Olaparib treatment significantly improved objective response rate (primary end point) and progression-free survival versus nonplatinum chemotherapy in patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer in the open-label phase III SOLO3 trial (ClinicalTrials.gov identifier: NCT02282020). We report final overall survival (OS; prespecified secondary end point), post hoc OS analysis by number of previous chemotherapy lines, and exploratory BRCA reversion mutation analysis. Two hundred sixty-six patients were randomly assigned 2:1 to olaparib tablets (300 mg twice daily; n = 178) or physician's choice of single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan; n = 88). OS was similar with olaparib versus chemotherapy (hazard ratio [HR], 1.07 [95% CI, 0.76 to 1.49]; P = .71, median 34.9 and 32.9 months, respectively, full analysis set). OS with olaparib was favorable in patients with two previous chemotherapy lines (HR, 0.83 [olaparib v chemotherapy] [95% CI, 0.51 to 1.38]; median 37.9 v 28.8 months); however, a potential detrimental effect was seen in patients with at least three previous chemotherapy lines (HR, 1.33 [95% CI, 0.84 to 2.18]; median 29.9 v 39.4 months). BRCA reversion mutations might have contributed to this finding. No patient randomly assigned to olaparib with a BRCA reversion mutation detected at baseline (6 of 170 [3.5%]) achieved an objective tumor response.

• MeSH
• deoxycytidin analogy a deriváty   aplikace a dávkování   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• doxorubicin analogy a deriváty   aplikace a dávkování   MeSH
• ftalaziny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• gemcitabin MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * farmakoterapie   MeSH
• nádory vaječníků * farmakoterapie   genetika   mortalita   patologie   MeSH
• paclitaxel aplikace a dávkování   MeSH
• PARP inhibitory * terapeutické užití   škodlivé účinky   MeSH
• piperaziny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• polyethylenglykoly aplikace a dávkování   MeSH
• protein BRCA1 genetika   MeSH
• protein BRCA2 genetika   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• senioři MeSH
• topotekan aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

OBJECTIVE: To describe the oncological and obstetrical outcomes of women diagnosed with borderline ovarian tumors or epithelial ovarian cancer during pregnancy. METHODS: This is an international retrospective cohort study. Patients were eligible for inclusion if they were diagnosed with borderline tumor or invasive ovarian cancer during pregnancy, with histologic confirmation either before or after delivery, and were registered in the International Network on Cancer, Infertility and Pregnancy database between 1982 and 2019. RESULTS: A total of 129 patients were included, of whom 69 (53%) with borderline and 60 (47%) with invasive cancer. Diagnosis was established in the first, second, and third trimesters in 59 (46%), 48 (37%), and 22 (17%) patients, respectively. In total, 47 (36%) patients did not receive any treatment during pregnancy. The majority of patients (64%) underwent surgery with or without chemotherapy during pregnancy. Birthweight was significantly lower in women who received chemotherapy during pregnancy as compared to those who did not (median birthweight 2528 g vs 3031 g, p = .01) Among patients with borderline tumors, 20 (29%) experienced a relapse of whom 2 subsequently died from the disease. The 5-year survival probability was 98.5% (95% CI 95.6 to 100). Recurrence was associated with incomplete surgical staging (p = .02). Among patients with epithelial ovarian cancer, the relapse rate was 25% and the 5-year survival probability was 83.6% (95% CI 74.3 to 94.1). The oncological outcome was worse for patients with advanced-stage disease (p = .03). In addition, 66% of patients who relapsed after pregnancy did not undergo adequate surgical staging. CONCLUSIONS: Treatment of patients with ovarian cancer during pregnancy can result in favorable oncological and obstetrical outcomes. Better oncological outcomes are achieved when treatment adheres to the standard of care in non-pregnant patients, as those who did not undergo surgical staging experienced a higher relapse rate.

• MeSH
• dospělí MeSH
• epiteliální ovariální karcinom * terapie   patologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• nádorové komplikace v těhotenství * terapie   patologie   MeSH
• nádory vaječníků * patologie   terapie   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• výsledek těhotenství epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Adult granulosa cell tumors (AGCTs) of the ovary are characterized by their propensity for late recurrences and are primarily managed surgically due to the limited efficacy of systemic treatment. The FOXL2 p.C134W somatic mutation has been identified in ∼95% of AGCT cases, and TERT promoter alterations have been linked to worse overall survival. This study highlights the potential prognostic significance of FOXO1 mutations, suggesting that they may be associated with poorer overall survival and shorter time to recurrence. A total of 183 primary AGCTs and 44 recurrences without corresponding primary tumors were analyzed. The primary AGCTs were categorized into 3 groups: 77 nonrecurrent tumors, 18 tumors that later recurred (including 9 cases with matched primary-recurrence pairs), and 88 tumors with unknown recurrence status. Targeted next-generation sequencing was conducted on 786 cancer-related genes to investigate their genetic profile. The study aimed to identify the molecular alterations associated with AGCT pathogenesis and recurrence rate, comparing primary versus recurrent tumors, and primary recurrent versus primary nonrecurrent cases. Our findings confirmed the high prevalence (99%) of the FOXL2 p.C134W mutation in AGCTs. Secondary truncating FOXL2 mutations were observed in 5% of cases. Two cases with typical AGCT morphology were FOXL2 wild-type, harboring mutations in KRAS or KMT2D instead, suggesting alternative genetic pathways. TERT promoter mutations were found in 43% of cases, more frequently in recurrences. Other recurrent mutations detected in the cohort included KMT2D (10%), FOXO1 (7%), CHEK2 (5%), TP53 (3.5%), PIK3CA (3.5%), and AKT1 (3%). Two recurrent, FOXL2-mutated cases also carried DICER1 mutations. One tumor exhibited MSI-high status and a tumor mutation burden of 19 mut/Mb.Our results indicate the need for further investigation into the role of FOXO1 as a potential prognostic marker in AGCTs.

