BACKGROUND: Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR) endometrial cancer, with greater magnitude of benefit in the dMMR phenotype. We evaluated the addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly diagnosed, high-risk endometrial cancer without any residual macroscopic disease following curative-intent surgery. METHODS: We included patients with histologically confirmed high-risk [International Federation of Gynecology and Obstetrics (FIGO) stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology] endometrial cancer following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for six cycles added to carboplatin-paclitaxel followed by pembrolizumab 400 mg or placebo every 6 weeks (Q6W) for six cycles per treatment assignment. Radiotherapy was at the investigator's discretion. The primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. RESULTS: A total of 1095 patients were randomised (pembrolizumab, n = 545; placebo, n = 550). At this interim analysis (data cut-off, 4 March 2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group [hazard ratio 1.02, 95% confidence interval (CI) 0.79-1.32; P = 0.570]. Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI 0.14-0.69) in the dMMR population (n = 281) and 1.20 (95% CI 0.91-1.57) in the pMMR population (n = 814). Grade ≥3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. CONCLUSIONS: Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly diagnosed, high-risk, all-comer endometrial cancer. Preplanned subgroup analyses for stratification factors suggest that pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04634877; EudraCT, 2020-003424-17. RESEARCH SUPPORT: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
- MeSH
- adjuvantní chemoterapie metody MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky * aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory endometria * patologie farmakoterapie terapie MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
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.
- MeSH
- lékařská onkologie * MeSH
- lidé MeSH
- molekulární biologie MeSH
- nádory vaječníků * genetika terapie MeSH
- společnosti lékařské MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
- Geografické názvy
- Španělsko MeSH
OBJECTIVE: To describe the clinical and sonographic characteristics of benign, retroperitoneal, pelvic peripheral-nerve-sheath tumors (PNSTs). METHODS: This was a retrospective study of patients with a benign, retroperitoneal, pelvic PNST who had undergone preoperative ultrasound examination at a single gynecologic oncology center between 1 January 2018 and 31 August 2022. All ultrasound images, videoclips and final histological specimens of benign PNSTs were reviewed side-by-side in order to: describe the ultrasound appearance of the tumors, using the terminology of the International Ovarian Tumor Analysis (IOTA), Morphological Uterus Sonographic Assessment (MUSA) and Vulvar International Tumor Analysis (VITA) groups, following a predefined ultrasound assessment form; describe their origin in relation to nerves and pelvic anatomy; and assess the association between their ultrasound features and histotopography. A review of the literature reporting benign, retroperitoneal, pelvic PNSTs with preoperative ultrasound examination was performed. RESULTS: Five women (mean age, 53 years) with a benign, retroperitoneal, pelvic PNST were identified, four with a schwannoma and one with a neurofibroma, of which all were sporadic and solitary. All patients had good-quality ultrasound images and videoclips and final biopsy of surgically excised tumors, except one patient managed conservatively who had only a core needle biopsy. In all cases, the findings were incidental. The five PNSTs ranged in maximum diameter from 31 to 50 mm. All five PNSTs were solid, moderately vascular tumors, with non-uniform echogenicity, well-circumscribed by hyperechogenic epineurium and with no acoustic shadowing. Most of the masses were round (n = 4 (80%)), and contained small, irregular, anechoic, cystic areas (n = 3 (60%)) and hyperechogenic foci (n = 5 (100%)). In the woman with a schwannoma in whom surgery was not performed, follow-up over a 3-year period showed minimal growth (1.5 mm/year) of the mass. We also summarize the findings of 47 cases of benign retroperitoneal schwannoma and neurofibroma identified in a literature search. CONCLUSIONS: On ultrasound examination, no imaging characteristics differentiate reliably between benign schwannomas and neurofibromas. Moreover, benign PNSTs show some similar features to malignant retroperitoneal tumors. They are solid lesions with intralesional blood vessels and show degenerative changes such as cystic areas and hyperechogenic foci. Therefore, ultrasound-guided biopsy may play a pivotal role in their diagnosis. If confirmed to be benign PNSTs, these tumors can be managed conservatively, with ultrasound surveillance. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory nervové pochvy * diagnóza patologie chirurgie MeSH
- nádory pánve * MeSH
- neurilemom * diagnostické zobrazování patologie MeSH
- neurofibrom * diagnóza patologie chirurgie MeSH
- retroperitoneální nádory * diagnostické zobrazování MeSH
- retrospektivní studie MeSH
- ultrasonografie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. METHODS: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. RESULTS: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence. CONCLUSION: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.
