NCT Research

NCT Clinical Cancer Program Head & Neck Cancer

Expertise

The multidisciplinary Clinical Head and Neck Cancer Program (CCP H&N) has been established by the Departments of Otorhinolaryngology (Director: Prof. Dr. P. Plinkert), Oral and Maxillofacial Surgery (Director: Prof. Dr. Dr. J. Hoffmann), Radiooncology (Director: Prof. Dr. Dr. J. Debus), NCT Medical Oncology (Director: Prof. Dr. D. Jäger), and Pathology (Director: Prof. Dr. P. Schirrmacher).

Head & Neck Cancer
 

As a leading center in Germany the program offers comprehensive multidisciplinary counseling and modern treatment concepts comprising radiooncology, tumor and reconstructive surgery, titanium implant epitheses, brachytherapy, and palliative care. Basic research groups from DKFZ and clinical departments cover functional genomics and proteomics, analyses of tumor-host interactions and tumor microenvironment, elucidation of gene regulatory networks, viral infection, and pathology of head and neck cancers. Translational research activities of the program include the identification of biomarkers and molecular targets as well as the development of head and neck cancer specific vaccines, peptides and fully human antibodies for therapeutic interventions.

  • Department of Otorhinolaryngology, Head and Neck Surgery
  • Department of Oral and Maxillofacial Surgery
  • Dept. of Radiooncology
  • Institute of Pathology
  • NCT, Dept. of Medical Oncology
  • Dept. of Diagnostic Radiology
  • NCT Social Services

  • HNO Molecular Cell Biology Group (Prof. Dr. C. Herold-Mende, Dr. G. Dyckhoff)
  • HNO and DKFZ Experimental Head and Neck Oncology Group (PD Dr. J. Hess, Dr. K. Zaoui)
  • DKFZ Immunotherapy and Prevention Group (PD Dr. A. Riemer)
  • MKG Oncology Group (Prof. Dr. K. Freier)
  • NCT Immunotherapy Group (Prof. Dr. D. Jäger, Dr. N. Halama, Dr. I. Zörnig)
  • NCT Antibody-based Immunotherapeutics Group (PD Dr. J. Krauss, Dr. M. Arndt)
  • NCT Virotherapy Group (PD Dr. Dr. G. Ungerechts, Dr. Karim Zaoui)
  • NCT Systems Biology Group (PD Dr. N. Grabe)
  • Dept. Of Pathology Predictive Pathology and Biomarker Validation Group (Prof. Dr. W. Weichert)
  • HNO Robotics and Surgical Epithetics Group (PD. Dr. P. Federspil)
  • DKFZ, Div. of Epigenetics  and Cancer Risk Factors (Prof. Dr. C. Plass

  • HNSCC patient-specific antibody phage display libraries from B cell repertoires of tumor-draining lymph nodes established (Arndt/Krauss)
  • Generation and analysis of tissue microarrays (Hess, Weichert)
  • Preclinical ex vivo culture and mouse tumor models (Hess, Freier, Weichert)
  • Global DNA methylome and transcriptome analysis (Hess, Plass)
  • Paraffin-embedded tissue based molecular profiling (multiple methods, including NG sequencing and other high throughput technologies) (Weichert)
  • Cultivation and ex vivo treatment of viable HNSCC tumor tissue slices (Weichert/Hess)
  • Engineering of retargeted and armed oncolytic measles Virus Vectors for HNSCC therapy (Ungerechts, Zaoui)
  • Proteomics-based identification of immunogenic antigens in HNSCC (Herold-Mende/Dyckhoff)

