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Pancreatic Neoplasms: HELP
Articles by Stephan Kruger
Based on 20 articles published since 2009
(Why 20 articles?)
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Between 2009 and 2019, S. Kruger wrote the following 20 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Safety of palliative chemotherapy in advanced pancreatic cancer. 2016

Westphalen, C Benedikt / Kruger, Stephan / Haas, Michael / Heinemann, Volker / Boeck, Stefan. ·a Department of Internal Medicine III and Comprehensive Cancer Center , Klinikum Grosshadern, Ludwig-Maximilians-University of Munich , Munich , Germany. ·Expert Opin Drug Saf · Pubmed #27070177.

ABSTRACT: INTRODUCTION: Pancreatic cancer is a major health burden. Currently, the majority of patients is diagnosed at advanced stages and thus qualifies for palliative chemotherapy. Gemcitabine monotherapy has been the gold standard for many years. Recently, more effective chemotherapeutic regimens have shown meaningful clinical activity in patients with metastatic pancreatic cancer. AREAS COVERED: In this review we have aimed to give an overview on the treatment options for patients diagnosed with metastatic pancreatic cancer with an emphasis on the safety and toxicity of the applied regimens. We have conducted a pubmed search using the terms 'metastatic pancreatic cancer', 'palliative chemotherapy', 'safety' and 'toxicity'. Our special focus rested on randomized phase III trials to provide readers with the highest level of available evidence. EXPERT OPINION: The emergence of new and more effective chemotherapy regimens gives clinicians more freedom in the treatment of metastatic pancreatic cancer. While being more effective, these regiments have a considerable degree of toxicity. Choosing the right treatment for any individual will be the next major challenge treating patients with pancreatic cancer.

2 Review Translational research in pancreatic ductal adenocarcinoma: current evidence and future concepts. 2014

Kruger, Stephan / Haas, Michael / Ormanns, Steffen / Bächmann, Sibylle / Siveke, Jens T / Kirchner, Thomas / Heinemann, Volker / Boeck, Stefan. ·Stephan Kruger, Michael Haas, Sibylle Bächmann, Volker Heinemann, Stefan Boeck, Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. ·World J Gastroenterol · Pubmed #25152580.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is one of the major causes for cancer death worldwide. Treatment of metastatic disease remains challenging as only certain patients benefit from advances made with the intensified chemotherapy regimen folinic acid, irinotecan and oxaliplatin, the epidermal growth factor receptor inhibitor erlotinib or the recently FDA-approved nab-paclitaxel. Up to date, no established approach for prediction of treatment response or specific treatment allocation exists. Translational research was able to identify a number of potential biomarkers that might help to improve the dismal prognosis of PDA by facilitating upfront treatment allocation. This topic highlight is focused on current evidence on potential biomarkers for tumor biology, prognosis and prediction of treatment efficacy.

3 Clinical Trial Efficacy of gemcitabine plus erlotinib in rash-positive patients with metastatic pancreatic cancer selected according to eligibility for FOLFIRINOX: A prospective phase II study of the 'Arbeitsgemeinschaft Internistische Onkologie'. 2018

Haas, M / Siveke, J T / Schenk, M / Lerch, M M / Caca, K / Freiberg-Richter, J / Fischer von Weikersthal, L / Kullmann, F / Reinacher-Schick, A / Fuchs, M / Kanzler, S / Kunzmann, V / Ettrich, T J / Kruger, S / Westphalen, C B / Held, S / Heinemann, V / Boeck, S. ·Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. Electronic address: michael.haas@med.lmu.de. · 2nd Medical Department, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Solid Tumor Translational Oncology (DKTK, Partner Site Essen), West German Cancer Center, University Hospital Essen, Essen, Germany. · Department of Haematology and Oncology, Hospital Barmherzige Brüder, Regensburg, Germany. · Department of Medicine A, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt University, Greifswald, Germany. · Department of Internal Medicine I, Klinikum Ludwigsburg, Ludwigsburg, Germany. · Practice for Haematology and Oncology, Dresden, Germany. · Department of Oncology, Gesundheitszentrum St. Marien, Amberg, Germany. · Department of Medicine I, Klinikum Weiden, Weiden, Germany. · Department of Haematology and Oncology, St. Josef-Hospital, Ruhr University, Bochum, Germany. · Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Klinikum Bogenhausen, Munich, Germany. · Department of Internal Medicine II, Leopoldina Krankenhaus Schweinfurt, Schweinfurt, Germany. · Department of Medical Oncology, University Hospital of Wuerzburg, Wuerzburg, Germany. · Department of Internal Medicine I, University of Ulm, Ulm, Germany. · Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. · ClinAssess GmbH, Leverkusen, Germany. ·Eur J Cancer · Pubmed #29549862.

ABSTRACT: INTRODUCTION: In metastatic pancreatic ductal adenocarcinoma (mPDAC) treatment, erlotinib is known to be more effective in patients developing skin rash. Treatment with the FOLFIRINOX regimen is only performed in fit patients following defined inclusion criteria. The present study investigates the efficacy of gemcitabine plus erlotinib (gem/erlotinib) in rash-positive patients fit for FOLFIRINOX. PATIENTS AND METHODS: For this prospective phase II study, 150 patients were recruited in 20 centres. All patients received gem/erlotinib for 4 weeks (run-in phase); the subsequent treatment was determined by the development of skin rash: patients with rash grades 1-4 continued with gem/erlotinib, rash-negative patients were switched to FOLFIRINOX. Primary study end-point was to achieve a 1-year survival rate in rash-positive patients ≥40%. RESULTS: Ninety patients were deemed positive for skin rash by the end of the run-in phase, showing a 1-year survival rate of 40.0% (95% confidence interval [CI] 29.8-50.9). Median overall survival (OS) was 10.1 months, progression-free survival (PFS) was 3.8 months and overall response rate (ORR) was 23.3%. Patients switched to FOLFIRINOX (n = 27) had a 1-year survival rate of 48.1% (95% CI 28.7-68.1), a median OS of 10.9 months, a median PFS of 6.6 months and an ORR of 33.3%. Rash-negative patients had a lower quality of life at baseline but seemed to experience an improved control of pain during FOLFIRINOX. CONCLUSIONS: First-line treatment with gem/erlotinib was effective in fit, rash-positive mPDAC patients achieving a 1-year survival rate comparable to previous reports for FOLFIRINOX. The study was registered at clinicaltrials.gov (NCT0172948) and Eudra-CT (2011-005471-17).

