Improving surgical treatment of patients with solid tumors
This ACE is a multidisciplinary collaboration of physicists, biomedical engineers, pathologists and surgeons with a clear clinical goal: improving oncological surgery.
By a variety of imaging techniques, including (Raman) spectroscopy and fluorescence, we study the molecular composition and physiology of tissues and tumors, in animal models and in humans (ex vivo and in vivo).
The aim of our fundamental research is to distinguish very precisely between healthy and tumor tissue.
Based on the results of our fundamental research, we are developing new tools for assessment of tumor resection margins during surgery. By exactly detecting the tumor cells by imaging techniques, subclinical tumors will be detected during surgery and healthy tissue surrounding the tumor will be spared.
Initially, we will primarily focus on head- and neck tumors and skin cancer, subsequently we will expand this to all kinds of solid tumors.
The developed new tools will be clinically implemented by surgeons and clinical studies will be performed on the effect of the new technologies on surgical success rates.
By retrospective and prospective studies we are measuring surgical success rates and patient outcome.
Focusgroup Fluorescence-Guided Surgery
To focus our activities, we have formed a focusgroup on fluorescence-guided surgery with all researchers that are involved in this field, extending over 8 different surgical disciplines. Our vision is that close collaboration will empower us as a group to facilitate a more efficient and productive research line. By forming trans-disciplinary partnerships, we are focusing on new clinical trials, improved coordination of the use of imaging facilities, coordinated and combined efforts for investments in new imaging devices and of research funding, and communication with secondary partners such as the pharmacy, medical ethical committee (METC), and the technology transfer office (TTO). This initiative flourishes through our close partnership with pioneering researchers at the Leiden University Medical Centre.
The ACE mainly provides education to PhD students. Within the ACE, 8 PhD students finished their theses during the last 5 years, one of them cum laude. Two of them are from abroad (Turkey and China). Currently, 14 PhD students are working within the ACE, 5 of which are from abroad.
Besides, the ACE has had multiple international post-doctoral fellows, amongst others from Slovakia, India and the USA. Prof. Nijsten hosts one 'European Mohs Fellowship' fellow annually, sponsored by the European Academy of Dermatology and Venereology.
The fellowship consists of 6 months of certified training with top MMS surgeons from the department of dermatology. Dr. Robinson contributes to a number of courses/lectures organized by the Postgraduate School of Molecular Medicine. We aim to investigate the potential overlap between our expertise in nanotechnology and the new Nanobiology program at the Erasmus MC and TU Delft.
We are in discussion with the department of Mechanical Engineering, TU Delft, to develop a new course on "tissue optics" at TU Delft, for students Mechanical Engineering, Electrical Engineering and Technical Physics. Teaching undergraduate students from TU Delft will not only increase their understanding of clinical applications of optical technologies, it will also enhance our visibility to those students, which is helpful for recruitment of new (technical) PhD students. In addition we will regularly host interns from these departments of the TU Delft, Hogeschool Rotterdam and final year medical students from the Erasmus MC and LUMC.
Societal Relevance to Research, Education and Patient Care
The ACE aims to detect tumor cells in the patient during surgery by imaging techniques. This will facilitate radical surgery in order to increase local control-rates and patient survival, spare healthy tissue surrounding a tumor which is usually removed for "security", detect subclinical tumors during surgery and reduce the need for adjuvant treatment and thereby reduce costs.
This will positively affect both life expectancy and quality of life of cancer patients. By the nature of this ACE "Innovative Oncological Surgery" it is yet unclear what the impact on future guidelines and standards will be. It goes without saying that we will pursue a change of current protocols once our results have been validated.
Viability of Research, Education and Patient Care
Every 3 months the participants of the ACE discuss their work in a progress meeting. Each meeting consists of a scientific programme, in which about five people present their results and plans, followed by food and drinks to stimulate detailed in depth discussions.
These meetings are very well attended by a multitude of clinical departments and highly appreciated. Within the ACE, 8 PhD students finished their theses during the last 5 years, one of them cum laude. Most of them now work as medical doctors in various hospitals in The Netherlands, sharing and using their obtained knowledge in a setting of patient care.
Two of the PhD graduates started an international career after their PhD: Bangwen Xie at the University of Cambridge (UK) and Thomas Snoeks at the Francis Crick Institute in London (UK). Currently, 14 PhD students are doing research within the ACE. The PhD students publish in international journals and attend one to three international conferences per year, where they present their results in oral or poster presentations.
In addition to the ACE-meetings, the Focusgroup Fluorescence-guided Surgery holds 6-weekly meetings with a more limited group of participants.
Allocated research grants Focusgroup Fluorescence-guided Surgery
1. 2019: Daniel den Hoed Award / Erasmus MC Fund
- PI: Stijn Keereweer (Personal Grant)
- Post-doc: TBA
- Title: “Improving surgical removal of oral cancer using a unique, innovative combination of fluorescence-guided surgery and Raman spectroscopy”
- Funding: €250.000,00
2. 2019: Young Investigator Grant from the Dutch Cancer Society
- PI: Stijn Keereweer (Personal Grant)
- PhD student: L. Lauwerends
- Title: “Guided by light: Optimizing surgical excision of oral cancer using real-time fluorescence imaging”
- Funding: €497.935,00
3. 2019: Applied Efficiency Grant / Erasmus MC
- PI: Dirk Grunhagen, Stijn Keereweer
- PhD Student: E. Mulder
- Title: “MOTOR pilot study - Ex Vivo Application of Multispectral Optoacoustic Tomography & Reflectance Spectroscopy in Lymph Nodes and Pigmented Tissue”
- Funding: €86.108,00
4. 2019: Maurits en Anna de Kock Stichting
- PI: Stijn Keereweer, Elisa Barroso
- Title: “Improving surgical removal of oral cancer using an innovative combination of fluorescence-guided surgery and Raman spectroscopy.”