  • Screening of scFv antibodies from patient-derived phage display libraries for therapeutic interventions in HNSCC (Arndt/Krauss)
  • Development of antibody-RNase fusion proteins (ImmunoRNases) for targeting head and neck cancer (Arndt/Krauss)
  • Photochemical internalization (PCI) of ImmunoRNases for increasing therapeutic effiacy in HNSCC (Collaboration with PCI Biotech, Arndt/Krauss)
  • Predictive biomarker highthroughput assessments in HNSCC tissue (Halama, Jäger, Grabe, Krauss)
  • Prospective study on head and neck squamous cell carcinoma patients to elucidate molecular mechanisms of treatment failure (Federspil, Freier, Weichert, Hess)
  • Generation of a preclinical model to establish and proof now concepts of targeted therapy (Freier, Weichert, Hess)
  • Signature of aberrant global DNA methylation as prognostic makers and for treatment decision making (Plass, Hess)
  • Assesment of function and predictive power of the miRNAome in HNSCC (Weichert/Charité Berlin)
  • Histonedeacetylases as novel chemotherapeutics in HNSCC (Weichert)
  • Comparative exome sequencing of primary HNSCC tumors and their metastases (Hess, Zaoui, Freier, Weichert)
  • HPV and response to radioimmunotherapy (Jensen, Weichert)
  • Arming of HNSCC-targeted Measles Virus Vectors with ImmunoRNases (Ungerechts, Zaoui, Arndt/Krauss)
  • Screening for immunogenic antigens in stroaml and tumor cells of HNSCC (Herold-Mende/Dyckhoff in collaboration with P. Beckhove, DKFZ)
  • Screening for tumor-affine peptides in HNSCC (Herold-Mende/Dyckhoff in collaboration with U. Haberkorn, Nuclear Medicine)

  • Impact of the pro-inflammatory tumor microenvironment in the pathogenesis and prognosis of HPV-driven OPSCC, Stiftung Tumorforschung Kopf-Hals (Hess)
  • Exzellenzzentrum Kopf-Hals Onkologie Heidelberg, Dietmar Hopp Stiftung (Hess)
  • German Cancer Aid (Weichert and Charité Berlin)
  • Personalized Oncology Program (POP) DKFZ/NCT (Hess, Zaoui, Freier, Weichert, Glimm)
  • Klaus Tschira Foundation (Krauss/Jäger)
  • DFG: Importance of ABC transporters for multidrug resistance of HNSCC (Herold-Mende/Dyckhoff)
  • EU: Role of human papillomavirus infection and other co-factors in the aetiology of head and neck cancer in India and Europe (Herold-Mende/Dyckhof

