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Pancreatic Neoplasms: HELP
Articles by Dirk Jäger
Based on 27 articles published since 2010
(Why 27 articles?)
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Between 2010 and 2020, D. Jäger wrote the following 27 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Chemotherapy for pancreatic cancer. 2019

Springfeld, Christoph / Jäger, Dirk / Büchler, Markus W / Strobel, Oliver / Hackert, Thilo / Palmer, Daniel H / Neoptolemos, John P. ·Heidelberg University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg, Germany. Electronic address: christoph.springfeld@med.uni-heidelberg.de. · Heidelberg University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg, Germany. · Heidelberg University Hospital, Department of Surgery, Heidelberg, Germany. · University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Liverpool, UK. ·Presse Med · Pubmed #30879894.

ABSTRACT: Chemotherapy is an important part of multimodality pancreatic cancer treatment. After curative resection, adjuvant chemotherapy can significantly improve disease free survival and overall survival. The current standard of care is six months adjuvant chemotherapy with modified folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) in patients fit enough for this protocol, otherwise six months of gemcitabine and capecitabine based on the European Study Group for Pancreatic Cancer (ESPAC)-4 study. In patients with metastatic disease, combination chemotherapy according to the FOLFIRINOX protocol or with gemcitabine plus nab-paclitaxel is an important improvement to gemcitabine monotherapy that was the standard for many years. Patients not fit for combination chemotherapy however may still benefit from gemcitabine. Patients with good performance status may benefit from second-line chemotherapy. Chemoradiation has long been used in locally advanced pancreatic cancer but is now tempered following the LAP07 study. This trial showed no difference in overall survival in those patients with stable disease after four months of gemcitabine (with or without erlotinib) randomized to either continuation of gemcitabine therapy or chemoradiation (54Gy with capecitabine). As an alternative to radiation, other forms local therapies including radiofrequency ablation, irreversible electroporation, high-intensity focused ultrasound, microwave ablation and local anti-KRAS therapy (using siG12D-LODER) are currently under investigation. Given the systemic nature of pancreas cancer from an early stage, the success of any local approach other than complete surgical resection (with adjuvant systemic therapy) is likely to be very limited. In patients with locally advanced, irresectable cancer, chemotherapy may offer the chance for secondary resection with a survival similar to patients with primary resectable disease. Downstaging regimens need to be evaluated in prospective randomized trials in order to make firm recommendations. Selection of patient groups for specific therapy including cytotoxics is becoming a reality using assays based on drug cellular transport and metabolism, and molecular signatures. Going forward, high throughput screening of different chemotherapy agents using molecular signatures based on patients' derived organoids holds considerable promise.

2 Review Optimizing the outcomes of pancreatic cancer surgery. 2019

Strobel, Oliver / Neoptolemos, John / Jäger, Dirk / Büchler, Markus W. ·Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. markus.buechler@med.uni-heidelberg.de. ·Nat Rev Clin Oncol · Pubmed #30341417.

ABSTRACT: Pancreatic cancer is likely to become the second most frequent cause of cancer-associated mortality within the next decade. Surgical resection with adjuvant systemic chemotherapy currently provides the only chance of long-term survival. However, only 10-20% of patients with pancreatic cancer are diagnosed with localized, surgically resectable disease. The majority of patients present with metastatic disease and are not candidates for surgery, while surgery remains underused even in those with resectable disease owing to historical concerns regarding safety and efficacy. However, advances made over the past decade in the safety and efficacy of surgery have resulted in perioperative mortality of around 3% and 5-year survival approaching 30% after resection and adjuvant chemotherapy. Furthermore, owing to advances in both surgical techniques and systemic chemotherapy, the indications for resection have been extended to include locally advanced tumours. Many aspects of pancreatic cancer surgery, such as the management of postoperative morbidities, sequencing of resection and systemic therapy, and use of neoadjuvant therapy followed by resection for tumours previously considered unresectable, are rapidly evolving. In this Review, we summarize the current status of and new developments in pancreatic cancer surgery, while highlighting the most important research questions for attempts to further optimize outcomes.

3 Review Improvement of surgical results for pancreatic cancer. 2013

Hartwig, Werner / Werner, Jens / Jäger, Dirk / Debus, Jürgen / Büchler, Markus W. ·Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · National Cancer Center, University of Heidelberg, Heidelberg, Germany. · Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany. · Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: markus.buechler@med.uni-heidelberg.de. ·Lancet Oncol · Pubmed #24079875.

ABSTRACT: Surgery is the only potential hope of cure for patients with pancreatic cancer. Advantageous tumour characteristics and complete tumour resection are the factors most relevant for a positive prognosis, so detection of premalignant or early invasive lesions, combined with safe and oncologically adequate surgery, is an important goal. The experience and volume of both the individual surgeon and hospital are of paramount importance to achieve low morbidity and adequate management of complications. Most pancreatic cancers are locally advanced or metastatic when diagnosed and need multimodal therapy. With increasing evidence on surgical and perioperative aspects of pancreatic cancer therapy, short-term and long-term outcomes of resectable and borderline resectable pancreatic cancer are improving.

4 Clinical Trial A non-controlled, single arm, open label, phase II study of intravenous and intratumoral administration of ParvOryx in patients with metastatic, inoperable pancreatic cancer: ParvOryx02 protocol. 2017

Hajda, Jacek / Lehmann, Monika / Krebs, Ottheinz / Kieser, Meinhard / Geletneky, Karsten / Jäger, Dirk / Dahm, Michael / Huber, Bernard / Schöning, Tilman / Sedlaczek, Oliver / Stenzinger, Albrecht / Halama, Niels / Daniel, Volker / Leuchs, Barbara / Angelova, Assia / Rommelaere, Jean / Engeland, Christine E / Springfeld, Christoph / Ungerechts, Guy. ·Coordination Centre for Clinical Trials, University Hospital Heidelberg, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany. Jacek.Hajda@med.uni-heidelberg.de. · Coordination Centre for Clinical Trials, University Hospital Heidelberg, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany. · Oryx GmbH & Co KG, Marktplatz 1, 85598, Baldham, Germany. · Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany. · Department of Neurosurgery, Klinikum Darmstadt, Grafenstraße 9, 64283, Darmstadt, Germany. · Department of Medical Oncology, National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. · Central Pharmacy, University Hospital Heidelberg, Im Neuenheimer Feld 670, 69120, Heidelberg, Germany. · Department of Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. · Department of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. · Tissue Imaging & Analysis Center (TIGA), University Heidelberg - BioQuant, Im Neuenheimer Feld 267, 69120, Heidelberg, Germany. · Institute of Immunology, Transplantation Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany. · Department of Applied Tumor Virology, German Cancer Research Center, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany. ·BMC Cancer · Pubmed #28851316.

