Comparison of adjuvant and neoadjuvant chemotherapy in the management of advanced ovarian cancer: a retrospective study of 574 patients

BACKGROUND: There is a lack of clinical data on the validity of neoadjuvant chemotherapy in the treatment of ovarian cancer. The aim of this study was to compare the impact of the adjuvant and neoadjuvant chemotherapy regimens on the clinical outcomes in patients with advanced ovarian cancer. METHODS: We performed a retrospective analysis of 574 patients with advanced ovarian cancer admitted to four Lithuanian oncogynaecology departments during 1993–2000. The conventional combined treatment of cytoreductive surgery and platinum-based chemotherapy was applied to both the group that underwent neoadjuvant chemotherapy (n = 213) and to the control group (n = 361). The selection criterion for neoadjuvant chemotherapy was large extent of the disease. Overall and progression-free survival rates and survival medians were calculated using life tables and the Kaplan-Meier method. RESULTS: There was no difference in median overall survival between stage III patients treated with adjuvant chemotherapy and neoadjuvant chemotherapy (25.9 months vs. 29.3 months, p = 0.2508) and stage IV patients (15.4 months vs. 14.9 months, p = 0.6108). Similarly, there was no difference in median progression-free survival between stage III patients treated with adjuvant chemotherapy and neoadjuvant chemotherapy (15.7 months vs. 17.5 months, p = 0.1299) and stage IV patients (8.7 months vs. 8.2 months, p = 0.1817). There was no difference in the rate of the optimal cytoreductive surgery between patients who underwent the neoadjuvant chemotherapy and patients primarily treated with surgery (n = 134, 63% vs. n = 242, 67%, respectively). CONCLUSION: There was no difference in progression-free or overall survival and in the rate of optimal cytoreductive surgery between the neoadjuvant and adjuvant chemotherapy groups despite the fact that patients receiving neoadjuvant chemotherapy had a more extensive disease. Multivariate analysis failed to prove that neoadjuvant chemotherapy could be considered as an independent prognostic factor for survival, and the findings need to be investigated in the future prospective randomised studies

New mathematical model for examination of cervical cancer by using diffusion–weighted magnetic resonance imaging

We compare the mean value of apparent diffusion coefficient (ADC) in a healthy cervix, cancer affected cervix and the cervix after chemoradiation therapy and evaluate the correlation of the value of ADC with the various clinical and histological findings. Prospective clinical study accomplished in Lithuanian University of Health Sciences University Clinical Hospital. Magnetic resonance imaging (MRI) examinations performed on 117 women with and 49 women without cervical cancer by using a 1.5 Tesla scanner. Diffusion–weighted (DW) imaging was performing by using b values of 50, 400 and 800 s/mm2. ADC measured in a healthy cervix, cancer affected cervix and the cervix 6 months after chemoradiation therapy. The mean ADC of the patients of the study group – 0.658±0.120×10-3 mm2/s was considerably lower than the mean of the control group – 1.169±0.134×10-3 mm2/s (t= 24.123, p= 0.02). There was no correlation between mean ADC and the stage of the disease, the histological type or grade of the tumor. A weak negative correlation was detected between ADC and the age of the subjects (r= –0,337, p= 0,000). The mean ADC of responders increased to 1.111±0.138×10-3 mm2/s, the mean ADC of non-responders remained lower – 0.733±0.073×10-3 mm2/s (t= 9.158, p= 0.04). The ADC value in the case of cervical cancer is significantly lower than in the non-affected cervical tissue. It increases after effective chemoradiation therapy and becomes closer to the coefficient value of non-affected cervical tissue but remains lower. We cannot credibly consider about the stage of the disease, the histological type and grade of the tumor, according to the ADC value of cervical cancer. Slight decreasing of ADC value closely relate with elderly of patients

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

POLG Gene Variants in Cervical Cancer Patients and Their Associations with Clinical and Pathomorphological Tumor Characteristics

Cervical cancer is one of the most common cancers in women worldwide. Human papillomaviruses are known to be the main, but not the only risk factor, of this cancer type. Despite all the knowledge on this cancer type, it is still a challenge to predict the course of the disease, and therefore, minimally invasive biomarkers are needed. This study aimed to analyze single-nucleotide variants in the POLG gene and assess the associations with tumor phenotype and patient outcome. A total of 172 cervical cancer patients were included in this study. Clinical and tumor data were gathered from medical records retrospectively. Single nucleotide variations were determined using TaqMan probes with Real-Time PCR. Significant associations between POLG rs3087374 and cervical cancer patients’ tumor histological type, stage, and tumor size were determined. The CA genotype and A allele of rs3087374 increased the probability of adenocarcinoma histological tumor type, IIIA stage, and T3 tumor size compared to CC genotype and C allele, respectively. Furthermore, patients with AA genotype in rs2072267 had longer metastasis-free survival than those with the GG genotype. Our data suggest that mitochondrial polymerase gamma encoded by nuclear POLG gene is important for specific tumor phenotype formation and patient outcome in cervical cancer