  • Development of multidisciplinary standard operating procedures (SOPs) for treatment of head and neck cancers (Freier, Federspil, Dyckhoff, Jensen, Krauss)
  • Establishment of weekly tumor boards (Freier, Federspil, Dyckhoff, Jensen, Krauss, Weichert)
  • Establishment of weekly interdisciplinary consultation hours (Freier, Federspil, Dyckhoff, Jensen, Krauss)
  • Particle therapy (protons, carbon ions) was established in clinical routine treatment (Debus, Jensen). Various phase II trials were initiated as IITs by the Dept of Radiation Oncology (COSMIC/ ACCEPT: malignant salivary gland tumours (MSGT); IMRT-HIT-SNT: paranasal sinus tumours; TPF-C-HIT: HNSCC). The COSMIC study recruited uncommonly fast and has therefore completed patient accrual. With more than 400 patients, our institution has treated the largest cohort of patients with MSGT worldwide. C12-carbon ion therapy was also introduced for re-irradiation of recurrent head and neck cancers. For HNSCC, the Dept of Radiation Oncology has initiated and coordinates a large phase IV multi-centre trial on radioimmunotherapy with cetuximab in order to differentiate skin reactions caused by radiation from those caused by the monoclonal antibody cetuximab, to evaluate the incidence and severity of these skin reactions, and to correlate them with outcome parameters
  • Establishment of a unit for microvascular free-tissue transfer with >100 patients/year (Freier, Hoffmann, Federspil, Plinkert)
  • First transoral robotic surgery case in Germany in 2010 (Federspil, Plinkert)
  • First H&N Oncology prospective trial with repetitive biomarker assessments in HNSCC tissue under specific therapy (PCI) initiated (Krauss, Freier, Lindel, Jensen, Halama, Jäger)
  • Demonstration of the relationship between serum papillomavirus antibodies and risk of head and neck cancer development (Kreimer et al., J Clin Oncol 2013)
  • Demonstration that KRAS-mutation positive, metastatic tonsil carcinoma may exhibit cancer stem-like cell features and may be suitable for long-term treatment with EGFR tyrosine kinase inhibitors (Gottschling et al., J Clin Oncol 2011)
  • Unraveling of HPV-related global alterations in the DNA methylome of oropharyngeal SCCs and identified a prognostic gene promoter methylation signature that reliably predicts clinical outcome in three independent international patient cohorts (Kostareli et al. J Clin Invest 2013)
  • Development of a novel proteomics-based method to identify targets of spontaneous T-cell responses in HNSCC patients (Beckhove et al., 2010 J Clin Invest)
  • Demonstration that viral load or RNA pattern analysis is better suited than p16INK4a expression to identify HPV16-driven tumors in OPSCC patient populations (Holzinger et al. Cancer Res 2012)
  • Application of global gene expression profiling on matched primary and recurrent tumors derived from a newly developed mouse model (Behren et al., 2010 Int J Oncol), and identification of a comprehensive list of candidate genes with putative implication in treatment failure (Acuna Sanhueza et al. BMC Cancer 2012, Koffler et al. Eur Arch Otorhinolaryngol 2013)
  • Demonstration that proteomic analyses of field cancerization with tissue samples of pharynx and oesophagus from protein profiles of small diagnostic biopsies hold great promise to improve personalized risk assessment in HNSCC (Roesch-Ely et al. 2010 J Pathol)
  • Generation of a large peptide phage and ribosome display library and selection of anaplastic thyroid carcinoma specific peptides for tumor imaging (Altmann et al., 2012 J Nucl Med)
  • Generation of the currently largest immune antibody phage display library from B cell repertoires of tumor draining lymph nodes from 20 head and neck cancer patients and first fully human antibodies with therapeutic potential selected (Diebolder et al., 2013 MAbs)
  • Generation of suicide-gene armed oncolytic Measles Virus Vectors for HNSCC therapy (Zaoui et al. Cancer Gene Ther 2012
  • Launch of an international collaboration with focus on molecular and cellular mechanisms underlying treatment failure and development of tumor recurrence, funded by SNF/DFG (PIs: Simon – Lausanne, Switzerland and Hess, Abdollahi – Heidelberg, Germany)
  • Participation in an international EU-funded consortium analyzing the “Role of human papillomavirus infection and other co-factors in the etiology of head and neck cancer in Europe and India” (HPV-AHEAD, PIs Heidelberg: Pawlita, Dyckhoff)

  • Coordination of national multicenter clinical trials with a personalized vaccine as add-on therapy after surgery and/or (chemo)radiation in patients with localized HNSCC being at high risk for recurrence (IIT in cooperation with TRON Mainz)
  • Participation in multinational trials evaluating palliative treatment in stage IVc HNSCC with immune modulating antibodies and vaccines
  • Further elucidation of the role of HPV infection, chronic inflammation, tumor-host immune interactions, and metabolic alterations in HNSCC and salivary gland cancers
  • Identification of novel drug targets for HNSCC/salivary gland cancers and establishment of improved mouse tumor models as preclinical test systems
  • Development of novel vaccines, virus-based anticancer technologies, phage display derived peptides and fully human antibodies with therapeutic potential
  • Identification of methylation signatures, multidrug resistance mechanisms and angiogenesis patterns in HNSCC
  • Development of titanium implants for anchorage of craniofacial prostheses

