NCT Research

CCRP Lung

Summary

The NCT Lung CCRP is based on the clinical backbone of the Thoraxklinik Heidelberg, an internationally renowned, comprehensive center for the treatment of lung diseases. Each year, the clinic handles 10,400 inpatient and 5,700 outpatient cases, 60% of which suffer from pulmonary malignancies, and provides more than 2,500 multidisciplinary board decisions in thoracic malignancies.

CCRP Lung
 

The clinic’s Department of Thoracic Surgery conducts about 1,800 surgical procedures in thoracic oncology annually. The Department of Respiratory Medicine provides outstanding expertise in all fields of bronchoscopy and leads the development of devices for diagnostic and therapeutic purposes. The Department of Thoracic Oncology provides the latest options in systemic therapy and multimodality approaches to care for about 3,100 cases of thoracic malignancy annually. It runs a clinical trial unit with almost 33 trials active from phase I to III and is a recognized driver in the creation and running of clinical trials in nationwide investigator-initiated trial networks. The Department of Chest Radiology conducts about 60,000 multimodality investigations per year and provides outstanding expertise in quick imaging-based decision-making. The translational research unit of the clinic, driven by two biologists, operates the NCT Tissue Bank, takes responsibility for the follow-up system and provides platform technologies on biomaterials. Strong interdisciplinary collaborations (DKFZ, EMBL, BMBF, EU CANCERALIA project, German Center for Lung Research) focus on: (1) mechanisms of lung cancer development and spread; (2) resistance; (3) immunooncology and (4) impact of interventions in palliative care.

Member designated as Contact Person

Prof. Dr. Thomas
Thoracic Oncology

 
 
 

Members:

Prof. Dr. med. U. Haberkorn
Dep. of Nuclear Medicine, Heidelberg University Hospital    

Prof. Dr. med. FJF Herth
Dep. of Respiratory Medicine, Thoraxklinik at Heidelberg University Hospital

Prof. Dr. med. C.P. Heußel
Dep. of Diagnostic Radiology, Thoraxklinik at Heidelberg University Hospital

PD Dr. med. S. Rieken
Dep. of Radio Oncology, Heidelberg University Hospital    

Prof. Dr. med. Michael Thomas
Dep. of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital    

Prof.  Dr. med. A. Warth
Institute of Pathology, Heidelberg University Hospital

Prof. Dr. med. H. Winter
Dep. of Thoracic  Surgery, Thoraxklinik at Heidelberg University Hospital    

Dr. med. J .Wiskemann
Dep. of Medical Oncology, NCT/Heidelberg University Hospital

Internal Partners:

Prof. Dr. U. Haberkorn
Nuclear Medicine, German Cancer Research Center (DKFZ)

Prof. Dr. R. Sotillo
Division of molecular thoracic oncology, German Cancer Research Center (DKFZ)

Prof. Dr. R. Eils
Theoretical Bioinformatics, German Cancer Research Center (DKFZ)    

Prof. Dr. R. Kaaks
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)    

Prof. Dr. U. Klingmüller
Division of Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ)

Dr. M. Meister; Dr. T. Muley; Dr. M. Schneider
Translational Research Unit, Thoraxklinik at Heidelberg University Hospital    

Prof. Dr. C. Plass
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ)

Prof. Dr. M. Platten
Division of Translational Immunology, German Cancer Research Center (DKFZ)

Prof. Dr. H. Schlemmer
Radiology, German Cancer Research Center (DKFZ)        

Prof. Dr. H. Sültmann
Division of Cancer Genome Research, German Cancer Research Center (DKFZ)

Prof. Dr. A. Trumpp
Stem Cells and Cancer, German Cancer Research Center (DKFZ)        

Prof. Dr. A. Warth
Dep. of Pathology, Heidelberg University Hospital

Scientific Aims:

