The clinical landscape of antibody-drug conjugates in endometrial cancer.

Clinical outcomes remain challenging in advanced or recurrent endometrial cancer due to tumor heterogeneity and therapy resistance. Antibody-drug conjugates are a novel class of cancer therapeutics, representing a promising treatment option for endometrial cancer. Antibody-drug conjugates consist of a high-affinity antibody linked to a cytotoxic payload through a stable linker. After binding to specific antigens on tumor cells, the drug is internalized, and the payload is released. In addition, the free intracellular drug may be released outside the target cell through a 'bystander effect' and kill neighboring cells, which is crucial in treating malignancies characterized by heterogeneous biomarker expression like endometrial cancer.This article aims to provide a comprehensive overview of the current clinical landscape of antibody-drug conjugates in the treatment of endometrial cancer. We conducted a thorough analysis of recent clinical trials focusing on efficacy, safety profiles, and the mechanisms by which antibody-drug conjugates target endometrial cancer. We focused particularly on the most promising antibody-drug conjugate targets in endometrial cancer under clinical investigation, such as human epidermal growth factor receptor 2 (HER2), folate receptor alpha (FRα), trophoblast cell-surface antigen-2 (TROP2), and B7-H4. We also briefly comment on the challenges, including the emergence of resistance mechanisms, and future development directions (especially agents targeting multiple antigens, combinatorial strategies, and sequential use of agents targeting the same antigen but using different payloads) in antibody-drug conjugate therapy for endometrial cancer.

Phase I Study of Rucaparib in Combination with Bevacizumab in Ovarian Cancer Patients: Maximum Tolerated Dose and Pharmacokinetic Profile.

BACKGROUND: Targeted agents, such as antiangiogenic drugs (e.g., bevacizumab) and poly(ADP-ribose) polymerase inhibitors (e.g., rucaparib), have been shown to improve outcomes in patients with newly diagnosed or recurrent ovarian cancer. Evidence suggests that combinations of these two classes of targeted agents may result in synergistic antitumor activity. OBJECTIVE: The phase I portion of MITO 25 was designed to determine the maximum tolerated dose, pharmacokinetics, and the safety profile of rucaparib when administered in combination with bevacizumab as maintenance treatment for patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. METHODS: This was a single-arm, phase I dose-escalation study. Cohorts of three patients were recruited to receive increasing rucaparib doses of 400 mg, 500 mg, or 600 mg twice daily for 28 days. Bevacizumab 15 mg/kg was administered at day 1 every 21 days. RESULTS: We enrolled nine patients. Two patients in the rucaparib 600-mg group had four grade 3 treatment-emergent adverse events: increased in alanine aminotransferase and aspartate aminotransferase levels, depression, and hallucinations. These were deemed to be dose-limiting toxicities related to rucaparib. Because these dose-limiting toxicities occurred in the 600-mg group and affected more than one in three patients, the maximum tolerated dose for rucaparib was considered 500 mg twice daily when combined with bevacizumab 15 mg/kg at day 1 every 21 days. There were no new safety concerns from using the combination. No substantial difference in pharmacokinetic parameters was found between the cohorts or in the pharmacokinetic profiles of rucaparib administered alone or with bevacizumab with respect to historical controls. CONCLUSIONS: The maximum tolerated dose of rucaparib is 500 mg twice daily when co-administered with bevacizumab. The plasma concentration-time profiles of rucaparib in combination with bevacizumab suggest no pharmacokinetic interactions between the drugs. The randomized phase II portion of MITO 25 will further investigate rucaparib maintenance treatment with or without bevacizumab in patients with newly diagnosed stage III-IV ovarian cancer who responded to carboplatin-paclitaxel chemotherapy with or without bevacizumab. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03462212; registered March 2018.

Advances in laparoscopic surgery for cervical cancer.