  1. Kostarli E, Holzinger D, Bogatyrova O, Hielscher T, Wichmann G, Keck M, Lahrmann B, Grabe N, Flechtenmacher C, Schmidt CR, Seiwert T, Dyckhoff G, Dietz A, Höfler D, Pawlita M, Benner A, Bosch FX, Plinkert P, Plass C, Weichenhan D, Hess J. HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas. J Clin Invest 2013, 123:2488-2501. JIF 12,8
  2. Kreimer AR, Johansson M, Waterboer T, Kaaks R, Chang-Claude J, Drogen D, Tjønneland A, Overvad K, Quirós JR, González CA, Sánchez MJ, Larrañaga N, Navarro C, Barricarte A, Travis RC, Khaw KT, Wareham N, Trichopoulou A, Lagiou P, Trichopoulos D, Peeters PH, Panico S, Masala G, Grioni S, Tumino R, Vineis P, Bueno-de-Mesquita HB, Laurell G, Hallmans G, Manjer J, Ekström J, Skeie G, Lund E, Weiderpass E, Ferrari P, Byrnes G, Romieu I, Riboli E, Hildesheim A, Boeing H, Pawlita M, Brennan P. Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer. J Clin Oncol 2013, 31(21):2708-15. JIF 18,0
  3. Holzinger D, Schmitt M, Dyckhoff G, Benner A, Pawlita M, Bosch FX. Viral RNA patterns and high viral load reliably define oropharynx carcinomas with active HPV16 involvement. Cancer Res 2012, 72(19): 4993-5003. JIF 8,6
  4. Gottschling S, Penzel R, Pelz T, Herpel E, Schnabel PA, Dyckhoff G, Thomas M, Kuhnt T. KRAS-mutation positive, metastatic tonsil carcinoma with cancer stem-like cell features and long-term response to gefitinib: a case report and review of the literature. J Clin Oncol 2011, 29(21). JIF 18,0
  5. Beckhove P, Warta R, Lemke B, Stoycheva D, Momburg F, Schnölzer M, Warnken U, Schmitz-Winnenthal H, Ahmadi R, Dyckhoff G, Bucur M, Jünger S, Schoeler T, Lennerz V, Woelfel T, Unterberg A, Herold-Mende C. Rapid T-cell based identification of tissue antigens by automated two-dimensional protein fractionation. J Clin Invest 2010, 120:2230-42. JIF 12,8