  • Prospective cohort assembly approach with longitudinal phenotyping and sequential biomaterial acquisition  (SBA) to a) assess signatures for outcome prediction and treatment stratification, b) explore hypotheses on modes of action of treatment, and c) elucidate mechanisms of resistance – started as Sequential Biomaterial Acquisition (SBA) Approach
  • Tackling resistance in molecularly altered cancer by a multidimensional approach comprehensively involving different project-lines
  • Development of novel therapeutic strategies as a major network partner (national, international) in designing and conducting clinical trials and biomarker assessment
  • Set up of investigator initiated trials in the field of immunooncology to foster treatment efficacy and enable biomarker detectionBiomarker exploration to guide treatment in thoracic immunooncology

Clinical Aims:

  • Advancement of cohort assembly with sequential biomaterial acquisition to
    a) assess signatures for outcome prediction and treatment stratification,
    b) explore hypotheses on modes of action of treatment, and
    c) elucidate mechanisms of resistance
  • Registry reflecting the longitudinal lung cancer disease trajectory (early-detection, clinical phenotyping; burden; imaging; biomaterial asservation)
  • Driver position in a national registry approach in metastatic lung cancer (CRISP)
  • Set up of investigator initiated trials in the field of immunooncology to foster treatment efficacy and enable biomarker detection
    - NEOIMMUN – Enabling lung cancer immune mediated response by anti-PDL1 – treatment;
    - DURATION – Assessment of anti-PDL1 – treatment in frail and elderly patients with NSCLC;
    - FORCE in NSCLC – Fostering efficacy of anti-PD1 – treatment in advanced and progressive NSCLC
  • Increase of patient numbers in IITs and early clinical trials
  • Implementation of coping-strategies facilitating self-efficacy and activity in metastatic disease patients (POSITIVE-trial; Lead: M. Thomas, S. Hummler; Thoraxklinik; German Cancer Aid – DKH 110116)
  • Pre-therapeutic risk assessment of sarcopenia in lung cancer (Nattenmüller J, Steins M, Hummler S, Wiskemann J, Thomas M, Heussel CP)
  • Implementation of outpatient palliative care in line with the outreach of the NCT (NCT-SAPV; medical responsibility: H. Bardenheuer / M. Thomas)
  • Investigation on the quality of life of patients with a limited life span and the optimization of patient care: „Versorgungsziele und individuelle Lebensqualität für Patienten mit begrenzter Prognose“
  • MCA (milestones communication approach): implementation of a longitudinal communication strategy for patients with limited prognosis and their care-givers to facilitate advance care planning and EOL-decision making (Lead: M. Thomas, M. Villalobos)
  • ERT (Early Response Trial): Ultra early prediction of response in first line systemic therapy of NSCLC advanced stage Adeno-Ca in non-surgical patients by usage of diffusion weighted and tumor perfusion MRI (PI: CP Heußel, F Bozorgmehr, G Heußel, N Batora)
  • Radimmun: Biopsy of low-stage NSCLC, non-ablative irradiation to allow for abscopal effect and delayed resection (H Hoffmann, S Safi, R Eberhard, CP Heußel)
  1. Christopoulos P, Engel-Riedel W, Grohe C, Kropf-Sanchen C, von Pawel J, Gutz S, Kollmeier J, Eberhardt W, Ukena D, Baum V, Nimmrich I, Sieder C, Schnabel PA, Serke M, Thomas M. Everolimus with paclitaxel and carboplatin as first-line treatment for metastatic large-cell neuroendocrine lung carcinoma: a multicenter phase II trial. Ann Oncol. 2017 May 23. doi: 10.1093/annonc/mdx268. [Epub ahead of print] (IF 11.855)