4 Clinical Trial The Impact of SMAD4 Loss on Outcome in Patients with Advanced Pancreatic Cancer Treated with Systemic Chemotherapy. 2017

Ormanns, Steffen / Haas, Michael / Remold, Anna / Kruger, Stephan / Holdenrieder, Stefan / Kirchner, Thomas / Heinemann, Volker / Boeck, Stefan. ·Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Str. 36, 80337 Munich, Germany. steffen.ormanns@med.uni-muenchen.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany. michael.haas@med.uni-muenchen.de. · Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Str. 36, 80337 Munich, Germany. annaremold@yahoo.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany. annaremold@yahoo.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany. stephan.kruger@med.uni-muenchen.de. · Institute of Laboratory Medicine, German Heart Centre Munich, Technische Universität München, 80333 Munich, Germany. holdenrieder@dhm.mhn.de. · Institute of Clinical Chemistry and Clinical Pharmacology, Universitätsklinikum Bonn, 53127 Bonn, Germany. holdenrieder@dhm.mhn.de. · Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Str. 36, 80337 Munich, Germany. thomas.kirchner@med.uni-muenchen.de. · Deutsches Konsortium für Translationale Krebsforschung (DKTK, German Cancer Consortium), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. thomas.kirchner@med.uni-muenchen.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany. volker.heinemann@med.uni-muenchen.de. · Deutsches Konsortium für Translationale Krebsforschung (DKTK, German Cancer Consortium), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. volker.heinemann@med.uni-muenchen.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany. stefan.boeck@med.uni-muenchen.de. · Deutsches Konsortium für Translationale Krebsforschung (DKTK, German Cancer Consortium), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. stefan.boeck@med.uni-muenchen.de. ·Int J Mol Sci · Pubmed #28534865.

ABSTRACT: The role of the tumor suppressor mothers against decapentaplegic homolog 4 (SMAD4) has not yet been defined in patients (pts) with advanced pancreatic cancer (aPC). This translational research study was designed to evaluate the impact of tumoral SMAD4 loss on clinicopathological parameters and outcome in PC patients receiving palliative chemotherapy. Using immunohistochemistry, we examined SMAD4 expression in tumor tissue of 143 aPC pts treated within completed prospective clinical and biomarker trials. In uni- and multivariate analyses, SMAD4 expression status was correlated to clinicopathological patient characteristics and outcome. At chemotherapy initiation, 128 pts had metastatic PC; most pts (

5 Clinical Trial Impact of hand-foot skin reaction on treatment outcome in patients receiving capecitabine plus erlotinib for advanced pancreatic cancer: a subgroup analysis from AIO-PK0104. 2015

Kruger, Stephan / Boeck, Stefan / Heinemann, Volker / Laubender, Ruediger P / Vehling-Kaiser, Ursula / Waldschmidt, Dirk / Kettner, Erika / Märten, Angela / Winkelmann, Cornelia / Klein, Stefan / Kojouharoff, Georgi / Gauler, Thomas C / Fischer von Weikersthal, Ludwig / Clemens, Michael R / Geissler, Michael / Greten, Tim F / Hegewisch-Becker, Susanna / Modest, Dominik P / Stintzing, Sebastian / Haas, Michael. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich , Munich , Germany. ·Acta Oncol · Pubmed #25924969.

ABSTRACT: BACKGROUND: Drug-induced skin toxicity may correlate with treatment efficacy in cancer patients receiving chemotherapy or biological agents. The correlation of the capecitabine-associated hand-foot skin reaction (HFS) on outcome parameters in pancreatic cancer (PC) has not yet been investigated. METHODS: Within the multicentre phase III AIO-PK0104 trial, patients with confirmed advanced PC were randomly assigned to first-line treatment with either capecitabine plus erlotinib (150 mg/day, arm A) or gemcitabine plus erlotinib (150 mg/day, arm B). A cross-over to either gemcitabine (arm A) or capecitabine (arm B) was performed after failure of the first-line regimen. Data on skin toxicity were correlated with efficacy study endpoints using uni- and multivariate analyses. To control for guarantee-time bias (GTB), we focused on subgroup analyses of patients who had completed two and three or more treatment cycles. RESULTS: Of 281 randomised patients, skin toxicity data were available for 255 patients. Median time to capecitabine-attributed HFS was two cycles, 36 of 47 (77%) HFS events had been observed by the end of treatment cycle three. Considering HFS during first-line treatment in 101 patients treated with capecitabine for at least two cycles within the capecitabine plus erlotinib arm, time to treatment failure after first- and second-line therapy (TTF2) and overall survival (OS) both were significantly prolonged for the 44 patients (44%) with HFS compared to 57 patients without HFS (56%) (TTF2: 7.8 vs. 3.8 months, HR 0.50, p = 0.001; OS: 10.4 vs. 5.9 months, HR 0.55, p = 0.005). A subgroup analysis of 70 patients on treatment with capecitabine for at least three cycles showed similar results (TTF2: 8.3 vs. 4.4 months, HR 0.53, p = 0.010; OS: 10.4 vs. 6.7 months, HR 0.62, p = 0.056). CONCLUSION: The present subgroup analysis from AIO-PK0104 suggests that HFS may serve as an independent clinical predictor for treatment outcome in capecitabine-treated patients with advanced PC.