ABSTRACT: BACKGROUND: Metastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy. METHODS: ParvOryx02 is a non-controlled, single arm, open label, dose-escalating, single center trial. In total seven patients with pancreatic cancer showing at least one hepatic metastasis are to be treated with escalating doses of ParvOryx according to the following schedule: i) 40% of the total dose infused intravenously in equal fractions on four consecutive days, ii) 60% of the total dose injected on a single occasion directly into the hepatic metastasis at varying intervals after intravenous infusions. The main eligibility criteria are: age ≥ 18 years, disease progression despite first-line chemotherapy, and at least one hepatic metastasis. Since it is the second trial within the drug development program, the study primarily explores safety and tolerability after further dose escalation of ParvOryx. The secondary objectives are related to the evaluation of certain aspects of anti-tumor activity and clinical efficacy of the drug. DISCUSSION: This trial strongly contributes to the clinical development program of ParvOryx. The individual hazards for patients included in the current study and the environmental risks are addressed and counteracted adequately. Besides information on safety and tolerability of the treatment after further dose escalation, thorough evaluations of pharmacokinetics and intratumoral spread as well as proof-of-concept (PoC) in pancreatic cancer will be gained in the course of the trial. TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT02653313 , Registration date: Dec. 4th, 2015.

5 Clinical Trial Prognostic and predictive value of immunological parameters for chemoradioimmunotherapy in patients with pancreatic adenocarcinoma. 2015

Karakhanova, S / Ryschich, E / Mosl, B / Harig, S / Jäger, D / Schmidt, J / Hartwig, W / Werner, J / Bazhin, A V. ·Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. · 1] Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany [2] National Centre for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany. · National Centre for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany. · 1] Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany [2] General and Visceral Surgery Center, 8002 Zurich, Switzerland. · Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, 81377 Munich, Germany. · 1] Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany [2] Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, 81377 Munich, Germany. ·Br J Cancer · Pubmed #25742476.

ABSTRACT: BACKGROUND: Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma from the CapRI trial did not show any benefit of interferon-α in addition to a 5-fluorouracil (5FU)-based treatment. The aim of this study was to identify immunological parameters in patients from this trial to be used for predictive and/or prognostic purposes. METHODS: The following methods were used: tumour immunohistology, FACS analyses, cytokine measurement, as well as cytotoxicity and ELIspot. Immunological parameters were correlated with patients' survival using the Kaplan-Meier method. RESULTS: Irrespective of therapy type, high lymphocyte accumulation in tumours and frequencies of NK cells and effector (eff) CD8(+) T cells in peripheral blood of the patients were associated with patients' survival. Amount of CD3(+) and effector-memory CD8(+) blood lymphocytes, expression of CD152 and interleukin (IL)-2 serum level showed a predictive value for chemoradioimmunotherapy. Tumoural accumulation of CD3(+) and CD8(+) cells was predictive for outcome of chemotherapy alone. Besides, we identified the frequencies of CD3(+) lymphocytes, effCD8(+) T cells and NK cells in the peripheral blood of the patients, and IL-10 amount in serum, to be predictive values for 5FU-based chemotherapy. CONCLUSIONS: Immunological parameters, identified in this trial as possible markers, may be of interest in personalized medicine towards the improvement of the treatment and prognosis of pancreatic carcinoma patients.

6 Clinical Trial Influence of interferon-alpha combined with chemo (radio) therapy on immunological parameters in pancreatic adenocarcinoma. 2014

Karakhanova, Svetlana / Mosl, Beate / Harig, Sabine / von Ahn, Katharina / Fritz, Jasmin / Schmidt, Jan / Jäger, Dirk / Werner, Jens / Bazhin, Alexandr V. ·Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Svetlana.karakhanova@med.uni-heidelberg.de. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. beate.mosl@med.uni-heidelberg.de. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Dirk.Jaeger@med.uni-heidelberg.de. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. katharinavonahn@hotmail.com. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. jasminfritz@web.de. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Jan.Schmidt@hirslanden.ch. · National Centre for Tumor Disease, University Hospital Heidelberg, 69120 Heidelberg, Germany. Dirk.Jaeger@med.uni-heidelberg.de. · Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, 81377 Munich, Germany. jens.werner@med.uni-heidelberg.de. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Alexandr.bazhin@med.uni-heidelberg.de. ·Int J Mol Sci · Pubmed #24608924.

ABSTRACT: Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of 17 patients with pancreatic cancer from the CapRI-2 study, and tumor-bearing mice treated with combination of chemo (radio) therapies with interferon-2α. Low doses of interferon-2α led to a decrease in total leukocyte and an increase in monocyte counts. Furthermore, we observed a positive effect of interferon-2α therapy on the dendritic cells and NK (natural killer) cell activation immediately after the first injection. In addition, we recorded an increased amount of interferon-γ and IL-10 in the serum following the interferon-2α therapy. These data clearly demonstrate that pancreatic carcinoma patients also show an immunomodulatory response to interferon-2α therapy. Analysis of immunosuppressive cells in the Panc02 orthotopic mouse model of pancreatic cancer revealed an accumulation of the myeloid-derived suppressor cells in spleens and tumors of the mice treated with interferon-2α and 5-fluorouracil. The direct effect of the drugs on myeloid-derived suppressor cells was also registered in vitro. These data expose the importance of immunosuppressive mechanisms induced by combined chemo-immunotherapy.

