An international joint statement about the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer was published in 2016, warning about the uncritical use of HIPEC outside controlled studies. This statement has now been updated after the most recent literature was reviewed by the participating study groups and societies. HIPEC became a treatment option in patients with advanced colon cancer after positive results of a randomized trial comparing surgery and HIPEC versus palliative treatment alone. Although this trial did not compare the added value of HIPEC to surgery alone, HIPEC for the treatment of peritoneal metastases was in the subsequent years generalized to many other cancer types associated with peritoneal carcinomatosis including epithelial ovarian cancer (EOC). In the meantime, new evidence from prospective randomized trials specifically for EOC-patients emerged, with however contradicting results and several quality aspects that made the interpretation of their findings critical. Moreover, three additional trials in colorectal cancer failed to confirm the previously presumed survival benefit through the implementation of HIPEC in peritoneally disseminated colorectal cancers. Based on a still unclear and inconsistent landscape, the authors conclude that HIPEC should remain within the remit of clinical trials for EOC-patients. Available evidence is not yet sufficient to justify its broad endorsement into the routine clinical practice.
- MeSH
- epiteliální ovariální karcinom patologie MeSH
- hypertermická intraperitoneální peroperační chemoterapie MeSH
- indukovaná hypertermie * metody MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- nádory vaječníků * farmakoterapie patologie MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Rakousko MeSH
- Švýcarsko MeSH
BACKGROUND: Phase III trial data have shown a significant benefit by the addition of a maintenance treatment with niraparib, irrespective of BRCA or HRD status, in patients with advanced high-grade ovarian cancers; and, a significant benefit of the combination of olaparib and bevacizumab compared with bevacizumab monotherapy in HRD positive patients. However, it is unclear whether a PARP inhibitor monotherapy is sufficient, or if the addition of bevacizumab is needed. PRIMARY OBJECTIVES: This trial will investigate if the treatment strategy of carboplatin/paclitaxel/bevacizumab/niraparib is superior to the treatment of carboplatin/paclitaxel/niraparib in an all-comer population. STUDY HYPOTHESIS: Adding bevacizumab to chemotherapy followed by niraparib maintenance improves progression-free survival in patients with newly diagnosed advanced ovarian cancer. TRIAL DESIGN: AGO-OVAR 28/ENGOT-ov57 is an international, multicenter, randomized, prospective phase III trial within the the European Network for Gynecological Oncological Trial (ENGOT), led by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) study group. All patients should have completed the first cycle of chemotherapy (carboplatin and paclitaxel) as part of the Study Run-In-Period. Prior to day 1 of cycle 2, patients with a valid central tumor BRCA (tBRCA) test result were randomized in a 1:1 ratio into either: Arm 1, to receive five additional cycles of carboplatin and paclitaxel q21d, followed by niraparib for up to 3 years; or Arm 2, to receive five additional cycles of carboplatin and paclitaxel plus bevacizumab q21d, followed by bevacizumab q21d (for up to 1 year), and niraparib for up to 3 years. MAJOR INCLUSION/EXCLUSION CRITERIA: The trial population is composed of adult patients with newly diagnosed, advanced high-grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer FIGO III/IV (except FIGO IIIA2 without nodal involvement). Patients who are scheduled for neoadjuvant chemotherapy and interval debulking surgery are also eligible for the trial. PRIMARY ENDPOINT: The primary endpoint is progression-free survival. SAMPLE SIZE: The study plans to recruit 970 patients (485 patients in each arm). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The Last-Patient-In is expected to be enrolled in September 2024, with presentation of the primary endpoint in 2028. TRIAL REGISTRATION: NCT05009082; EudraCT Number: 2021-001271-16.
- MeSH
- bevacizumab MeSH
- dospělí MeSH
- epiteliální ovariální karcinom farmakoterapie patologie MeSH
- karboplatina MeSH
- lidé MeSH
- nádory vaječníků * patologie MeSH
- paclitaxel MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.