6 Clinical Trial pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104. 2014

Ormanns, Steffen / Siveke, Jens T / Heinemann, Volker / Haas, Michael / Sipos, Bence / Schlitter, Anna Melissa / Esposito, Irene / Jung, Andreas / Laubender, Rüdiger P / Kruger, Stephan / Vehling-Kaiser, Ursula / Winkelmann, Cornelia / Fischer von Weikersthal, Ludwig / Clemens, Michael R / Gauler, Thomas C / Märten, Angela / Geissler, Michael / Greten, Tim F / Kirchner, Thomas / Boeck, Stefan. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, München, Germany. stefan.boeck@med.uni-muenchen.de. ·BMC Cancer · Pubmed #25164437.

ABSTRACT: BACKGROUND: The role of pERK, pAKT and p53 as biomarkers in patients with advanced pancreatic cancer has not yet been defined. METHODS: Within the phase III study AIO-PK0104 281 patients with advanced pancreatic cancer received an erlotinib-based 1st-line regimen. Archival tissue from 153 patients was available for central immunohistochemistry staining for pERK, pAKT and p53. Within a subgroup analysis, biomarker data were correlated with efficacy endpoints and skin rash using a Cox regression model. RESULTS: Fifty-five out of 153 patients were classified as pERKlow and 98 patients as pERKhigh; median overall survival (OS) was 6.2 months and 5.7 months, respectively (HR 1.29, p = 0.16). When analysing pERK as continuous variable, the pERK score was significantly associated with OS (HR 1.06, 95% CI 1.0-1.12, p = 0.05). Twenty-one of 35 patients were pAKTlow and 14/35 pAKThigh with a corresponding median OS of 6.4 months and 6.8 months, respectively (HR 1.03, p = 0.93). Four out of 50 patients had a complete loss of p53 expression, 20 patients a regular expression and 26 patients had tumors with p53 overexpression. The p53 status had no impact on OS (p = 0.91); however, a significant improvement in progression-free survival (PFS) (6.0 vs 1.8 months, HR 0.24, p = 0.02) and a higher rate of skin rash (84% vs 25%, p = 0.02) was observed for patients with a regular p53 expression compared to patients with a complete loss of p53. CONCLUSION: pERK expression may have an impact on OS in erlotinib-treated patients with advanced pancreatic cancer; p53 should be further investigated for its potential role as a predictive marker for PFS and skin rash. TRIAL REGISTRATION: NCT00440167 (registration date: February 22, 2007).

7 Clinical Trial Human equilibrative nucleoside transporter 1 is not predictive for gemcitabine efficacy in advanced pancreatic cancer: translational results from the AIO-PK0104 phase III study with the clone SP120 rabbit antibody. 2014

Ormanns, Steffen / Heinemann, Volker / Raponi, Mitch / Isaacson, Jeff / Laubender, Rüdiger P / Haas, Michael / Kruger, Stephan / Kleespies, Axel / Mann, Elaina / Bartosiewicz, Mike / Kirchner, Thomas / Boeck, Stefan. ·Department of Pathology, Ludwig-Maximilians-University of Munich, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. · Clovis Oncology Inc., San Francisco, CA, USA. · German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany. · Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany. · Department of Pathology, Ludwig-Maximilians-University of Munich, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany. Electronic address: stefan.boeck@med.uni-muenchen.de. ·Eur J Cancer · Pubmed #24857044.

ABSTRACT: BACKGROUND: The role of human equilibrative nucleoside transporter 1 (hENT1) as a predictive biomarker for gemcitabine efficacy in advanced pancreatic cancer remains unclear to date. PATIENTS AND METHODS: AIO-PK0104 was a German multicenter phase III trial comparing gemcitabine/erlotinib followed by capecitabine (GEC) with capecitabine/erlotinib followed by gemcitabine (CEG) in advanced pancreatic cancer. Archival tumour tissue from 169 of the 274 eligible study patients was available for a central and standardised immunohistochemistry staining for hENT1 expression using the SP120 rabbit monoclonal anti-hENT1 antibody. Within a retrospective translational subgroup analysis, biomarker data were correlated with efficacy end-points. RESULTS: Thirty-nine out of 130 fresh-cut slides were scored as hENT1(high) (30%), whereas 91 samples were classified as hENT1(low) (70%). For the 62 patients randomised to CEG median overall survival was estimated with 6.4 months in the hENT1(low) compared to 6.9 months in the hENT1(high) subgroup (Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.48-1.61, p=0.67). For the 68 patients randomised to GEC survival was 5.7 months in the hENT1(low) compared to 4.4 months in the hENT1(high) subgroup (HR 1.16, 95% CI 0.69-1.96, p=0.57). In 101 patients receiving gemcitabine at any time during study treatment (either within the 1st- or 2nd-line setting) hENT1(low) cases had a median overall survival of 7.5 months and hENT1(high) patients an overall survival of 4.4 months (HR 1.30, 95% CI 0.84-2.03, p=0.24), respectively. CONCLUSION: Within this subgroup analysis from Arbeitsgemeinschaft Internistische Onkologie-pancreatic cancer (AIO-PK0104), no evidence supporting the use of hENT1 as a predictive biomarker for gemcitabine efficacy in patients with advanced pancreatic cancer was found.

