Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 876
Filtrar
1.
Int J Gynecol Cancer ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931498

RESUMO

OBJECTIVE: To explore the clinical and biological prognostic factors for advanced ovarian cancer patients receiving first-line treatment with carboplatin, paclitaxel, and bevacizumab. METHODS: A multicenter, phase IV, single arm trial was performed. Patients with advanced (FIGO (International Federation of Gynecology and Obstetrics) stage IIIB-IV) or recurrent, previously untreated, ovarian cancer received carboplatin (AUC (area under the curve) 5), paclitaxel (175 mg/m2) plus bevacizumab (15 mg/kg) on day 1 for six 3-weekly cycles followed by bevacizumab single agent (15 mg/kg) until progression or unacceptable toxicity up to a maximum of 22 total cycles. Here we report the final analysis on the role of clinical prognostic factors. The study had 80% power with a two-tailed 0.01 α error to detect a 0.60 hazard ratio with a factor expressed in at least 20% of the population. Both progression-free and overall survival were used as endpoints. RESULTS: From October 2012 to November 2014, 398 eligible patients were treated. After a median follow-up of 32.3 months (IQR 24.1-40.4), median progression-free survival was 20.8 months (95% CI 19.1 to 22.0) and median overall survival was 41.1 months (95% CI 39.1 to 43.5). Clinical factors significantly predicting progression-free and overall survival were performance status, stage, and residual disease after primary surgery. Neither baseline blood pressure/antihypertensive treatment nor the development of hypertension during bevacizumab were prognostic. There were two deaths possibly related to treatment, but no unexpected safety signal was reported. CONCLUSIONS: Efficacy and safety of bevacizumab in combination with carboplatin and paclitaxel and as maintenance were comparable to previous data. Hypertension, either at baseline or developed during treatment, was not prognostic. Performance status, stage, and residual disease after primary surgery remain the most important clinical prognostic factors. TRIAL REGISTRATION NUMBER: EudraCT 2012-003043-29; NCT01706120.

2.
Gynecol Oncol ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33934848

RESUMO

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease.

3.
J Pers Med ; 11(4)2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33801668

RESUMO

Clinical trials in cancer treatment are imperative in enhancing patients' survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients' accrual in clinical trials. We developed a specific platform, called "Digital Research Assistant" (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients' records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients' records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient's data and clinical trial's inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis.

4.
J Pers Med ; 11(3)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803592

RESUMO

The advent of Precision Medicine has globally revolutionized the approach of translational research suggesting a patient-centric vision with therapeutic choices driven by the identification of specific predictive biomarkers of response to avoid ineffective therapies and reduce adverse effects. The spread of "multi-omics" analysis and the use of sensors, together with the ability to acquire clinical, behavioral, and environmental information on a large scale, will allow the digitization of the state of health or disease of each person, and the creation of a global health management system capable of generating real-time knowledge and new opportunities for prevention and therapy in the individual person (high-definition medicine). Real world data-based translational applications represent a promising alternative to the traditional evidence-based medicine (EBM) approaches that are based on the use of randomized clinical trials to test the selected hypothesis. Multi-modality data integration is necessary for example in precision oncology where an Avatar interface allows several simulations in order to define the best therapeutic scheme for each cancer patient.

5.
Cancers (Basel) ; 13(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33803954

RESUMO

Ovarian cancer treatment strategy is mainly based on three pillars: cytoreductive surgery, platinum-based chemotherapy, and targeted therapies. The latter in the last decade has provided a remarkable improvement in progression free patients and, hopefully, in overall survival. In particular, poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors exploit BRCA 1/2 mutations and DNA damage response deficiencies, which are believed to concern up to 50% of high grade epithelial ovarian cancer cases. While these agents have an established role in ovarian cancer treatment strategy in BRCA mutated and homologous recombination deficient patients, an appropriate predictive molecular test to select patients is lacking in clinical practice. At the same time, the impressive results of immunotherapy in other malignancies, have opened the space for the introduction of immune-stimulatory drugs in ovarian cancer. Despite immune checkpoint inhibitors as a monotherapy bringing only modest efficacy when assessed in pretreated ovarian cancer patients, the combination with chemotherapy, anti-angiogenetics, PARP inhibitors, and radiotherapy is believed to warrant further investigation. We reviewed literature evidence on PARP inhibitors and immunotherapy in ovarian cancer treatment.