In the recent years, minimally invasive surgery has emerged as the gold standard for the treatment of both benign and malignant gynecological conditions. Growing evidence suggest that laparoscopic and robotic-assisted treatments allow to archived the same long-term outcomes than conventional open abdominal treatments, minimizing peri-operative morbidity. In the present review we analyzed the advances in the treatment of cervical cancer patients, reporting the advances in both the evolution of concept of radical hysterectomy and of the adoption of minimally invasive surgery. We discussed the advantages related to the introduction of minimally invasive treatment for cervical cancer patients; innovation of conventional laparoscopic surgery as discussed as well. Recent evidence suggested a potential detrimental effect on long-term survival outcomes related to the use of minimally invasive surgery in patients affected by cervical cancer. However, reasons why minimally invasive surgery might have a detrimental effect are still unclear. Further evidence is needed in order to improve quality of treatment for cervical cancer patients.

RECIST 1.1 criteria predict recurrence-free survival in advanced ovarian cancer submitted to neoadjuvant chemotherapy.

OBJECTIVE: Neoadjuvant chemotherapy plus interval debulking surgery is growing treatment strategy for advanced ovarian cancer patients with unresectable disease. Here, we aimed to assess predictors of surgical unresectability and survival of patients submitted to neoadjuvant chemotherapy plus interval debulking surgery. METHODS: Data of consecutive 193 patients undergoing neoadjuvant chemotherapy plus interval debulking surgery were retrospectively evaluated in four Italian oncologic centers. RECIST 1.1 guidelines were used to assess response to neoadjuvant chemotherapy. Survival outcomes were evaluated using Kaplan-Meier and Cox proportional hazard models. RESULTS: Overall, 155 (80.3%) and 38 (19.7%) patients had optimal and non-optimal cytoreduction at the time of interval debulking surgery. Via multivariate analysis, age (OR: 2.87 (95%CI: 1.29, 6.36) per 10-year increase) and radiological response to neoadjuvant chemotherapy (OR: 48.1 (95%CI: 6.33, 365.3)) impact on the inability to perform a complete cytoreduction. Patients having complete or partial response experienced a significant better disease-free survival than patients having stable or progressive disease at radiological examination (median disease-free survival 16.8 vs. 11.0 months; HR: 0.42 (95%CI: 0.09, 0.78); p = .001). Radiological response did not predict for overall survival (p = .719). CONCLUSIONS: RECIST1.1 response criteria might be helpful to predict surgical resectability and disease-free survival of advanced stage ovarian cancer patients undergoing neoadjuvant chemotherapy plus interval debulking surgery.

Treatment of recurrent ovarian cancer with pegylated liposomal doxorubicin: a reappraisal and critical analysis.

The vast majority of ovarian cancer relapses on front-line therapy and the optimal treatment of recurrent ovarian cancer remains controversial. This review is based on the relevant published literature indexed in PubMed on pegylated liposomal doxorubicin (PLD), either alone or in combination with other drugs, as one option in relapsed disease. PLD showed an improved pharmacokinetic profile, with a slower plasma clearance and a longer circulation time, compared to other conventional doxorubicin formulations. PLD is considered to have little potential for cardiotoxicity, even at prolonged and high cumulative doses, although there appears to be room for improvement in terms of maximal dose allowed. Notwithstanding, there remain some concerns about cardiac safety, and patient monitoring is generally advocated. No data are available on the possibility to rechallenge PLD treatment in recurrent ovarian cancer, as already known for other drugs. Optimization of treatment regimens with PLD will allow a more rational treatment in advanced ovarian cancers for which few therapeutic options are available.

Capecitabine in patients with platinum-pretreated advanced or recurrent cervical carcinoma: a retrospective study.