- MeSH
- biopsie sentinelové lymfatické uzliny MeSH
- lidé MeSH
- lokální recidiva nádoru patologie MeSH
- lymfadenektomie škodlivé účinky MeSH
- lymfadenopatie * patologie MeSH
- lymfatické metastázy patologie MeSH
- lymfatické uzliny patologie chirurgie MeSH
- nádory vulvy * patologie MeSH
- sentinelová uzlina * patologie chirurgie MeSH
- spinocelulární karcinom * patologie MeSH
- třísla MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The aim of the study was to compare health-related quality of life (QoL) and oncological outcome between gynaecological cancer patients undergoing pelvic exenteration (PE) and extended pelvic exenteration (EPE). EPEs were defined as extensive procedures including, in addition to standard PE extent, the resection of internal, external, or common iliac vessels; pelvic side-wall muscles; large pelvic nerves (sciatic or femoral); and/or pelvic bones. METHODS: Data from 74 patients who underwent PE (42) or EPE (32) between 2004 and 2019 at a single tertiary gynae-oncology centre in Prague were analysed. QoL assessment was performed using EORTC QLQ-C30, EORTC CX-24, and QOLPEX questionnaires specifically developed for patients after (E)PE. RESULTS: No significant differences in survival were observed between the groups (P > 0.999), with median overall and disease-specific survival in the whole cohort of 45 and 49 months, respectively. Thirty-one survivors participated in the QoL surveys (20 PE, 11 EPE). No significant differences were observed in global health status (P = 0.951) or in any of the functional scales. The groups were not differing in therapy satisfaction (P = 0.502), and both expressed similar, high willingness to undergo treatment again if they were to decide again (P = 0.317). CONCLUSIONS: EPEs had post-treatment QoL and oncological outcome comparable to traditional PE. These procedures offer a potentially curative treatment option for patients with persistent or recurrent pelvic tumour invading into pelvic wall structures without further compromise of patients ́ QoL.
- MeSH
- exenterace pánve * metody MeSH
- kvalita života MeSH
- lidé MeSH
- nádory pánve * chirurgie MeSH
- průzkumy a dotazníky MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: To compare the performance of transvaginal and transabdominal ultrasound with that of the first-line staging method (contrast-enhanced computed tomography (CT)) and a novel technique, whole-body magnetic resonance imaging with diffusion-weighted sequence (WB-DWI/MRI), in the assessment of peritoneal involvement (carcinomatosis), lymph-node staging and prediction of non-resectability in patients with suspected ovarian cancer. METHODS: Between March 2016 and October 2017, all consecutive patients with suspicion of ovarian cancer and surgery planned at a gynecological oncology center underwent preoperative staging and prediction of non-resectability with ultrasound, CT and WB-DWI/MRI. The evaluation followed a single, predefined protocol, assessing peritoneal spread at 19 sites and lymph-node metastasis at eight sites. The prediction of non-resectability was based on abdominal markers. Findings were compared to the reference standard (surgical findings and outcome and histopathological evaluation). RESULTS: Sixty-seven patients with confirmed ovarian cancer were analyzed. Among them, 51 (76%) had advanced-stage and 16 (24%) had early-stage ovarian cancer. Diagnostic laparoscopy only was performed in 16% (11/67) of the cases and laparotomy in 84% (56/67), with no residual disease at the end of surgery in 68% (38/56), residual disease ≤ 1 cm in 16% (9/56) and residual disease > 1 cm in 16% (9/56). Ultrasound and WB-DWI/MRI performed better than did CT in the assessment of overall peritoneal carcinomatosis (area under the receiver-operating-characteristics curve (AUC), 0.87, 0.86 and 0.77, respectively). Ultrasound was not inferior to CT (P = 0.002). For assessment of retroperitoneal lymph-node staging (AUC, 0.72-0.76) and prediction of non-resectability in the abdomen (AUC, 0.74-0.80), all three methods performed similarly. In general, ultrasound had higher or identical specificity to WB-DWI/MRI and CT at each of the 19 peritoneal sites evaluated, but lower or equal sensitivity in the abdomen. Compared with WB-DWI/MRI and CT, transvaginal ultrasound had higher accuracy (94% vs 91% and 85%, respectively) and sensitivity (94% vs 91% and 89%, respectively) in the detection of carcinomatosis in the pelvis. Better accuracy and sensitivity of ultrasound (93% and 100%) than WB-DWI/MRI (83% and 75%) and CT (84% and 88%) in the evaluation of deep rectosigmoid wall infiltration, in particular, supports the potential role of ultrasound in planning rectosigmoid resection. In contrast, for the bowel serosal and mesenterial assessment, abdominal ultrasound had the lowest accuracy (70%, 78% and 79%, respectively) and sensitivity (42%, 65% and 65%, respectively). CONCLUSIONS: This is the first prospective study to document that, in experienced hands, ultrasound may be an alternative to WB-DWI/MRI and CT in ovarian cancer staging, including peritoneal and lymph-node evaluation and prediction of non-resectability based on abdominal markers of non-resectability. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
- MeSH
- celotělové zobrazování statistika a číselné údaje MeSH