6.
Diagnostics (Basel) ; 11(4)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807494

RESUMO

The aim of this study was to create a radiomics model for Locally Advanced Cervical Cancer (LACC) patients to predict pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) analysing T2-weighted 1.5 T magnetic resonance imaging (MRI) acquired before treatment start. Patients with LACC and an International Federation of Gynecology and Obstetrics stage from IB2 to IVA at diagnosis were retrospectively enrolled for this study. All patients underwent NACRT, followed by radical surgery; pCR-assessed on surgical specimen-was defined as absence of any residual tumour. Finally, 1889 features were extracted from MR images; features showing statistical significance in predicting pCR at the univariate analysis were selected following an iterative method, which was ad-hoc developed for this study. Based on this method, 15 different classifiers were trained considering the most significant features selected. Model selection was carried out using the area under the receiver operating characteristic curve (AUC) as target metrics. One hundred eighty-three patients from two institutions were analysed. The model, showing the highest performance with an AUC of 0.80, was the random forest method initialised with default parameters. Radiomics appeared to be a reliable tool in pCR prediction for LACC patients undergoing NACRT, supporting the identification of patient risk groups, which paves treatment pathways tailored according to the predicted outcome.

7.
J Exp Clin Cancer Res ; 40(1): 116, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789687

RESUMO

BACKGROUND: High grade serous ovarian cancer (HGSOC) is among the deadliest human cancers and its prognosis remains extremely poor. Tumor heterogeneity and rapid acquisition of resistance to conventional chemotherapeutic approaches strongly contribute to poor outcome of patients. The clinical landscape of HGSOC has been radically transformed since the advent of targeted therapies in the last decade. Nevertheless, the lack of predictive biomarkers informing on the differential clinical benefit in select subgroups, and allowing patient-centric approaches, currently limits the efficacy of these novel therapies. Thus, rational selection of the best possible treatment for each patient represents a clinical priority in order to improve outcome, while limiting undesirable effects. MAIN BODY: In this review, we describe the state of the art and the unmet needs in HGSOC management, illustrate the treatment options that are available and the biomarkers that are currently employed to orient clinical decisions. We also describe the ongoing clinical trials that are testing new therapeutic approaches for HGSOC. Next, we introduce the organoid technology as a promising, expanding strategy to study cancer and to develop personalized therapeutic approaches. In particular, we discuss recent studies that have characterized the translational potential of Patient's Derived Organoids (PDOs) to inform on drug sensitivity of HGSOC patients. CONCLUSIONS: PDOs can predict the response of patients to treatments and may therefore guide therapeutic decisions. Although preliminary results appear encouraging, organoids still need to be generated and expanded efficiently to enable drug screening in a clinically meaningful time window. A new generation of clinical trials based on the organoid technology should guarantee tailored approaches to ovarian cancer management, as it is now clear that the one-size-fits-all approach cannot lead to efficient and meaningful therapeutic advancements.

8.
Eur J Cancer ; 149: 134-152, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33862496

RESUMO

BACKGROUND: Poly (ADP-ribose) polymerase-inhibitors (PARPis) showed antitumour activity in BRCA1/2-mutated cancers, with more heterogeneous outcomes in tumours harbouring mutations that impair other genes involved in the DNA homologous recombination repair (HRR) or wild-type (wt). METHODS: We conducted a systematic review and meta-analysis to better assess the role of PARPis in the treatment of metastatic solid tumours, with and without BRCA1/2 mutations. The primary end-point was progression-free survival (PFS). The secondary end-points were overall response rate (ORR) and overall survival (OS). A random-effects model was applied. RESULTS: Twenty-nine studies (8,839 patients) were included. PFS was significantly improved (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.51-0.68, p < 0.001), without being affected by BRCA mutational status (p = 0.65). Significant subgroup differences were observed with regard to the tumour site (p = 0.001), line of therapy (p = 0.002), control arm (p < 0.001), type of PARPi (p < 0.001) and trials' phase (p = 0.006). PARPis were associated with ORR (relative risk: 1.35, 95% CI: 1.16-1.56, p < 0.001), with significant subgroup differences observed with regard to treatment line (p = 0.03), control arm (p = 0.04) and PARPis (p < 0.001) and independent of mutational status (p = 0.44), tumour site (p = 0.86) and trials' phase (p = 0.09). OS was significantly improved by PARPis (HR: 0.86, 95% CI: 0.80-0.92, p < 0.001), regardless of mutational status (p = 0.57), tumour site (p = 0.82), treatment line (p = 0.22), control arm (p = 0.21), PARPis (p = 0.30) and trials' phase (p = 0.26). Finally, an exploratory subgroup analysis showed a significant PFS improvement (HR: 0.51, 95% CI: 0.43-0.60, p < 0.001) with PARPis in BRCA-wt/HRR-deficient tumours. CONCLUSION: Our results confirm the efficacy of already approved PARPi-based treatments in BRCA1/2-mutant solid tumours, support their role also in BRCA-independent HRR-deficient tumours and suggest a potentially broader efficacy in some wt tumours, perhaps with appropriate therapeutic partners. Prospective studies are warranted.

