The research within our LUMC departments is conducted within departmental research programmes. The research programme below is embedded within the department of Surgery.
- Research programme: Surgical Oncology
- Department: Surgery
- Programme leader: Prof. Dr. R.A.E.M. Tollenaar
- Principal investigators: Dr. P.J.K. Kuppen, Dr. W.E. Mesker, Dr. A.L. Vahrmeijer, Dr. G.J. Liefers, Dr. P.J. Voorham-van der Zalm, Dr. G. van der Pluijm
- Biomedical research profile: Cancer Pathogenesis and Therapy
- Generic research profile: Ageing, Innovation in Health Strategy and Quality of Care
Aim and focus
The aim of The Surgical Oncology research program is to improve diagnosis and treatment of cancer focussing on
- technological innovation in surgical intervention
- personalized medicine
- clinical trials and outcome research
Our research aims to contribute to better individualized health care for patients by technical innovations, improved evidence based medicine through clinical trials and improved risk prediction. This will result in better cancer control and better functional outcome. Where possible it will reduce costs by identifying redundant or unnecessary treatment or by doing less harm by more effective treatments in less time. The cancer types around which our research evolves are breast, GI and urological malignancies
Technological innovations in surgical interventions
The challenge for this theme is to obtain more efficiency and to do less harm with surgical interventions using markers for improved identification of anatomic structures and neoplastic tissues.
This line aims at:
- Image guided surgery (IGS) research program: Improvement of surgical treatment and detection methods using new imaging agents for intra- or peri-operative tumour detection and protection of vital structures. Focus on real time tumour identification for clinical decision making and precision surgery.
- Development of new, tumour-targeted therapy, before or after surgery, to induce tumour regression and make a tumour operable or to prevent tumour recurrence. This includes drug repositioning and nanodrug delivery ( bench-to-bedside approach).
Specific therapy assignment for the individual patient is the challenge of this theme. It aims to prevent under-, and over-treatment. New prognostic markers based on genotypic and phenotypic characterization of blood and tissue and their association with outcome will be used. Furthermore clinicopathological data from validated nationwide registries can also be utilized for individualized risk assessment and therapy selection. Additionally data from prospective cohort studies with detailed registration of tumour and patient related variables may identify subgroups of vulnerable patients or patients at particular high risk that need personalized treatment planning.
This line aims at:
- Early tumour detection methods and improvement of diagnostics, prognosis and prediction for both sporadic and hereditary patients and the (frail) elderly patient.
- Implementation of ‘near-patient’ disease models for functional studies, drug development and imaging probe development studies.
- Functional studies on the identification of pathophysiological mechanisms of tumour progression and therapy resistance as a basis for the development of novel therapy.
Improvement of patient treatment guidelines as a result of large clinical trials and prospective cohort studies is the main focus of this theme. Innovative methodology needs to be developed to adequately reflect ‘real world’ patients (external validity) specifically the growing numbers of older patients. Outcome registration in different health domains (physical, cognitive, social) is essential for health improvement beyond cancer specific outcome measures.
To achieve the above mentioned aims research is performed at several levels: translational and implementation research, clinical trials and quality assessment programs. The Surgical Oncology program has an infrastructure with datacentre, biobank and laboratories. The department has at their disposal an extensive database with patient information that is in many cases completed with biological patient material). In addition, several tumour models, both syngeneic and xenogeneic (human-mice), are available as well as many established tumour cell lines.
Position in international context
The research of the Surgical Oncology has a strong multidisciplinary character. Technological innovations in surgical interventions is leading in the Netherlands and has prestigious international collaborations with Harvard, Stanford, Max Planck Institute, Göttingen and EPFL, Lausanne. Personalized medicine collaborates with international trial partners (TEAM, IDEAL, RAPIDO, AVANT, Quasar) at the level of tissue exchange for biomarker research. National initiatives on biomarkers are initiated (ASPRIN, TESTBREAST). A European network (UNITED) conducted from the LUMC evaluating tumour-stroma cell ratio (TSR), is currently validating TS as a new prognostic marker in the UICC classification.
Clinical trial and outcome research is Large clinical trials on breast-, colorectal-, and gastric cancer have been initiated from our department. Our clinical trial centre has a strong international reputation. This line is further embedded in multiple international collaborations such as Eurecca, EBCTCG, BIG-98. Next to meta-analysis of trial data, these collaborations contribute to exchange tissues for translational research. Outcome data generated through DICA (Dutch Institute of Clinical Auditing) are aligned with the International Consortium for Health Outcome Measures (ICHOM).
Content / highlights / achievementsTechnological innovations in surgical interventions
Image guided surgery has developed a research line from basic, preclinical experiments, through animal studies to first in human studies. It is uniquely positioned for the development and introduction of fluorescent probes for real time surgical guidance with the gaol to improve patient care. Five new compounds have been developed so far and are currently evaluated in multicentre (international) clinical trials. Multiple Investigator initiated trials as well as contract research have been conducted. The potential of this theme is reflected in the large funding (NIH, KWF, H-2020) up-to 10 million euro over the past 6 years.
