RESUMO
The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.
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Oncologia , Neoplasias Ovarianas , Humanos , Feminino , Sociedades Médicas , Espanha , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Biologia MolecularRESUMO
BACKGROUND: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. PATIENTS AND METHODS: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for â¼60% maturity or 3 years after the primary analysis. RESULTS: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. CONCLUSIONS: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure.
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Antineoplásicos , Neoplasias Ovarianas , Humanos , Feminino , Bevacizumab , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Antineoplásicos/uso terapêutico , Ftalazinas , Inibidores de Poli(ADP-Ribose) Polimerases , Quimioterapia de ManutençãoRESUMO
Human papillomaviruses (HPV)-related gynecological cancers are a major health care issue, and a leading cause of cancer death in low- and middle-income countries (LMIC). In 2020, the World Health Organization launched a program aimed at cervical cancer elimination, by screening and vaccination strategies. Offering the best possible care to women diagnosed with invasive cancer is a complementary objective. Treatment of cervical cancer as per modern standards is complex and multimodal, mainly relying on surgery, external-beam radiotherapy (+/-chemotherapy) and brachytherapy. In parallel with the pivotal role of multidisciplinary discussion, international societies provide guidance to define the most effective and least toxic anti-cancer strategy, homogenize treatment protocols and provide benchmark quality indicators as a basis for accreditation processes. The challenge is to offer the appropriate diagnostic workup and treatment upfront and to avoid non- evidence-based treatment that consumes resources, impairs quality of life (QoL), and compromises oncological outcome. Various strategies may be applied for improving treatment quality: development of surgical mentorship, companion-training programs and international cooperation. The lack of radiotherapy/brachytherapy facilities is a major concern in LMIC. Reinforcing international support in terms of education, training, research and development and technical cooperation with national projects is required to increase access to minimum requirements but also introduce modern techniques, upgrade radiotherapy/brachytherapy services, and expand access to modern systemic treatments. In countries with robust economies, compliance to standards should also be increased. Integrative cancer care and multidisciplinary approaches are needed to tackle the dual challenge of increasing cure rates while minimizing QoL impairment. Appropriate dimensioning of the resources to avoid harmful treatment delays and access to expert referral centers is also a priority.
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Acessibilidade aos Serviços de Saúde , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Braquiterapia , Feminino , Saúde Global , Humanos , Programas de Rastreamento , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/radioterapia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/radioterapia , VacinaçãoRESUMO
BACKGROUND: Several techniques can be proposed as fertility sparing surgery in young patients treated for cervical cancer but uncertaincies remain concerning their outcomes. Analysis of oncological issues is then the first aim of this review in order to evaluate the best strategy. RESULTS: Data were identified from searches of MEDLINE, Current Contents, PubMed and from references in relevant articles from January 1987 to 15th of September 2021. We carry out an updated systematic review involving 5862 patients initially selected for fertility-sparing surgery in 275 series. FINDINGS: In patients having a stage IB1 disease, recurrence rate/RR in patients undergoing simple conisation/trachelectomy, radical trachelectomy/RT by laparoscopico-vaginal approach, laparotomic or laparoscopic approaches are respectively: 4.1%, 4.7%, 2.4% and 5.2%. In patients having a stage IB2 disease, RR after neoadjuvant chemotherapy or RT by laparotomy are respectively 13.2% and 4.8% (pâ¯=â¯.0035). After neoadjuvant treatment a simple cone/trachelectomy was carried out in 91 (30%) patients and a radical one in 210 (70%) cases. But the lowest pregnancy rate is observed in patients undergoing RT by laparotomy (36%). CONCLUSIONS: The choice between these treatments should be based above all, on objective oncological data that strike a balance for each procedure between the best chances for cure and the fertility results. In patients having a stage IB1 disease, oncological results are quite similar according to the procedure used. In patients having a stage IB2 disease, RT by open approach has the lowest RR. Anyway the lowest pregnancy rate is observed in patients undergoing RT by laparotomy.
