Publications (8)40.95 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Background: Local and systemic recurrence are important sources of treatment failure following surgical resection of esophageal adenocarcinoma. We hypothesized that adding preoperative cetuximab and radiotherapy (cetux-RT) to perioperative chemotherapy would increase treatment efficacy with acceptable toxicity. Methods: In this prospective phase II trial, patients were treated with three cycles of epirubicin, cisplatin, and capecitabine (ECX), followed by cetux-RT. After surgery with curative intent, patients received three more cycles of ECX. Primary endpoints were efficacy, determined by histopathological complete response (pCR) rate, and safety, which was assessed with resectability rate. Results: Of the 12 patients enrolled in this trial, six received at least one dose of cetux-RT. In five patients, cetux-RT was not started because of adverse events (AEs) related to preoperative chemotherapy; one patient had progressive disease. Addition of cetux-RT was well tolerated and did not interfere with the resectability rate (100%). However, the pCR rate was 0, and 50% of patients experienced serious adverse events (SAEs) postoperatively. Conclusion: With 12 patients enrolled, the lack of initial signs of efficacy and a high incidence of postoperative SAEs prompted us to end this study prematurely. Perioperative ECX was associated with considerable toxicity, and further treatment intensification is problematic.
- [Show abstract] [Hide abstract] ABSTRACT: Background: This study investigates the possible benefits of radiofrequency ablation (RFA) in patients with non-resectable colorectal liver metastases. Methods: This phase II study, originally started as a phase III design, randomly assigned 119 patients with non-resectable colorectal liver metastases between systemic treatment (n = 59) or systemic treatment plus RFA (± resection) (n = 60). Primary objective was a 30-month overall survival (OS) rate >38% for the combined treatment group. Results: The primary end point was met, 30-month OS rate was 61.7% [95% confidence interval (CI) 48.2-73.9] for combined treatment. However, 30-month OS for systemic treatment was 57.6% (95% CI 44.1-70.4), higher than anticipated. Median OS was 45.3 for combined treatment and 40.5 months for systemic treatment (P = 0.22). PFS rate at 3 years for combined treatment was 27.6% compared with 10.6% for systemic treatment only (hazard ratio = 0.63, 95% CI 0.42-0.95, P = 0.025). Median progression-free survival (PFS) was 16.8 months (95% CI 11.7-22.1) and 9.9 months (95% CI 9.3-13.7), respectively. Conclusions: This is the first randomized study on the efficacy of RFA. The study met the primary end point on 30-month OS; however, the results in the control arm were in the same range. RFA plus systemic treatment resulted in significant longer PFS. At present, the ultimate effect of RFA on OS remains uncertain. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
- [Show abstract] [Hide abstract] ABSTRACT: Oxaliplatin is frequently used in the treatment of metastatic colorectal cancer (CRC). Our previous work shows that oxaliplatin induces the pro-apoptotic protein Noxa in CRC cells. The Bcl2-inhibitor ABT-737 is particularly effective in cells with high Noxa levels. Therefore, we tested whether oxaliplatin and ABT-737 display synergy in killing CRC cells. A panel of CRC cell lines was treated with oxaliplatin and ABT-737, either alone or in combination. Apoptosis was measured by FACS analysis of sub-G1 DNA content and by Western blot analysis of caspase-3 processing. Noxa expression was suppressed by lentiviral RNA interference. Oxaliplatin and ABT-737 displayed a strong synergistic apoptotic response, which was dependent on wildtype TP53 and oncogenic KRAS. TP53 and KRAS were required for drug-induced Noxa expression and this was essential for tumor cell apoptosis. Oxaliplatin, but not ABT-737, induced p53 accumulation, but both drugs stimulated Noxa expression. Combination treatment of mice with subcutaneous tumor xenografts drastically reduced tumor volume, while single drug treatment had no effect. ABT-737 synergizes with oxaliplatin to kill colorectal cancer cells. This requires induction of Noxa by wildtype TP53 and oncogenic KRAS. Future studies should explore the anti-tumor efficacy of this drug combination in mouse models for spontaneous CRC development and in patient-derived tumor cell cultures and xenografts.
- [Show abstract] [Hide abstract] ABSTRACT: Magnetic resonance imaging (MRI) of the breast has become a well-established method for detection of invasive breast carcinoma. However, the role and use of breast MRI for ductal carcinoma in situ (DCIS) has remained controversial. The purpose of this study was to assess the diagnostic performance of breast MRI for detection and characterization of pure DCIS based on the currently published reports. A systematic review was performed in which studies on breast MRI for diagnosis of patients with pure DCIS were selected. A total of 26 articles were finally included, a total of 1051 patients with 1059 lesions. Sensitivity for diagnosis of pure DCIS ranged from 58% to 100%, with an overall of 84%. Sensitivity was highest for high-grade DCIS (95%). Overall specificity was 74%. The majority of DCIS lesions were characterized as non-mass-like enhancement (75%) with a segmental distribution of enhancement (50%). Suspicious kinetic curves were found in 49% of the DCIS cases. A few studies reported on size assessment. This review shows that MRI has a moderate sensitivity for detection of DCIS in general, and a good sensitivity for high-grade DCIS. The morphologic and kinetic appearance of DCIS can be very variable. Although mammography is the current standard for detection of DCIS, MRI could help improve the ability to diagnose DCIS, especially in high-grade DCIS.
Article: Surgical Training in the Netherlands[Show abstract] [Hide abstract] ABSTRACT: Surgical training in the Netherlands has traditionally been characterized by learning on the job under the classic master-trainee doctrine. Over the past decades, it has become regionally organized with intensive structural training courses, and a peer-based quality control system. Recently, the nationwide programme has been modernized further and now involves a systematic, competency-based education with structural training courses, formalized assessment and room for reflection by residents under the supervision of surgical teaching groups. To this end, a uniform web-based digital portfolio is being introduced to facilitate monitoring of the individual resident's progress. Though requiring inspirational leadership, commitment, and determination, this modernization has sparked enthusiasm among trainees and teachers.
- [Show abstract] [Hide abstract] ABSTRACT: The aim of this study was to assess the efficacy of treatment of patients with papillary thyroid carcinoma (PTC) and lymph node metastases at the time of diagnosis and its influence on the course of the disease. It is a retrospective review of all 51 patients with PTC and histologically proven lymph node metastases treated with I-131 ablation in our center between January 1990 and January 2003. Patients were considered disease-free if during follow-up thyroglobulin levels were undetectable and scintigraphy with 370 MBq (131)I was negative during thyroid-stimulating hormone stimulation. Staging of patients was in accordance with the 5th edition of the TNM system. After a median follow-up of 84 months, 33 (65%) patients were never free of detectable disease; and 3 of these patients had died of the PTC. In total, 22 patients still showed persistent activity in the neck outside the thyroid bed, which was suspect to be cervical lymph node metastasis on postablation scintigraphy; it was not related to the initial clinical presentation (lymph node metastasis or a thyroid nodule without suspicion of metastatic disease) or to the extent of surgery. Altogether, 34 patients required additional treatment. Patients presenting with clinically overt lymph node metastasis showed a significantly (p = 0.022) lower rate of becoming disease-free than those in whom microscopic lymph node involvement was unexpectedly found upon pathologic examination. There was no significant association of the eventual outcome with the extent of surgical treatment, TNM staging, or age. Patients with lymph node metastasis are considerably less likely to become disease-free. If the initial treatment does not result in a disease-free status, chances are low that additional treatment will succeed in achieving it.
University Medical Center Utrecht
Utrecht, Utrecht, Netherlands
- Department of Surgery