  1. Häfner MF, Fetzner L, Hassel JC, Debus J, Potthoff K. Prophylaxis of Acute Radiation Dermatitis with an Innovative FDA-Approved Two-Step Skin Care System in a Patient with Head and Neck Cancer Undergoing a Platin-Based Radiochemotherapy: A Case Report and Review of the Literature. Dermatology. 2013 in press. JIF 2,0
  2. Diebolder P, Keller A, Haase S, Schlegelmilch A, KieferJD, Karimi T, Weber T, Moldenhauer G, Kehm R, Eis-Hübinger AM, Jäger D, Federspil PA, Herold-Mende C, Dyckhoff G, Kontermann RE, Arndt MAE, Krauss J. Generation of ‘LYmph Node Derived Antibody Libraries’ (LYNDAL) for selecting fully human antibodies with therapeutic potential. MaBs 2013, in press. JIF 5,2
  3. Stoiber EM, Schwarz M, Debus J, Bendl R, Giske K. An optimised IGRT correction vector determined from a displacement vector field: A proof of principle of a decision-making aid for re-planning. Acta Oncol. 2013 Apr 25 JIF 2,8
  4. Mark R, Bermejo JL, Bierhaus A, Plinkert PK, Angel P, Hess J. The receptor for advanced glycation end products is dispensable in a mouse model of oral and esophageal carcinogenesis. Histol Histopathol 2013, in press. JIF 2,2
  5. Thiele OC, Mertens C, Bacon C, Flechtenmacher C, Zaoui K, Mischkowski RA. Facial basal cell carcinoma with successive metastases to the neck, thyroid gland and lung. J Craniomaxillofac Surg. 2013 in press. JIF 1,2
  6. Thiele OC, Seeberger R, Engel M, Freier K, Hoffmann J. Development of the clinical use of distant flaps for head and neck reconstruction. J Craniomaxillofac Surg. 2013 in press. JIF 1,2
  7. Bulut OC, Lindel K, Hauswald H, Brandt R, Klauschen F, Wolf J, Wolf T, Plinkert PK, Simon C, Weichert W, Stenzinger A. Clinical and molecular characteristics of HNSCC patients with brain metastases: a retrospective study. Eur Arch Otorhinolaryngol 2013, in press. JIF 1,4
  8. Habl G, Potthoff K, Haefner MF, Abdollahi A, Hassel JC, Boller E, Indorf M, Debus J. Differentiation of irradiation and cetuximab induced skin reactions in patients with locally advanced head and neck cancer undergoing radioimmunotherapy: the HICARE protocol (head and neck cancer: immunochemo and radiotherapy with erbitux) - a multicenter phase IV trial. BMC Cancer. 2013 Jul 15;13:345. JIF 3,3
  9. Amelio D, Winter M, Habermehl D, Jäkel O, Debus J, Combs SE. Analysis of inter- and intrafraction accuracy of a commercial thermoplastic mask system used for image-guided particle radiation therapy. J Radiat Res. 2013 Jul;54 Suppl 1:i69-76 JIF 1,4
  10. Finimundy, T. C., G. Gambato, R. Fontana, M. Camassola, M. Salvador, S. Moura, J. Hess, J. A. Henriques, A. J. Dillon and M. Roesch-Ely. Aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exhibit high antioxidant capability and promising in vitro antitumor activity. Nutr Res 2013 33(1): 76-84. JIF 2,2
  11. Stoiber EM, Schwarz M, Debus J, Huber PE, Bendl R, Giske K. Regional cumulative maximum dose to the spinal cord in head-and-neck cancer: considerations for re-irradiation. Radiother Oncol. 2013 Jan;106(1):96-100 JIF 4,5
  12. Rigalli JP, Reuter T, Herold-Mende C, Dyckhoff G, Haefeli WE, Weiss J, Theile D. Minor role of pregnane-x-receptor for acquired multidrug resistance in head and neck squamous cell carcinoma in vitro. Cancer Chemother Pharmacol 2013, 71(5):1335-43. JIF 2,7
  13. Schwarz M, Giske K, Stoll A, Nill S, Huber PE, Debus J, Bendl R, Stoiber EM. IGRT versus non-IGRT for postoperative head-and-neck IMRT patients: dosimetric consequences arising from a PTV margin reduction. Radiat Oncol. 2012 Aug 8;7:133. JIF 2,1
  14. Bodem JP, Gülicher D, Engel M, Hoffmann J, Freudlsperger C. Role of neck dissection in the treatment of melanoma of the head and neck. J Craniofac Surg. 2013;24(2):483-7. JIF 0,6
