1. The purpose of this prospective study is to determine the accuracy of USPIO-MRI for predicting of the nodal status in primary colorectal cancer patients. 40 Patients with primary rectal cancer underwent MRI after administration of Sinerem® contrast agent. All these patients were treated with TME surgery, after pre-operative radiotherapy. A radiologist prospectively recorded the amount, localization and signal-intensity of mesorectal and extramesorectal lymph nodes. Lesion by lesion analysis was performed with histology as the Gold Standard. The patient-based sensitivity, specificity, PPV and NPV were respectively 100%, 69%, 62% and 100%. The lesion by lesion analysis results in sensitivity, specificity, PPV and NPV of 95%, 95%, 65% and 99%, respectively. This prospective study suggests that USPIO-MRI is highly accurate in identifying N0 patients, allowing individual tailored treatment according to risks.
2. FDG-CT-PET after neoadjuvant chemoradiation of locally advanced rectal cancer
To assess the accuracy of post chemoradiation 18F-deoxyglucose (FDG)-CT-PET for the prediction of tumor downstaging and invasion of the mesorectal fascia. An abdominal radiologist and radiotherapist both experienced in CT-PET imaging retrospectively evaluated pre and post CT-PET images. Results are pending.
3. Determination of the predictive value of repetitive FDG-PET-CT scans and blood proteins for the prognosis of patients with rectal cancer
To investigate the evolution of the FDG uptake and the tumour characteristics determined in the plasma of patients with rectal cancer during and after radiotherapy or combined radiotherapy and chemotherapy. Study hypothesis: The changes of the FDG uptake of the primary tumour and the evolution of key tumour characteristics during radiotherapy alone or in combination with chemotherapy will be predictive for the outcome. Endpoints: Prediction of the tumour response shortly after radiotherapy by a PET-CT scan and blood samples for the patients receiving short-course radiotherapy alone. Prediction of the tumour response 6-8 weeks after radiochemotherapy treatment by PET-CT scans and by blood samples during concurrent radiotherapy and chemotherapy.
4. The combination of molecular targeted drugs with radiotherapy in rectal cancer - towards individualized therapy
We will start two new phase I/II phase clinical trials. High quality translational research will test the activity of the drugs in modulating the microenvironment and tumor cellular responses and will identify predictors of activity. 3a. Rapamycin (mTor inhibitor) will be administered before and during preoperative short-term RT (5 x 5Gy) in operable rectal cancer. 3b. Nelfinavir (Akt inhibitor) will be administered before and during preoperative radiochemotherapy (28 x 1.8 Gy + Capecitabine daily) in locally advanced rectal cancer.The optimal dose found in phase I will be administered in phase II. The primary endpoint of Rapamycin activity will be the tumor blood flow assessed by dynamic contrast-enhanced (DCE-) MRI.The primary endpoint of Nelfinavir activity will be the rate of pathological complete remission (pCR) at the time of surgery.
Funding
2006 - 2010. Profileringsfond, University Hospital Maastricht, phase I-II
clinical trial testing Rapamycin (Sirolimus) in combination with preoperative
radiotherapy in operable rectal cancer. 110.000 Euro
Selected publications
Baeten CI, Castermans K, Lammering G, Hillen F, Wouters BG, Hillen HF, Griffioen AW, Baeten CG.
Effects of radiotherapy and chemotherapy on angiogenesis and leukocyte infiltration in rectal cancer.
Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):1219-1227.
Wolberink SV, Beets-Tan RG, Nagtegaal ID, Wiggers T.
Preoperative assessment of the circumferential margin in rectal cancer is more informative in treatment planning than the T stage.
Tech Coloproctol. 2006 Oct;10(3):171-6.
Figure: False positive PET-CT interpretation of a circumferential resection margin invasion after radiochemotherapy: the histology reveals an inflammatory reaction into vagina wall, but not a tumoral invasion.
Research group
Dr. R.G.H. Beets-Tan, project leader
Dr. G. Lammering
Dr. G.L. Beets
Prof.dr. P. Lambin
Prof.dr. A. de Bruine
Prof.dr. BG. Wouters
Prof.dr. J. Teulen
Prof.dr. AW. Griffioen
Prof.dr. CG. Baeten
Post-doctoral fellows
Dr. M. Oellers
Dr. R. Jansen
Dr. M. van Engeland
Dr. M. van Kroonenburgh
PhD students
R. Vliegen
S.M.E. Engelen
M.J. Lahaye
J. Buijsen
B. Vanhouten
H. Aerts
CI. Baeten
Technicians
J. van den Boogaard
N. Lieuwes
Students
M. Janssen
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