9.
J Clin Oncol ; : JCO2100306, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33891472

RESUMO

PURPOSE: To evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC). METHODS: This multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery. Patients were stratified by FIGO stage, Eastern Cooperative Oncology Group performance status, tumor immune cell PD-L1 staining, and treatment strategy and randomly assigned 1:1 to receive 3-weekly cycles of atezolizumab 1,200 mg or placebo (day 1, cycles 1-22), with paclitaxel plus carboplatin (day 1, cycles 1-6) plus bevacizumab 15 mg/kg (day 1, cycles 2-22), omitting perioperative bevacizumab in neoadjuvant patients. The co-primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat and PD-L1-positive populations. RESULTS: Between March 8, 2017, and March 26, 2019, 1,301 patients were enrolled. The median progression-free survival was 19.5 versus 18.4 months with atezolizumab versus placebo, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.07; stratified log-rank P = .28), in the intention-to-treat population and 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI, 0.65 to 0.99; P = .038), in the PD-L1-positive population. The interim (immature) overall survival results showed no significant benefit from atezolizumab. The most common grade 3 or 4 adverse events were neutropenia (21% with atezolizumab v 21% with placebo), hypertension (18% v 20%, respectively), and anemia (12% v 12%). CONCLUSION: Current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.

10.
Eur J Surg Oncol ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33895023

RESUMO

INTRODUCTION: The primary aim of the present study was to assess the incidence of ovarian metastasis/recurrence and the survival of patients undergoing radical hysterectomy with ovarian conservation (CONSERV) versus oophorectomy (OOPHOR). Secondary aim was to assess the incidence and the characteristics of menopausal symptoms in both groups. MATERIALS AND METHODS: Retrospective, multi-center, observational cohort study including patients <50 years with clinical FIGO 2009 stage IA1-IB1/IIA1 cervical carcinoma, treated by primary surgical treatment between 02/2007 and 07/2019. One-to-one case-control matching was used to adjust the baseline prognostic characteristics in survival analysis. RESULTS: 419 patients were included. 264 in the OOPHOR (63.0%) and 155 (37.0%) in the CONSERV group. Ovarian transposition was performed in 28/155 (18.1%) patients. 1/264 (0.4%) patient had ovarian metastasis from endocervical adenocarcinoma. After propensity-matching, 310 patients were included in the survival analysis (155 per group). 5-year disease-free survival of patients undergoing CONSERV versus OOPHOR was 90.6% versus 82.2%, respectively (p = 0.028); 5-year overall survival was 94.3% versus 90.8%, respectively (p = 0.157). Two patients (1.3%) developed recurrence on the conserved ovary. CONSERV represented an independent protective factor of recurrence (HR:0.361, 95%CI 0.169-0.769; p = 0.008). 28 (20.6%) in the CONSERV group versus 116 (60.4%) in the OOPHOR group complained of menopausal symptoms during follow up (p < 0.001). HRT was prescribed to 12.0% of patients (median HRT time was 20 months). CONCLUSION: CONSERV was associated with reduced risk of recurrence and menopausal symptoms in early-stage cervical cancer. As the risk of ovarian metastasis and ovarian recurrence is relatively low, CONSERV in pre-menopausal women has to be considered.