BACKGROUND: Cervical cancer is a common malignancy among women and, when recurring, presents a dismal prognosis. After platinum failure, second-line treatments report response rates ranging from 3-15%, a median progression-free survival of about 3 months and a median overall survival of about 5.5 months.To retrospectively evaluate the activity and safety of capecitabine in patients with advanced/recurrent cervical carcinoma.MethodsA retrospective review of medical records of recurrent cervical cancer patients, who had failed a previous platinum-paclitaxel treatment and received oral capecitabine 1250 mg/m2 twice daily continuously from day 1 to day 14 every 21 days, was performed from December 2013 to March 2018 at the Gynecologic Oncology Unit of the Fondazione IRCCS National Cancer Institute of Milan, Italy. The response rate was evaluated every three cycles according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Common Terminology Criteria for Adverse Events version 4.0 were used to evaluate adverse events. RESULTS: We retrospectively analyzed 35 patients with recurrent cervical carcinoma, treated with oral capecitabine. All patients had previously received and failed a combination of carboplatin plus paclitaxel as first-line therapy for advanced/recurrent disease. Median age at the first capecitabine administration was 53 years (range 27-82). All patients were evaluable for response: the overall response rate was 34.2% (2.8% complete responses and 31.4% partial responses) with a clinical benefit rate of 57% (overall response rate plus 22.8% stabilizations of disease). The most common grade 1-2 adverse events per patient were fatigue (71.3%), hand-foot syndrome (57.0%), diarrhea (31.3%), constipation (17.0%), and nausea (10.4%). Only three patients (8.5%) reported grade 3 adverse events. CONCLUSIONS: Our data suggest that oral capecitabine should be considered an active and safe treatment in patients with recurrent cervical carcinoma after platinum failure. Based on these results, we consider capecitabine as warranting further clinical evaluation.

Predicting Factors for High-Grade Cervical Dysplasia in Women With Low-Grade Cervical Cytology and Nonvisible Squamocolumnar Junction.

OBJECTIVE: To assess the risk of developing high-grade cervical dysplasia among women with low-grade cervical cytology and nonvisible squamocolumnar junction (SCJ) at colposcopic examination. METHODS: Data of consecutive women with low-grade intraepithelial lesion(≤LSIL) undergoing colposcopic examination, which was unsatisfactory (due to the lack of the visualization of the entire SCJ), were retrospectively reviewed. The risk of developing high-grade cervical intraepithelial neoplasia (CIN2+) was assessed using Kaplan-Meier and Cox models. RESULTS: Data of 86 women were retrieved. Mean (standard deviation [SD]) age was 36.3 (13.4) years. A total of 71 (82.5%) patients had high-risk human papillomavirus (HR-HPV) at the time of diagnosis. Among the 63 patients undergoing repetition of HPV testing, 15 (24%) and 48 (76%) women had positive and negative tests for HR-HPV at 12 months, respectively. We observed that 5 (33%) of 15 patients with HPV persistence developed CIN2+, while only 1 (2%) patient of 48 patients without HPV persistence developed CIN2+ (odds ratio [OR]: 23.5; 95% confidence interval [CI]: 2.46-223.7; P < .001). The length of HR-HPV persistence correlated with an increased risk of developing CIN2+ ( P < .001; P for trend). High-risk HPV persistence is the only factor predicting for CIN2+ (hazard ratio: 3.19; 95% CI: 1.55-6.57; P = .002). CONCLUSIONS: High-risk HPV persistence predicts the risk of developing CIN2+ in patients with unsatisfactory colposcopic examination. Further studies are warranted in order to implement the use of HPV testing in patients with unsatisfactory colposcopy.

Surgical Efforts Might Mitigate Difference in Response to Neoadjuvant Chemotherapy in Stage IIIC-IV Unresectable Ovarian Cancer: A Case-Control Multi-institutional Study.

