard to prognostic factors in patients with recurrent disease. Overall survival from disease recurrence (OS 2) and disease-free survival (DFS) from the day of surgery were expressed by Kaplan-Meier method and compared using log-rank testing and Cox regression.Of 912 patients treated within the previously mentioned CONKO trials, we identified 689 patients with disease recurrence and defined site of relapse. In multivariable analysis, the presence of isolated pulmonary metastasis, low tumour grading, and low postoperative level of CA 19-9 remained significant factors for improved OS 2 and DFS. Furthermore, completeness of adjuvant gemcitabine-based treatment (OS 2: P = 0.006), number of relapse sites (OS 2: P = 0.015), and type of palliative first-line treatment (OS 2: P 0.001) significantly affected overall survival after disease recurrence in PDAC.Determining tumour subgroups using prognostic factors may be helpful to stratify PDAC patients for future clinical trials. In case of disease recurrence, the site of relapse may have a prognostic impact on subsequent survival. Further investigations are needed to identify differences in tumour biology, reflecting relapse patterns and the differing survival of PDAC patients.

Automated driving is dramatically changing the way we perceive and control cars and lorries. In partially automated driving, the driver is still responsible for the vehicle control, but is strongly supported. In highly automated driving, the driver can give control and responsibility to the automation for a certain time and can get control back, e.g. when the automation encounters limits. However, an intuitive way to interact with these automated modes is largely missing. Vorreiter is addressing this by using the inspiration of a rider and a horse to provide intuitive steering gestures on the steering wheel or an alternative device, which initiate manoeuvres to be executed by the automation and to be supervised, influenced or interrupted by the driver. The gestures are built up in a design-for-all which helps all drivers, including beginners and drivers with disabilities. A consortium of RWTH Aachen University, Fraunhofer IAO, University of Stuttgart, Valeo and Hochschule fur Wirtschaft und Recht Berlin defined a concept, built up prototypes and investigated its impact in workshops and simulator experiments.

Background The prognostic effect of tumour budding was retrospectively analysed in a cohort of 173 patients with resected pancreatic ductal adenocarcinomas (PDACs) of the prospective clinical multicentre CONKO-001 trial. Methods Haematoxylin and eosin (H&E)-stained whole tissue slides were evaluated. In two independent approaches, the mean number of tumour buds was analysed according to the consensus criteria in colorectal cancer, in one 0.785 mm2 field of view and additionally in 10 high-power fields (HPF) (HPF = 0.238 mm2). Results Tumour budding was significantly associated with a higher tumour grade (p

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

Background We studied the prognostic effect of CD3-, CD8- and CD103-positive T lymphocytes in a cohort of 165 patients with resected pancreatic ductal adenocarcinomas (PDACs) of the treatment group (adjuvant gemcitabine) and the untreated control group of the CONKO-001 study. Methods Immunohistochemical stainings on tissue microarrays (TMAs) against CD3, CD8 and CD103 were performed according to standard procedures. Results A high number of CD8-positive lymphocytes were significantly and independently associated with longer disease-free survival (DFS) and overall survival (OS) in the overall study population. Median DFS/OS were 7.4/18.1 months for patients with a low number of CD8-positive intratumoural lymphocytes ( ≤ 42 per 1 mm tissue core) and 12.7/25.2 months for patients with high numbers (>42 per 1-mm tissue core; p = 0.008/0.020; HR 0.62/0.65). The ratio of intraepithelial to total CD103-positive lymphocytes, but not total numbers of CD103-positive lymphocytes or CD103-positive intraepithelial lymphocytes, was associated with significantly improved DFS and OS in the overall study population (p = 0.022/0.009). Median DFS/OS was 5.9/15.7 for patients with a ratio of intraepithelial to total CD103-positive intratumoural lymphocytes higher than 0.3 and 11.6/24.7 for patients with a lower ratio. Conclusion T-lymphocyte subpopulations might be prognostic in resectable PDAC but need standardization and verification by further studies.