8 Article POLE gene hotspot mutations in advanced pancreatic cancer. 2018

Guenther, Michael / Veninga, Vivien / Kumbrink, Joerg / Haas, Michael / Westphalen, C Benedikt / Kruger, Stephan / Heinemann, Volker / Kirchner, Thomas / Boeck, Stefan / Jung, Andreas / Ormanns, Steffen. ·Institute of Pathology, Medical Faculty, Ludwig-Maximilians-University, Thalkirchner Str. 36, 80337, Munich, Germany. · Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Comprehensive Cancer Center Munich (CCCM), Munich, Germany. · Institute of Pathology, Medical Faculty, Ludwig-Maximilians-University, Thalkirchner Str. 36, 80337, Munich, Germany. steffen.ormanns@med.uni-muenchen.de. ·J Cancer Res Clin Oncol · Pubmed #30194485.

ABSTRACT: PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, lacking relevant prognostic and predictive biomarkers. DNA polymerase epsilon (POLE) has important functions in the maintenance of genetic stability during DNA replication and has previously been associated with favorable prognosis in endometrial and colorectal cancer. However, its relevance in advanced pancreatic cancer (aPDAC) has not been examined to date. METHODS: Using pyrosequencing on tumoral DNA extracted from 60 samples from the AIO-PK0104 study as well as 55 samples from completed translational trials, we examined POLE hotspot mutations in exon 9 (P286R) and exon 13 (V411R/L/M) in the POLE gene exonuclease domain. DNA extracted from 37 endometrial carcinomas were tested as positive controls. Publically available sequencing databases were searched for POLE mutations in PDAC samples. RESULTS: Fifty-three patients (pts) were men, 62 pts were women, median age was 61.2 years. Median overall survival (OS) was 7.4 months and median progression free survival (PFS) was 4.0 months. In four of the 37 endometrial carcinomas POLE mutations were detected in exon 9 (10.8%) and none in exon 13. In none of the overall 115 aPDAC tumors POLE gene hotspot mutations could be detected. CONCLUSION: Mutations in the hotspot regions of exon 9 and 13 of the POLE gene are very rare events in advanced pancreatic cancer. Thus, it is unlikely that POLE gene mutations contribute to genetic instability in the vast majority of aPDAC. POLE mutation does not serve as a relevant biomarker and should not be tested on a regular basis in PDAC.

9 Article Immune Cell and Stromal Signature Associated With Progression-Free Survival of Patients With Resected Pancreatic Ductal Adenocarcinoma. 2018

Mahajan, Ujjwal Mukund / Langhoff, Eno / Goni, Elisabetta / Costello, Eithne / Greenhalf, William / Halloran, Christopher / Ormanns, Steffen / Kruger, Stephan / Boeck, Stefan / Ribback, Silvia / Beyer, Georg / Dombroswki, Frank / Weiss, Frank-Ulrich / Neoptolemos, John P / Werner, Jens / D'Haese, Jan G / Bazhin, Alexandr / Peterhansl, Julian / Pichlmeier, Svenja / Büchler, Markus W / Kleeff, Jörg / Ganeh, Paula / Sendler, Matthias / Palmer, Daniel H / Kohlmann, Thomas / Rad, Roland / Regel, Ivonne / Lerch, Markus M / Mayerle, Julia. ·Department of Medicine II, University Hospital, LMU Munich, Germany; Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. · Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. · Department of Medicine II, University Hospital, LMU Munich, Germany. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany. · Department of Medicine III, University Hospital, LMU Munich, Germany. · Department of Pathology, University Medicine Greifswald, Greifswald, Germany. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther University Halle-Wittenberg, Halle, Germany. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK. · Department of Community Medicine, University Medicine Greifswald, Greifswald, Germany. · Center for Translational Cancer Research (TranslaTUM), Technische Universität München, Munich, Germany. · Department of Medicine II, University Hospital, LMU Munich, Germany; Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. Electronic address: julia.mayerle@med.uni-muenchen.de. ·Gastroenterology · Pubmed #30092175.

ABSTRACT: BACKGROUND & AIMS: Changes to the microenvironment of pancreatic ductal adenocarcinomas (PDACs) have been associated with poor outcomes of patients. We studied the associations between composition of the pancreatic stroma (fibrogenic, inert, dormant, or fibrolytic stroma) and infiltration by inflammatory cells and times of progression-free survival (PFS) of patients with PDACs after resection. METHODS: We obtained 1824 tissue microarray specimens from 385 patients included in the European Study Group for Pancreatic Cancer trial 1 and 3 and performed immunohistochemistry to detect alpha smooth muscle actin, type 1 collagen, CD3, CD4, CD8, CD68, CD206, and neutrophils. Tumors that expressed high and low levels of these markers were compared with patient outcomes using Kaplan-Meier curves and multivariable recursive partitioning for discrete-time survival tree analysis. Prognostic index was delineated by a multivariable Cox proportional hazards model of immune cell and stromal markers and PFS. Findings were validated using 279 tissue microarray specimens from 93 patients in a separate cohort. RESULTS: Levels of CD3, CD4, CD8, CD68, and CD206 were independently associated with tumor recurrence. Recursive partitioning for discrete-time survival tree analysis identified a high level of CD3 as the strongest independent predictor for longer PFS. Tumors with levels of CD3 and high levels of CD206 associated with a median PFS time of 16.6 months and a median prognostic index of -0.32 (95% confidence interval [CI] -0.35 to -0.31), whereas tumors with low level of CD3 cell and low level of CD8 and high level of CD68 associated with a median PFS time of 7.9 months and a prognostic index of 0.32 (95% CI 0.050-0.32); we called these patterns histologic signatures. Stroma composition, when unassociated with inflammatory cell markers, did not associate significantly with PFS. In the validation cohort, the histologic signature resulted in an error matrix accuracy of predicted response of 0.75 (95% CI 0.64-0.83; accuracy P < .001). CONCLUSIONS: In an analysis of PDAC tissue microarray specimens, we identified and validated a histologic signature, based on leukocyte and stromal factors, that associates with PFS times of patients with resected PDACs. Immune cells might affect the composition of the pancreatic stroma to affect progression of PDAC. These findings provide new insights into the immune response to PDAC.