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Preservação da Fertilidade , Traquelectomia , Neoplasias do Colo do Útero , Feminino , Preservação da Fertilidade/métodos , Humanos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Gravidez , Traquelectomia/métodos , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: Homologous recombination repair deficiency (HRD) is a frequent feature of high-grade serous ovarian, fallopian tube and peritoneal carcinoma (HGSC) and is associated with sensitivity to PARP inhibitor (PARPi) therapy. HRD testing provides an opportunity to optimise PARPi use in HGSC but methodologies are diverse and clinical application remains controversial. MATERIALS AND METHODS: To define best practice for HRD testing in HGSC the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project that incorporated a systematic review approach. The main aims were to (i) define the term 'HRD test'; (ii) provide an overview of the biological rationale and the level of evidence supporting currently available HRD tests; (iii) provide recommendations on the clinical utility of HRD tests in clinical management of HGSC. RESULTS: A broad range of repair genes, genomic scars, mutational signatures and functional assays are associated with a history of HRD. Currently, the clinical validity of HRD tests in ovarian cancer is best assessed, not in terms of biological HRD status per se, but in terms of PARPi benefit. Clinical trials evidence supports the use of BRCA mutation testing and two commercially available assays that also incorporate genomic instability for identifying subgroups of HGSCs that derive different magnitudes of benefit from PARPi therapy, albeit with some variation by clinical scenario. These tests can be used to inform treatment selection and scheduling but their use is limited by a failure to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies. Existing tests lack negative predictive value and inadequately address the complex and dynamic nature of the HRD phenotype. CONCLUSIONS: Currently available HRD tests are useful for predicting likely magnitude of benefit from PARPis but better biomarkers are urgently needed to better identify current homologous recombination proficiency status and stratify HGSC management.
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Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Biomarcadores , Carcinoma Epitelial do Ovário , Feminino , Recombinação Homóloga , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêuticoRESUMO
OBJECTIVE: This study assessed outcomes of inoperable endometrial cancer (IEC) patients treated with definitive external beam radiation therapy (EBRT) followed by a 3D image-guided brachytherapy boost. METHODS: All consecutive patients treated with EBRT followed by 3D image-guided brachytherapy for IEC were retrospectively included. EBRT delivered a dose of 45Gy. Then, patients had an uterovaginal brachytherapy guided by 3D imaging. Clinical target volume (CTVBT) included the whole uterus and the initial disease extent. Gross tumour volume (GTVres) included the residual disease at time of brachytherapy. RESULTS: Twenty-seven patients were identified. Causes of inoperability were comorbidities (37%) or tumour loco regional extent (63%). Including EBRT and brachytherapy, the median D90 (minimal dose delivered to 90% of the volume) was 60.7 GyEQD2 (IQR = 56.4-64.2) for the CTVBT, and was 73.6 GyEQD2 (IQR = 64.1-83.7) for the GTVres. The median overall treatment time was 50 days (IQR = 46-54). The mean follow-up was 36.5 months (SD = 30.2). The cumulative incidence of local, pelvic and distant failures was 19% (n = 5), 7% (n = 2) and 26% (n = 7), respectively. Five-year overall survival was 63% (95% CI = 43-91). Late urinary and gastro intestinal toxicities ≥ grade 2 were reported in four (15%) and two patients (7%) respectively. No vaginal toxicity ≥ grade 2 was reported. CONCLUSIONS: EBRT followed by intracavitary brachytherapy seems to be an effective option for IEC. The implementation of 3D concepts at time of brachytherapy may contribute to high local control probability and low toxicity profile. Large scale retrospective or prospective data are needed to confirm these early data.