7 Clinical Trial Phase I study evaluating the treatment of patients with locally advanced pancreatic cancer with carbon ion radiotherapy: the PHOENIX-01 trial. 2013

Combs, Stephanie E / Habermehl, Daniel / Kieser, Meinhard / Dreher, Constantin / Werner, Jens / Haselmann, Renate / Jäkel, Oliver / Jäger, Dirk / Büchler, Markus W / Debus, Jürgen. ·Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Stephanie.combs@med.uni-heidelberg.de. ·BMC Cancer · Pubmed #24034562.

ABSTRACT: BACKGROUND: Treatment options for patients with locally advanced pancreatic cancer include surgery, chemotherapy as well as radiotherapy. In many cases, surgical resection is not possible, and therefore treatment alternatives have to be performed. Chemoradiation has been established as a convincing treatment alternative for locally advanced pancreatic cancer. Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 1.16 and 2.46 depending on the pancreatic cancer cell line as well as the endpoint analyzed. Japanese Data on the evaluation of carbon ion radiation therapy showed promising results for patients with pancreatic cancer. METHODS AND DESIGN: The present PHOENIX-01 trial evaluates carbon ion radiotherapy using the active rasterscanning technique in patients with advanced pancreatic cancer in combination with weekly gemcitabine and adjuvant gemcitabine. Primary endpoint is toxicity, secondary endpoints are overall survival, progression-free survival and response. DISCUSSION: The physical and biological properties of the carbon ion beam promise to improve the therapeutic ratio in patients with pancreatic cancer: Due to the inverted dose profile dose deposition in the entry channel of the beam leads to sparing of normal tissue; the Bragg peak can be directed into the defined target volume, and the sharp dose fall-off thereafter again spares normal tissue behind the target volume. The higher RBE of carbon ions, which has been shown also for pancreatic cancer cell lines in the preclinical setting, is likely to contribute to an increase in local control, and perhaps in OS. Early data from Japanese centers have shown promising results. In conclusion, this is the first trial to evaluate actively delivered carbon ion beams in patients with locally advanced pancreatic cancer within a dose-escalation strategy. TRIAL REGISTRATION: NCT01795274.

8 Clinical Trial Open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon Alfa-2b versus fluorouracil and folinic acid for patients with resected pancreatic adenocarcinoma. 2012

Schmidt, Jan / Abel, Ulrich / Debus, Jürgen / Harig, Sabine / Hoffmann, Katrin / Herrmann, Thomas / Bartsch, Detlef / Klein, Justus / Mansmann, Ulrich / Jäger, Dirk / Capussotti, Lorenzo / Kunz, Reiner / Büchler, Markus W. ·Department of Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. ·J Clin Oncol · Pubmed #23008325.

ABSTRACT: PURPOSE: Adjuvant chemotherapy prolongs survival in patients with pancreatic cancer, but its benefit is limited. Long-term survival times of up to 44 months after adjuvant chemoradioimmunotherapy in phase II trials motivated the present study. PATIENTS AND METHODS: Between 2004 and 2007, 132 R0/R1 resected patients received either fluorouracil (FU), cisplatin, and interferon alfa-2b (IFN α-2b) plus radiotherapy followed by two cycles of FU (arm A, n=64) or six cycles of FU monotherapy (arm B, n=68). One hundred ten patients (arm A, n=53; arm B, n=57) received at least one dose of the study medication, and these patients composed the per-protocol (PP) population. Biomarkers were analyzed longitudinally for their predictive value. RESULTS: Median survival for all randomly assigned patients was 26.5 months (95% CI, 21.6 to 39.5 months) in arm A and 28.5 months (95% CI, 20.4 to 38.6 months) in arm B. The hazard ratio was 1.04 (arm A v arm B: 95% CI, 0.66 to 1.53; P=.99). Median survival for the PP population was 32.1 months (95% CI, 22.8 to 42.2 months) in arm A and 28.5 months (95% CI, 19.5 to 38.6 months) in arm B (P=.49). Eighty-five percent of patients in arm A and 16% of patients in arm B experienced grade 3 or 4 toxicity. The quality of life was temporarily negatively affected in arm A. CONCLUSION: The FU, cisplatin, and IFN α-2b plus radiotherapy regimen did not improve the survival compared with FU monotherapy. Given the substantial adverse effects, this treatment can currently not be recommended. Nevertheless, the outcome in both arms represents the best survival, to our knowledge, ever reported for patients with resected pancreatic cancer in randomized controlled trials. Future studies will demonstrate whether immune response to IFN α-2b challenge has a predictive value.

9 Clinical Trial Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients with advanced pancreatic cancer: a randomized controlled phase II trial. 2012

Löhr, J M / Haas, S L / Bechstein, W-O / Bodoky, G / Cwiertka, K / Fischbach, W / Fölsch, U R / Jäger, D / Osinsky, D / Prausova, J / Schmidt, W E / Lutz, M P / Anonymous3910704. ·Department of Medicine II, University Hospital Mannheim, Mannheim, Germany. matthias.lohr@ki.se ·Ann Oncol · Pubmed #21896540.

ABSTRACT: BACKGROUND: Paclitaxel embedded in cationic liposomes (EndoTAG™-1; ET) is an innovative agent targeting tumor endothelial cells. This randomized controlled phase II trial evaluated the safety and efficacy of ET in combination with gemcitabine (GEM) in advanced pancreatic cancer (PDAC). PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced or metastatic disease were randomly assigned to receive weekly GEM 1000 mg/m(2) or GEM plus twice-weekly ET 11, 22 or 44 mg/m(2) for 7 weeks. After a safety run-in of 100 patients, a second cohort continued treatment. End points included overall survival (OS), progression-free survival (PFS), tumor response and safety. RESULTS: Two hundred and twelve patients were randomly allocated to the study and 200 were treated (80% metastatic, 20% locally advanced). Adverse events were manageable and reversible. Transient thrombocytopenia and infusion reactions with chills and pyrexia mostly grade 1 or 2 occurred in the ET groups. Disease control rate after the first treatment cycle was 43% with GEM and 60%, 65% and 52% in the GEM + ET cohorts. Median PFS reached 2.7 compared with 4.1, 4.6 and 4.4 months, respectively. Median OS was 6.8 compared with 8.1, 8.7 and 9.3 months, respectively. CONCLUSIONS: Treatment of advanced PDAC with GEM + ET was generally well tolerated. GEM + ET showed beneficial survival and efficacy. A randomized phase III trial should confirm this positive trend.