Purpose Advanced pancreatic cancer (APC), in addition to its high mortality, accounts for the highest rates of venous thromboembolic events (VTEs). Enoxaparin, a low–molecular weight heparin, is effective in prevention and treatment of VTEs. Some small studies have indicated that this benefit might extend to patients with cancer. Patients and Methods Patients with histologically proven APC were randomly assigned to ambulant first-line chemotherapy and prophylactic use of enoxaparin or chemotherapy alone to investigate the probable reduction in symptomatic VTEs and the impact on survival. Results A total of 312 patients were recruited as one of the protocol end points was reached. Within the first 3 months, the numbers of symptomatic VTEs were as follows: 15 of 152 patients in the observation group and two of 160 patients in the enoxaparin group (hazard ratio [HR], 0.12; 95% CI, 0.03 to 0.52; χ2 P = .001). The numbers of major bleeding events were as follows: five of 152 patients in the observation arm and seven of 160 patients in the enoxaparin arm (HR, 1.4; 95% CI, 0.35 to 3.72; χ2 P = 1.0). Overall cumulative incidence rates of symptomatic VTEs were 15.1% (observation) and 6.4% (enoxaparin; HR, 0.40; 95% CI, 0.19 to 0.83; P = .01). Progression-free (HR, 1.06; 95% CI, 0.84 to 1.32; P = .64) and overall survival (HR, 1.01; 95% CI, 0.87 to 1.38; P = .44) did not differ between groups. Conclusion This study demonstrates the high efficacy and feasibility of primary pharmacologic prevention of symptomatic VTEs in outpatients with APC. Treatment efficacy was not affected by simultaneous treatment with enoxaparin in this trial setting.

Background: National and international guidelines for the diagnosis and treatment of cancer associated venous thromboembolism (CAT) recommend anticoagulation treatment for 3 to 6 months and a re-evaluation for resumption depending on the individual risk of every patient. In CAT low molecular weight heparin (LMWH) was estimated to be the most effective and safest treatment option in 2015. However, it remains unclear how cancer patients with VTE were (treated in clinical daily care in Germany. In former register trials, the specific characteristics of individual cancer patients were insufficiently characterized and inadequately discussed. Special aspects of daily care are lacking in most publications. Methods: The GECAT register was set up for Berlin´s two main hospital companies Charité-Universitaetsmedizin Berlin and Vivantes, (both covering about 50 % of the hospital beds in Berlin) to document prospectively patients with a newly diagnosed VTE . Patients with the diagnosis of cancer within 2 years prior to the VTE got basis documentation by a physician after informed consent. A follow up of these patients was scheduled after 3 and 6 months per telephone interview. Points of interest were: kind and location of the VTE event, diagnostic procedures, drug and dosage of initial and follow-up anti-coagulation treatment, relapse of VTE or bleeding complications, serious adverse events, mortality, and date and reason for determination of anticoagulation. Primary objective was to evaluate the treatment reality of patients with cancer associated VTE in clinical daily practice. Results: Between May 2015 and May 2017, 382 patients (pts) with active cancer within the last 2 years and newly diagnosed VTE gave consent to this register trial. 193 (50.5%) were female, median age was 65 years (range 19-89). For 133 pts (34.8%), VTE was the primary reason for admission at hospital, 34.3% were referred by their oncologist, 13,6% by their general practitioner, 15,5% by other treating physicians and 36.6% directly via the emergency department. 182 pts (47.6%) had pulmonary embolism, 268 pts (70.2%) had venous thrombosis and 18,6%71 pts (18.6%) had both. The most common cancer sites were lung (n=57, 14,9%), gynecological (n=44, 11,5%), colorectal (n=40, 10,5%) and pancreatic cancer (n=33 8,6%); 204 pts (56%) with solid tumors presented with stage IV diseases; 60 pts (15.7%) had hematological malignancies. 279 pts (73%) received anticancer treatments at the time of diagnosis of VTE. 148 (38.7%) pts died in the 6 months study period (20 pts died in hospital after admission, 90 pts within the first 3 months and 38 pts within the 6 months follow up). Initially, the majority of pts (n=350; 91.6%) was treated with LMWH. After discharge from hospital 78.7% remained on LMWH and 12.7% were treated with direct oral anticoagulants (DOACs). After 3 months 64.9% of pts received LMWH and 26.1% DOACs; after 6 months 48.4% LMWH and 44% DOACs. Responsible for the anticoagulation treatment decisions was mostly the oncologist (58%), followed by the general practitioner (26.3%) and other physicians (15,7%) . During the initial hospital stay, 2.6% of pts had a bleeding complication and 0.8% were diagnosed with a progress of VTE. At 6 months follow up, 6.4% reported bleeding complications and 2.4% recurrent VTE. Conclusion: The GECAT register trial gives new and clinically relevant information about the clinical daily care practice of cancer patients with newly diagnosed VTE in Berlin, Germany. The treating oncologist is in most cases responsible for the treatment. Disclosures Sinn: LEO: Research Funding; Bayer Healthcare AG: Research Funding; Servier: Honoraria, Research Funding; Astra Zeneca: Honoraria, Research Funding; Amgen: Honoraria; Sanofi: Honoraria. Scholz:Celgene: Consultancy; GILEAD: Consultancy, Speakers Bureau; Roche: Consultancy; Janssen-Cilag: Consultancy; Hexal: Consultancy; Novartis: Consultancy; Pfizer: Speakers Bureau; Takeda: Consultancy; Daiichi Sankio: Consultancy. Klamroth:Bayer, Biomarin, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, SOBI, Takeda: Consultancy; Bayer, Novo Nordisk, SOBI: Research Funding.

