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Human papillomavirus 16 (HPV16) infection is the aetiologic factor for the development of cervical dysplasia and is regarded as highly carcinogen, because it is implicated in more than 50% of cervical cancer cases, worldwide. The tumourigenic potential of HPV16 has triggered the extensive sequence analysis of viral genome in order to identify nucleotide variations and amino acid substitutions that influence viral oncogenicity and subsequently the initiation and progression of cervical cancer. Nowadays, specific mutations of HPV16 DNA have been associated with an increased risk of high-grade squamous intraepithelial lesions and invasive cervical cancer (ICC) development, including E6: Q14H, H78Y, L83V, Ε7: N29S, S63F, E2: H35Q, P219S, T310K, E5: I65V, whereas highly conserved regions of viral DNA have been extensively characterised. In addition, numerous novel HPV16 mutations are observed among the studied populations from various geographic regions, hence advocating that different HPV16 strains seem to emerge with different tumourigenic capacities. The present review focuses on the variability of the early genes and the long control region, emphasising on the association of specific mutations with the development of severe dysplasia. Finally, it evaluates whether specific regions of HPV16 DNA are able to serve as valuable biomarkers for cervical cancer risk.

Background Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is the recommended approach in patients with advanced epithelial ovarian cancer (EOC). However, most patients eventually relapse despite the initial high response rate to chemotherapy. Neutrophil-to-lymphocyte ratio is a well-known biomarker that reflects severe inflammation, critical illness, and mortality in various diseases. Chemotherapy response score (CRS) and neutrophil-to-lymphocyte ratio (NLR) have been identified as potential biomarkers of platinum resistance and disease prognosis. We retrospectively evaluated 132 patients with stage IIIc or IV ovarian/fallopian tube/primary peritoneal cancer who had received NACT followed by IDS from 01/01/2003 to 31/12/2018. CRS was assessed on omental specimens collected from IDS according to ICCR guidelines. Results Median age was 64.57 years (SD: 9.72; range 39.2–87.1). Most ovarian tumors were serous epithelial (90.9%; 120/132). An elevated NLR (defined as > 3) was observed in 72% (95/132) of patients in contrast with 28% (37/132) of patients characterized by low NLR status. Median PFS (mPFS) and median overall survival (mOS) were 13.05 months (95% CI: 11.42–14.67)) and 34.69 months (95% CI: 23.26–46.12) respectively. In univariate analysis, CRS3 score was significantly associated with prolonged mPFS (CRS1/2: 12.79 months vs CRS3: 17.7 months; P  = 0.008). CRS score was not associated with mOS ( P = 0.876 ). High NLR was not significantly associated with mPFS ( P = 0.128 ), however it was significantly associated with poor mOS ( P = 0.012 ). In multivariate analysis, only performance of surgery maintained its statistical significance with both PFS ( P = 0.001 ) and OS ( P = 0.008 ). Conclusion NLR could serve as a useful predictor of OS but not PFS in ovarian cancer patients receiving NACT. In accordance with our previous study, CRS score at omentum was found to be associated with PFS but not OS in ovarian cancer patients treated with NACT and IDS. Research highlights Biomarkers that would predict response to neoadjuvant chemotherapy in advanced ovarian cancer patients are eagerly needed: • Neutrophil to Lymphocyte Ratio (NLR) is an indicator of systemic inflammatory response to the malignancy. • NLR was evaluated in 132 patients undergoing Neoadjuvant Chemotherapy for advanced ovarian cancer. • Elevated NLR was associated with worse prognosis. • No association between NLR and response to chemotherapy was noted.

Background: The mesenchymal–epithelial transition (MET) pathway is frequently altered in tumours. The purpose of our study was to determine the prognostic value of tumour MET expression levels in patients with triple-negative breast cancer (TNBC), in order to strengthen the rationale for targeted therapy of TNBC using MET inhibitors. Methods: We determined expression of MET in formalin-fixed paraffin-embedded surgical specimens of TNBC by immunohistochemistry. Recurrence-free and overall survival was analysed with Cox models adjusted for clinical and pathological factors. Results: Immunostaining for MET was classified as high in 89 of 170 (52%) tumours. MET expression was more frequently observed in G3 carcinomas ( P =0.02) but was not significantly associated to any of the other clinical or pathological parameters. High MET expression predicted shorter survival of the patients. Multivariate Cox proportional hazards regression analyses identified MET to be an independent prognostic factor for recurrence (adjusted hazard ratio (HR) for recurrence 3.43; 95% confidence interval (CI) 1.65–7.12; P =0.001) and death (adjusted HR for death 3.74; 95% CI 1.65–8.46; P =0.002). Conclusion: These results provide further evidence that the MET pathway could be exploited as a target for TNBC.

