BackgroundAdvanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer.MethodsTwenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient’s 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest.ResultsA 2859-gene signature was identified to distinguish between responder and non-responder patients. ‘DNA Replication, Recombination and Repair’ represented one of the most important mechanisms activated in non-responsive cervical tumors, and the ‘Role of BRCA1 in DNA Damage Response’ was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples.ConclusionsOur findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information about the patients at risk for treatment failure.

The results of this study prove the obvious superiority of concurrent RTCT with 5-day cisplatin compared to RT alone in patients with locally advanced cervical carcinoma, regarding local control (78% vs. 67%) and 5-year survival rates (74% vs. 64%).

Aims: The aim of this study was to evaluate the use of pre and post-therapy transrectal and transvaginal ultrasonography (TRUS, TVUS) with contrast enhancement and strain elastography compared with clinical examination and magnetic resonance imaging (MRI) in the assessment of advanced stage cervical cancer. Material and methods: This was a prospective study, carried out over a period of nine months on subjects with advanced-stage cervical cancer (stage ≥IIB). All included patients were examined clinically and underwent abdomino-pelvic contrast enhanced MRI and multimodal US examinations (TRUS with strain elastography and contrast enhanced TVUS) at the time of diagnosis and after radiochemotherapy. Tumor size and staging at TRUS and TVUS was compared with the same data obtained by clinical examination and MRI. Pathology was the golden standard. Results: Eight patients accomplished the inclusion criteria. In five cases the tumor stage was identical on clinical and MRI examinations. In all cases parametrial infiltration was diagnosed by all pre-treatment examinations. No significant differences were observed in tumor size between clinical, US and MRI exams either at baseline or post-therapy, in native or post-contrast examinations. The size of the tumor evaluated pre-treatment proved to be significantly smaller post-contrast in both US and MRI examinations compared with the native images. Post-therapy, no significant differences were observed on US measured tumor dimensions when comparing native with post-contrast images. Oppositely, significant smaller dimensions were observed on post-contrast MRI compared with native scans. Conclusions: TRUS is accurate in the estimation of pre-therapy cervical cancer dimension. The post therapy tumor evaluation is better performed with MRI. The use of intravenous contrast agents on both examinations did not improved the accuracy of tumor evaluation pre-or post-therapy.

The results of our study demonstrate that RCT with cisplatin, 20 mg/m × 5 days every 21 days, is superior regarding local efficacy and is less toxic compared with the weekly chemotherapy regimen.