Neoadjuvant sorafenib treatment of clear cell renal cell carcinoma and release of circulating tumor fragments

Autor: Stijn Muselaers, J.C. Oosterwijk-Wakka, Cathy Maass, Peter F.A. Mulders, William P.J. Leenders, Ingrid M.E. Desar, Carla M.L. van Herpen, Robert M.W. de Waal, Han van Krieken, Christina A. Hulsbergen-van de Kaa, Mirjam de Weijert, Egbert Oosterwijk, Gursah Kats-Ugurlu
Rok vydání: 2014
Předmět:
Male
Niacinamide
Vascular Endothelial Growth Factor A
Sorafenib
Cancer Research
Pathology
medicine.medical_specialty
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
medicine.medical_treatment
Antineoplastic Agents
Kaplan-Meier Estimate
Kidney
Nephrectomy
lcsh:RC254-282
Article
Metastasis
chemistry.chemical_compound
Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15]
medicine
Carcinoma
Humans
Carcinoma
Renal Cell
Neoadjuvant therapy
Aged
business.industry
Phenylurea Compounds
Cancer
Middle Aged
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Kidney Neoplasms
Neoadjuvant Therapy
Vascular endothelial growth factor
Clear cell renal cell carcinoma
Treatment Outcome
chemistry
Cancer research
Female
business
Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]
Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
medicine.drug
Zdroj: Neoplasia: An International Journal for Oncology Research, Vol 16, Iss 3, Pp 221-228 (2014)
Neoplasia, 16, 3, pp. 221-8
Neoplasia, 16, 221-8
ISSN: 1476-5586
Popis: Contains fulltext : 136369.pdf (Publisher’s version ) (Open Access) BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is characterized by high constitutive vascular endothelial growth factor A (VEGF-A) production that induces a specific vascular phenotype. We previously reported that this phenotype may allow shedding of multicellular tumor fragments into the circulation, possibly contributing to the development of metastasis. Disruption of this phenotype through inhibition of VEGF signaling may therefore result in reduced shedding of tumor fragments and improved prognosis. To test this hypothesis, we investigated the effect of neoadjuvant sorafenib treatment on tumor cluster shedding. PATIENTS AND METHODS: Patients with renal cancer (n = 10, of which 8 have ccRCC) received sorafenib for 4 weeks before tumor nephrectomy. The resection specimens were perfused, and the perfundate was examined for the presence of tumor clusters. Effects of the treatment on the tumor morphology and overall survival were investigated (follow-up of 2 years) and compared with a carefully matched control group. RESULTS: Neoadjuvant sorafenib treatment induced extensive ischemic tumor necrosis and, as expected, destroyed the characteristic ccRCC vascular phenotype. In contrast to the expectation, vital groups of tumor cells with high proliferation indices were detected in postsurgical renal venous outflow in 75% of the cases. Overall survival of patients receiving neoadjuvant treatment was reduced compared to a control group, matched with regard to prognostic parameters. CONCLUSIONS: These results suggest that neoadjuvant sorafenib therapy for ccRCC does not prevent shedding of tumor fragments. Although this is a nonrandomized study with a small patient group, our results suggest that neoadjuvant treatment may worsen survival through as yet undefined mechanisms.
Databáze: OpenAIRE
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