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Braquiterapia/métodos , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/radioterapia , Radioterapia Guiada por Imagem/métodos , Idoso , Estudos de Casos e Controles , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imageamento Tridimensional/métodos , Metástase Linfática , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Since dose escalation allowed by image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer (LACC), local relapses have become a rare event. Only scarce data are available on the outcome of patients experiencing a local relapse after IGABT. METHODS: Between 2004 and 2016, all consecutive patients treated at Gustave Roussy Institute for LACC and receiving concomitant chemoradiation and IGABT were analysed. Clinical and treatment-related prognostic factors for survival after local relapse were searched, in order to potentially identify patients requiring salvage treatment. RESULTS: Two hundred and fifty-nine patients were treated during this period. With a median follow-up of 4.1 years, 10.8% (n = 28) had a local relapse. Among these patients, 53.6% had synchronous lymph nodes or distant metastatic relapse and only 13 patients (5% of all patients) had isolated local relapse. After local relapse, median survival was 47 months and three patients were alive at last follow-up. Only three patients with local relapse could receive salvage surgery (10.7%). Metastases occurrence and pelvic wall involvement were the main contraindications (67.9%) for salvage surgery. Among the three patients treated with surgery, two are still alive at last follow-up without significant complication. Improved survival was observed among the two patients who could have surgery (p = .02). Local progression led to serious symptoms in 75% of patients. Only the time interval between brachytherapy and relapse (<1 year) was prognostic for 2-year overall survival (p = .005). CONCLUSION: Salvage surgery is feasible in a very low number of highly selected patients with local relapse following IGABT. Local failure is a major cause of severe local symptoms, confirming that every effort should be done to achieve long-term local control through dose escalation.
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Braquiterapia/métodos , Quimiorradioterapia/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias do Colo do Útero/diagnóstico por imagem , Adulto JovemRESUMO
Background: Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent antimitotic agent, monomethyl auristatin E, which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug conjugate (ADC) to standard-of-care in ovarian cancer (OC) patients. Patients and methods: Platinum-resistant OC patients were randomized to receive LIFA [2.4 mg/kg, intravenously, every 3 weeks (Q3W)] or pegylated liposomal doxorubicin (PLD) (40 mg/m2, intravenously, Q4W). NaPi2b expression and serum CA-125 and HE4 levels were assessed. The primary end point was progression-free survival (PFS) in intent-to-treat (ITT) and NaPi2b-high patients. Results: Ninety-five patients were randomized (47 LIFA; 48 PLD). The stratified PFS hazard ratio was 0.78 [95% confidence interval (95% CI), 0.46-1.31; P = 0.34] with a median PFS of 5.3 versus 3.1 months (LIFA versus PLD arm, respectively) in the ITT population, and 0.71 (95% CI, 0.40-1.26; P = 0.24) with a median PFS of 5.3 months versus 3.4 months (LIFA versus PLD arm, respectively) in NaPi2b-high patients. The objective response rate was 34% (95% CI, 22% to 49%, LIFA) versus 15% (95% CI, 7% to 28%, PLD) in the ITT population (P = 0.03), and 36% (95% CI, 22% to 52%, LIFA) versus 14% (95% CI, 6% to 27%, PLD) in NaPi2b-high patients (P = 0.02). Toxicities included grade ≥3 adverse events (AEs) (46% LIFA; 51% PLD), serious AEs (30% both arms), and AEs leading to discontinuation of drug (9% LIFA; 8% PLD). Five (11%) LIFA versus 2 (4%) PLD patients had grade ≥2 neuropathy. Conclusion: LIFA Q3W was well tolerated and improved objective response rate with a modest, nonstatistically significant improvement of PFS compared with PLD in platinum-resistant OC. While the response rate for the monomethyl auristatin E-containing ADC was promising, response durations were relatively short, thereby highlighting the importance of evaluating both response rates and duration of response when evaluating ADCs in OC. Clinical trials.gov: NCT01991210.