10 Article Incidence, outcome and risk stratification tools for venous thromboembolism in advanced pancreatic cancer - A retrospective cohort study. 2017

Kruger, Stephan / Haas, Michael / Burkl, Carolin / Goehring, Peter / Kleespies, Axel / Roeder, Falk / Gallmeier, Eike / Ormanns, Steffen / Westphalen, Christoph Benedikt / Heinemann, Volker / Rank, Andreas / Boeck, Stefan. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. · Institute of Laboratory Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany. · Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany. · Department of Radiation Oncology, Ludwig-Maximilians-University of Munich, Munich, Germany; Department of Molecular Radiation Oncology, German Cancer Research Center, Heidelberg, Germany. · Department of Gastroenterology, Endocrinology and Metabolism, University Hospital of Marburg, Philipps-University of Marburg, Marburg, Germany. · Institute of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany. · Department of Hematology and Oncology, Klinikum Augsburg, Augsburg, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. Electronic address: stefan.boeck@med.uni-muenchen.de. ·Thromb Res · Pubmed #28675831.

ABSTRACT: INTRODUCTION: Venous thromboembolism (VTE) is frequent in advanced pancreatic cancer (APC). Recent studies demonstrated that the Khorana score - an established risk stratification tool for VTE in cancer - performs poorly in identifying pancreatic cancer patients at high risk for VTE. MATERIALS AND METHODS: We performed a retrospective cohort study in order to define incidence, treatment and outcome of VTE as well as the performance of VTE risk stratification tools (Khorana score, CONKO score and aPTT ratio) in a "real life" clinical cohort of APC patients undergoing palliative chemotherapy. RESULTS AND CONCLUSIONS: One hundred and seventy-two eligible APC patients from our comprehensive cancer center were identified. VTE after start of palliative chemotherapy was diagnosed in 71 patients (41.3%). Most VTE events were asymptomatic (n=50, 29.1%) with only 21 symptomatic events (12.2%). On multivariate analysis - including age, performance status and carbohydrate antigen 19-9 (CA 19-9) - symptomatic VTE was an independent risk factor for death (hazard ratio [HR]: 2.22, 95% CI: 1.05-2.60, p<0.05). Khorana score, CONKO score and aPTT ratio alone were not able to predict the risk for symptomatic VTE. High risk patients could only be identified by using a combination of either Khorana or CONKO score with aPTT ratio (30% vs. 10% symptomatic VTE events in high vs. low risk patients, p<0.05). The combination of Khorana or CONKO score with aPTT thus may represent a novel risk stratification tool for symptomatic VTE in APC and should further be validated within prospective clinical trials.

11 Article Switch in KRAS mutational status during an unusual course of disease in a patient with advanced pancreatic adenocarcinoma: implications for translational research. 2017

Baechmann, Sibylle / Ormanns, Steffen / Haas, Michael / Kruger, Stephan / Remold, Anna / Modest, Dominik Paul / Kirchner, Thomas / Jung, Andreas / Werner, Jens / Heinemann, Volker / Boeck, Stefan. ·Institute of Pathology, Ludwig-Maximilians University of Munich, Munich, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377, Munich, Germany. · DKTK, German Cancer Consortium, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of General, Visceral, Vascular and Transplantation Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377, Munich, Germany. stefan.boeck@med.uni-muenchen.de. ·BMC Cancer · Pubmed #28549417.

ABSTRACT: BACKGROUND: Despite the introduction of novel effective treatment regimens like gemcitabine plus nab-paclitaxel and FOLFIRINOX, pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive epithelial tumors. Among the genetic alterations frequently found in PDAC, mutations in the KRAS gene might play a prognostic role regarding overall survival and may also have the potential to predict the efficacy of anti-EGFR treatment. CASE PRESENTATION: We report the clinical case of a 69 year old Caucasian female that was diagnosed with histologically confirmed locally advanced PDAC with lymph node involvement in August 2010. At the time of first diagnosis, tumor tissue obtained from an open regional lymph node biopsy showed a poorly differentiated adenocarcinoma with a wild type sequence within exon 2 (codon 12/13) of the KRAS gene. The patient initially received single-agent gemcitabine and a subsequent 5-FU-based chemoradiotherapy with a sequential maintenance chemotherapy with oral capecitabine resulting in a long term disease control. Local disease progression occurred in May 2014 and the patient underwent pancreaticoduodenectomy in September 2014. A novel KRAS gene mutation (c.35G > T, p.G12 V) in exon 2 (codon 12) was detected within the surgical specimen. As of January 2016 the patient is still alive and without evidence of the underlying disease. CONCLUSIONS: Specifically in the context of clinical trials and translational research in PDAC a re-assessment of molecular biomarkers, i. e. KRAS, at defined time points (e. g. relapse, disease progression, unusual clinical course) may be indicated in order to detect a potential switch in biomarker status during the course of disease.

