Clinical significance of VEGFR-2 and 18F-FDG PET/CT SUVmax pretreatment score in predicting the long-term outcome of patients with locally advanced rectal cancer treated with neoadjuvant therapy |
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Authors: | Claudio V Sole Felipe A Calvo Emilio Alvarez Isabel Peligros Pilar Garcia-Alfonso Carlos Ferrer Enrique Ochoa Rafael Herranz Jose L Carreras |
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Institution: | 1. Department of Oncology, Hospital General Universitario Gregorio Mara?ón, Madrid, Spain 2. School of Medicine Complutense University, Madrid, Spain 6. Institute for Sanitary Research, Hospital General Universitario Gregorio Mara?ón, Madrid, Spain 9. Hospital General Universitario Gregorio Mara?on, C/ Doctor Esquerdo, 46, 28007, Madrid, Spain 5. Department of Pathology, Hospital General Universitario Gregorio Mara?ón, Madrid, Spain 4. Service of Medical Oncology, Hospital General Universitario Gregorio Mara?ón, Madrid, Spain 7. Institute of Oncology, Hospital Provincial de Castellon, Castellon de la Plana, Spain 3. Service of Radiation Oncology, Hospital General Universitario Gregorio Mara?ón, Madrid, Spain 8. Department of Radiology and Medical Physics, Hospital General Universitario Gregorio Mara?ón, Madrid, Spain
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Abstract: | Purpose Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR), and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumor progression and are important targets for cancer drugs. 18F-FDG maximum standardized uptake value (SUVmax) is a marker of tumor metabolic activity. The purpose of this study was to measure SUVmax combined with VEGFR-2, EGFR and COX-2 proteins in pretreatment tumor biopsies from patients with locally advanced rectal cancer receiving intensive neoadjuvant treatment and to correlate the findings with clinical outcome. Methods VEGFR-2, EGFR and COX-2 were measured using the immunoreactive score (IRS). SUVmax (median 8.4) was quantified in tumors with molecular overexpression (IRS ≥3 + SUVmax ≥ 8.4 indicating active tumors; SUVmax <8.4 indicating inactive tumors). The Cox proportional hazards model was used to explore associations between tumor markers, disease-free survival (DFS) and overall survival (OS). Results The study group comprised 38 patients with a median follow-up of 69.3 months (range 4.5 – 92 months). Multivariate analysis showed that active tumors (overexpressing VEGFR-2, high SUVmax) were associated with worse DFS (HR 4.73, 95 % CI 1.18 – 22.17; p?=?0.04) and OS (HR 4.28, 95 % CI 1.04 – 20.12; p?=?0.05). Conclusion Active tumors overexpressing VEGFR-2 are associated with a worse overall outcome in patients with rectal cancer treated with induction chemotherapy followed by pelvic chemoradiation and surgery. The optimal diagnostic cut-off level for this novel biomarker association should be investigated. Evaluation in a clinical trial is required to determine whether selected patients could benefit from a VEGFR-targeting drug. |
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