Paraneoplastic pemphigus is an autoimmune skin and mucosal disorder, rarely associated with solid malignancies, with devastating impact.Herein, we report the case of a middle-aged patient who presented with recalcitrant stomatitis and was ultimately diagnosed with advanced-stage cervical cancer.Despite the prompt initiation of immunosuppressive medications, in parallel with systemic therapy for her underlying neoplasm, she eventually died within 10 months.Considering its heterogeneous clinicopathological and immunological manifestations, paraneoplastic pemphigus remains a genuine diagnostic challenge, whereas its abysmal prognosis highlights the need of additional effective immunosuppressants.

Suppression of uninvolved immunoglobulins is common in multiple myeloma (MM) but the prognostic significance of this phenomenon has not been assessed. We evaluated the prognostic significance of the preservation of uninvolved immunoglobulins in 1755 consecutive, unselected, patients with newly diagnosed, symptomatic MM with pre-therapy immunoglobulin levels measured by nephelometry. Suppression of at least one uninvolved immunoglobulin was observed in 87% of patients and was more common in patients with immunoglobulin A myeloma, those aged over 65 years, in patients with advanced-International Staging System (ISS) stage, extensive-bone marrow infiltration, anemia, low platelet counts, high levels of serum M-monoclonal protein or renal dysfunction. Patients with preserved immunoglobulins had a better survival than patients with suppressed immunoglobulins (median survival 55 vs 41.5 months, P <0.001). In multivariate analysis, preservation of uninvolved immunoglobulins was independently associated with better survival (hazard ratio: 0.781, 95% confidence interval: 0.618–0.987, P =0.039); irrespective of the treatment. In a subset of 500 patients, which were strictly followed for disease progression, preservation of uninvolved immunoglobulins was associated with a significantly longer progression-free survival (60 vs 25 months, P <0.001), independently of other common prognostic factors. In conclusion, preservation of uninvolved immunoglobulins in newly diagnosed patients with symptomatic MM was independently associated with long term disease control and improved survival.

Background: Data regarding the safety and effectiveness of aromatase inhibitors (AIs) as monotherapy or combined with gonadotropin-releasing hormone (GnRH) analogue in male breast cancer are scarce. Methods: In this retrospective chart review, cases of male breast cancer patients treated with AIs with or without a GnRH analogue were evaluated. Results: Twenty-three men were included into this case series. Aromatase inhibitors in combination with or without a GnRH analogue were given as first-line therapy in 60.9% and as second-line therapy in 39.1% of patients, respectively. All patients had visceral metastases, whereas in five of them bone lesions coexisted. In all cases AIs were tolerated well, and no case of grade 3 and 4 adverse events was reported. A partial response was observed in 26.1% of patients and stable disease in 56.5%. Median overall survival (OS) was 39 months and median progression-free survival (PFS) was 13 months. Regarding OS and PFS, no significant effects of GnRH analogue co-administration or type of AI were noted. Conclusion: Our study shows that AIs with or without GnRH analogues may represent an effective and safe treatment option for hormone-receptor positive, pretreated, metastatic, male breast cancer patients.

Purpose The efficacy of nab -paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited. Patients and methods The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab -paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument. Results Eligible patients ( N  = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6–33.7], the median PFS was 6.2 months (95% CI 5.2–7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients < and ≥ 70 years of age. The patients’ baseline FACT-B total score remained unchanged. The serious and non-serious adverse event incidence rates were 13% and 48%, respectively. Conclusions This prospective study provides further evidence on quality of life, efficacy, and safety of nab- paclitaxel in patients with MBC and sheds more light in special subpopulations such as the elderly and those treated beyond the second line.