12 Article Extended RAS analysis and correlation with overall survival in advanced pancreatic cancer. 2017

Haas, Michael / Ormanns, Steffen / Baechmann, Sibylle / Remold, Anna / Kruger, Stephan / Westphalen, Christoph B / Siveke, Jens T / Wenzel, Patrick / Schlitter, Anna Melissa / Esposito, Irene / Quietzsch, Detlef / Clemens, Michael R / Kettner, Erika / Laubender, Ruediger P / Jung, Andreas / Kirchner, Thomas / Boeck, Stefan / Heinemann, Volker. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, Munich 81377, Germany. · Institute of Pathology, Ludwig-Maximilians-University of Munich, Germany and German Cancer Consortium (DKTK), Partner Site Munich, Thalkirchner Str. 36, Munich 80377, Germany. · 2nd Medical Department, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, Munich 81675, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany. · Division of Solid Tumour Translational Oncology, German Cancer Consortium (DKTK), Partner Site Essen, University Hospital Essen, Hufelandstr. 55, Essen 45147, Germany. · Institute of Pathology, Technical University of Munich, Trogerstr. 18, Munich 81675, Germany. · Institute of Pathology, Heinrich Heine University of Duesseldorf, Moorenstr. 5, Duesseldorf 40225, Germany. · Department of Internal Medicine II, Klinikum Chemnitz gGmbH, Flemmingstr. 2, Chemnitz 09116, Germany. · Department of Hematology and Oncology, Mutterhaus der Boromaeerinnen, Feldstr. 16, Trier 54290, Germany. · Department of Hematology and Oncology, Klinikum Magdeburg, Birkenallee 34, Magdeburg 39130, Germany. · Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, Munich 81377, Germany. ·Br J Cancer · Pubmed #28449008.

ABSTRACT: BACKGROUND: Mutations in the KRAS gene can be detected in about 70-90% of pancreatic cancer (PC) cases. Whether these mutations have a prognostic or predictive value remains elusive. Furthermore, the clinical relevance of the extended RAS (KRAS+NRAS) mutational status is unclear in PC. METHODS: We prospectively defined a PC patient population who received erlotinib-free chemotherapy regimens. A statistically significant difference between KRAS wild-type and KRAS mutated tumours in at least 160 patients in this population would support the assumption of a rather prognostic role of KRAS. RESULTS: One hundred and seventy-eight tumour samples were collected from prospective clinical studies and successfully analysed for the extended RAS status: 37 tumours were KRAS wild-type (21%), whereas 141 (79%) carried a KRAS mutation; 132 of these mutations were found in KRAS exon 2 (74%), whereas only 9 mutations (5%) were detected in KRAS exon 3. Within KRAS exon 4 and NRAS exons 2-4, no mutations were apparent. There was no significant difference in overall survival for KRAS wild-type vs mutant patients (9.9 vs 8.3 months, P=0.70). CONCLUSIONS: Together with the results of the AIO-PK-0104-trial, the present analysis supports the notion that KRAS mutation status is rather predictive than prognostic in advanced PC.

13 Article Impact of SPARC expression on outcome in patients with advanced pancreatic cancer not receiving nab-paclitaxel: a pooled analysis from prospective clinical and translational trials. 2016

Ormanns, Steffen / Haas, Michael / Baechmann, Sibylle / Altendorf-Hofmann, Annelore / Remold, Anna / Quietzsch, Detlef / Clemens, Michael R / Bentz, Martin / Geissler, Michael / Lambertz, Helmut / Kruger, Stephan / Kirchner, Thomas / Heinemann, Volker / Boeck, Stefan. ·Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Strasse 36, D-80337 Munich, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistrasse 15, D-81377 Munich, Germany. · Department of Surgery, Jena University Hospital, Jena, Germany. · Department of Internal Medicine II, Klinikum Chemnitz gGmbH, Chemnitz, Germany. · Department of Hematology and Oncology, Mutterhaus der Boromaeerinnen, Trier, Germany. · Department of Internal Medicine III, Klinikum Karlsruhe, Karlsruhe, Germany. · Department of Gastroenterology and Oncology, Klinikum Esslingen, Esslingen, Germany. · Department of Hematology and Oncology, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany. ·Br J Cancer · Pubmed #27802454.

ABSTRACT: BACKGROUND: Conflicting results on the role of secreted protein acidic and rich in cysteins (SPARC) expression have been reported in resected pancreatic ductal adenocarcinoma (PDAC), and its prognostic and/or predictive role in advanced PDAC (aPDAC) has not been extensively investigated yet. This study was designed to evaluate SPARC expression as a biomarker in aPDAC patients (pts) not receiving nab-paclitaxel. METHODS: Using immunohistochemistry, we examined the stromal as well as the tumoral (i.e., cytoplasmic) SPARC expression in tumour tissue (primary tumours and metastases) of 134 aPDAC pts participating in completed prospective clinical and biomarker trials. The SPARC expression levels were correlated to the pts' clinicopathological parameters and survival times. RESULTS: Sixty-seven per cent of the analysed tumours showed high stromal SPARC expression, which was not associated with overall survival (OS, median 9.1 vs 7.6 months, P=0.316). A positive cytoplasmic SPARC expression was detected in 55% of the tumours and correlated significantly with inferior progression-free survival (PFS, 6.2 vs 8.6 months, P=0.004) and OS (7.8 vs 8.4 months, P=0.032). This association was strongest for pts, where primary tumour tissue was examined (PFS: 6.7 vs 10.8 months, P=0.004; OS: 7.9 vs 11.9 months, P=0.030), whereas no significant correlation was detected for pts, where only metastatic tissue was available (PFS: 5.8 vs 6.6 months, P=0.502; OS: 7.0 vs 7.8 months, P=0.452). In pts receiving gemcitabine-based chemotherapy cytoplasmic SPARC expression was significantly associated with an inferior PFS and OS (PFS: 6.2 vs 9.2 months, P=0.002; OS 7.3 vs 9.9 months, P=0.012), whereas no such association was detected for stromal SPARC expression or for pts receiving fluoropyrimidine-based chemotherapy. CONCLUSION: We identified cytoplasmic SPARC expression in the primary tumour as a biomarker associated with inferior PFS and OS in aPDAC. Cytoplasmic SPARC expression may furthermore act as a negative predictive biomarker in pts treated with gemcitabine-based chemotherapy.