10 Article A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts. 2018

Loktev, Anastasia / Lindner, Thomas / Mier, Walter / Debus, Jürgen / Altmann, Annette / Jäger, Dirk / Giesel, Frederik / Kratochwil, Clemens / Barthe, Philippe / Roumestand, Christian / Haberkorn, Uwe. ·Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany. · Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Faculty of Biosciences, Heidelberg University, Heidelberg, Germany. · Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany. · Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg, Germany. · Centre de Biochimie Structurale, Université de Montpellier, CNRS, INSERM, Montpellier, France; and. · Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany uwe.haberkorn@med.uni-heidelberg.de. · Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany. ·J Nucl Med · Pubmed #29626120.

ABSTRACT: The tumor stroma, which accounts for a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, the focus is notably on a subpopulation of stromal cells, known as cancer-associated fibroblasts, which are present in more than 90% of epithelial carcinomas, including pancreatic, colon, and breast cancer. Cancer-associated fibroblasts feature high expression of fibroblast activation protein (FAP), which is not detectable in adult normal tissue but is associated with a poor prognosis in cancer patients.

11 Article Pancreatic Ductal Adenocarcinoma Subtyping Using the Biomarkers Hepatocyte Nuclear Factor-1A and Cytokeratin-81 Correlates with Outcome and Treatment Response. 2018

Muckenhuber, Alexander / Berger, Anne Katrin / Schlitter, Anna Melissa / Steiger, Katja / Konukiewitz, Björn / Trumpp, Andreas / Eils, Roland / Werner, Jens / Friess, Helmut / Esposito, Irene / Klöppel, Günter / Ceyhan, Güralp O / Jesinghaus, Moritz / Denkert, Carsten / Bahra, Marcus / Stenzinger, Albrecht / Sprick, Martin R / Jäger, Dirk / Springfeld, Christoph / Weichert, Wilko. ·Institute of Pathology, Technical University Munich and German Cancer Consortium (DKTK; partner site Munich), Munich, Germany. · Department of Medical Oncology, Heidelberg University Hospital and National Center for Tumor Diseases, Heidelberg, Germany. · Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany. · Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GmbH, Heidelberg, Germany. · German Cancer Consortium (DKTK), Heidelberg, Germany. · Division of Theoretical Bioinformatics and Heidelberg Center for Personalised Oncology (DKFZ-HIPO), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department for Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology (IPMB) and BioQuant, Heidelberg University, Heidelberg, Germany. · Department of Surgery, University Hospital of the Ludwig-Maximilian University, Munich, Germany. · Department of Surgery, University Hospital of the Technical University Munich, Munich, Germany. · Institute of Pathology, University Hospital Düsseldorf, Düsseldorf, Germany. · Institute of Pathology, Charité University Medicine Berlin and German Cancer Consortium (DKTK; partner site Berlin), Berlin, Germany. · Department of Surgery, Charité University Medicine Berlin, Berlin, Germany. · Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. · Institute of Pathology, Technical University Munich and German Cancer Consortium (DKTK; partner site Munich), Munich, Germany. wilko.weichert@tum.de. ·Clin Cancer Res · Pubmed #29101303.

ABSTRACT:

12 Article Palliative chemotherapy for pancreatic adenocarcinoma: a retrospective cohort analysis of efficacy and toxicity of the FOLFIRINOX regimen focusing on the older patient. 2017

Berger, Anne Katrin / Haag, Georg Martin / Ehmann, Martin / Byl, Anne / Jäger, Dirk / Springfeld, Christoph. ·Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. anne.berger@med.uni-heidelberg.de. · Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. · Pharmacy Department, Heidelberg University Hospital, Heidelberg, Germany. · NCT Clinical Cancer Registry, German Cancer Research Center, Heidelberg, Germany. ·BMC Gastroenterol · Pubmed #29207968.

ABSTRACT: BACKGROUND: Pancreatic cancer occurs more frequently in older patients, but these are underrepresented in the phase III clinical studies that established the current treatment standards. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens like FOLFIRINOX. METHODS: We conducted a retrospective analysis of patients treated according to the FOLFIRINOX protocol at our institution between 2010 and 2014 with a focus on older patients. RESULTS: Overall survival in our cohort was 10.2 months. Only 43% of patients did not need dose adaptations, but dose reductions did not lead to an inferior survival. We did not find evidence that patients aged 65 years and older deemed fit enough for palliative treatment had more toxicities or a worse outcome than younger patients. CONCLUSION: We conclude that treatment with the FOLFIRINOX protocol in patients with pancreatic cancer should not be withhold from patients solely based on their chronological age but rather be based on the patient's performance status and comorbidities.

13 Article High prevalence of incidental and symptomatic venous thromboembolic events in patients with advanced pancreatic cancer under palliative chemotherapy: A retrospective cohort study. 2017

Berger, Anne Katrin / Singh, Hans Martin / Werft, Wiebke / Muckenhuber, Alexander / Sprick, Martin R / Trumpp, Andreas / Weichert, Wilko / Jäger, Dirk / Springfeld, Christoph. ·National Center for Tumor Diseases (NCT), Department of Medical Oncology, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: anne.berger@med.uni-heidelberg.de. · National Center for Tumor Diseases (NCT), Department of Medical Oncology, University Hospital Heidelberg, Heidelberg, Germany. · Hochschule Mannheim, University of Applied Sciences, Mannheim, Germany. · Institute of Pathology, Technische Universität München (TUM), München, Germany. · Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany. ·Pancreatology · Pubmed #28462862.