Background Long-term survival (LTS) in patients (pts) with pancreatic cancer is still uncommon, little data is available to identify long-term survivors. The CONKO-001 study, which established gemcitabine after resection as adjuvant therapy, may provide data to answer this question. Methods CONKO-001 pts with an overall survival ≥5 years were compared to those who survived

Background: The low incidence and the variable presentation complicate clinical investigations on biliary tract cancer. The results of Valle et al. in 2009 provided, for the first time, an evidence-based palliative treatment for this rare tumor type. So far no data are available in Germany regarding the current daily care practice. Methods: We started this national survey in May 2011, including about 3,400 members of the AIO (Working Group Medical Oncology), DGHO (German Society of Hematology and Oncology) and GGHBB (Society of Gastroenterology and Hepatology in Berlin and Brandenburg). The standardized online form contained questions concerning field of action and diagnostic and therapeutic procedures. Evaluation was conducted anonymously. Results: 162 responses could be obtained, corresponding to a response rate of about 5%. 70.4% of the respondents were physicians in hospitals, 23.5% stated to work in private practices. 61.7% of the respondents were medical oncologists and 27.2% gastroenterologists. 52.5% of the participants pointed out to use the standard regimen of gemcitabine and cisplatin. For second-line regimen, the most frequent answer (29%) specified the administration of oxaliplatin in combination with 5-fluorouracil (5-FU) or capecitabine. Conclusions: This survey may help to clarify the current oncologic daily care procedures for patients with biliary tract cancer in Germany. The results can be helpful for further clinical investigations or the implementation of a tumor-specific register.

OBJECTIVES: With increasing numbers of therapeutic options in inoperable pancreatic cancer (PAC), patients tend to receive more than just a first line (FL) therapy. METHODS: All patients who started FL for PAC at our institution (1997-2012) were retrospectively studied to identify patient's and treatment characteristics. Significant parameters in regard to second-line (SL) related survival were looked for as the basis for a prognostic model. This score was validated in a patient cohort from the CONKO-003 study. RESULTS: Two hundred eighty of 521 (53.7%) patients received SL therapy, median overall survival (OS) from the beginning of SL (OS2) was 5.1 months. Significant more SL patients had undergone surgery, a higher Karnofsky performance state (KPS) and a duration of FL longer than 4 months.Prognostic factors impacting OS2 were KPS, carbohydrate antigen 19-9 levels at start of SL and the duration of FL. These 3 factors establish a prognostic score-validated in CONKO-003-for SL patients with 3 subgroups: "good" (median OS2, 9.3 months), "intermediate" (median OS2, 7.1 months), "poor" prognosis (median OS2, 3.8 months; P < 0.001). CONCLUSIONS: Among patients with PAC, more than 50% receive SL therapy. Our prognostic model identifies 3 subgroups and can identify patients with a maximum benefit of SL therapy.