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Antibióticos Antineoplásicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doxorrubicina/análogos & derivados , Imunoconjugados/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Anticorpos Monoclonais Humanizados/química , Biomarcadores/metabolismo , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoconjugados/efeitos adversos , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas/metabolismo , Polietilenoglicóis/uso terapêutico , Análise de SobrevidaRESUMO
This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian cancers (eOC), sex-cord stromal tumours (SCST) and germ cell tumours (GCT)): (i) What are the research and trial issues that are unique to rare ovarian tumours? There is a lack of randomised phase III data defining standards of care which makes it difficult to define control arms, but identifies unmet needs that merit investigation. Internationally agreed upon diagnostic criteria, expert pathological review and translational research are crucial. (ii) What should be investigated in rare eOC, GCT and SCST? Trials dedicated to each rare ovarian tumour should be encouraged. Nonetheless, where the question is relevant, rare eOC can be included in eOC trials but with rigorous stratification. Although there is emerging evidence suggesting that rare eOC have different molecular profiles, trials are needed to define new type-specific standards for each rare eOC (clear cell, low grade serous and mucinous). For GCTs, a priority is reducing toxicities from treatment while maintaining cure rates. Both a robust prognostic scoring system and more effective treatments for de novo poor prognosis and relapsed GCTs are needed. For SCSTs, validated prognostic markers as well as alternatives to the current standard of bleomycin/etoposide/cisplatin (BEP) should be identified. (iii) Are randomised trials feasible? Randomised controlled trials (RCT) should be feasible in any of the rare tumours through international collaboration. Ongoing trials have already demonstrated the feasibility of RCT in rare eOC and SCST. Mucinous OC may be considered for inclusion, stratified, into RCTs of non-gynaecological mucinous tumours, while RCTs in high risk or relapsed GCT may be carried out as a subset of male and/or paediatric germ cell studies.
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Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Projetos de Pesquisa , Feminino , HumanosRESUMO
Background: Lymphocytic infiltration at diagnosis is prognostic in EOC, however, the impact of NACT on tumour infiltrating lymphocytes (TILs) or PD-L1 expression remains poorly described. Patients and methods: Patients with EOC and sequential samples (pre-NACT, post-NACT or relapse) were retrospectively identified. TILs were evaluated on whole sections; stromal TILs (sTILs) scored as percentage of stromal area with high sTILs defined as ≥50%; intra-epithelial TILs (ieTILs) scored semi-quantitatively (0-3) with high ieTILs ≥2. A smaller number were available for PD-L1 evaluation, cut-off for positivity was ≥5% staining. Results: sTILs were detected in all tumours at diagnosis (range 2-90%, median 20%), with 22% (25/113) showing high sTILs. Among evaluable paired pre/post-NACT samples (N = 83), an overall increase in median sTILs from 20% to 30% was seen following NACT (P = 0.0005); individually the impact of NACT varied with sTILs increasing in 51% (42/83), decreasing in 25%, and stable in 24%. Post-NACT sTILs were predictive of platinum-free interval (PFI), patients with PFI ≥6 months had significantly higher post-NACT sTILs (sTILs 28% versus 18% for PFI <6 months, P = 0.026); pre-NACT sTILS were not predictive. At diagnosis, 23% showed high ieTILs, and following NACT 33% showed increasing ieTILs. Proportion of tumours with PD-L1-positive immune cells was 30% (15/50) pre-NACT and 53% (27/51) post-NACT (P = 0.026). Among paired tumours, 63% of PD-L1-negative tumours became positive after NACT, furthermore cisplatin induced PD-L1 expression in PD-L1-negative EOC cell lines. On multivariate analysis, high sTILs both pre- and post-NACT were independent prognostic factors for progression-free survival (PFS) (HR 0.49, P = 0.02 and HR 0.60, P = 0.05, respectively). No prognostic impact of ieTILs or PD-L1 expression was detected. Conclusions: In EOC, sTILs levels are prognostic at diagnosis and remain prognostic after NACT. TILs and PD-L1 expression increase following NACT. Evaluation of immune parameters in the post-NACT tumour may help select patients for immunotherapy trials.