Many prognostic and predictive tumour markers have been tested and validated in the past years. Parallel to cohort studies biomaterials (tumour, blood) is collected from most of the patients. This wealth of biomaterial is studied to discover prognostic and predictive markers that can guide early detection and personalized therapy. The identification of these markers is also important for the development of tumour specific imaging agents for our IGS research ;program.
- For example, tumour-stroma ratio is currently studied in an European study (UNITED) as routine prognosticator and on the brink of clinical implementation.
- For patients with urological malignancies, novel candidate nanodrug compounds were developed in patented ‘near-patient’ models for treatment with advanced, therapy-resistant disease resulting in the initiation of a phase I/IIa clinical studies. FDA-approved drugs have been identified for repurposing/repositioning of these compounds for the use in oncology, in particular urological malignancies.
- The MAPLe (Multiple Array Probe Leiden) that has been developed at the department of Urology in collaboration with Medical Delta (Maxam Medical) went to the market (Novuqare/Medtronic) in 2014 and is currently available in many countries.(patents obtained).
Future themesFor the coming years focus of the research program of departments of Surgery and Urology will be strongly combined in the three themes. With this bench-to-bedside approach (and back again) there will be partnerships in collaborative research activities, working groups, research proposals and teaching activities.
There will be special focus on research in:
Technological innovations in surgical interventions
The development and testing of new fluorescent probes for various solid tumours will be one of the major themes for coming years. The number of clinical sites where new probes can be studied in multicentre trials will be increased. The current laboratory facilities will be more focused to facilitate the preclinical phase of this research line. The recent incorporation of the research line Urological malignancies will strengthen technological innovations both by a strong basic research input as well as by increase of the clinical oncological spectrum and the collaboration with companies as the LHCDR.
New techniques such as proteomics and gene expression research will be explored and results, where feasible, will be tested as markers for early detection, risk prediction and therapeutic outcome in prospective cohorts or clinical trials.
For the coming years focus of the research program will be on the following themes:
- Early tumour detection using proteomics and metabolomics methods for simple blood samples will have high-impact on the development of new screening tests.
- National studies for breast and pancreatic cancer are evaluating, in the LUMC developed methodology and will emphasis further developments in this field.
- Prognostic and predictive biomarkers offer possibilities for tailored treatment. A comprehensive program using multicolour immunohistochemically and immunofluorescent techniques at the level of DNA-RNA-protein is currently performed using patient-derived material.
- Focus in the field of the tumour microenvironment, especially tumour-immune interactions and tumour stroma development, results in new insights in tumour prognostication and treatment. The stroma parameter will be further investigated at the molecular level (internationally) and validated in full collaboration with the European Society of Pathology for clinical implementation.
- The clinical applications of the novel molecular signatures of the stroma response in prostate cancer have been generated and will be functionally validated (identification of therapeutic targets, prognostic value) and developed for (pre)clinical imaging purposes (imaging probe development).
- In the context of oncolytic viro-Immunotherapy, the direct anti-tumour efficacy of selected oncolytic viruses (reoviruses) are currently being evaluated in ‘near-patient’ models of prostate and bladder cancer, in particular ex vivo cultured patient-derived tissues and patient-derived xenograft models (PDX). The indirect immunomodulatory effects of oncolytic viruses in the tumour microenvironment will be determined.
- The development of tumour-targeted nanodrug formulations (micellar docetaxel) in urological malignancies.
- In the field of cancer immunotherapy, new clinical immunotherapy trials are performed and further developed in colorectal cancer in which patients are vaccinated with p53-derived peptides.
- Clinical trials and outcome research
- New randomized clinical trials are being initiated based on “choose wisely / do less harm” with the same efficacy within the departments own clinical trial unit (‘datacentre Surgery).
- Emphasis will be put on specific groups such as the older patients. As a result of this focus, new trial methodology need to be developed to test best practice in a often frail and very heterogeneous group of patients. Prospective cohort studies and international comparisons are examples for clinical research that will improve guidelines for specific subgroups. Outcome research will be complemented with patient reported outcome measures (PROM’s) to measure the true added value for patients. The DICA facilitates quality registries for professional associations of medical specialists (DICA.nl).
Cohesion within LUMC
The research of Surgical Oncology and Urology is multidisciplinary by nature and is conducted in close collaboration with many departments within the LUMC, especially with the departments of Pathology, Immunohematology and Blood bank, Molecular Cell Biology and Chemical Immunology, Centre for Proteomics and Metabolomics, Medical Statistics, Endocrinology, Radiology, Radiotherapy and Clinical Oncology. The research program is embedded in the biomedical focus area “Cancer Pathogenesis and Therapy”, with high profile area’s; Molecular Therapeutics, Immunotherapy of Cancer and Genetics, the research theme “Biomedical Imaging” and the ‘LUMC Cancer Centre’.
The geriatric oncology program links two of the key LUMC themes: ‘Cancer’ and ‘Aging’ and is conducted in close collaboration with the departments of Gerontology and Geriatrics and Public Health and Primary Care.