NCT Research

Program

Mission and Strategy

Unique features of this interdisciplinary area are the integration of non-invasive imaging with radiation planning and biology-guided, individualized radiotherapy. The program has a central integrative function within NCT’s concept as comprehensive cancer center. Its principal investigators have participated in more than 30 interdisciplinary phase I-IV trials covering more than 14 different tumor entities. The mission of this program is to provide the best available individualized care for cancer patients. To achieve this goal and to position NCT at the forefront of translational radiation oncology research, this program emphasizes the development of modern methods of radiotherapy and identification of novel, molecular therapy targets and predictive biomarkers of therapy response.

Integrative Radiation Oncology
 
Translational Radiation Oncology

Achievements

This program helped pioneer modern radiotherapy, including intensity-modulated radiotherapy (IMRT) (Bortfeld Phys Med Biol 1990), cranial and extracranial stereotactic radiosurgery (Herfarth J Clin Oncol 2001), image-guided adaptive radiotherapy (IGRT), and raster scanning particle therapy using protons and heavy ions (Debus Strahlenther Onkol 2000). 

Figure 5: Establishment of first preclinical models of lung irradiation with carbon ions (left), examples for verification of carbon ion dose distribution by PET/CT, evaluation of radiation-induced lung toxicity and microvascular damage detected by vascular corrosion casting combined with high-resolution micro-CT. Clinical translation (right): irradiation of the first lung cancer patient with carbon ions at HIT in fall 2011.

The range of conformal and image-guided radiotherapy (IMRT/IGRT) techniques was further expanded using in-line cone beam imaging by clinical implementation of helical tomotherapy as Germany’s first center (Sterzing Cancer 2010). Within the framework of the DFG Priority Research Program (SPP1190), tumor vessels were identified as a central target of radiotherapy. Multimodal therapies consisting of radiotherapy, chemotherapy, and targeted antiangiogenic modulators of tumor microenvironment (i.e., inhibitors of VEGF, PDGF, bFGF, IMPDH, c-Kit, SDF, COX-2, TGFß, EGFR, HDAC, mTOR, and integrin signaling) were then investigated and successfully translated into Phase I-III clinical trials (Abdollahi and Folkman Drug Resist Updat 2010; Zhang Cancer Res 2011, Domhan Curr Pharm Des 2013).

In analogy to the NCT Tumor Board, several entity-specific taskforces were established, and the number of treated patients as well as the quality of treatment has steadily increased for a broad spectrum of cancers, ranging from Hodgkin’s Lymphoma (Engert N Engl J Med 2010; Eich J Clin Oncol 2010) to NSCLC (Hof Int J Radiat Oncol Biol Phys 2010; Jensen Cancer 2011) and neurooncology (Rieken and Combs Radiother Oncol 2013). To identify novel molecular predictors of therapy response and therapy surrogates, a comprehensive peripheral blood bank was established, and peripheral blood-based CTC and transcriptomics analysis was implemented at NCT (Liangos PLoS One 2010; Blanchard J Clin Oncol 2010; Zabel-du Bois Strahlenther Onkol 2010). Numerous milestones were achieved in terms of the development of IMRT, correction of organ motion and adaptive radiotherapy within the strategic alliance with DKFZ-Siemens and the recently initiated DFG-TR-SFB-125. The Software Platform for Adaptive Multimodal Radio and Particle Therapy consortium (BMBF-SPARTA, 2013-2016) will continue the successful work conducted in BMBF-DOT-MOBI (2009-2011). Finally, the establishment of the Heidelberg Ion Therapy Center (HIT) constitutes a landmark development in high-precision radiotherapy using active raster scanning technology for particle therapy with protons and heavier ions such as carbon ions (Section B1).

To strengthen the long-term multi-disciplinary activities that exist between the NCT radiation oncology, radiation biology, and medical physics groups, the Heidelberg Institute of Radiation Oncology (HIRO) was established and awarded by BMBF as the National Center for Radiation Research in Oncology (NCRO). HIRO has joined forces with the DKTK to identify novel druggable targets for translation into multimodal phase I/II trials. Germany’s first young investigator group in the field of radiation oncology was awarded by DKH (Max-Eder, Amir Abdollahi) to NCT/HIT. It provides a unique interface for synergistic activities beyond classical research boundaries of radiation biophysics. This unit has already taken steps towards developing next-generation “molecular” targets and diagnostics in radiation oncology.

Goals

The range of conformal and image-guided radiotherapy (IMRT/IGRT) techniques was further expanded using in-line cone beam imaging by clinical implementation of helical tomotherapy as Germany’s first center (Sterzing Cancer 2010). Within the framework of the DFG Priority Research Program (SPP1190), tumor vessels were identified as a central target of radiotherapy. Multimodal therapies consisting of radiotherapy, chemotherapy, and targeted antiangiogenic modulators of tumor microenvironment (i.e., inhibitors of VEGF, PDGF, bFGF, IMPDH, c-Kit, SDF, COX-2, TGFß, EGFR, HDAC, mTOR, and integrin signaling) were then investigated and successfully translated into Phase I-III clinical trials (Abdollahi and Folkman Drug Resist Updat 2010; Zhang Cancer Res 2011, Domhan Curr Pharm Des 2013).

In analogy to the NCT Tumor Board, several entity-specific taskforces were established, and the number of treated patients as well as the quality of treatment has steadily increased for a broad spectrum of cancers, ranging from Hodgkin’s Lymphoma (Engert N Engl J Med 2010; Eich J Clin Oncol 2010) to NSCLC (Hof Int J Radiat Oncol Biol Phys 2010; Jensen Cancer 2011) and neurooncology (Rieken and Combs Radiother Oncol 2013). To identify novel molecular predictors of therapy response and therapy surrogates, a comprehensive peripheral blood bank was established, and peripheral blood-based CTC and transcriptomics analysis was implemented at NCT (Liangos PLoS One 2010; Blanchard J Clin Oncol 2010; Zabel-du Bois Strahlenther Onkol 2010). Numerous milestones were achieved in terms of the development of IMRT, correction of organ motion and adaptive radiotherapy within the strategic alliance with DKFZ-Siemens and the recently initiated DFG-TR-SFB-125. The Software Platform for Adaptive Multimodal Radio and Particle Therapy consortium (BMBF-SPARTA, 2013-2016) will continue the successful work conducted in BMBF-DOT-MOBI (2009-2011). Finally, the establishment of the Heidelberg Ion Therapy Center (HIT) constitutes a landmark development in high-precision radiotherapy using active raster scanning technology for particle therapy with protons and heavier ions such as carbon ions (Section B1).

To strengthen the long-term multi-disciplinary activities that exist between the NCT radiation oncology, radiation biology, and medical physics groups, the Heidelberg Institute of Radiation Oncology (HIRO) was established and awarded by BMBF as the National Center for Radiation Research in Oncology (NCRO). HIRO has joined forces with the DKTK to identify novel druggable targets for translation into multimodal phase I/II trials. Germany’s first young investigator group in the field of radiation oncology was awarded by DKH (Max-Eder, Amir Abdollahi) to NCT/HIT. It provides a unique interface for synergistic activities beyond classical research boundaries of radiation biophysics. This unit has already taken steps towards developing next-generation “molecular” targets and diagnostics in radiation oncology.