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Antígeno B7-H1/genética , Quimioterapia Adjuvante , Recidiva Local de Neoplasia/genética , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , PrognósticoRESUMO
BACKGROUND: The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway. METHODS: We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data were used to analyse TP63 mutations and copy-number alterations using cBioPortal. TP53 was silenced in two endometrial cancer cell lines to study its effect on p21 and p63. RESULTS: About half of the tumours showed a p53 mutant phenotype and there was a strong negative correlation with p21 expression. Being marker positive for pp63 or mdm2 was associated with a significantly increased likelihood of dying, [hazard ratios 5.93 (95% CI 2.37-7.27) and 7.48 (95% CI 3.04-9.39), respectively]. These findings were seen in both p53 wildtype and p53 mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63 alteration. Upon silencing of TP53, p21 expression was decreased in one cell line, but no effects on p63 were observed. CONCLUSION: Markers of the p53 pathway improve stratification of endometrial cancers and provide novel insights into the role of this pathway in the disease.
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Adenocarcinoma de Células Claras/metabolismo , Carcinoma Endometrioide/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias do Endométrio/metabolismo , Neoplasias Císticas, Mucinosas e Serosas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Linhagem Celular Tumoral , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Inativação Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Invasividade Neoplásica , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/mortalidade , Neoplasias Císticas, Mucinosas e Serosas/patologia , Fosfoproteínas , Prognóstico , Modelos de Riscos Proporcionais , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Adulto JovemRESUMO
Since the last two decades, the feasibility of fertility-sparing surgery (FSS) in early-stage epithelial ovarian cancer (EOC) has been explored by several teams and is reconsidered in this systematic review undertaken using the PRISMA guidelines. Borderline ovarian tumours and non-EOCs were excluded. This review comprises 1150 patients and 139 relapsing patients reported by 21 teams. This conservative treatment can be safely carried out for stage IA and IC grade 1 and 2 disease and stage IC1 according to the new FIGO staging system. Nevertheless, the number of patients reported with grade 2 disease is too small to definitively confirm whether FSS is safe in this subgroup. For patients with 'less favourable' prognostic factors (grade 3 or stage IC3 disease), the safety of FSS could not be confirmed, but patients should be informed that radical treatment probably may not necessarily improve their oncological outcome, because the poorest survival observed could be related to the natural history of the disease itself and not specifically to the use of conservative therapy. FSS could probably be considered in stage I clear-cell tumours but should remain contraindicated for stage II/III disease (whatever the histologic subtype). As the disease stage and the histologic data (tumour type and grade) are crucial to patient selection for this treatment, this implies careful and mandatory complete surgical staging surgery in this context and a pathological analysis (or review) of the tumour by an expert pathologist.
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Preservação da Fertilidade , Fertilidade/fisiologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Carcinoma Epitelial do Ovário , Feminino , Humanos , Oncologia , Recidiva Local de Neoplasia/fisiopatologia , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/fisiopatologia , Neoplasias Ovarianas/fisiopatologiaRESUMO
Given the increasing budget impact of Hepatitis C virus (HCV) treatment, robust real-world cost data are essential for healthcare decision-makers to evaluate and understand the costs and benefits of these treatments. To determine the direct cost of treating HCV infection in a hospital-based ambulatory care setting in Ireland based on available data from the Irish national hepatitis C treatment registry. A microcosting study of the direct costs of patients with hepatitis C treated with interferon-based and interferon-free direct-acting antiviral regimens was conducted. Attendance at the outpatient clinic for clinical assessment, the quantity of resources used per patient, the medication prescribed and the identification and timing of staff involvement was measured and combined to establish a mean cost of treatment per patient and a cost per sustained virological response (SVR). One hundred and sixty-eight patients were included in the analysis; 119 treated with interferon-based direct-acting antiviral regimens and 47 treated with interferon-free regimens. The mean costs of treatment with the interferon-based regimens per patient were 38 286 (95% CI 35 305-41 061). The cost per SVR was 62 457. The mean cost of treatment with interferon-free regimens per patient was 55 734 (95% CI 50 906-60 880). The cost per SVR was 81 873. Real-world cost data provide valuable information to enhance reimbursement decisions. While the direct costs associated with hepatitis C treatment in Ireland are substantial, it is reasonable to expect that the mean cost of treatment and the cost per SVR will reduce as patients with less advanced disease are treated with interferon-free therapies.