Background Kidney cancer is a lethal neoplasm that affects several thousands of people every year. Renal cell carcinoma (RCC) is the most common histologic type. Recent developments in the therapeutic approach include antiangiogenic targeted approaches and Immunotherapy. Thus, the therapeutic algorithm of RCC patients and the survival outcomes have changed dramatically. Methods Herein we present a retrospective study of the patients treated in our Department with an antiangiogenic agent -Axitinib, a tyrosine kinase inhibitor- as a third or further line treatment. Statistical analysis was performed with SPSS, including the available clinicopathological data of the patients included. Results Axitinib was found to be active in patients who received this treatment beyond second line. The toxicity profile of this regimen did not reveal any unknown adverse events. Conclusions Our real world data reflect that axitinib is a safe and effective option, even beyond the second line.

Introduction/BackgroundOvarian cancer (OC) is one of the most lethal gynecological malignancies. Primary Debulking Surgery (PDS) followed by chemotherapy has been the standard of care. However, two randomized trials have demonstrated that Neoadjuvant Chemotherapy(NACT) followed by Interval Debulking Surgery(IDS) is not inferior to PDS. Therefore, we conducted a retrospective analysis to determine patterns of practice in our institution.MethodologyMedical records of women with epithelial OC treated at Alexandra Hospital from 2011 to 2016 were retrospectively identified. Clinicopathological data, treatment and survival data were analyzed. Kaplan-Meier Survival curves were generated using IBM SPSS version 20; survival differences were estimated using the long-rank test.Results198 patients were identified. Median age was 60.8 years. 169 patients had serous carcinoma, 10 clear cell, 10 endometrial, 3 mucous and 4 adenocarcinoma. 171 had advanced (stage III/IV) disease. PDS was performed in 128 patients, while 70 received NACT. 48 performed IDS, while 6 had LDS. No surgery was performed in 16 patients. With a median follow-up of 27.3 months, mPFS was 21.8 months and mOS was 58.5 months. Patients treated with NACT-IDS had statistical significant shorter mPFS and mOS than those treated with PDS (PFS: 16.2 m vs 25.9 m P<0.001 and OS 44.4 m vs Not Reached, P=0.05). NACT-IDS retained its statistical significance as an adverse prognostic factor in multivariate analysis when controlled for stage, grade and histology of the disease (P=0.003). No statistical significant difference in the percentage of patients with platinum resistant disease among PDS and IDS was identified.ConclusionNACT followed by IDS is frequently used in the treatment of ovarian cancer patients in a tertiary centre in Greece and was correlated with adverse outcome. A selection bias favoring NACT for patients with high risk for perioperative morbidity may affect the results of this retrospective analysis. Large randomized trials to address this issue are underway.DisclosureNothing to disclose.

Introduction/BackgroundTreatment of elderly patients with neoplasia is challenging due to the frailty of the patients, existing comorbidities and increased number of concomitant medications. In addition, elderly patients are usually underrepresented in clinical trials. Age is a known prognostic factor in ovarian cancer but optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced stage ovarian cancer patients older than 75 years of age.MethodologyMedical records of women with high grade serous and endometrial ovarian cancer, stage III and IV, treated at Alexandra Hospital from 2011 to 2016 were retrospectively identified. Clinicopathological data, treatment and survival data were analyzed. Kaplan-Meier Survival curves were generated using IBM SPSS version 20; survival differences were estimated using the long-rank test.ResultsIn total, 158 patients were identified with a median age of 61.1 years. Among them 20 (12.7%) were older than 75 years of age at diagnosis (range 75.03–92.72 years). First line Progression Free Survival (PFS) and Overall Survival (OS) were statistically significant worse in elderly patients in comparison to the younger ones (mPFS 13.4 months vs 21.9 months, P<0.001 and mOS 25.3 months vs 51,5 months, P<0.001). However, elderly patients were characterized by worse ECOG-PS, more frequent treatment with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, more frequently denied debulking surgery, and received monotherapy with platinum as frontline treatment, while were less frequently tested for BRCA mutations. In contrast, there was no statistical significant difference in the outcome of the debullking surgery in comparison to the younger patients. Age over 75 years retained its statistical significance for OS when adjusted for all other reported prognostic factors.ConclusionElderly ovarian cancer patients have worse prognosis independent of treatment. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.DisclosureNothing to disclose.