OBJECTIVE: The aim of the study was to evaluate outcomes of patients with unresectable advanced ovarian cancer experiencing complete response (CR) to neoadjuvant chemotherapy. METHODS: Data of consecutive patients undergoing neoadjuvant chemotherapy plus interval debulking surgery (IDS) were retrospectively reviewed in 4 Italian centers. Using a propensity-matching algorithm, we compared data of patients achieving CR with neoadjuvant chemotherapy (no macroscopic either microscopic residual disease (RD) at the time of IDS) with patients achieving partial response (PR). This latter group was stratified by the presence of RD (RD = 0 vs RD > 0). RESULTS: Overall, 193 had IDS after neoadjuvant chemotherapy: 25 (13%), 81 (41.9%), and 74 (38.3%) patients had CR, PR with RD of 0, and PR with RD of more than 0, respectively. In addition, 13 (6.7%) patients had no macroscopic disease detected at DS but just microscopic disease at pathological examination. For the study purpose, 25 patients achieving CR were matched (1:2) with 50 patients having PR and RD of 0 and 50 patients having PR and RD of more than 0. As the result of propensity matching, baseline characteristics were similar between groups. Comparing survival outcomes of patients having CR and PR with RD of 0, we observed that type of response to chemotherapy did not influence disease-free (hazard ratio = 1.53 [95% confidence interval = 0.88-2.66], P = 0.127) and overall (hazard ratio = 1.74 [95% confidence interval = 0.76-4.01], P = 0.189) survivals. Patients achieving CR experienced significantly better disease-free survival (P = 0.004) and a trend toward better overall survival (P = 0.06) than patients achieving PR with RD of more than 0 at IDS. CONCLUSIONS: Complete cytoreduction might mitigate the difference in response to neoadjuvant chemotherapy. The presence of RD at IDS is associated with worse survival outcomes.

The addition of lymphadenectomy to secondary cytoreductive surgery in comparison with bulky node resection in patients with recurrent ovarian cancer.

OBJECTIVE: To evaluate the role of full lymphadenectomy in patients with isolated nodal recurrence of ovarian cancer. METHODS: In a retrospective study, the data of women undergoing secondary cytoreduction at the National Cancer Institute, Milan, Italy, between January 1, 2001, and December 31, 2015, were collected and patients with isolated nodal recurrence were identified. Factors predicting for disease-free interval (DFI) and overall survival were estimated using Kaplan-Meier survival analysis and Cox regression analysis. RESULTS: Of the 199 consecutive patients whose data were collected, isolated nodal recurrence (defined as the presence of lymphatic disease) was observed in 35 women. Among this study cohort, lymphadenectomy and bulky node removal were performed in 11 (31%) and 24 (69%) patients, respectively. Women who underwent lymphadenectomy experienced better DFI compared with those who had bulky node removal only (median 21 and 12 months, respectively; P=0.019), and lymphadenectomy, but not bulky node removal, significantly improved rates of DFI (P=0.043). No factors were independently associated with overall survival; however, a trend toward an improved overall survival rate was observed in patients undergoing complete resection at the time of primary surgery (P=0.055). CONCLUSION: Lymphadenectomy at the time of secondary cytoreduction improved DFI but did not have a significant effect on overall survival.

Locally Advanced Cervical Cancer: Is a Trimodality Treatment a Safe and Effective Approach?

BACKGROUND: Chemoradiotherapy (CRT) is the standard of care for locally advanced cervical cancer (LACC). Pre-treatment lymph nodes (LN) assessment may have an important therapeutic role. CRT followed by adjuvant chemotherapy increased progression free survival (PFS) and overall survival (OS). Our study evaluated the feasibility and the effectiveness of a trimodality strategy in patients with LACC and positive LN. METHODS: Consecutive patients with LACC treated at the National Cancer Institute of Milan were enrolled. All patients underwent pelvic and para-aortic extraperitoneal laparoscopic lymphadenectomy to assess the nodal status. After surgery, patients received radiotherapy followed by chemotherapy according to the stage of disease. RESULTS: Between April 2012 and October 2013, 19 cervical cancer patients were enrolled. Overall, 10 (52.6%) patients presented with positive LN: 6 in the pelvic area and 4 both in the pelvic and para-aortic area. No perioperative major complications occurred. The most common surgical-related adverse events were bleeding (26%), respiratory distress (5%), infection (5%) and the development of lymphoceles (25%). Overall, 15 (78.9%) complete responses and 2 (10.5%) partial responses were registered. After a median follow-up of 43.3 months, 89.5% of patients were alive at the last visit, and 3-year PFS was 63%. CONCLUSIONS: Trimodality treatment appears feasible, well tolerated and promising in terms of oncologic outcome.