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Antivirais/economia , Antivirais/uso terapêutico , Custos de Cuidados de Saúde , Hepatite C Crônica/tratamento farmacológico , Inibidores de Proteases/economia , Inibidores de Proteases/uso terapêutico , Adolescente , Adulto , Idoso , Assistência Ambulatorial , Feminino , Humanos , Interferon-alfa/economia , Interferon-alfa/uso terapêutico , Irlanda , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Adjuvant therapy increases disease-free survival in endometrial cancer (EC), but has no impact on overall survival and negatively influences the quality of life. We investigated the discriminatory power of classical and immunological predictors of recurrence in a cohort of EC patients and confirmed the findings in an independent validation cohort. METHODS: We reanalysed the data from 355 EC patients and tested our findings in an independent validation cohort of 72 patients with EC. Predictors were selected and Harrell's C-index for concordance was used to determine discriminatory power for disease-free survival in the total group and stratified for histological subtype. RESULTS: Predictors for recurrence were FIGO stage, lymphovascular space invasion and numbers of cytotoxic and memory T-cells. For high risk cancer, cytotoxic or memory T-cells predicted recurrence as well as a combination of FIGO stage and lymphovascular space invasion (C-index 0.67 and 0.71 vs 0.70). Recurrence was best predicted when FIGO stage, lymphovascular space invasion and numbers of cytotoxic cells were used in combination (C-index 0.82). Findings were confirmed in the validation cohort. CONCLUSIONS: In high-risk EC, clinicopathological or immunological variables can predict regional or distant recurrence with equal accuracy, but the use of these variables in combination is more powerful.
Assuntos
Neoplasias do Endométrio/patologia , Recidiva Local de Neoplasia/prevenção & controle , Idoso , Intervalo Livre de Doença , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Fatores de Risco , Linfócitos T Citotóxicos/imunologia , Resultado do TratamentoRESUMO
One of the worst HIV/AIDS epidemics in the world is occurring in South Africa, where heterosexual exposure is the main mode of HIV transmission. Young people 15-24 years of age, particularly women, account for a large share of new infections. Accordingly, there is an urgent need for behavior-change interventions to reduce the incidence of HIV among adolescents in South Africa. However, there are few such interventions with proven efficacy for South African adolescents, especially young adolescents. A recent cluster-randomized controlled trial of the 'Let Us Protect Our Future!' HIV/STD risk-reduction intervention for Grade 6 South African adolescents (mean age = 12.4 years) found significant decreases in self-reported sexual risk behaviors compared with a control intervention. This article describes the intervention, the use of the social cognitive theory and the reasoned action approach to develop the intervention, how formative research informed its development and the acceptability of the intervention. Challenges in designing and implementing HIV/STD risk-reduction interventions for young adolescents in sub-Saharan Africa are discussed.