- MeSH
- lékařská onkologie normy MeSH
- lidé MeSH
- nádory endometria diagnóza patologie terapie MeSH
- nádory ženských pohlavních orgánů diagnóza terapie MeSH
- předoperační péče MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- směrnice pro lékařskou praxi MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: Quality of surgical care as a crucial component of a comprehensive multi-disciplinary management improves outcomes in patients with endometrial carcinoma, notably helping to avoid suboptimal surgical treatment. Quality indicators (QIs) enable healthcare professionals to measure their clinical management with regard to ideal standards of care. OBJECTIVE: In order to complete its set of QIs for the surgical management of gynecological cancers, the European Society of Gynaecological Oncology (ESGO) initiated the development of QIs for the surgical treatment of endometrial carcinoma. METHODS: QIs were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for the identification of potential QIs and documentation of the scientific evidence, two consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians and patient representatives. QIs were defined using a structured format comprising metrics specifications, and targets. A scoring system was then developed to ensure applicability and feasibility of a future ESGO accreditation process based on these QIs for endometrial carcinoma surgery and support any institutional or governmental quality assurance programs. RESULTS: Twenty-nine structural, process and outcome indicators were defined. QIs 1-5 are general indicators related to center case load, training, experience of the surgeon, structured multi-disciplinarity of the team and active participation in clinical research. QIs 6 and 7 are related to the adequate pre-operative investigations. QIs 8-22 are related to peri-operative standards of care. QI 23 is related to molecular markers for endometrial carcinoma diagnosis and as determinants for treatment decisions. QI 24 addresses the compliance of management of patients after primary surgical treatment with the standards of care. QIs 25-29 highlight the need for a systematic assessment of surgical morbidity and oncologic outcome as well as standardized and comprehensive documentation of surgical and pathological elements. Each QI was associated with a score. An assessment form including a scoring system was built as basis for ESGO accreditation of centers for endometrial cancer surgery.
- MeSH
- konsensus MeSH
- lékařská onkologie normy MeSH
- lidé MeSH
- nádory endometria chirurgie MeSH
- společnosti lékařské MeSH
- ukazatele kvality zdravotní péče * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined.
- MeSH
- konsensus MeSH
- lidé MeSH
- nádory endometria * radioterapie MeSH
- radiační onkologie * MeSH
- rizikové faktory MeSH
- směrnice jako téma * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined.
- MeSH
- biopsie normy MeSH
- diagnostické techniky molekulární normy MeSH
- hodnocení rizik MeSH
- karcinom genetika patologie terapie MeSH
- lékařská onkologie normy MeSH
- lidé MeSH
- medicína založená na důkazech normy MeSH
- nádorové biomarkery genetika MeSH
- nádory endometria genetika patologie terapie MeSH
- prediktivní hodnota testů MeSH
- rizikové faktory MeSH
- staging nádorů normy MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
- směrnice pro lékařskou praxi MeSH
- systematický přehled MeSH
PURPOSE: Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC. METHODS: This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician's choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after ≥ 1 prior platinum-based chemotherapy but ≤ 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety. RESULTS: A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to ≥ 12.0 months) versus 6.7 months (0.03 to ≥ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade ≥ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent. CONCLUSION: Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary end point, binimetinib showed activity in LGSOC across the efficacy end points evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib.
- MeSH
- benzimidazoly škodlivé účinky terapeutické užití MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- doxorubicin analogy a deriváty terapeutické užití MeSH
- inhibitory proteinkinas škodlivé účinky terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- MAP kinasa-kinasa 1 antagonisté a inhibitory MeSH
- MAP kinasa-kinasa 2 antagonisté a inhibitory MeSH
- mladý dospělý MeSH
- nádory vaječníků farmakoterapie enzymologie patologie MeSH
- nádory vejcovodů farmakoterapie enzymologie patologie MeSH
- paclitaxel terapeutické užití MeSH
- peritoneální nádory farmakoterapie enzymologie patologie MeSH
- polyethylenglykoly terapeutické užití MeSH
- senioři MeSH
- serózní cystadenokarcinom farmakoterapie enzymologie patologie MeSH
- stupeň nádoru MeSH
- topotekan terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Research Support, N.I.H., Extramural MeSH
OBJECTIVE: Laparoscopy is one of the diagnostic tools available for the complex clinical decision-making process in advanced ovarian, fallopian tube, and peritoneal carcinoma. This article presents the results of a survey conducted within the European Network of Gynaecological Oncology Trial (ENGOT) group aimed at reviewing the current patterns of practice at gynecologic oncology centers with regard to the evaluation of resection in advanced ovarian, fallopian tube, and peritoneal carcinoma. METHODS: A 24-item questionnaire was sent to the chair of the 20 cooperative groups that are currently part of the ENGOT group, and forwarded to the members within each group. RESULTS: A total of 142 questionnaires were returned. Only 39 respondents (27.5%) reported using some form of clinical (not operative) score for the evaluation of resection. The frequency of use of diagnostic laparoscopy to assess disease status and feasibility of resection was as follows: never, 21 centers (15%); only in select cases, 83 centers (58.5%); and routinely, 36 centers (25.4%). When laparoscopy was performed, 64% of users declared they made the decision to proceed with maximal effort cytoreductive surgery based on their personal/staff opinion, and 36% based on a laparoscopic score. To the question of whether laparoscopy should be considered the gold standard in the evaluation of resection, 71 respondents (50%) answered no, 66 respondents (46.5%) answered yes, whereas 5 respondents (3.5%) did not provide an answer. CONCLUSIONS: This study found that laparoscopy was routinely performed to assess feasibility of cytoreduction in only 25.4% of centers in Europe. However, it was commonly used to select patients and in a minority of centers it was never used . When laparoscopy was adopted, the treatment strategy was based on laparoscopic scores only in a minority of centers.
