Investigation of Resistance Mechanisms to Treatment in Patients Treated with Radiochemotherapy in Locally Advanced Stage Cervical Cancers
Project no. 20504 · Status: Kapanmış (Yayın bekleniyor) · 2019
Summary
Aim: To investigate the relationship between pretreatment hypoxia inducible factor 1?(HIF-1?) and Excision Repair Cross Complement 1(ERCC-1) expression levels with the treatment outcomes such as overall survival(OS), local recurrence-free survival(LRFS), and distant metastasis-free survival(DMFS) for the patients with locally advanced and/or inoperable cervical carcinoma. Patients and method: Pathology specimens of 87 patients treated with definitive CRT, HIF-1? and ERCC-1 protein expression were evaluated and scored semi-quantitatively by 2 pathologists blinded to their treatment outcomes. Results were grouped according to HIF-1?(H-score: ?100 and >100) and ERCC-1(H-score: ?130 and >130) H-scores, taking into account the Reciever Operating Characteristic(ROC) curves. The OS, LRFS and DMFS rates were calculated using the Kaplan-Meier method and the differences between the groups were evaluated by log-rank and cox regression analysis. Results: The median age of the included patients was 57 (range 37 and 85), and the FIGO IIB and IIIC1 stage rates were the same, being 28.7%. While 95% of the pathologies are squamous cell carcinoma, only 5% are adenosquamous cell carcinoma, no lymph node metastasis has been reported in 60% of the patients. The rates of 5-y OS, LRFS and DMFS for the whole group were 57.8%, 69.7% and 69.1%, respectively. In the comparison of H scores of immune markers, it has been shown that the ERCC-1 score >130 affects both LRFS (p=0.032) and DMFS (p=0.054) negatively. Conclusions: HIF-1? expression has not been found to be successful in predicting treatment response or outcomes in cervical cancer patients treated with definitive CRT. However, high ERCC-1 expression was found a negative prognostic factor for both LRFS and DMFS. For the patients with high ERCC-1 expression, different chemotherapy agents may be considered for concomitantly used with RT.