Working group "Statistics for Translational Oncology"
© dkfz.de
The working group contributes to bridging from research on molecular data to new therapeutic options for cancer patients ("The Bridge", painted by Deborah Kunz, 7 years)
One main focus is the exploitation of high-dimensional molecular data to improve the understanding of carcinogenesis and prediction of disease progression and treatment outcome. In the era of precision medicine, another area of focus is the search for prognostic biomarkers associated with disease progression and treatment outcome and for predictive genetic and genomic factors, i.e. the identification of biologically defined patient subgroups, who benefit from specific treatment or who are susceptible to serious adverse events due to their genomic profile. Another research topic is the development and validation of statistical methods for classification, prognosis and prediction using high-dimensional data. Further, we evolve data-driven model selection strategies in the framework of more complex multi-state models incorporating molecular data to capture pathogenic disease processes and underlying etiologies more precisely.
In addition to our methodological research, we also contribute to transferring research results from experimental and observational data into clinical practice. We collaborate on clinical trials and other forms of clinical research to convert the knowledge gained in the basic research into effective clinical applications.
For example, we support several trials of the NCT Precision Medicine in Oncology (PMO) program which has been established at the NCT Heidelberg. One example is the NCT-PMO-1602 phase II study CRAFT - Continuous ReAssessment With Flexible ExTension in Rare Malignancies.
We participate in the high-dimensional data topic group of the STRATOS (STRengthening Analytical Thinking for Observational Studies) initiative [Sauerbrei et al. 2014]. The main goal of STRATOS is to provide guidance for the design and analysis of studies with observational data.
Furthermore, we are involved in the HARMONY alliance, a European public-private partnership in hematology including hospitals, research institutes, patient organizations, pharmaceutical and IT companies. The primary aim of the alliance is to use big data to improve outcomes for patients with blood cancers.
For a broader overview of the projects we are or have been involved in, have a look at some of our long-term collaborations.
Collaborations
We collaborate with many researchers within and outside of DKFZ. We provide support for experimental design and perform statistical analyses tailored to the specific scientific question. Examples of major collaborations are:
Multiple Myeloma:
The German-speaking Myeloma-Multicenter Group (GMMG) conducts active research to improve treatment methods for multiple myeloma. Therein our long-term collaboration with the GMMG has witnessed treatment modifications that have been/will be implemented in the German health system. So, the current standard of care for patients with newly diagnosed multiple myeloma includes chemo-combination therapy followed by autologous stem cell transplantation. Based on the analysis of the GMMG-MM5 trial, it was shown that patients aged 65 to 70 years benefit from stem cell transplantation in the same way as the age group <= 65 without additional safety risks [Mai EK, Miah K et al. 2021]. As a consequence, cost absorption of ASCT is now admissible for multiple myeloma patients up to the age of 70 years by statutory health insurances (cf. https://gmmg.info/atp/). In addition, in part 1 of the randomized phase III study GMMG-HD7, it could be shown that the addition of a novel immunotherapy client significantly reduces the risk of detecting residual disease in the bone marrow which is a surrogate for prolongation of progression-free survival. Based on the results of this IIT trial, the monoclonal antibody will be sought for regulatory approval [Goldschmidt et al 2022]. Furthermore, the test for free light chains in the blood has so far been an easy-to-use diagnostic tool for predicting tumor activity. It has now been shown that the normalization of free light chains has a prognostic impact on progression-free survival, allowing an individualized therapy for this subgroup of responding patients. [Klein EM, Tichy D et al., 2021]
Acute Myeloid Leukemia (AML):
The German-Austrian AML Study Group (AMLSG) is one of the world's largest study groups for the research and treatment of AML, initiating a number of innovative national and interventional clinical trials and running the AMLSG BiO Registry Study with around 1,500 newly diagnosed AML patients being recruited annually. All patients included in the AMLSG BiO Registry Study agree to a systematic central biobanking and undergo in-depth molecular and genetic diagnostics which allow for prestigious translational research projects that are published in high-impact journals. Members of the working group have been responsible statisticians in the clinical trials since the study group was founded in 2003 and support many of the accompanying research projects.
Endothelial Activation and Stress Index (EASIX): In cooperation with the Section of Allogeneic Stem Cell Transplantation at Heidelberg University Hospital we investigate the usefulness of EASIX as prognostic and predictive biomarker for several diseases and endpoints. For instance, we illustrate the prognostic and predictive value of EASIX for time-to-sepsis, the effectiveness of statin-based prophylaxis for non-relapse mortality in different EASIX subgroups and the prognostic value of EASIX for severe complications after CAR-T cell therapy.
- Goldschmidt et al. Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial. Lancet Hematology 9(11):e810-821 (2022). doi: 10.1016/S2352-3026(22)00263-0
- Klein EM, Tichy D et al. Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial. Cancers 13(9): 4856 (2021). DOI: 10.3390/cancers13194856
- Mai EK, Miah K. et al. Bortezomib-based induction, high-dose melphalan and lenalidomide maintenance in myeloma up to 70 years of age. Leukemia 35(12): 3636 (2021). doi: 10.1038/s41375-021-01357-4.
- Sauerbrei W, et al. STRengthening analytical thinking for observational studies: the STRATOS initiative. Stat Med. 33(30):5413-5432 (2014)