  2. Thomas M, Sadjadian P, Kollmeier J, Lowe J, Mattson P, Trout JR, Gargano M, Patchen ML, Walsh R, Beliveau M, Marier JF, Bose N, Gorden K, Schneller F, 3rd. A randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of BTH1677 (1,3-1,6 beta glucan; Imprime PGG) in combination with cetuximab and chemotherapy in patients with advanced non-small cell lung cancer. Invest New Drugs. 2017 Jun;35(3):345-58. (IF 3.484)
  3. Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, Ready N, Hiltermann TJN, Nair S, Juergens R, Peters S, Minenza E, Wrangle JM, Rodriguez-Abreu D, Borghaei H, Blumenschein GR, Jr., Villaruz LC, Havel L, Krejci J, Corral Jaime J, Chang H, Geese WJ, Bhagavatheeswaran P, Chen AC, Socinski MA, CheckMate I. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Jun 22;376(25):2415-26. (IF 72.406)
  4. Riediger AL, Dietz S, Schirmer U, Meister M, Heinzmann-Groth I, Schneider M, Muley T, Thomas M, Sultmann H. Mutation analysis of circulating plasma DNA to determine response to EGFR tyrosine kinase inhibitor therapy of lung adenocarcinoma patients. Sci Rep. 2016 Sep 19;6:33505. (IF 4.259)
  5. Bernhardt D, Bozorgmehr F, Adeberg S, Opfermann N, von Eiff D, Rieber J, Kappes J, Foerster R, Konig L, Thomas M, Debus J, Steins M, Rieken S. Outcome in patients with small cell lung cancer re-irradiated for brain metastases after prior prophylactic cranial irradiation. Lung cancer. 2016 Nov;101:76-81. (IF 4.294)
  6. Sklenarova H, Krumpelmann A, Haun MW, Friederich HC, Huber J, Thomas M, Winkler EC, Herzog W, Hartmann M. When do we need to care about the caregiver? Supportive care needs, anxiety, and depression among informal caregivers of patients with cancer and cancer survivors. Cancer. 2015 May 01;121(9):1513-9. (IF 5.649)
  7. Thomas M, Fischer J, Andreas S, Kortsik C, Grah C, Serke M, von Eiff M, Witt C, Kollmeier J, Muller E, Schenk M, Schroder M, Villalobos M, Reinmuth N, Penzel R, Schnabel P, Acker T, Reuss A, Wolf M, Group AB-LC. Erlotinib and bevacizumab versus cisplatin, gemcitabine and bevacizumab in unselected nonsquamous nonsmall cell lung cancer. Eur Respir J. 2015 Jul;46(1):219-29. (IF 8.332)
  8. Firnkorn D, Ganzinger M, Muley T, Thomas M, Knaup P. A Generic Data Harmonization Process for Cross-linked Research and Network Interaction. Construction and Application for the Lung Cancer Phenotype Database of the German Center for Lung Research. Methods Inf Med. 2015;54(5):455-60. (IF 2.248)
  9. Schneider MA, Granzow M, Warth A, Schnabel PA, Thomas M, Herth FJ, Dienemann H, Muley T, Meister M. Glycodelin: A New Biomarker with Immunomodulatory Functions in Non-Small Cell Lung Cancer. Clin Cancer Res. 2015 Aug 01;21(15):3529-40. (IF 8.738)
  10. Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med.2014 Mar 27;370(13):1189-97. (IF 55.873)
  11. Cancer Genome Atlas Research N. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014 Jul 31;511(7511):543-50. (IF 41.456)
  12. Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M, investigators T. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. (IF 6.578)
  13. Reinmuth N, Stumpf A, Stumpf P, Muley T, Kobinger S, Hoffmann H, Herth FJ, Schnabel PA, Warth A, Bischoff H, Thomas M. Characteristics and outcome of patients with second primary lung cancer. Eur Respir J. 2013 Dec;42(6):1668-76. (IF 7.125)