11.
Br J Cancer ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854209

RESUMO

BACKGROUND: The aim of the present study was to assess the prognostic value of tumour-free distance (TFD), defined as the minimum distance of uninvolved stroma between the tumour and peri-cervical stromal ring, in early-stage cervical cancer. METHODS: Patients with pathologic FIGO 2009 stage IA1-IIA2 cervical cancer, treated by primary radical surgical treatment between 01/2000 and 11/2019, were retrospectively included. Adjuvant treatment was administered according to the presence of previously established pathologic risk factors. TFD was measured histologically on the hysterectomy specimen. Pre-operative TFD measured at MRI-scan from a cohort of patients was reviewed and compared with pathology TFD. RESULTS: 395 patients were included in the study. 93 (23.5%) patients had TFD ≤ 3.0 mm and 302 (76.5%) had TFD > 3.0 mm. TFD ≤ 3.0 mm together with lymph vascular space involvement represented the strongest predictor for lymph node metastasis at multivariate analysis. TFD ≤ 3.0 mm was associated with worse 5-year disease-free survival (DFS) and overall survival (OS), compared with TFD > 3.0 mm (p = 0.022 and p = 0.008, respectively). DFS difference was more evident in the subgroup of patients with low-risk factors who did not receive adjuvant treatment (p = 0.002). Cohen's kappa demonstrated an agreement between TFD measured at pre-operative MRI-scan and histology of 0.654. CONCLUSIONS: Pathologic TFD ≤ 3.0 mm represents a poor prognostic factor significantly associated with lymph node metastasis and it may be considered a novel marker to select candidates for adjuvant treatment. The possibility to obtain this parameter by radiological imaging makes it a potential easy-measurable pre-operative marker to predict the presence of high-risk pathologic factors in early-stage cervical cancer.

12.
Int J Gynecol Cancer ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883231

RESUMO

BACKGROUND: During the COVID-19 pandemic, cancer care had to be reorganized; national and international recommendations were published to manage anticancer treatments safely and to reduce the risk of SARS-CoV-2 infection for patients and health workers. OBJECTIVE: To evaluate whether the adoption of recommendations for the management of patients with gynaecologic cancer receiving treatment during the pandemic resulted in containment of infections and continuing oncologic care. METHODS: Based on the published recommendations, and according to the local Health Direction guidelines, we developed and drafted a security protocol to modify access of patients with gynaecologic cancer to the "Fondazione Policlinico Agostino Gemelli-IRCCS, Rome" between February 1 and April 30, 2020 and compared results with the corresponding 3 months of 2019. RESULTS: Between February and April 2019, we registered 3254 admissions, including 2253 patients receiving intravenous chemotherapies, 298 receiving oral therapies, and 703 having hospital visits. Between February and April 2020, we registered 3213 admissions, including 2221 patients receiving intravenous chemotherapies, 401 receiving oral therapies, and 591 having hospital visits. Oral treatments and general visits were different in the two time periods (p<0.001). Despite the elevated patient flow, only one patient (0.1%) tested positive for COVID-19 and there were no cases among healthcare staff. CONCLUSIONS: Based on the adopted security protocol we provided continuity of care for all patients and limited the spread of the COVID-19 infection.

13.
Gynecol Oncol ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33812697

RESUMO

OBJECTIVE: Deficient expression of mismatch repair proteins (MMR) has been suggested to be a predictor of resistance of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EEC) to conservative treatment. AIMS: To assess the predictive value of MMR immunohistochemistry in patients conservatively treated for AEH and EEC, and to calculate its predictive accuracy. MATERIALS AND METHODS: All patients with AEH or EEC conservatively treated with hysteroscopic resection plus progestins in two referral centers from January 2004 to July 2019 were retrospectively assessed. Immunohistochemistry for MMR was ad hoc performed. Study outcomes were: (i) the association of a deficient immunohistochemical expression of MMR with resistance and recurrence of AEH and EEC after conservative treatment, and (ii) the accuracy of MMR immunohistochemistry in predicting the outcome of conservative treatment. Relative risk (RR) for the associations, and sensitivity, specificity and area under the curve (AUC) on receiver operating characteristic curve for the predictive accuracy were calculated. RESULTS: Sixty-nine women, (47 AEH and 22 EEC) were included; deficient MMR expression was observed in 8.7% of cases. Resistance to conservative treatment was more common in MMR-deficient than MMR-proficient cases (33.3% vs 15.9%; RR = 2.1), but with no statistical significance (p = 0.2508). On the other hand, recurrence was significantly more common in MMR-deficient than MMR-proficient cases (100% vs 26.4%; RR = 3.8; p < 0.0001). In predicting recurrence, a deficient immunohistochemical expression of MMR showed sensitivity = 22.2%, specificity = 100%, and AUC = 0.61. CONCLUSION: Deficient MMR immunohistochemical expression does not imply resistance of AEH/EEC to conservative treatment. On the other hand, MMR-deficiency appears as a highly specific predictor of recurrence of AEH/EEC after initial regression.