Assuntos
Competência Cultural , Assunção de Riscos , Educação Sexual/organização & administração , Infecções Sexualmente Transmissíveis/prevenção & controle , Adolescente , Comportamento do Adolescente , Criança , Feminino , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Sexo Seguro , África do Sul/epidemiologiaRESUMO
Health misinformation is pervasive on the internet and social media, and can have wide-ranging and devastating repercussions. Burn injuries are highly prevalent, especially in resource-poor countries with less rigorous health and safety regulations and reduced access to quality healthcare, and especially among the pediatric population who rely on caregivers to tend to their injuries. Correct first aid is crucial to improving burn outcomes and avoiding further complications. The aim of this study was to qualitatively assess the content of misinformation related to burns online. A literature search was conducted on PubMed using search terms 'burns' OR 'burn injury' OR 'burns trauma' OR 'major burns' AND 'first aid' AND 'conspiracy' OR 'disinformation' OR 'misinformation' OR 'fake news'. Combinations of these terms were searched via Google, YouTube, Facebook, Instagram, TikTok and PubMed. Key areas of misinformation included unfounded use of 'natural' remedies, injudicious use of antibiotics, omission of key steps of first aid, and errors in specific details of first aid. Clinicians should be aware of misinformation available online related to first aid for burns, be aware that patients presenting with burns may have caused further injury with insufficient first aid or inappropriate home remedies, and lead public health campaigns to educate on the initial emergency management of burns.
RESUMO
INTRODUCTION: Dementia is a syndrome associated with a decline in brain function, impacting how we speak, think, feel, and behave. Misunderstanding of dementia and how it affects patients and their carers is common. There is limited research on how radiographers provide adequate care to those with dementia. Radiographers with knowledge and positive attitudes can reduce stigma and fear, improving the quality of care. This study aimed to assess radiographers' knowledge and attitudes towards dementia. METHODS: A cohort of registered radiographers in Ireland participated in an online survey. Two pre-existing validated questionnaires: The Alzheimer's Disease Knowledge Scale (ADKS) and the Dementia Attitudes Scale (DAS), assessed radiographers' knowledge and attitudes towards dementia and people with dementia. Scores were compared across variables such as gender, age, grade, qualification, work setting, and the number of years qualified. RESULTS: A total of 123 radiographers responded. Knowledge scores did not significantly differ across demographic groups (p > 0.05). Total knowledge scores ranged from 60% to 100%. Total attitude scores ranged from 50% to 100%. Participants with a BSc, MSc, and other post-graduate degrees scored higher on the attitude scale than those with a diploma qualification (p = 0.027). Those with less than 20 years' experience scored higher than those with more. Knowledge had little correlation with attitude (r = 0.0522; p = 0.5667). CONCLUSION: Findings indicate variations in attitudes linked to age and experience, and some misconceptions can be observed across varying groups. Interventions to improve attitudes and raise awareness are needed. IMPLICATIONS FOR PRACTICE: There is a need for further research and education on dementia care in the imaging department. We have identified areas requiring further education.
Assuntos
Pessoal Técnico de Saúde , Demência , Humanos , Atitude do Pessoal de Saúde , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
OBJECTIVES: The strategy of fertility preservation (FP) in cervical cancer has been challenged for several years and a therapeutic de-escalation seems to be necessary. In this context, we evaluated the oncological, fertility and obstetric outcomes of surgical techniques performed in our centre for FP. METHODS: This retrospective uni centric trial included 75 patients, managed at the Gustave Roussy Institute between 1995 and 2020, for cervical cancer (stage IB1 FIGO 2018) and having conducted a fertility preservation project after a complete pre-therapy work-up. The objective of this study was to understand our results on fertility and obstetrical outcomes and to correlate them with oncological data and finally to evaluate the evolution of our surgical practices. RESULTS: 54 patients benefited from an extended trachelectomy and no lymph node involvement was found. 1 patient received a complementary treatment postoperatively which did not allow to preserve her fertility. The recurrence rate was 4.8% (4/75) with one death described. 31 pregnancies were obtained, representing a pregnancy rate of 50%. 74% of pregnancies were obtained spontaneously and 60% of pregnancies were carried to term. CONCLUSION: Our results are similar to those in the literature. Despite a fertility preservation project, only half of the patients were able to achieve a pregnancy.