ABSTRACT: OBJECTIVES: Pancreatic cancer patients are at high risk for venous thromboembolic events (VTEs), and chemotherapy is a known additional risk factor. In this context, there is a controversial discussion whether prophylactic anticoagulation should be offered to all outpatients receiving chemotherapy. METHODS: In this retrospective study, we analyzed incidental and symptomatic VTEs in 150 pancreatic cancer patients receiving either gemcitabine-based chemotherapy or chemotherapy according to the FOLFIRINOX protocol. RESULTS: VTEs were identified in 25% of patients, but were not associated with an adverse survival. There was no significant difference in VTE incidence between patients treated with gemcitabine-based chemotherapy or the more intensive FOLFIRINOX protocol. A commonly used risk score to predict VTEs in cancer patients did not predict the occurrence of VTEs in our patients. The occurrence of VTEs was not associated with one of the recently described pancreatic cancer subtypes. CONCLUSION: One quarter of pancreatic cancer patients treated with palliative chemotherapy develops symptomatic or incidental VTEs that cannot be predicted by type of chemotherapy, subtype of pancreatic cancer or a commonly used risk score. Further studies are necessary to identify patients at risk, and to better define which patients at risk should be treated with prophylactic anticoagulation.

14 Article Pancreatic Cancer Surgery: The New R-status Counts. 2017

Strobel, Oliver / Hank, Thomas / Hinz, Ulf / Bergmann, Frank / Schneider, Lutz / Springfeld, Christoph / Jäger, Dirk / Schirmacher, Peter / Hackert, Thilo / Büchler, Markus W. ·*Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany †Institute of Pathology Heidelberg, Heidelberg, Germany ‡National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany. ·Ann Surg · Pubmed #27918310.

ABSTRACT: OBJECTIVE: To assess the relevance of resection margin status for survival outcome after resection and adjuvant therapy for pancreatic cancer. BACKGROUND: The definitions for R0 and R1 margin status after resection for pancreatic cancer are controversial. The strict definition of R0 requiring a 1 mm tumor-free margin is not commonly accepted. Reported R0/R1 rates and associated survival are highly heterogeneous. METHODS: A standardized protocol with rigorous assessment of circumferential margins and the R0 definition with a 1 mm free margin were introduced into clinical routine in 2005. From a prospective database, patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma between January 1, 2006 and December 12, 2012 were identified. The rates of R0 (≥1 mm margin), R1 (<1 mm clearance), and R1 (direct margin involvement) status and associated survival were assessed by uni- and multivariable analyses. RESULTS: Of 561 patients included, 112 patients (20.0%) had R0 and 449 patients (80.0%) had R1 resections, including 123 (21.9%) R1 (≤1 mm) and 326 (58.1%) R1 (direct) resections. A total of 438 (85.9%) received adjuvant therapy. With R0, R1 (<1 mm), and R1 (direct) status the median survival times and 5-year survival rates were 41.6, 27.5, and 23.4 months; and 37.7%, 30.1%, and 20.3%, respectively (P < 0.0001). By multivariable analysis, margin status was confirmed to be independently associated with survival. CONCLUSIONS: In the context of adjuvant therapy, the resection margin status remains an important independent determinant of postresection survival. R0/R1 resection rates and associated survival vary significantly with the definitions used. An international consensus is urgently needed to achieve comparability with respect to studies and protocols on patients with adjuvant therapy.

15 Article Locally Advanced Pancreatic Cancer: Neoadjuvant Therapy With Folfirinox Results in Resectability in 60% of the Patients. 2016

Hackert, Thilo / Sachsenmaier, Milena / Hinz, Ulf / Schneider, Lutz / Michalski, Christoph W / Springfeld, Christoph / Strobel, Oliver / Jäger, Dirk / Ulrich, Alexis / Büchler, Markus W. ·*Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany †Department of Medical Oncology, University Hospital Heidelberg, Heidelberg, Germany. ·Ann Surg · Pubmed #27355262.

ABSTRACT: OBJECTIVE: For patients with locally advanced and unresectable pancreatic cancer (PDAC), neodadjuvant treatment and consecutive surgical exploration have been studied during the last decade with various neoadjuvant therapies including chemotherapy and combinations with radiation. Aim of the study was the evaluation of neoadjuvant therapy with a focus on Folfirinox. METHODS: All consecutive patients undergoing surgery for PDAC after neoadjuvant treatment were analyzed (clinico-pathological characteristics, secondary resection rates, outcome). Patients receiving Folfirinox were compared with other treatment regimens. RESULTS: Between December 2001 and June 2015, 575 patients received neoadjuvant treatment and were scheduled for resection after re-staging. A successful resection was achieved in 292 patients (50.8%). Resection rates following Folfirinox were 61% (76/125 patients) compared with 46% (150/322 patients) after gemcitabine and radiation, and 52% (66/128 patients) after other treatments (P = 0.026). Median overall survival was 15.3 months after resection vs 8.5 months after exploration alone (P < 0.0001). Subgroup median survival was 16.0 months (Folfirinox) vs 16.5 months (gemcitabine) and 14.5 months (others) with 3-year survival of 28.1%, 23.2%, and 19.7%, respectively (P = 0.8582). By multivariable analysis, Folfirinox was confirmed to be independently associated with a favorable prognosis. CONCLUSIONS: Folfirinox is a valuable treatment option in the neoadjuvant therapy of PDAC. From the present data, which represent the largest available study population to date, Folfirinox seems to be the most effective protocol resulting in a significantly better secondary resection rate and overall survival than other treatments. It should be considered in all patients fit for this regimen and consecutive surgical exploration.