14.
J Gynecol Oncol ; 32(3): e45, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33825360

RESUMO

OBJECTIVE: The aim of this study is to analyze and draw the potential differences between the robotic-assisted surgery (RS) and the laparoscopy (LPS) in endometrial cancer staging. METHODS: In this single-institution retrospective study we enrolled 1,221 consecutive clinical stage I-III endometrial cancer patients undergone minimally invasive surgical staging. We compared patients treated by LPS and by RS, on the basis of perioperative and oncological outcomes (disease-free survival [DFS] and overall survival [OS]). A sub-analysis of the high-risk endometrial cancer population was performed in the 2 cohorts. RESULTS: The 2 cohorts (766 treated by LPS and 455 by RS) were homogeneous in terms of perioperative and pathological data. We recorded differences in number of relapse/progression (11.7% in LPS vs. 7% in RS, p=0.008) and in number of deaths (9.8% in LPS vs. 4.8% in RS, p=0.002). Whereas, univariate and multivariate analyses according to DFS and OS confirmed that the surgical approach did not influence the DFS or the OS. In the multivariable analysis the association of the age and grading was significant for DFS and OS. In the sub-analysis of the 426 high risk EC patients (280 in LPS and 146 in RS) the univariate and the multivariate confirmed the influence of the age in DFS and OS, independently of the minimally invasive approach. CONCLUSIONS: In our large retrospective analysis, we confirmed that the RS and LPS have similar efficacy and safety for endometrial cancer staging also for the high-risk endometrial cancer patients.

15.
Genes (Basel) ; 12(4)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920939

RESUMO

Intracranial hemorrhage (ICH) is reported in premature infants and rarely, in prenatal life. Fetal ICH can be accurately identified in utero and categorized by antenatal sonography and/or MRI. Infectious disease, maternal drug exposure, alloimmune thrombocytopenia, maternal trauma, coagulation disorders and twin-to-twin transfusion syndrome can cause fetal ICH. However, in many cases, the cause is not identified and a genetic disorder should be taken into consideration. We conducted a review of the literature to investigate what we know about genetic origins of fetal ICH. We conducted targeted research on the databases PubMed and EMBASE, ranging from 1980 to 2020. We found 311 studies and 290 articles were excluded because they did not meet the inclusion criteria, and finally, 21 articles were considered relevant for this review. Hemostatic, protrombotic, collagen and X-linked GATA 1 genes were reported in the literature as causes of fetal ICH. In cases of ICH classified as idiopathic, possible underlying genetic causes should be accounted for and investigated. The identification of ICH genetic causes can guide the counselling process with respect to the recurrence risk, in addition to producing relevant clinical data to the neonatologist for the optimal management and prompt treatment of the newborn.

17.
Lancet Oncol ; 22(5): 632-642, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33862001

RESUMO

BACKGROUND: In the phase 3 SOLO1 trial, maintenance olaparib provided a significant progression-free survival benefit versus placebo in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation in response after platinum-based chemotherapy. We analysed health-related quality of life (HRQOL) and patient-centred outcomes in SOLO1, and the effect of radiological disease progression on health status. METHODS: SOLO1 is a randomised, double-blind, international trial done in 118 centres and 15 countries. Eligible patients were aged 18 years or older; had an Eastern Cooperative Oncology Group performance status score of 0-1; had newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with a BRCA mutation; and were in clinical complete or partial response to platinum-based chemotherapy. Patients were randomly assigned (2:1) to either 300 mg olaparib tablets or placebo twice per day using an interactive voice and web response system and were treated for up to 2 years. Treatment assignment was masked for patients and for clinicians giving the interventions, and those collecting and analysing the data. Randomisation was stratified by response to platinum-based chemotherapy (clinical complete or partial response). HRQOL was a secondary endpoint and the prespecified primary HRQOL endpoint was the change from baseline in the Functional Assessment of Cancer Therapy-Ovarian Cancer Trial Outcome Index (TOI) score for the first 24 months. TOI scores range from 0 to 100 (higher scores indicated better HRQOL), with a clinically meaningful difference defined as a difference of at least 10 points. Prespecified exploratory endpoints were quality-adjusted progression-free survival and time without significant symptoms of toxicity (TWiST). HRQOL endpoints were analysed in all randomly assigned patients. The trial is ongoing but closed to new participants. This trial is registered with ClinicalTrials.gov, NCT01844986. FINDINGS: Between Sept 3, 2013, and March 6, 2015, 1084 patients were enrolled. 693 patients were ineligible, leaving 391 eligible patients who were randomly assigned to olaparib (n=260) or placebo (n=131; one placebo patient withdrew before receiving any study treatment), with a median duration of follow-up of 40·7 months (IQR 34·9-42·9) for olaparib and 41·2 months (32·2-41·6) for placebo. There was no clinically meaningful change in TOI score at 24 months within or between the olaparib and placebo groups (adjusted mean change in score from baseline over 24 months was 0·30 points [95% CI -0·72 to 1·32] in the olaparib group vs 3·30 points [1·84 to 4·76] in the placebo group; between-group difference of -3·00, 95% CI -4·78 to -1·22; p=0·0010). Mean quality-adjusted progression-free survival (olaparib 29·75 months [95% CI 28·20-31·63] vs placebo 17·58 [15·05-20·18]; difference 12·17 months [95% CI 9·07-15·11], p<0·0001) and the mean duration of TWiST (olaparib 33·15 months [95% CI 30·82-35·49] vs placebo 20·24 months [17·36-23·11]; difference 12·92 months [95% CI 9·30-16·54]; p<0·0001) were significantly longer with olaparib than with placebo. INTERPRETATION: The substantial progression-free survival benefit provided by maintenance olaparib in the newly diagnosed setting was achieved with no detrimental effect on patients' HRQOL and was supported by clinically meaningful quality-adjusted progression-free survival and TWiST benefits with maintenance olaparib versus placebo. FUNDING: AstraZeneca and Merck Sharp & Dohme.