Spotlight on olaparib in the treatment of BRCA-mutated ovarian cancer: design, development and place in therapy.

Epithelial ovarian cancer is the sixth most common cancer among women worldwide and the first cause of death among gynecological malignancies. Most of the patients present recurrent disease and unfortunately cannot be cured. The unsatisfactory results obtained with salvage chemotherapy have elicited investigators to search for novel biological agents capable of achieving a better control of the disease. In the setting of homologous recombination deficiency, the DNA errors that occur cannot be accurately repaired, and the treatment with poly(ADP-ribose) polymerase (PARP) inhibition results in definitive cell death in a process called synthetic lethality. As a result of two positive clinical trials, Olaparib was approved in 2014 by U.S. Food and Drug Administration and European Medicines Agency as the first-in-class PARP inhibitor. Olaparib is effective and well tolerated in homologous recombination deficient patients. Several studies with Olaparib have been conducted in the recurrent setting either as maintenance in platinum-responsive patients or as a single agent. Ongoing trials are focused on the use of olaparib as maintenance in the first-line ovarian cancer setting alone or in combination with antiangiogenic agents. Future perspectives will probably investigate the association of olaparib with novel agents as check-point inhibitors and PI3K-AKT inhibitors. The PARP inhibitor era is just at the beginning.

LASER treatment for women with high-grade vaginal intraepithelial neoplasia: A propensity-matched analysis on the efficacy of ablative versus excisional procedures.

OBJECTIVE: To investigate the long-term effectiveness of LASER treatment in women affected by high-grade vaginal intra-epithelial neoplasia. METHODS: Data of consecutive women treated for high-grade vaginal intra-epithelial neoplasia were retrieved. Efficacy and long-term effectiveness of ablative and excisional procedures were tested using a propensity-matched algorithm. Risk of recurrence over the time was assessed using Kaplan-Meier and Cox models. RESULTS: Overall, 204 patients met the inclusion criteria. LASER ablation and exicision were performed in 169 (82.8%) and 35 (17.2%) patients. A total of 41 (20%) patients developed high-grade vaginal intraepithelial neoplasia at a median follow-up of 65 (range, 6-120) months. We observed that only HPV persistence (HR: 2.37 [95%CI:1.03, 5.42]; P = 0.04) was associated with the risk of recurrence at multivariate analysis. Seven (3.4%) invasive cancers of the lower genital tract were observed in our population. Considering the efficacy of type of procedure (after we applied the propensity-matched analysis), we observed that type of procedure did not influence persistence of HPV infection (22.8% after excision and 15.7% after ablation; P = 0.424). Similarly, recurrence (17.1% vs. 18.6%; P = 1.00) and lower genital tract (2.8% vs. 1.4%; P = 1.00) rates were similar between groups. CONCLUSIONS: Women affected by high-grade vaginal intra-epithelial neoplasia are at high risk of recurrence. LASER ablation seems to be equivalent to excision in term of long-term effectiveness. Lasers Surg. Med. 50:933-939, 2018. © 2018 Wiley Periodicals, Inc.

Rucaparib: a new treatment option for ovarian cancer.

INTRODUCTION: Approximately 50% of high-grade serous ovarian cancers present a deficiency in the pathways involved in homologous recombination (HR). PARP inhibitors prevent single-strand DNA damage repair and determine a progression of the defect towards double-strand breaks, which results in a process known as 'synthetic lethality'. Areas covered: In this review, the authors discuss the efficacy and toxicity of rucaparib either as a single agent or as a maintenance treatment for ovarian cancer. This includes the NGS Foundation Medicine evaluation of the role of this drug in the treatment algorithm of ovarian cancer. Moreover, perspectives on the future development of this drug are presented. Expert opinion: The FDA has approved this drug for the treatment of recurrent BRCA-mutated ovarian cancers, which were previously treated with at least two chemotherapies and has accepted the supplemental new drug application for maintenance use in patients who respond to platinum-based chemotherapy via the Prescription Drug User Fee Act (PDUFA) on 6 April 2018. European Medicines Agency (EMA) approval in the same setting is awaited. The possibility of using PARP inhibitors as a maintenance therapy, as a front-line therapy to combat recurrence, and in combination with anti-angiogenic agents and immune-therapies appears to be of particular interest.