281 Background: The role of T lymphocytes, frequently found in the tumor microenvironment, on development and behavior of several solid tumors is well recognized. Studies on breast cancer and colon carcinoma showed the prognostic and predictive impact of tumor infiltrating T lymphocytes (TILs) while there are no similar studies on pancreatic cancer (PC) until now. Methods: We evaluated the prognostic effect of CD8 and CD103 positive TILs in a cohort of PC patients in the CONKO-001 study treated with adjuvant Gemcitabine or observed only. In 165 formalin-fixed paraffin-embedded (FFPE) tissue samples suitable for tissue microarray construction, CD 8 und CD 103 positive TILs were identified by immunohistochemical staining and counted manually; a ratio of intraepithelial to total CD 103 positive TILs was calculated. Results: The mean number of CD8 positive TILs was 69, a high number ( > 42 TILs) of CD8 positive lymphocytes was significantly associated with longer disease-free (DFS) and overall survival (OS) in the overall study population (high vs low median DFS 12.8 vs 7.4 months; p = 0.007, median OS 26.7 vs 18.1 months; p = 0.018). Furthermore, a ratio of intraepithelial to total CD103 positive lymphocytes < 0.3 was associated with significantly improved DFS and OS in the overall study population (high vs low median DFS 6.5 vs 11.8 months; p = 0.031, median OS 16.6 vs 24.7 months; p = 0.009). Conclusions: Our results suggest that the presence of TILs is important for prognosis in resected PC. We showed for the first time a prognostic effect of CD 8 and CD 103 expressing lymphocytes in PC. Therefore, we suggest further analysis of lymphocyte populations in this dismal entity.

Purpose To assess the efficacy of a second-line regimen of oxaliplatin and folinic acid–modulated fluorouracil in patients with advanced pancreatic cancer who have experienced progression while receiving gemcitabine monotherapy. Patients and Methods A randomized, open-label, phase III study was conducted in 16 institutions throughout Germany. Recruitment ran from January 2004 until May 2007, and the last follow-up concluded in December 2012. Overall, 168 patients age 18 years or older who experienced disease progression during first-line gemcitabine therapy were randomly assigned to folinic acid and fluorouracil (FF) or oxaliplatin and FF (OFF). Patients were stratified according to the presence of metastases, duration of first-line therapy, and Karnofsky performance status. Results Median follow-up was 54.1 months, and 160 patients were eligible for the primary analysis. The median overall survival in the OFF group (5.9 months; 95% CI, 4.1 to 7.4) versus the FF group (3.3 months; 95% CI, 2.7 to 4.0) was significantly improved (hazard ratio [HR], 0.66; 95% CI, 0.48 to 0.91; log-rank P = .010). Time to progression with OFF (2.9 months; 95% CI, 2.4 to 3.2) versus FF (2.0 months; 95% CI, 1.6 to 2.3) was significantly extended also (HR, 0.68; 95% CI, 0.50 to 0.94; log-rank P = .019). Rates of adverse events were similar between treatment arms, with the exception of grades 1 to 2 neurotoxicity, which were reported in 29 patients (38.2%) and six patients (7.1%) in the OFF and FF groups, respectively (P < .001). Conclusion Second-line OFF significantly extended the duration of overall survival when compared with FF alone in patients with advanced gemcitabine-refractory pancreatic cancer.

Background Previous investigations in pancreatic cancer suggested a prognostic role for secreted protein acidic and rich in cysteine (SPARC) expression in the peritumoral stroma but not for cytoplasmic SPARC expression. The aim of this study was to evaluate the impact of SPARC expression in pancreatic cancer patients treated with gemcitabine compared with untreated patients. Patients and methods CONKO-001 was a prospective randomized phase III study investigating the role of adjuvant gemcitabine when compared with observation. Tissue samples of 160 patients were available for SPARC immunohistochemistry on tissue microarrays to evaluate its impact on patient outcome. Results Strong stromal SPARC expression was associated with worse disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P = 0.005, OS: P = 0.033). Its negative prognostic impact was restricted to patients treated with gemcitabine (DFS: P = 0.007, OS: P = 0.006). High cytoplasmic SPARC expression also was associated with worse patient outcome (DFS: P = 0.041, OS: P = 0.011). Again the effect was restricted to patients treated with gemcitabine (DFS: P = 0.002, OS: P = 0.003). In multivariable analysis, SPARC expression was independently predictive of patient outcome. Conclusions Our data confirm the prognostic significance of SPARC expression after curatively intended resection. The negative prognostic impact was restricted to patients who received adjuvant treatment with gemcitabine, suggesting SPARC as a predictive marker for response to gemcitabine.