18.
Eur J Obstet Gynecol Reprod Biol ; 260: 212-217, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33862432

RESUMO

OBJECTIVE: Laparoscopic high uterosacral ligament suspension (l-HUSLS) is a laparoscopic-transposed vaginal technique for the treatment of pelvic organ prolapse. Nowadays data regarding quality of life and sexual functions in patients who underwent l-HUSLS for pelvic organ prolapse are few and generic with most of the study investigating the anatomical outcome. For these reasons, the aim of our study is to evaluate these subjective outcomes in women undergoing this surgical procedure with the support of validated questionnaires. STUDY DESIGN: This is a retrospective study with the primary aim of analysing the quality of life, sexual function, patient satisfaction rates and anatomical outcome among patients who underwent l-HUSLS in our institution. The SPSS Version 26.0 for Windows (Statistical package for the social studies, Chicago, IL, USA) was used for the statistical analysis. RESULTS: A total of 60 patients underwent l-HUSLS between 2016 and 2018. All patients had a high grade of apical prolapse. No intraoperative and major postoperative complications were registered. The median follow-up was 24 months (24-48). PGI-I score was 1-2 in 55 (91.6 %) women. We observed a significant improvement of EQ-5D index and VAS scores from the baseline to the 2 years follow-up: from 0.72 (0.67-1) to 0.91 (0.79-1) and from 50 (30-90) to 70 (50-100) respectively (p = 0.000). All women showed a statistically significant amelioration of FSDS and ICIQ-SF scores. Anatomical success rate after 24 months was 83.7 %. CONCLUSIONS: l-HUSLS appears to be a safe, feasible and effective treatment for advanced pelvic organ prolapse with high rates of patient self-reported cure.

19.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808791

RESUMO

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.


Assuntos
Biomarcadores Tumorais , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , RNA não Traduzido/genética , Transformação Celular Neoplásica/genética , Metilação de DNA , Suscetibilidade a Doenças , Neoplasias do Endométrio/diagnóstico , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico
20.
Artigo em Inglês | MEDLINE | ID: mdl-33794043

RESUMO

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis group (IOTA) and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based consensus statements on the pre-operative diagnosis of ovarian tumours, including imaging techniques, biomarkers and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group consisting of expert practising clinicians and researchers who have demonstrated leadership and expertise in the pre-operative diagnosis of ovarian tumours and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence based, the current literature was reviewed and critically appraised. Preliminary consensus statements were drafted based on a review of the relevant literature. During a conference call, the whole group discussed each preliminary consensus statement and a first round of voting was organised. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. Then the consensus statements were revised accordingly. Another round of voting was organised according to the same rules to allow the whole group to evaluate the revised version of the consensus statements. The group achieved consensus on 18 statements. This article presents these ESGO/ISUOG/IOTA/ESGE consensus statements on the pre-operative diagnosis of ovarian tumours and to the assessment of carcinomatosis, together with a summary of evidence supporting each statement. This article is protected by copyright. All rights reserved.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...