Clinical Activities

Multidisciplinary patient management

  • Multidisciplinary out-patient consultation
  • Multidisciplinary in-patient management
  • Interdisciplinary board on thoracic oncology (daily)
  • Treatment according to NCT SOPs; set up of SOPs
  • High quality thoracic surgery facility
  • High quality RFA-facility
  • High quality radio oncology facility; innovative trials
  • Leading edge endoscopy unit
  • Up to date provisions in systemic treatment
  • Clinical trials in the field of thoracic oncology
  • Integrative oncology approach in patients with limited life span
  • High quality palliative care (inpatient; outpatient; palliative care ward; case conferences)

Specific Treatment Options

  • Innovative studies in lung cancer (phase I/II trials, including targeted therapy and immunotherapy)
  • High quality tumor surgery (primary, metastases)
  • Radio oncology (high precision therapy; brachytherapy)
  • Interventional tissue asservation (bronchoscopically: 5000 p.a., CT guided: 400 p.a.)
  • Loco regional treatment of lung cancer and metastases (e.g. interventional tumor ablation, e.g. RFA)
  • Interventional bronchoscopy
  • Novelties of multimodality treatment (e.g. oligometastatic disease; locally advanced lung cancer; HITOC in mesothelioma)
  • High quality palliative care (including early palliative care)
  • Comprehensive Counseling at the Thoraxklinik Heidelberg:
    - “Ohne Kippe” – smoking prevention program, smoking cessation courses
    - dietary counseling
    - hospital social service
    - psychological service
    - hospital spiritual care, different religions
    - CT-based program for early detection of lung cancer
  • Gaining the long-term funding of the Bundesministry for Science as German lung research centre
  • Establishment of a clinical trial network and conceptualize and conduct Investigator Initiated trials holding the lead-position (e.g. Carbone et al., N Engl J Med. 2017; Thomas et al., Eur Respir J. 2015; Shaw et al., N Eng J Med. 2013; Kreuter et al., Ann Oncol. 2013)
  • Establishment of technical / logistic platforms providing sequential biomaterial acquisition (SBA) at every state of disease progression; thus to elucidate predictive biomarkers / mechanisms of resistance (e.g. Firnkorn et al., Stud Health Technol Inform. 2014)
  • Assessment of the impact of physical exercise on self-efficacy, physical strength and immune activation in metastatic lung cancer – DKH Förderung (Wiskemann et al., BMC Cancer 2016)
  • Assessment of burden in patients and relatives with metastatic lung cancer (e.g. Sklenarova et al., Cancer. 2015)
  • Establishment and lead of investigator initiated trials aiming to foster the efficacy of checkpoint-inhibitors; exploration of biomarkers (e.g. FORCE; DURATION; NEOMUN)
  • Advanced management strategies of non-aggressive metastatic disease (e.g. treatment of oligometastatic disease with high quality surgery; precision radio oncology; RFA)
  • High quality multimodality approach in mesothelioma patients with loco regional disease utilizing HITOC
  • Comprehensive approach on early palliative care in metastatic disease (counselling service; case conferences; multidisciplinary team approach; research strategies) - HeiMeKOM
  • Advancement of palliative care (24 palliative care beds; two distinguished wards; consultancy service)

Preclinical Activities

Established Technologies

  • Tissue processing (high quality DNA/RNA extraction) (Methylation screening/analysis; analysis of specific signaling proteins; Exome, RNA, miRNA sequencing)
  • Isolation and cultivation of primary cells from lung tissue (normal, tumor), organoid cultures, spheroids (CTOS), air-liquid interface (ALI) culture
  • Gene expression analyses (Affymetrix platform, qPCR)
  • NGS Panel-sequencing Illumina-platform
  • See established technologies of above mentioned divisions and working groups at Thoraxklinik, DKFZ, NCT Heidelberg
  • Establishment and harmonization of patient cohort assembly across different DZL sites and validation of biomaterial procurement strategie
  • Identification of an immunomodulatory biomarker (Glycodelin) for NSCLC (Schneider et al., Clin Cancer Res. 2015; Schneider et al., Oncotarget 2016)
  • Identification of altered phospholipid profiles in NSCLC (Marien et al., Int J Cancer 2015)
  • Provision of a generic approach for the harmonization process in research networks enabling joint data analysis (Firnkorn et al., Methods Inf Med. 2015)
  • Development and application of a comprehensive data management workflow to provide a common data base enabling data mining and statistical analysis approaches (Firnkorn et al., Stud Health Technol Inform. 2016)
  • Identification of serum miR-142-3p as a biomarker for early recurrence (Kaduthanam et al., Lung Cancer 2013)