16 Article Adjuvant radiotherapy and chemoradiation with gemcitabine after R1 resection in patients with pancreatic adenocarcinoma. 2015

Habermehl, Daniel / Brecht, Ingo C / Bergmann, Frank / Rieken, Stefan / Werner, Jens / Büchler, Markus W / Springfeld, Christoph / Jäger, Dirk / Debus, Jürgen / Combs, Stephanie E. ·Department of Radiation Oncology, Klinikum rechts der Isar, TU München, Ismaninger Str. 22, 81675, Munich, Germany. daniel.habermehl@tum.de. · Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. ingobrecht@googlemail.com. · Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, 69120, Heidelberg, Germany. frank.bergmann@med.uni-heidelberg.de. · Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. Stefan.rieken@med.uni-heidelberg.de. · Department of Visceral Surgery, Klinikum der Universität München (LMU), Marchioninistraße 15, 81377, Munich, Germany. jens.werner@med.uni-muenchen.de. · Department of Visceral Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. markus.buechler@med.uni-heidelberg.de. · National Center for Tumor Diseases, Medical Oncology, University Hospital Heidelberg, University of Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. christoph.springfeld@med.uni-heidelberg.de. · National Center for Tumor Diseases, Medical Oncology, University Hospital Heidelberg, University of Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. dirk.jaeger@med.uni-heidelberg.de. · Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. juergen.debus@med.uni-heidelberg.de. · Department of Radiation Oncology, Klinikum rechts der Isar, TU München, Ismaninger Str. 22, 81675, Munich, Germany. stephanie.combs@tum.de. ·World J Surg Oncol · Pubmed #25889749.

ABSTRACT: BACKGROUND: The purpose of the study was to evaluate the effect of radiation therapy and chemoradiation with gemcitabine (GEM) after R1 resection in patients with pancreatic adenocarcinoma (PAC). METHODS: We performed a retrospective analysis of 25 patients who were treated with postoperative radiotherapy (RT) or chemoradiation (CRT) after surgery with microscopically positive resection margins for primary pancreatic cancer (PAC). Median age was 60 years (range 34 to 74 years), and there were 17 male and 8 female patients. Fractionated RT was applied with a median dose of 49.6 Gy (range 36 to 54 Gy). Eight patients received additional intraoperative radiotherapy (IORT) with a median dose of 12 Gy. RESULTS: Median overall survival (mOS) of all treated patients was 22 months (95% confidence interval (CI) 7.9 to 36.1 months) after date of resection and 21.1 months (95% CI 7.6 to 34.6 months) after start of (C)RT. Median progression-free survival (mPFS) was 13.0 months (95% CI 0.93 to 25 months). Grading (G2 vs. G3, P = 0.005) and gender (female vs. male, P = 0.01) were significantly correlated with OS. There was a significant difference in mPFS between male and female patients (P = 0.008). A total of 11 from 25 patients experienced local tumour progression, and 19 patients were diagnosed with either locoregional or distant failure. CONCLUSIONS: We demonstrated that GEM-based CRT can be applied in analogy to neoadjuvant protocols in the adjuvant setting for PAC patients at high risk for disease recurrence after incomplete resection. Patients undergoing additive CRT have a rather good OS and PFS compared to historical control patient groups.

17 Article Unresectable isolated hepatic metastases from solid pseudopapillary neoplasm of the pancreas: a case report of chemosaturation with high-dose melphalan. 2014

Hofmann, Helene / von Haken, Rebecca / Werner, Jens / Kortes, Nikolas / Bergmann, Frank / Schemmer, Peter / Jäger, Dirk / Radeleff, Boris / Schulze-Bergkamen, Henning. ·National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany. Electronic address: Helene.Hofmann@med.uni-heidelberg.de. · Department of Anesthesiology, University Clinic of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. · Department of Surgery, University Clinic of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. · Department of Radiology, University Clinic of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. · Department of Pathology, University Clinic of Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany. · National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany. · National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany; Marienhospital Wesel, Medical Department II, Pastor-Janssen-Strasse 8-38, 46483 Wesel, Germany. ·Pancreatology · Pubmed #25280592.

ABSTRACT: BACKGROUND/OBJECTIVES: Solid pseudopapillary neoplasms of the pancreas (SPN) are rare tumors. For patients with unresectable liver metastases of SPN, no standard treatment has been defined so far. Here we report a case of a 40-year-old woman with SPN and metastases confirmed to the liver, and disease progression in the liver after primary tumor resection and chemotherapy with gemcitabine and cisplatin. METHODS: Chemosaturation with percutaneous hepatic perfusions is a minimally invasive, repeatable regional therapy which delivers chemotherapy directly to the liver while limiting systemic toxicity. As an individual treatment approach, the patient was treated with chemosaturation with percutaneous hepatic perfusions of melphalan. RESULTS: The procedure was performed twice within 8 weeks after which the liver metastases showed a marked reduction in size and vascularization (partial response). Grade 3 leukopenia after the second procedure was managed effectively with granulocyte colony-stimulating factor. No other toxicities were observed. Ten months after initiating treatment, the patient had a good performance status and remained stable. CONCLUSIONS: For SPN with unresectable liver metastases and progression despite systemic treatment, repeat chemosaturation with high-dose melphalan may also offer an effective regional treatment option.

18 Article Prognostic impact of CA 19-9 on outcome after neoadjuvant chemoradiation in patients with locally advanced pancreatic cancer. 2014

Combs, Stephanie E / Habermehl, Daniel / Kessel, Kerstin A / Bergmann, Frank / Werner, Jens / Naumann, Patrick / Jäger, Dirk / Büchler, Markus W / Debus, Jürgen. ·Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany, Stephanie.Combs@tum.de. ·Ann Surg Oncol · Pubmed #24916745.

ABSTRACT: BACKGROUND: To asses the impact of CA 19-9 and weight loss/gain on outcome after neoadjuvant chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: We analyzed 289 patients with LAPC treated with CRT for LAPC. All patients received concomitant chemotherapy parallel to radiotherapy and adjuvant treatments. CA 19-9 and body weight were collected as prognostic and predictive markers. All patients were included into a regular follow-up with reassessment of resectability. RESULTS: Median overall survival in all patients was 14 months. Actuarial overall survival was 37 % at 12 months, 12 % at 24 months, and 4 % at 36 months. Secondary resectability was achieved in 35 % of the patients. R0/R1 resection was significantly associated with increase in overall survival (p = 0.04). Intraoperative radiotherapy was applied in 50 patients, but it did not influence overall survival (p = 0.05). Pretreatment CA 19-9 significantly influenced overall survival using different cutoff values. With increase in CA 19-9 levels, the possibility of secondary surgical resection decreased from 46 % in patients with CA 19-9 levels below 90 U/ml to 31 % in the group with CA 19-9 levels higher than 269 U/ml. DISCUSSION: This large group of patients with LAPC treated with neoadjuvant CRT confirms that CA 19-9 and body weight are strong predictive and prognostic factors of outcome. In the future, individual patient factors should be taken into account to tailor treatment.