- Funding: €36.370,00
5. 2018: Dutch Cancer Society Consortium Grant
- PI: Denise Hilling, Kees Verhoef, Alexander Vahrmeijer (LUMC), Harm Rutten (CZE)
- PhD student: Job van Kooten
- Title: Tumour-specific near-infrared fluorescence imaging in locally advanced and recurrent rectal cancer
- Funding: €1.071.553,00
Key and relevant publications of the last five years
- Keereweer S, Kerrebijn JD, van Driel PB, Xie B, Kaijzel EL, Snoeks TJ, Que I, Hutteman M, van der Vorst JR, Mieog JS, Vahrmeijer AL, van de Velde CJ, Baatenburg de Jong RJ, Löwik CW. Optical image-guided surgery--where do we stand? Mol Imaging Biol. 2011 Apr;13(2):199-207. (best cited, 170 citations)
- Xie BW, Mol IM, Keereweer S, van Beek ER, Que I, Snoeks TJ, Chan A, Kaijzel EL, Löwik CW. Dual-wavelength imaging of tumor progression by activatable and targeting near-infrared fluorescent probes in a bioluminescent breast cancer model. PLoS One. 2012;7(2):e31875.
- Keereweer S, Mol IM, Vahrmeijer AL, Van Driel PB, Baatenburg de Jong RJ, Kerrebijn JD, Löwik CW. Dual wavelength tumor targeting for detection of hypopharyngeal cancer using near-infrared optical imaging in an animal model. Int J Cancer. 2012 Oct 1;131(7):1633-40.
- van Lee CB, Ip Vai Ching EE, Nasserinejad K, Neumann HA, Bol MG, Dikrama PK, Kelleners-Smeets NW, Koljenović S, Munte K, Noordhoek Hegt V, de Vijlder HC, Nijsten T, van den Bos RR. Reliability of Mohs slides diagnosis: interpersonal and intrapersonal agreement on basal cell carcinoma presence and histological subtype. Br J Dermatol. 2016 Apr 1.
- van Driel PB, Boonstra MC, Slooter MD, Heukers R, Stammes MA, Snoeks TJ, de Bruijn HS, van Diest PJ, Vahrmeijer AL, van Bergen En Henegouwen PM, van de Velde CJ, Löwik CW, Robinson DJ, Oliveira S. EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer. J Control Release. 2016 May 10;229:93-105.
- Barroso EM, Smits RW, Bakker Schut TC, ten Hove I, Hardillo JA, Wolvius EB, Baatenburg de Jong RJ, Koljenović S, Puppels GJ. Discrimination between oral cancer and healthy tissue based on water content determined by Raman spectroscopy. Anal Chem. 2015 Feb 17;87(4):2419-26.
- Cals FLJ, Bakker Schut TC, Koljenović S, Puppels GJ. Baatenburg de Jong RJ. Method development: Raman spectroscopy‐based histopathology of oral mucosa. J Raman Spectroscopy 2013; 44:963-972.
- Karakullukcu B, Kanick SC, Aans JB, Sterenborg HJ, Tan IB, Amelink A, Robinson DJ. Clinical feasibility of monitoring m-THPC mediated photodynamic therapy by means of fluorescence differential path-length spectroscopy. J Biophotonics. 2011 Oct;4(10):740-51.
- Cals FL, Bakker Schut TC, Hardillo JA, Baatenburg de Jong RJ, Koljenović S, Puppels GJ. Investigation of the potential of Raman spectroscopy for oral cancer detection in surgical margins. Lab Invest. 2015 Oct;95(10):1186-96.
- van Leeuwen-van Zaane F, Gamm UA, van Driel PB, Snoeks TJ, de Bruijn HS, van der Ploeg-van den Heuvel A, Sterenborg HJ, Löwik CW, Amelink A, Robinson DJ. Intrinsic photosensitizer fluorescence measured using multi-diameter single-fiber spectroscopy in vivo. J Biomed Opt. 2014 Jan;19(1):15010.
PhD theses of the last five years
- S. Keereweer (2014): Towards Fluorescence-Guided Head and Neck Cancer Surgery (cum laude)
- B. Karakullukçu (2014): New Insights into Photodynamic Therapy of the Head and Neck
- F. van Leeuwen – van Zaane (2014): Fiber Optic Spectroscopy for the Optimization of Photodynamic Therapy
- S. de Visscher (2014): mTHPC mediated PDT of Head and Neck Cancer
- T. A. Middelburg (2014): Photodynamic Therapy of Skin using Porphyrin Precursors
- B.W. Xie (2013): Optical Imaging of Cancer and Cell Death
- H. C. de Vijlder (2013): New insights into photodynamic therapy using porphyrin precursors
- T.J. Snoeks (2012): Imaging in Pre-Clinical Cancer Research applied to bone metastases