A score system for complete cytoreduction in selected recurrent ovarian cancer patients undergoing secondary cytoreductive surgery: predictors- and nomogram-based analyses.

OBJECTIVE: To test the applicability of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Memorial Sloan Kettering (MSK) criteria in predicting complete cytoreduction (CC) in patients undergoing secondary cytoreductive surgery (SCS) for recurrent ovarian cancer (ROC). METHODS: Data of consecutive patients undergoing SCS were reviewed. The Arbeitsgemeinschaft Gynäkologische Onkologie OVARian cancer study group (AGO-OVAR) and MSK criteria were retrospectively applied. Nomograms, based on AGO criteria, MSK criteria and both AGO and MSK criteria were built in order to assess the probability to achieve CC at SCS. RESULTS: Overall, 194 patients met the inclusion criteria. CC was achieved in 161 (82.9%) patients. According to the AGO-OVAR criteria, we observed that CC was achieved in 87.0% of patients with positive AGO score. However, 45 out of 71 (63.4%) patients who did not fulfilled the AGO score had CC. Similarly, CC was achieved in 87.1%, 61.9% and 66.7% of patients for whom SCS was recommended, had to be considered and was not recommended, respectively. In order to evaluate the predictive value of the AGO-OVAR and MSK criteria we built 2 separate nomograms (c-index: 0.5900 and 0.5989, respectively) to test the probability to achieve CC at SCS. Additionally, we built a nomogram using both the aforementioned criteria (c-index: 0.5857). CONCLUSION: The AGO and MSK criteria help identifying patients deserving SCS. However, these criteria might be strict, thus prohibiting a beneficial treatment in patients who do not met these criteria. Further studies are needed to clarify factors predicting CC at SCS.

The role of human papillomavirus vaccines in cervical cancer: Prevention and treatment.

Human papillomavirus (HPV) is the most common sexually transmitted disease, worldwide. Primary prevention thorough vaccination si able to reduce the burden of HPV-related lesions. Ten years ago the Food and drug Administration (FDA) approved the first vaccine against HPV. In the last decades, growing data on safety and effectiveness have been collected. In the present review we report the current knowledge on vaccine against HPV, highlighting the current value and prospective regarding the widespread diffusion of HPV vaccines. The role of emerging therapeutic vaccines is reviewed.

Nerve-Sparing Approach Improves Outcomes of Patients Undergoing Minimally Invasive Radical Hysterectomy: A Systematic Review and Meta-Analysis.

Few studies have investigated the efficacy and safety of the nerve-sparing approach via minimally invasive surgery for the treatment of cervical cancer. We aimed to review the current evidence comparing nerve-sparing minimally invasive radical hysterectomy (NS-MRH) with conventional minimally invasive radical hysterectomy (MRH). This systematic review was registered in the International Prospective Register of Systematic Reviews (CRD#57655). Overall, 675 patients were included: 350 (51.9%) and 325 (48.1%) patients undergoing MRH and NS-MRH, respectively. MRH was associated with a shorter operative time in comparison with NS-MRH (mean difference = 32.57 minutes; 95% CI, 22.87-42.48). The estimated blood loss (mean difference = 97.14 mL, 20.01-214.29) and transfusion rate (odds ratio [OR] = 0.67; 95% confidence interval [CI], 0.15-3.01) did not differ statistically between the 2 groups. The risk of developing intraoperative (OR = 0.43; 95% CI, 0.08-2.23) and severe postoperative (OR = 0.63; 95% CI, 0.17-2.39) complications was similar between NS-MRH and MRH. Patients undergoing NS-MRH experienced lower voiding (OR = 0.39; 95% CI, 0.19-0.81) dysfunction rates than patients undergoing MRH. Moreover, a trend toward lower sexual (OR = 0.25; 95% CI, 0.06-1.07) and rectal (OR = 0.12; 95% CI, 0.01-1.02) issues was observed for patients having NS-MRH compared with patients undergoing MRH. Survival outcomes are not influenced by the type of surgical approach (recurrence [OR = 1.27; 95% CI, 0.49-3.28] and death [OR = 1.01; 95% CI, 0.36-2.83]) rates. The pooled data suggested that NS-MRH is equivalent to MRH for the treatment of cervical cancer and may be superior in reducing pelvic floor dysfunction rates. However, because of the low level of evidence of the included studies, further randomized trials are warranted.

