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Purpose. A single-institution prospective pilot study was conducted to the assess correlation between salivary amylase and xerostomia in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT). Methods and materials. Serum saliva amylase, clinician-reported xerostomia (using Common Terminology Criteria for Adverse Events), and patient-reported xerostomia (using 8-item self-reported xerostomia-specific questionnaire) were prospectively collected at baseline, during treatment and thereafter. Correlations between variables were assessed by correlation matrices. Results. Twelve patients with locally advanced HNSCC formed the cohort. Eighty-three percent were male, 75% were smokers, 100% had clinical positive lymph nodes at diagnosis, and 42% received induction chemotherapy. All patients received IMRT with concurrent cisplatin-based chemotherapy. No grade ≥4 xerostomia was observed. Severe (G3) acute and late xerostomia occurred in five cases (41.7%) and two cases (16.7%), respectively. Patient-reported xerostomia scores were highly correlated with the clinician-reported scores (ρ = 0.73). A significant correlation was recorded between the concentration of amylase and the acute (ρ = −0.70) and late (ρ = −0.80) xerostomia. Conclusion. Preliminary results are encouraging. Prospective clinical trials are needed to define the value of salivary amylase in the management of HNSCC tumors.

Abstract Background High-grade serous ovarian cancer (HGSOC) has poor survival rates due to a combination of diagnosis at advanced stage and disease recurrence as a result of chemotherapy resistance. In BRCA1 (Breast Cancer gene 1) - or BRCA2-wild type (BRCAwt) HGSOC patients, resistance and progressive disease occur earlier and more often than in mutated BRCA. Identification of biomarkers helpful in predicting response to first-line chemotherapy is a challenge to improve BRCAwt HGSOC management. Methods To identify a gene signature that can predict response to first-line chemotherapy, pre-treatment tumor biopsies from a restricted cohort of BRCAwt HGSOC patients were profiled by RNA sequencing (RNA-Seq) technology. Patients were sub-grouped according to platinum-free interval (PFI), into sensitive (PFI > 12 months) and resistant (PFI

Abstract Laboratory-markers of the systemic inflammatory-response, such as neutrophil/lymphocyte-ratio (NLR) have been studied as prognostic factors in several tumors but in OC-patients their role is still controversial and no data about the possible correlation with the BRCA-status has been ever reported. We consecutively enrolled a series of 397 newly diagnosed high-grade serous-advanced OC-patients. All patients were tested for BRCA-mutational-status and blood-parameters have been collected 48 h before staging-surgery. A significant correlation of NLR with disease distribution (p 4 (BRCA-mutated: 35 vs 23 months, p = 0.03; BRCA-wt: 19 vs 16 months, p = 0.05). At multivariate-analysis, independent factors of prolonged PFS were BRCA mutational status, having received complete cytoreduction and NLR

Abstract Background Ovarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood. The aim of this study is to identify target genes within the tumor cells that might cause resistance to Olaparib. We focused on Neuropilin 1 (NRP1), a transmembrane receptor expressed in OC and correlated with poor survival, which has been also proposed as a key molecule in OC multidrug resistance. Methods Using three OC cell lines (UWB, UWB-BRCA and SKOV3) as model systems, we evaluated the biological and molecular effects of Olaparib on OC cell growth, cell cycle, DNA damage and apoptosis/autophagy induction, through MTT and colony forming assays, flow cytometry, immunofluorescence and Western blot analyses. We evaluated NRP1 expression in OC specimens and cell lines by Western blot and qRT-PCR, and used RNA interference to selectively inhibit NRP1. To identify miR-200c as a regulator of NRP1, we used miRNA target prediction algorithms and Pearsons’ correlation analysis in biopsies from OC patients. Then, we used a stable transfection approach to overexpress miR-200c in Olaparib-resistant cells. Results We observed that NRP1 is expressed at high levels in resistant cells (SKOV3) and is upmodulated in partially sensitive cells (UWB-BRCA) upon prolonged Olaparib treatment, leading to poor drug response. Our results show that the selective inhibition of NRP1 is able to overcome Olaparib resistance in SKOV3 cells. Moreover, we demonstrated that miR-200c can target NRP1 in OC cells, causing its downmodulation, and that miR-200c overexpression is a valid approach to restore Olaparib sensitivity in OC resistant cells. Conclusions These data demonstrate that miR-200c significantly enhanced the anti-cancer efficacy of Olaparib in drug-resistant OC cells. Thus, the combination of Olaparib with miRNA-based therapy may represent a promising treatment for drug resistant OC, and our data may help in designing novel precision medicine trials for optimizing the clinical use of PARPi.