14 Article Acinar cell carcinoma of the pancreas: a rare disease with different diagnostic and therapeutic implications than ductal adenocarcinoma. 2016

Kruger, Stephan / Haas, Michael / Burger, Philipp Johannes / Ormanns, Steffen / Modest, Dominik Paul / Westphalen, Christoph Benedikt / Kleespies, Axel / Angele, Martin Kurt / Hartwig, Werner / Bruns, Christiane Josephine / Kirchner, Thomas / Werner, Jens / Heinemann, Volker / Boeck, Stefan. ·Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany. · Institute of Pathology, Ludwig-Maximilians-University of Munich, 81377, Munich, Germany. · Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, 81377, Munich, Germany. · Department of General, Visceral and Tumor Surgery, University of Cologne, 50937, Köln-Lindenthal, Germany. · Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany. stefan.boeck@med.uni-muenchen.de. ·J Cancer Res Clin Oncol · Pubmed #27629876.

ABSTRACT: PURPOSE: Acinar cell carcinoma (ACC) of the pancreas is a very rare cancer, constituting 1 % of all malignant non-endocrine pancreatic tumors. Only very limited data exist to guide treatment in patients with advanced ACC. METHODS: Between 2000 and 2015, 15 patients with ACC were diagnosed and/or treated at our high-volume comprehensive cancer center. Medical records and correlating serum levels of the potential serum tumor markers CA 19-9, CEA and lipase were analyzed retrospectively. RESULTS: A substantial antitumor activity was observed for treatment regimens containing 5-FU and oxaliplatin with partial responses or prolonged disease stabilizations (>12 months) observed in 6 out of 7 patients (86 %). Activity was also observed for single-agent 5-FU and its oral prodrugs. Serum lipase levels were elevated in 7 of 12 patients with advanced disease (58 %), whereas CEA and CA 19-9 seemed to be of minor importance for ACC (elevated pre-treatment levels in 4/12 and 3/12 cases, respectively). In selected patients, repeated serum lipase measurements were available and accurately predicted response to chemotherapy and relapse after surgery. CONCLUSIONS: 5-FU- and oxaliplatin-containing regimens are active in advanced ACC. Lipase kinetics may be a useful novel tool to monitor the course of disease as well as treatment effects in ACC.

15 Article Isolated pulmonary metastases define a favorable subgroup in metastatic pancreatic cancer. 2016

Kruger, Stephan / Haas, Michael / Burger, Philipp Johannes / Ormanns, Steffen / Modest, Dominik Paul / Westphalen, Christoph Benedikt / Michl, Marlies / Kleespies, Axel / Angele, Martin Kurt / Hartwig, Werner / Bruns, Christiane Josephine / Niyazi, Maximilian / Roeder, Falk / Kirchner, Thomas / Werner, Jens / Heinemann, Volker / Boeck, Stefan. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. · Institute of Pathology, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. · Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. · Department of General, Abdominal and Vascular Surgery, Otto-von-Guericke-University, D-39120 Magdeburg, Germany. · Department of Radiation Oncology, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. · Department of Radiation Oncology, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany; Department of Molecular Radiation Oncology, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. Electronic address: stefan.boeck@med.uni-muenchen.de. ·Pancreatology · Pubmed #27067420.

ABSTRACT: PURPOSE: Liver metastasis represents the first site of dissemination in >80% of metastatic pancreatic cancer (PC) patients. Pulmonary metastasis as first site of dissemination in PC is a rare event and might define a biologically distinct subgroup in metastatic PC. METHODS: Consecutive PC patients who were diagnosed or treated with isolated pulmonary metastases at our high-volume comprehensive cancer center were included in a prospectively maintained database between 2002 and 2015. Medical records and correlating computed tomography findings (CT) were retrospectively analyzed. RESULTS: A total of 40 PC patients with isolated pulmonary metastases were identified. Pulmonary metastases represented disease recurrence after initial resection of PC in 22 patients and disease progression of locally advanced pancreatic cancer in 5 patients. 14 out of 27 PC patients (56%) had received chemoradiotherapy for localized disease prior to pulmonary metastasis. Data on 1st-line treatment for pulmonary metastases was available for 38 patients: most patients (71%) received a gemcitabine-based chemotherapy regimen, 5 patients (13%) received best supportive care. After a median follow-up of 37.3 months, median survival after diagnosis of pulmonary metastasis was estimated with 25.5 months (95% CI 19.1-31.8); a significantly improved survival after diagnosis of pulmonary metastasis was observed for patients with less than 10 lung metastases (31.3 vs 18.7 months, p = 0.003) and for an unilateral localization of lung involvement (31.3 vs 21.8 months, p = 0.03). CONCLUSIONS: Our results suggest a favorable outcome of PC patients with isolated pulmonary metastases. Further research is warranted to elucidate the specific molecular characteristics of this rare subgroup.

16 Article Assessing novel prognostic serum biomarkers in advanced pancreatic cancer: the role of CYFRA 21-1, serum amyloid A, haptoglobin, and 25-OH vitamin D3. 2015

Haas, Michael / Kern, Christoph / Kruger, Stephan / Michl, Marlies / Modest, Dominik P / Giessen, Clemens / Schulz, Christoph / von Einem, Jobst C / Ormanns, Steffen / Laubender, Rüdiger P / Holdenrieder, Stefan / Heinemann, Volker / Boeck, Stefan. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany, michael.haas@med.uni-muenchen.de. ·Tumour Biol · Pubmed #25472579.