[Il ruolo di niraparib nel trattamento del carcinoma ovarico: attualità e prospettive.] / The role of niraparib in the treatment of ovarian cancer: actuality and perspectives.

Riassunto. I PARP inibitori interferiscono con la riparazione del danno nella singola elica del DNA determinando una progressione del difetto nella doppia elica. In circa il 50% delle pazienti con carcinoma dell'ovaio sieroso di alto grado sono presenti difetti nei meccanismi di ricombinazione omologa, deputati alla riparazione del danno della doppia elica del DNA. L'incapacità di riparare il danno si traduce nella morte cellulare, un processo definito "letalità sintetica". Nella famiglia dei PARP inibitori il niraparib è stato il primo a essere approvato dalla FDA nel trattamento delle pazienti con carcinoma ovarico ricorrente indipendentemente dalla presenza o assenza di mutazioni BRCA. Questo risultato è stato raggiunto grazie ai dati emersi dal trial di fase III ENGOT-OV16/NOVA, favorevoli in termini di prolungamento della sopravvivenza libera da progressione e associati a un buon profilo di tossicità. Ulteriori trial clinici sono in corso per valutare ulteriori indicazioni all'impiego di niraparib nel trattamento del carcinoma ovarico.

The association of pre-treatment HPV subtypes with recurrence of VIN.

OBJECTIVE: To assess whether pre-treatment HPV types are associated with recurrence of high-grade vulvar intraepithelial neoplasia (VIN2+). STUDY DESIGN: Data of consecutive patients with pretreatment HPV DNA test undergoing treatment for VIN2+ were retrospectively collected. Risk factors promoting the risk of VIN2+ persistence and recurrence were analyzed using Kaplan-Meier and Cox hazard proportional models. RESULTS: 64 patients had pretreatment vulvar-vaginal HPV DNA test. Two were excluded due to the presence of synchronous vulvar cancer, thus leaving 62 patients for the final analysis. HPV16, HPV18, HPV31 and HPV33 were the most common HPV genotype detected, occurring in 15 (24.2%), 4 (6.5%), 8 (12.9%) and 5 (8.0%) patients, respectively. HPV was not detected in 19 (30.6%) patients. During a mean (SD) follow up of 56.7 (±26.7) months, 10 (16.1%) patients had VIN2+ persistence/recurrence. Mean (SD) lesion-free interval was 51.7 (±31.4) months. Via multivariate analysis, pretreatment infection from HPV31 (HR:46.7(95%CI:4.21,518.4); p=0.02) and HPV33 (HR:77.0(95%CI:6.73,881.9); p<0.001) correlated with an increased risk of VIN2+ persistence/recurrence. Additionally, we observed that patients undergoing surgical excision followed by LASER ablation experienced a trend towards lower recurrence rate than patients undergoing other surgical or medical treatments (HR:0.20(95%CI:0.03,1.09); p=0.05). Two (3.2%) patients developed progression to vulvar cancer. CONCLUSIONS: Owing to the inherent biases of the retrospective study design and the small sample size, our data have to be corroborated by larger and prospective studies. HPV31 and HPV33 have a potential role in predicting VIN2+ persistence/recurrence. These findings will be paramount, owing to the implementation of new immunization programs.