19 Article Chemotherapy for advanced pancreatic adenocarcinoma in elderly patients (≥70 years of age): a retrospective cohort study at the National Center for Tumor Diseases Heidelberg. 2014

Berger, Anne Katrin / Abel, Ulrich / Komander, Christine / Harig, Sabine / Jäger, Dirk / Springfeld, Christoph. ·National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany. Electronic address: anne.berger@med.uni-heidelberg.de. · National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany. · NCT Clinical Cancer Registry, German Cancer Research Center, Heidelberg, Germany. ·Pancreatology · Pubmed #24854617.

ABSTRACT: BACKGROUND: Pancreatic cancer is mainly a disease of the elderly population, but clinical trials do not reflect this age distribution. Data on treatment strategies and outcome of older patients are limited. The aim of our study was to analyze safety and outcome in elderly patients with advanced pancreatic cancer treated with palliative chemotherapy at the outpatient clinic of the National Center for Tumor Diseases (NCT) at Heidelberg University Hospital. MATERIALS AND METHODS: We retrospectively analyzed 53 patients ≥70 years using a prospectively maintained database. Requirements were (1) histologically proven diagnosis of ductal pancreatic adenocarcinoma, (2) age ≥70 at time of diagnosis of advanced disease, and (3) measurable advanced disease. RESULTS: The median age was 73 years. 81% of the patients received a gemcitabine-based first-line therapy. Median overall survival was 6.7 months. Survival differed significantly between patient groups with low (≤1) and high (≥2) Eastern Cooperative Oncology Group performance status (7.8 vs. 3.9 months, p = 0.002). 30.2% of the patients developed side effects resulting in dosage reductions. 39.6% of the patients received second-line treatment. Residual survival after disease progression was significantly longer for second-line treatment compared to best supportive care (151 vs. 39 days, p = 0.019). CONCLUSIONS: Overall, our older patients did not have an inferior outcome compared to the reported trial populations that included younger patients. Thus, palliative chemotherapy should be considered independently from chronological age, but the performance status should be carefully noticed. Second-line therapy should be considered for patients in good performance status after first progression.

20 Article Successful treatment with nab-paclitaxel and gemcitabine after FOLFIRINOX failure in a patient with metastasized pancreatic adenocarcinoma. 2013

Berger, Anne K / Weber, Tim F / Jäger, Dirk / Springfeld, Christoph. ·National Center for Tumor Diseases, University Medical Center Heidelberg, Heidelberg, Germany. ·Onkologie · Pubmed #24356569.

ABSTRACT: BACKGROUND: Advanced pancreatic adenocarcinoma still remains associated with a desperate prognosis. Nevertheless, treatment options for patients with metastasized disease have improved considerably over the last few years. Recently, cytotoxic combination therapies such as the FOLFIRINOX regimen and combined nab-paclitaxel/gemcitabine have shown improved overall survival compared to gemcitabine alone. There is still no standard of care in second-line therapy for patients with disease progression. CASE REPORT: We report the case of a 47-year-old patient who dramatically responded to second-line treatment with nab-paclitaxel and gemcitabine after primary progression to the FOLFIRINOX protocol. CONCLUSION: Second-line treatment after FOLFIRINOX is feasible for patients with good performance status. Our case report supports preclinical findings that suggest that pancreatic cancer is a heterogeneous disease. Further studies that characterize possible subgroups and identify predictive molecular markers to guide therapy are warranted.

21 Article Low-dose irradiation programs macrophage differentiation to an iNOS⁺/M1 phenotype that orchestrates effective T cell immunotherapy. 2013

Klug, Felix / Prakash, Hridayesh / Huber, Peter E / Seibel, Tobias / Bender, Noemi / Halama, Niels / Pfirschke, Christina / Voss, Ralf Holger / Timke, Carmen / Umansky, Ludmila / Klapproth, Kay / Schäkel, Knut / Garbi, Natalio / Jäger, Dirk / Weitz, Jürgen / Schmitz-Winnenthal, Hubertus / Hämmerling, Günter J / Beckhove, Philipp. ·Division of Translational Immunology, German Cancer Research Center (DKFZ) and National Center of Tumor Diseases (NCT), 69120 Heidelberg, Germany. ·Cancer Cell · Pubmed #24209604.

ABSTRACT: Inefficient T cell migration is a major limitation of cancer immunotherapy. Targeted activation of the tumor microenvironment may overcome this barrier. We demonstrate that neoadjuvant local low-dose gamma irradiation (LDI) causes normalization of aberrant vasculature and efficient recruitment of tumor-specific T cells in human pancreatic carcinomas and T-cell-mediated tumor rejection and prolonged survival in otherwise immune refractory spontaneous and xenotransplant mouse tumor models. LDI (local or pre-adoptive-transfer) programs the differentiation of iNOS⁺ M1 macrophages that orchestrate CTL recruitment into and killing within solid tumors through iNOS by inducing endothelial activation and the expression of TH1 chemokines and by suppressing the production of angiogenic, immunosuppressive, and tumor growth factors.

22 Article Intensity modulated radiotherapy as neoadjuvant chemoradiation for the treatment of patients with locally advanced pancreatic cancer. Outcome analysis and comparison with a 3D-treated patient cohort. 2013

Combs, S E / Habermehl, D / Kessel, K / Bergmann, F / Werner, J / Brecht, I / Schirmacher, P / Jäger, D / Büchler, M W / Debus, J. ·Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. Stephanie.Combs@med.uni-heidelberg.de ·Strahlenther Onkol · Pubmed #23896630.