ABSTRACT: The present prospective single-center study investigated the prognostic role of novel serum biomarkers in advanced pancreatic cancer (PC). Patients (pts) with locally advanced or metastatic PC treated with first-line palliative chemotherapy were included. Among others, the serum markers CYFRA 21-1, haptoglobin, serum-amyloid A (SAA), and 25-OH vitamin D3 were determined at baseline and categorized by pre-defined cut-offs [median values (MV), upper limits of normal (ULN), lower limits of normal (LLN), or the natural logarithm (ln)] and correlated with overall survival (OS). Among the 59 pts included, pre-treatment CYFRA 21-1 levels showed a strong correlation with OS independent of the applied cut-off (MV 4.9 ng/ml-14.2 vs. 4.2 months, HR 0.18, p = 0.001; ULN 3.3 ng/ml-14.2 vs. 4.4 months, HR 0.28, p = 0.003; [ln] CYFRA 21-1-HR 0.77, p = 0.013). Lower values of haptoglobin were additionally associated with an improvement in OS (categorized by LLN of 2.05 g/l-10.4 vs. 5.5 months, HR 0.46, p = 0.023; [ln] haptoglobin-HR 0.51, p = 0.036). Pts with baseline SAA values below the MV of 22 mg/l also had a prolonged OS (10.4 vs. 5.0 months, HR 0.47, p = 0.036). For 25-OH vitamin D3 levels, no significant correlation with OS was found. In multivariate analyses, pre-treatment CYFRA 21-1 levels (categorized by MV-HR 0.15, p = 0.032) as well as [ln] haptoglobin (HR 0.30, p = 0.006) retained their independent prognostic significance for OS. CYFRA 21-1, haptoglobin, and SAA might provide useful prognostic information in advanced PC. An external multicenter validation of these results is necessary.

17 Article Long-term progression-free survival in a metastatic pancreatic cancer patient treated with first-line nab-paclitaxel and gemcitabine. 2014

Boeck, Stefan / Haas, Michael / Kruger, Stephan / Heinemann, Volker. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany stefan.boeck@med.uni-muenchen.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. ·In Vivo · Pubmed #25398821.

ABSTRACT: BACKGROUND: Prognosis of patients with metastatic pancreatic cancer is dismal. Recently, two first-line combination chemotherapy regimens have shown a survival benefit over single-agent gemcitabine. PATIENTS AND METHODS: A 57-year old metastatic pancreatic cancer patient from our department (Eastern Cooperative Oncology Group performance status (ECOG PS): 0, baseline carbohydrate antigen (CA) 19-9 level: 2,900 U/ml) received 12 cycles of first-line chemotherapy with nab-paclitaxel and gemcitabine until disease progression within the pivotal Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT). RESULTS: Treatment with nab-paclitaxel and gemcitabine resulted in a partial response by Response Evaluation Criteria in Solid Tumors (RECIST), a rapid biochemical CA 19-9 response, a progression-free survival of 13 months and an overall survival of 20 months. Leukopenia grade 3 prompted dose reduction by two dose levels. Non-hematological toxicities included alopecia, skin rash, nail changes and peripheral neuropathy (all grade 2 or less). CONCLUSION: First-line combination chemotherapy with nab-paclitaxel and gemcitabine is an effective and manageable treatment option for patients with metastatic pancreatic cancer with the potential for long-term disease control.

18 Article ALK expression is absent in pancreatic ductal adenocarcinoma. 2014

Ormanns, Steffen / Assmann, Gerald / Reu, Simone / Gallmeier, Eike / Bader, Dominik C / Kleespies, Axel / Haas, Michael / Kruger, Stephan / Heinemann, Volker / Kirchner, Thomas / Boeck, Stefan. ·Institute of Pathology, Ludwig-Maximilians-University of Munich, Thalkirchnerstr. 36, 80337, Munich, Germany, steffen.ormanns@med.uni-muenchen.de. ·J Cancer Res Clin Oncol · Pubmed #25017418.

ABSTRACT: PURPOSE: It has not yet been clearly defined whether anaplastic lymphoma kinase (ALK) expression can be detected in pancreatic ductal adenocarcinoma (PDAC). METHODS: Within a retrospective study, archival PDAC surgical specimens were screened for ALK expression in tumor and normal tissue by immunohistochemistry (IHC) with the use of a specific ALK detection kit on a tissue microarray (TMA). RESULTS: PDAC tumor tissue was available from 99 resected cases: fifty-eight out of 99 patients (59 %) had nodal-positive disease, and 80 patients (81 %) had pT3 tumors. Forty-nine patients underwent R0 resection, and in 48 cases, resection status was classified R1. Regarding ALK expression, five cases showed faint immunoreactivity on TMA, which was negative on whole mount sections. All other 94 cases showed no ALK expression. CONCLUSION: In 99 PDAC cases, no ALK expression was detected by IHC; ALK thus may not serve as a relevant drug target in PDAC.

19 Minor Mismatch-repair-deficient metastatic pancreatic ductal adenocarcinoma with a germline PALB2 mutation: unusual genetics, unusual clinical course. 2017

Boeck, S / Mehraein, Y / Ormanns, S / Kruger, S / Westphalen, C Benedikt / Haas, M / Jung, A / Kirchner, T / Heinemann, V. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. · Institute of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany · DKTK, German Cancer Consortium, German Cancer Research Center,Heidelberg, Germany. ·Ann Oncol · Pubmed #27803004.

ABSTRACT: -- No abstract --

20 Minor Neoadjuvant chemotherapy in pancreatic cancer: innovative, but still difficult. 2014

Boeck, S / Haas, M / Ormanns, S / Kruger, S / Siveke, J T / Heinemann, V. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. · Department of Pathology, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. · Department of Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, D-81377 Munich, Germany. ·Br J Cancer · Pubmed #24642615.

ABSTRACT: -- No abstract --