Microinvasive squamous cell cervival carcinoma is characterized by an exceptional incidence of lymph nodal metastasis. We report the case of a 45-year-old woman affected by IA1 squamous cell carcinoma, found to have massive pelvic lymph nodal metastasis. After a systematic pelvic and aortic selective lymphadenectomy, at 16 months of follow-up, she is still disease-free. Patients suitable for conservative therapy should be carefully counselled about the established risks and benefits of nondestructive treatment options.

Carmela Pisano, Giovanni S Bruni, Gaetano Facchini, Claudia Marchetti, Sandro PignataOncologia Medica, Dipartimento Uro-Ginecologico, Istituto Nazionale Tumori, Napoli, ItalyAbstract: Epidemiologic analysis reveals that the mortality rate from ovarian cancer is continuously decreasing due to the improvement of surgery and chemotherapy. However, the prognosis of ovarian cancer patients is still unsatisfactory overall considering that only 30% of patients are alive after five years. In fact, although surgery and first-line systemic chemotherapy induces complete and partial response in up to 80% of patients with about a 25% pathological complete remission rate, recurrences occur in the majority of patients. The role of surgery in recurrent disease has been recently studied and many patients can receive an optimal secondary cytoreduction. Most of the recurrent patients are subject to a number of treatment regimens that, although palliative in nature, are also able to prolong survival. Important results have been obtained in particular in platinum-sensitive recurrent disease where a platinum-based chemotherapy is able to prolong progression-free survival and overall survival. Overall, our armamentarium for the treatment of progressive or recurrent ovarian cancer is significantly richer than in the past, and in many patients it is possible to achieve our goal of controlling the chronic behavior of the disease.Keywords: ovarian cancer, chemotherapy

Ovarian cancer is the most important cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease. Although surgery and chemotherapy can improve survival rates, it is necessary to integrate alternative strategies to improve the outcomes. Advances in understanding the role of immune system in the pathogenesis of cancer have led to the rapid evolvement of immunotherapy, which might establish a sustained immune system response against recurring cancer cells. Recently, it has emerged that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called “immune checkpoints,” which turn off the immune system. Similarly, cancer cells are able to use these checkpoints to avoid immune control and rejection. Inhibition of these inhibitory pathways represents a potent strategy in the fight against cancer and is currently under investigation with encouraging results in some cancers, such as melanoma. In ovarian cancer researches are still in an early phase, but with promising results. In this review we will explore the rationale of immunotherapy in ovarian cancer with a special focus on these emerging molecules.

Vulvar cancer represents approximately 3%–5% of all gynecological malignancies. Squamous cell carcinoma is the most frequent histotype, whereas melanomas, adenocarcinomas, basal cell carcinomas, and sarcomas are much less common. Intestinal-type adenocarcinoma is a rare variant of vulvar carcinoma with only few cases found in the literature. The origin of this neoplasia is still much debated, but the most reliable hypothesis is the origin from cloacal remnants that may persist in the adult in different organs. Because of its extremely low incidence, the optimal management of this kind of vulvar cancer is still debated. We report the case of a woman affected by advanced intestinal-type vulvar adenocarcinoma, who achieved a complete clinical and pathological response after neoadjuvant chemotherapeutic treatment with platinum and paclitaxel.

Introduction Bartholin gland carcinoma is an extremely rare condition. Because of its, phase III trials have not been carried out, there exists no unanimous consensus on treatment and guidelines are missing. Methods All studies reporting cases of Bartholin cancer were collected and screened for the evaluations. Baseline characteristics of studies were extracted and were queried in a database. Results A total number of 133 manuscripts collected were available for the review process, representing a total number of 275 reported cases. The histological type of Bartholin gland cancer was specified in 90.4% cases: 30.7% cases were squamous cell carcinoma, 29.6% adenoid cystic carcinoma, 25% adenocarcinomas. At multivariate analysis adenocarcinoma histotype and positive lymph node were statistical correlated with worse prognosis. Conclusion Bartholin gland cancer remains a challenge for gynecologic oncologists. To better understand and treat this disease, centralization to referral centers and design of multi institutional trials is crucial. [ABSTRACT FROM AUTHOR]