The scope of this interdisciplinary area is the integration of non-invasive imaging with radiation planning and biology-guided, individualized radiotherapy (Figure 2-4). To achieve this goal and position the NCT at the forefront of translational radiation oncology research, this program focuses on the development of modern methods of radiotherapy and identification of new molecular therapy targets and predictive biomarkers for therapy response. Both sites, NCT/UCC Dresden and NCT Heidelberg are constantly widening their interface for synergistic activities beyond classical research boundaries.
The joint organization of both sites within the National Center for Radiation Research in Oncology (NCRO), the Helmholtz Program-oriented funding and recently also within the NCT has led to numerous collaborative and complementary initiatives in biological, physics, translational and clinical research. This also includes the preclinical evaluation and clinical introduction of dual-energy computer tomography (CT) for proton radiotherapy planning, the evaluation of magnet resonance-guided radiotherapy using linear accelerator technology, development of magnet resonance-guided proton therapy or the joint performance of clinical trials.
Specifically, the following joint activities underline the strong cooperation of both centers, e.g.
- Joint funding program within NCRO
- Regular joint scientific retreats within NCRO and a monthly multidisciplinary lecture series broadcasted to both sites
- Interdisciplinary and cross-institutional programs for particle beam therapy as well as joint or inter-connected clinical trials
- Joint leadership within the Radiooncology program of the DKTK
- Clinical trial IT-platform (RadPlanBio supported by DKTK)
Research Profile NCT Heidelberg
The NCT radiation oncology program focuses on the development of particle therapy with clinical proton and carbon ion beams as well as novel sources of radiation at Heidelberg Ion Beam Therapy Center (HIT), such as helium and oxygen ions. Beyond established radiobiological concepts centered on tumor cell killing, this program aims to decipher the biological effect landscape of a prescribed physical dose (NCT-Biodose), to shed light on the differential effects of radiation qualities at relevant “tumor niches” i.e., angiogenic, hypoxic, fibrotic and immune niches.
To exploit the full potential of high-precision and enhanced radiobiological effectiveness of particle beams towards personalized oncology (NCT-PRO), biomarker-tailored patient stratification and rationally designed multimodal therapy strategies are developed. As the third cornerstone, the clinical translation program converges and implements findings by PRO and Biodose with cutting-edge image (MRI) guidance towards the development of next-generation multidisciplinary adaptive radiotherapy with ions and x-rays (NCT-MATRIX). The NCT radiation oncology program forms an important seed for numerous national and international research initiatives e.g., DFG (SFB-1389), BMBF (ARTEMIS) and EU consortia (PREDICT).
Radiation Oncology NCT Heidelberg - Selected Activities
Carbon irradiation (CIR) overcomes glioma radioresistance - exploring the potential of carbon ions in modulation of the tumor microenvironment and normal tissue response
This project aims to explore the potential of particle radiotherapy to eradicate radioresistant glioblastoma (GBM) subpopulations and overcome GBM therapy refractoriness by resensitizing tumors to antiangiogenic, immune- and tumor-targeting agents. Compared to conventional low-LET photon irradiation, high-LET CIR more efficiently eradicate radioresistant patient-derived glioma stem cells leading to growth inhibition and prolonged survival. CIR exhibited superior antiangiogenic effects and eradication of radioresistant hypoxic- and stem cell-like tumor cells. CIR led to modulation of the GBM niche toward an antiangiogenic and less immunosuppressive state. Current approaches aim to utilize these positive tumor microenvironment effects for the rational design of novel multimodal therapy strategies.
Chiblak et al., JCI Insight 2019; Zhou et al., Int J Cancer 2019
Carbon irradiation for recurrent high-grade glioma
Local recurrence hinders lasting therapy success in high-grade glioma treatment. Preclinical data show the efficacy of carbon ion radiotherapy (CRT) in glioma; the implication for clinical therapy, however, remains elusive. Survival data from 197 patients with recurrent high-grade glioma (rHGG) treated at Heidelberg Ion Beam Therapy Center with CRT (RiCi) was compared to the DKTK-ROG GBM multicenter cohort (n=564) treated with conventional photon radiotherapy (RiP). The ReRT risk score (RRRS) established in the latter (including initial tumor grade, Karnofsky performance score and age at re-irradiation) was used to match cohorts. CRT showed activity for overall survival, HR 0.52 (95% CI 0.49-0.72) and HR 0.66 (95% CI 0.51-0.85) in RRRS matched cohorts. Effects are most prominent in grade III tumors. Based on these encouraging results, prospective randomized trials using RRRS for stratification are recommended.
Knoll et al., J Clin Oncol 2019; Debus et al., Sci Rep. 2018
Development and verification of multi-ion particle treatments: the PRECISE platform
In hadron therapy, there are two widely used particles: protons (P) and carbon ions (C) while helium ions (He) are considered for future clinical translation, with each ion species having its own unique benefits and tradeoffs. In order to combine the advantages of these ion beams and minimize disadvantages, multi-ion particle treatment modalities were developed and verified. The PRECISE system was introduced, which supports both single and multi-ion optimizations, as well as various biophysical effect models and LET. With PRECISE, combined ion-beam with constant RBE (relative biological effectiveness; CICR) plans using C and P (CICRC-p) or C and He (CICRC-He) have been realized. By combining ions, more biologically robust and more conformal treatment plans can be delivered. The first biological and dosimetric verification of multi-ion treatments in a homogenous and heterogeneous setting was also performed.
Kopp et al., Int J Radiat Oncol Biol Phys 2020; Mein et al., Sci Rep. 2018