ABSTRACT: BACKGROUND: To evaluate outcome after intensity modulated radiotherapy (IMRT) compared to 3D conformal radiotherapy (3D-RT) as neoadjuvant treatment in patients with locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: In total, 57 patients with LAPC were treated with IMRT and chemotherapy. A median total dose of 45 Gy to the PTV_baseplan and 54 Gy to the PTV_boost in single doses of 1.8 Gy for the PTV_baseplan and median single doses of 2.2 Gy in the PTV_boost were applied. Outcomes were evaluated and compared to a large cohort of patients treated with 3D-RT. RESULTS: Overall treatment was well tolerated in all patients and IMRT could be completed without interruptions. Median overall survival was 11 months (range 5-37.5 months). Actuarial overall survival at 12 and 24 months was 36 % and 8 %, respectively. A significant impact on overall survival could only be observed for a decrease in CA 19-9 during treatment, patients with less pre-treatment CA 19-9 than the median, as well as weight loss during treatment. Local progression-free survival was 79 % after 6 months, 39 % after 12 months, and 13 % after 24 months. No factors significantly influencing local progression-free survival could be identified. There was no difference in overall and progression-free survival between 3D-RT and IMRT. Secondary resectability was similar in both groups (26 % vs. 28 %). Toxicity was comparable and consisted mainly of hematological toxicity due to chemotherapy. CONCLUSION: IMRT leads to a comparable outcome compared to 3D-RT in patients with LAPC. In the future, the improved dose distribution, as well as advances in image-guided radiotherapy (IGRT) techniques, may improve the use of IMRT in local dose escalation strategies to potentially improve outcome.

23 Article Necrolytic migratory erythema in a patient with neuroendocrine carcinoma. 2013

Gronau, Michaela / Jäger, Dirk / Enk, Alexander H / Hassel, Jessica C. ·National Center for Tumor Diseases Heidelberg, Germany. michaela.gronau@med.uni-heidelberg.de ·Intern Med · Pubmed #23291692.

ABSTRACT: Necrolytic migratory erythema is an obligatory paraneoplastic syndrome. Here we describe a patient with a neuroendocrine tumor of probably pancreatic origin. She developed the typical skin lesions under chemotherapy with temozolomide and capecitabine.

24 Article Re-resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with encouraging survival. 2013

Strobel, Oliver / Hartwig, Werner / Hackert, Thilo / Hinz, Ulf / Berens, Viktoria / Grenacher, Lars / Bergmann, Frank / Debus, Jürgen / Jäger, Dirk / Büchler, Markus / Werner, Jens. ·Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany. ·Ann Surg Oncol · Pubmed #23233235.

ABSTRACT: BACKGROUND: Local recurrence of pancreatic cancer occurs in 80% of patients within 2 years after potentially curative resections. Around 30% of patients have isolated local recurrence (ILR) without evidence of metastases. In spite of localized disease these patients usually only receive palliative chemotherapy and have a short survival. PURPOSE: To evaluate the outcome of surgery as part of a multimodal treatment for ILR of pancreatic cancer. METHODS: All consecutive operations performed for suspected ILR in our institution between October 2001 and October 2009 were identified from a prospective database. Perioperative outcome, survival, and prognostic parameters were assessed. RESULTS: Of 97 patients with histologically proven recurrence, 57 (59%) had ILR. In 40 (41%) patients surgical exploration revealed metastases distant to the local recurrence. Resection was performed in 41 (72%) patients with ILR, while 16 (28%) ILR were locally unresectable. Morbidity and mortality were 25 and 1.8% after resections and 10 and 0% after explorations, respectively. Median postoperative survival was 16.4 months in ILR versus 9.4 months in metastatic disease (p < 0.0001). In ILR median survival was significantly longer after resection (26.0 months) compared with exploration without resection (10.8 months, p = 0.0104). R0 resection was achieved in 18 patients and resulted in 30.5 months median survival. Presence of metastases, incomplete resection, and high preoperative CA 19-9 serum values were associated with lesser survival. CONCLUSIONS: Resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with favorable survival outcome. This concept warrants further evaluation in other institutions and in randomized controlled trials.

25 Article Resection after neoadjuvant therapy for locally advanced, "unresectable" pancreatic cancer. 2012

Strobel, Oliver / Berens, Viktoria / Hinz, Ulf / Hartwig, Werner / Hackert, Thilo / Bergmann, Frank / Debus, Jürgen / Jäger, Dirk / Büchler, Markus W / Werner, Jens. ·Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany. ·Surgery · Pubmed #22770956.

ABSTRACT: BACKGROUND: For pancreatic cancer, complete macroscopic resection in combination with chemotherapy is the only potentially curative treatment. Many patients present with locally advanced cancers deemed unresectable. We sought to assess the results of exploration after neoadjuvant therapy for locally advanced possibly unresectable pancreatic cancer. METHODS: From a prospective database, all consecutive patients undergoing operation from October 2001 to December 2009 after neoadjuvant therapy for locally advanced pancreatic cancer were identified. Main criteria for "unresectability" were infiltration of the celiac axis or superior mesenteric artery. Resection rates, perioperative results, and survival were analyzed. RESULTS: Of 257 patients, 199 (77.4%) had received neoadjuvant chemoradiation, and 58 (22.6%) chemotherapy only. Of 257 patients, 120 (46.7%) underwent successful resection, whereas 137 patients underwent exploration only; 47 (39.2%) multivisceral and 45 (37.5%) vascular resections (12 arterial reconstructions) were performed. There were 6 (5%) ypT0 neoplasms, 36 (30.0%) R0, 61 (50.8%) R1, and 16 (13.3%) R2 resections. The median follow-up of surviving patients (n = 22) was 22 months. Median postoperative survival was greater after resection (12.7 months) than after exploration alone (8.8 months; P < .0001). Median postoperative survival was 24.6 months after R0, 11.9 months after R1, and 8.9 months after R2 resection. The 3-year survival rate after R0 resection was 24%. To determine survival after start of neoadjuvant therapy, 3.7 months (median) have to be added. CONCLUSION: In locally advanced, unresectable pancreatic cancer, R0/R1 resections can be achieved in up to 40% of patients who undergo operation after neoadjuvant therapy. In these cases, survival rates are similar to those observed for initially resectable pancreatic cancer.

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