- MeSH
- chirurgická onkologie statistika a číselné údaje MeSH
- cytoredukční chirurgie * MeSH
- gynekologie statistika a číselné údaje MeSH
- laparoskopie statistika a číselné údaje MeSH
- lidé MeSH
- nádory vaječníků diagnóza chirurgie MeSH
- nádory vejcovodů diagnóza chirurgie MeSH
- peritoneální nádory diagnóza chirurgie MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Ovarian carcinoma features pronounced clinical, histopathological, and molecular heterogeneity. There is good reason to believe that parts of this heterogeneity can be explained by differences in the respective cell of origin, with a self-renewing fallopian tube secretory cell being likely responsible for initiation of an overwhelming majority of high-grade serous ovarian carcinomas (i.e., type II tumors according to the recent dualistic classification), whereas there are several mutually non-exclusive possibilities for the initiation of type I tumors, including ovarian surface epithelium stem cells, endometrial cells, or even cells of extra-Müllerian origin. Interestingly, both fallopian tube self-renewing secretory cells and ovarian surface epithelium stem cells seem to be characterized by an overlapping array of stemness signaling pathways, especially Wnt/β-catenin. Apart from this variability in the respective cell of origin, the particular clinical behavior of ovarian carcinoma strongly suggests an underlying stem cell component with a crucial impact. This becomes especially evident in high-grade serous ovarian carcinomas treated with classical chemotherapy, which entails a gradual evolution of chemoresistant disease without any apparent selection of clones carrying obvious chemoresistance-associated mutations. Several cell surface markers (e.g., CD24, CD44, CD117, CD133, and ROR1) as well as functional approaches (ALDEFLUOR™ and side population assays) have been used to identify and characterize putative ovarian carcinoma stem cells. We have recently shown that side population cells exhibit marked heterogeneity on their own, which can hamper their straightforward therapeutic targeting. An alternative strategy for stemness-depleting interventions is to target the stem cell niche, i.e., the specific microanatomical structure that secures stem cell maintenance and survival through provision of a set of stem cell-promoting and differentiation-antagonizing factors. Besides identifying direct or indirect therapeutic targets, profiling of side population cells and other ovarian carcinoma stem cell subpopulations can reveal relevant prognostic markers, as exemplified by our recent discovery of the Vav3.1 transcript variant, which filters out a fraction of prognostically unfavorable ovarian carcinoma cases.
BACKGROUND: Systematic pelvic and paraaortic lymphadenectomy has been widely used in the surgical treatment of patients with advanced ovarian cancer, although supporting evidence from randomized clinical trials has been limited. METHODS: We intraoperatively randomly assigned patients with newly diagnosed advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage IIB through IV) who had undergone macroscopically complete resection and had normal lymph nodes both before and during surgery to either undergo or not undergo lymphadenectomy. All centers had to qualify with regard to surgical skills before participation in the trial. The primary end point was overall survival. RESULTS: A total of 647 patients underwent randomization from December 2008 through January 2012, were assigned to undergo lymphadenectomy (323 patients) or not undergo lymphadenectomy (324), and were included in the analysis. Among patients who underwent lymphadenectomy, the median number of removed nodes was 57 (35 pelvic and 22 paraaortic nodes). The median overall survival was 69.2 months in the no-lymphadenectomy group and 65.5 months in the lymphadenectomy group (hazard ratio for death in the lymphadenectomy group, 1.06; 95% confidence interval [CI], 0.83 to 1.34; P = 0.65), and median progression-free survival was 25.5 months in both groups (hazard ratio for progression or death in the lymphadenectomy group, 1.11; 95% CI, 0.92 to 1.34; P = 0.29). Serious postoperative complications occurred more frequently in the lymphadenectomy group (e.g., incidence of repeat laparotomy, 12.4% vs. 6.5% [P = 0.01]; mortality within 60 days after surgery, 3.1% vs. 0.9% [P = 0.049]). CONCLUSIONS: Systematic pelvic and paraaortic lymphadenectomy in patients with advanced ovarian cancer who had undergone intraabdominal macroscopically complete resection and had normal lymph nodes both before and during surgery was not associated with longer overall or progression-free survival than no lymphadenectomy and was associated with a higher incidence of postoperative complications. (Funded by Deutsche Forschungsgemeinschaft and the Austrian Science Fund; LION ClinicalTrials.gov number, NCT00712218.).
- MeSH
- antigen CA-125 krev MeSH
- délka operace MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfadenektomie * škodlivé účinky MeSH
- lymfatické metastázy MeSH
- míra přežití MeSH
- mladý dospělý MeSH
- nádory vaječníků patologie chirurgie MeSH
- pooperační komplikace MeSH
- proporcionální rizikové modely MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- terapie neúspěšná MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