- difuzní magnetická rezonance statistika a číselné údaje MeSH
- dospělí MeSH
- epiteliální ovariální karcinom diagnostické zobrazování patologie MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické uzliny patologie MeSH
- magnetická rezonanční tomografie statistika a číselné údaje MeSH
- nádory vaječníků diagnostické zobrazování patologie MeSH
- peritoneální nádory diagnostické zobrazování patologie MeSH
- prospektivní studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The phase IIIb OPINION trial (NCT03402841) investigated olaparib maintenance monotherapy in patients without a deleterious or suspected deleterious germline BRCA1/BRCA2 mutation (gBRCAm) who had platinum-sensitive relapsed ovarian cancer (PSROC) and had received ≥2 previous lines of platinum-based chemotherapy. METHODS: In this single-arm, open-label, international study, patients who had responded to platinum-based chemotherapy received maintenance olaparib tablets (300 mg twice daily) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS) (modified RECIST version 1.1). A key secondary endpoint was PFS by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. The primary analysis of PFS was planned for 18 months after the last patient received their first dose. RESULTS: Two hundred and seventy-nine patients were enrolled and received olaparib. At data cutoff (October 2, 2020), 210 PFS events had occurred (75.3% maturity) and median PFS was 9.2 months (95% confidence interval [CI], 7.6-10.9) in the overall population. At 12 and 18 months, 38.5% and 24.3% of patients were progression-free, respectively. In the predefined biomarker subgroups, median PFS was 16.4, 11.1, 9.7, and 7.3 months in sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative patients, respectively. The most common treatment-emergent adverse events (TEAEs) were nausea (48.4%) and fatigue/asthenia (44.1%). TEAEs led to dose interruption, dose reduction, and treatment discontinuation in 47.0%, 22.6%, and 7.5% of patients, respectively. CONCLUSION: Maintenance olaparib demonstrated clinical benefit in patients without a gBRCAm, and across all subgroups, compared with historical placebo controls. There were no new safety signals.
- MeSH
- epiteliální ovariální karcinom farmakoterapie genetika MeSH
- ftalaziny * škodlivé účinky MeSH
- lidé MeSH
- lokální recidiva nádoru * farmakoterapie genetika MeSH
- mutace MeSH
- nádory vaječníků * farmakoterapie genetika MeSH
- piperaziny * škodlivé účinky MeSH
- platina terapeutické užití MeSH
- protein BRCA1 genetika MeSH
- protein BRCA2 genetika MeSH
- udržovací chemoterapie MeSH
- zárodečné buňky MeSH
- zárodečné mutace MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
BACKGROUND: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. PATIENTS AND METHODS: We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA-IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. RESULTS: The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799-1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458-1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690-1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. CONCLUSION: We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. CLINICAL TRIALS IDENTIFIER: NCT04037124.
- MeSH
- analýza přežití MeSH
- dospělí MeSH
- hysterektomie metody MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory děložního čípku mortalita patologie chirurgie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- gynekologické chirurgické výkony normy MeSH
- gynekologie normy MeSH
- klinické rozhodování MeSH
- konsensus MeSH
- lidé MeSH
- medicína založená na důkazech normy MeSH
- nádorové biomarkery analýza MeSH
- nádory vaječníků diagnóza MeSH
- nemoci děložních adnex diagnóza MeSH
- předoperační období MeSH
- společnosti lékařské MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
In centers with access to high-end ultrasound machines and expert sonologists, ultrasound is used to detect metastases in regional lymph nodes from melanoma, breast cancer and vulvar cancer. There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from lymph nodes infiltrated by cancer or lymphoma cells. The Vulvar International Tumor Analysis (VITA) collaborative group consists of gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The work herein is a consensus opinion on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature need not be limited to the description of inguinal lymph nodes as part of vulvar cancer staging; it can be used to describe peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes if these can be visualized clearly. The association between the ultrasound features described here and histopathological diagnosis has not yet been established. VITA terms and definitions lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes and studies to elucidate the role of ultrasound in staging of vulvar and other malignancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
- MeSH
- gynekologie MeSH
- lidé MeSH
- lymfatické metastázy diagnostické zobrazování patologie MeSH
- nádory vulvy diagnostické zobrazování patologie MeSH
- směrnice pro lékařskou praxi jako téma * MeSH
- společnosti lékařské MeSH
- ultrasonografie normy MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
- práce podpořená grantem MeSH