  15. Mertens C, Löwenheim H, Hoffmann J. Image data based reconstruction of the midface using a patient-specific implant in combination with a vascularized osteomyocutaneous scapular flap. J Craniomaxillofac Surg. 2013;41(3):219-25. JIF 1,2
  16. Grimm M, Alexander D, Munz A, Hoffmann J, Reinert S. Is 1,25-dihydroxyvitamin D3 receptor expression a potential Achilles' heel of CD44+ oral squamous cell carcinoma cells? Target Oncol. 2013;8(3):189-201. JIF 2,7
  17. Eichhorn W, Precht C, Wehrmann M, Hickmann E, Eichhorn M, Zeuch J, Löning T, Friedrich RE, Heiland M, Hoffmann J. First description of a hybrid tumor of the sublingual gland. Anticancer Res. 2013 Oct;33(10):4567-71. JIF 1,7
  18. Grimm M, Alexander D, Munz A, Hoffmann J, Reinert S. Increased LDH5 expression is associated with lymph node metastasis and outcome in oral squamous cell carcinoma. Clin Exp Metastasis. 2013;30(4):529-40. JIF 3,4
  19. Koffler, J., D. Holzinger, G. A. Sanhueza, C. Flechtenmacher, K. Zaoui, B. Lahrmann, N. Grabe, P. K. Plinkert and J. Hess. Submaxillary gland androgen-regulated protein 3A expression is an unfavorable risk factor for the survival of oropharyngeal squamous cell carcinoma patients after surgery. Eur Arch Otorhinolaryngol 2013, 270(4): 1493-1500 JIF 1,4
  20. Friedman JA, Wise SC, Hu M, Gouveia C, Vander Broek R, Freudlsperger C, Kannabiran VR, Arun P, Mitchell JB, Chen Z, Van Waes C. HSP90 Inhibitor SNX5422/2112 Targets the Dysregulated Signal and Transcription Factor Network and Malignant Phenotype of Head and Neck Squamous Cell Carcinoma. Transl Oncol. 2013 1;6(4):429-41. JIF 1,2
  21. Grimm M, Krimmel M, Alexander D, Munz A, Kluba S, Keutel C, Hoffmann J, Polligkeit J, Reinert S, Hoefert S. Prognostic value of histamine H1 receptor expression in oral squamous cell carcinoma. Clin Oral Investig. 2013;17(3):949-55. JIF 2,2
  22. Listl S, Jansen L, Stenzinger A, Freier K, Emrich K, Holleczek B, Katalinic A, Gondos A, Brenner H; GEKID Cancer Survival Working Group. Survival of patients with oral cavity cancer in Germany. PLoS One. 2013;8(1): e53415. JIF 3,7
  23. Freier K, Mertens C, Engel M, Hoffmann J.Therapeutic strategies for the reconstruction of extensive mandibular defects. HNO. 2013 Jul;61(7):551-8 JIF 0,4
  24. Halec G, Holzinger D, Schmitt M, Flechtenmacher C, Dyckhoff G, Lloveras B, Höfler D, Bosch FX, Pawlita M. Biological evidence for a causal role of HPV16 in a small fraction of laryngeal squamous cell carcinoma. Br J Cancer 2013, 109(1):172-83. JIF 5,0
  25. Reuschenbach M, Kansy K, Garbe K, Vinokurova S, Flechtenmacher C, Toth C, Prigge ES, Thiele OC, Reinert S, Hoffmann J, von Knebel Doeberitz M, Freier K. Lack of evidence of human papillomavirus-induced squamous cell carcinomas of the oral cavity in southern Germany. Oral Oncol. 2013; 49(9):937-42. JIF 2,7
  26. Jonas R, Schaal T, Krimmel M, Gülicher D, Reinert S, Hoffmann J. Monitoring in microvascular tissue transfer by measurement of oxygen partial pressure: four years experience with 125 microsurgical transplants. J Craniomaxillofac Surg. 2013;41(4):303-9. JIF 1,2
  27. Holzinger, D., C. Flechtenmacher, N. Henfling, I. Kaden, N. Grabe, B. Lahrmann, M. Schmitt, J. Hess, M. Pawlita and F. X. Bosch. Identification of oropharyngeal squamous cell carcinomas with active HPV16 involvement by immunohistochemical analysis of the retinoblastoma protein pathway. Int J Cancer 2013 133(6): 1389-1399. JIF 6,1
  28. Freudlsperger C, Bian Y, Contag Wise S, Burnett J, Coupar J, Yang X, Chen Z, Van Waes C. TGF-β and NF-κB signal pathway cross-talk is mediated through TAK1 and SMAD7 in a subset of head and neck cancers. Oncogene. 2013; 32(12):1549-59. JIF 7,3