The influence of the nature of the anions on the conductivity of polypyrrole films in aqueous solution was investigated by photocurrent spectroscopy combined with electrochemical impedance spectroscopy in dependence on the potential. As demonstrated, the conductivity of polypyrrole films at negative potentials can vary from a semiconducting to an ionic conducting state, depending on the size of the charge-compensating counter-anion incorporated during the electropolymerization. The reduced polypyrrole shows semiconducting properties when small anions are inserted, releasing the polymer matrix during the reduction process. The polymer can than be considered as a two-layer system, consisting of a semiconducting layer and a porous layer. Measurements at different thickness of polypyrrole films have shown that the position of the semiconducting layer is in the electrode/polymer interface. The ohmic resistance of the semiconducting layer is in the range 1–5 kΩ, the capacitance approaches a value of 100–500 nF and the flatband potential is −0.62 VSCE. If large anions are incorporated, cation insertion takes place during reduction, the electrolyte content in the polymer then is relatively high and the polymer's behaviour is similar to that of an ionic conductor. The results are presented and discussed together with the example of methylsulfonate as a relatively small anion and polystyrenesulfonate as a large anion.

Long-term survival (LTS) in patients (pts) with pancreatic cancer is still uncommon, little data is available to identify long-term survivors. The CONKO-001 study, which established gemcitabine after resection as adjuvant therapy, may provide data to answer this question.CONKO-001 pts with an overall survival ≥5 years were compared to those who survived5 years. Central re-evaluation of primary histology was performed. Univariate analysis with the χ(2) -test identified qualifying factors. Logistic regression was used to investigate the influence of these covariates on LTS.Of the evaluable 354 CONKO-001 pts, 54 (15%) with an overall survival ≥5 years were identified. It was possible to obtain tumor specimens of 39 pts (72%). Histological re-evaluation confirmed adenocarcinoma in 38 pts, 1 showed a high-grade neuroendocrine tumor. Univariate analysis for all 53 LTS pts with adenocarcinoma compared to the remaining 300 non-LTS pts revealed as relevant active treatment, tumor grading, tumor size, lymph nodes. No significance could be demonstrated for resection margin, sex, age, Karnofsky performance status, CA 19-9 at study entry. In multivariate analysis, tumor grading, active treatment, tumor size, lymph node involvement were independent prognostic factors for LTS.Long-term survival can be achieved in adenocarcinoma of the pancreas.

e15717Background: The combination of nabpaclitaxel/gemcitabine (AG) is one standard of care treatment for patients (pts) with advanced pancreatic adenocarcinoma (APC). Only insufficient data accord...

e15219 Background: Although recurrences occur after most curatively intended PA resections with ensuing adjuvant G chemotherapies, it remains unclear, whether and from which point in time after adj...

e15218 Background: It remains unclear, whether survival from the initiation of Gem-based first-line therapy differs between previously operated patients with or without adjuvant chemotherapy with Gem and patients receiving palliative therapy after a diagnosis of PC in an initially unresectable disease stage. Methods: We retrospectively analysed prospectively collected data of 702 PC-patients treated at “Charite Campus Virchow-Klinikum” between 1991 and 2014. Kaplan-Meier estimates of the primary endpoints PFS and OS from the initiation of palliative first-line therapy were compared with the aid of log-rank test with two-sided p-values of < 0.05 for 462 patients with Gem-based palliative first-line therapy. Among them, 140 had been operated with curative intent, 45 having, 95 not having received adjuvant therapy; 322 had been treated palliatively after first diagnosis of PC. Prognostic factors of statistical significance were established by Cox regression analysis. Results: PFS and OS were significantly lo...

4044 Background: Patients (pts) with advanced pancreatic cancer (APC) often suffer from symptomatic thromboembolic events (sVTE). The CONKO-004 trial showed that the low molecular weight heparin (LMWH) enoxaparin reduces sVTE (p