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%).

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.

Background. Brain metastases are the most frequent intracranial neoplasms in adults. Although overall survival (OS) is an important endpoint in patients receiving radiotherapy, given their poor life expectancy in general, quality of life is becoming an increasingly useful endpoint. Objectives: to evaluate whole brain radiotherapy (WBRT) with 3D conformal boost in brain metastases patients with regard to OS and quality of life.Methods. During April 2015-May 2017, a total of 35 patients with ≤5, previously untreated, inoperable brain metastases were included prospectively. All patients underwent WBRT followed by 3D conformal boost to the metastatic lesions. EORTC quality of life questionnaires QLQ-C30 and QLQ-BN20 were used at baseline and at end of treatment. The mean initial and final scores were compared using Student test. One-year OS with brain metastases was computed with Kaplan Maier method.Results. Median survival with brain metastases was 4.43 months (0.73-78.53). The one-year OS for patients with one metastasis was 42% versus 15% for more than one (p<0.04). The presence of extracerebral metastases significantly decreased OS from 39% without extracerebral metastases to 19%. (p<0.05). Quality of life improved significantly in several functional domains: physical (48 vs 60.29), role functioning (28.1 vs 44.7), emotional (47.1 vs 80.2), global health status (40.9 vs 62.3). Symptom scores decreased significantly in most items, corresponding to an improvement in the symptom burden: headache (61.9 vs 0.9), nausea and vomiting (45.7 vs 7.1), visual disorder (26.3 vs 9.2), seizures (30.4 vs 0.9), motor dysfunction (46.6 vs 17.1). Symptom scores for fatigue and drowsiness increased significantly (51.1 vs 74.9, respectively 37.1 vs 70.4), indicating worsening of symptoms.Conclusions. WBRT with 3D conformal boost is a feasible technique which improves quality of life in brain metastases patients. Since survival is limited, the assessment of quality of life is a good indicator of the treatment outcome.

A high correlation between the three examinations was obtained. As such, TRUS can be considered a suitable method in the evaluation of tumor dimensions.