• MeSH
• dospělí MeSH
• forkhead box protein O1 * genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * genetika   MeSH
• mutace * MeSH
• nádor z folikulárních buněk * genetika   patologie   MeSH
• nádory vaječníků * genetika   patologie   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• protein FOXL2 genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• telomerasa genetika   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
• práce podpořená grantem MeSH

Using immunohistochemistry, we examined a large cohort of 135 ovarian tumors, made up of 96 low-grade serous carcinomas (LGSCs) and 39 serous borderline tumors (micropapillary variant, mSBT), with the aim of exploring their HER2 status (overexpression). We followed with comprehensive genomic analyses on this sample set from our previous study, which revealed HER2 mutation in 5% (4/75) of LGSC and 10% (3/29) of mSBT. No cases were evaluated as HER2-positive, but 6 LGSCs and 1 mSBT were scored as HER2 1+, and 2 LGSCs and 1 mSBT showed the so-called HER2 "ultra-low" phenotype. This could be of clinical value as a potential therapeutical target concerning emerging therapeutic treatments (antibody conjugates). However, the clinical significance of this expression still needs to be established.

• MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory vaječníků * patologie   genetika   metabolismus   MeSH
• receptor erbB-2 * genetika   metabolismus   MeSH
• senioři MeSH
• serózní cystadenokarcinom * patologie   genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• HGSOC, olaparib,
• MeSH
• cytostatické látky farmakologie   terapeutické užití   MeSH
• dědičný syndrom nádoru prsu a vaječníků diagnóza   genetika   MeSH
• dospělí MeSH
• geny BRCA1 MeSH
• lidé MeSH
• míra přežití MeSH
• nádory vaječníků * chirurgie   diagnóza   farmakoterapie   genetika   MeSH
• PARP inhibitory farmakologie   terapeutické užití   MeSH
• udržovací chemoterapie * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• Klíčová slova
• serózní tubulární intraepiteliální karcinom,
• MeSH
• dědičný syndrom nádoru prsu a vaječníků diagnóza   genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• lidé MeSH
• management nemoci MeSH
• nádory vaječníků * chirurgie   diagnóza   genetika   patologie   klasifikace   MeSH
• ovarium diagnostické zobrazování   patologie   MeSH
• profylaktické chirurgické výkony metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), approved by the US Food and Drug Administration for the treatment of platinum-resistant ovarian cancer in the USA. Here, we report patient-reported outcomes for participants treated with MIRV compared with investigator's choice of chemotherapy from the phase 3 MIRASOL trial, which met its primary endpoint of progression-free survival and key secondary endpoints of objective response rate and overall survival. METHODS: The MIRASOL trial was a confirmatory, phase 3, randomised, controlled, open-label trial, building on the phase 2 SORAYA trial which had previously demonstrated the safety and efficacy of MIRV in platinum-resistant ovarian cancer. Patients 18 years or older with a confirmed platinum-resistant, recurrent high-grade serous epithelial ovarian cancer diagnosis were recruited from 253 sites including hospitals, academic centres, and community centres in 21 countries. Patients must have received one to three previous systemic anticancer therapies, and have high FRα tumour expression (≥75% tumour cells with an immunohistochemistry score of ≥2+ membrane staining using the PS2+ scoring method), one or more lesions with measurable disease, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to MIRV or investigator's choice of chemotherapy, stratified by number of previous therapy lines and the type of investigator's choice of chemotherapy. Therapies were administered in an open-label manner; MIRV was administered intravenously at 6 mg/kg of adjusted ideal bodyweight every 3 weeks. The primary endpoint was progression-free survival. Key secondary endpoints were objective response rate, overall survival, and a 15·0-point or greater improvement at week 8 or 9 in abdominal and gastrointestinal symptoms using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module (EORTC QLQ-OV28) in the intention-to-treat population. The MIRASOL trial was registered at ClinicalTrials.gov (NCT04209855), the Gynecologic Oncology Group (GOG 3045), and the European Network of Gynaecological Oncological Trial Groups (ENGOT-ov55), and is complete. FINDINGS: Between Feb 3, 2020, and Aug 3, 2022, 453 patients were enrolled and randomly assigned to treatment (227 to the MIRV group and 226 to the investigator's choice of chemotherapy group). All patients were female; 301 (66%) participants were White, 53 (12%) were Asian, 13 (3%) were Black, and 86 (19%) were of another race or not reported; 27 (6%) were Hispanic or Latino. The median follow-up for the study, determined by the reverse Kaplan-Meier method, was 13·1 months (95% CI 12·1-14). QLQ-OV28 completion rates were 86% (365 of 425) at baseline and 81% (282 of 349) at week 8 or 9. 34 (21·0%; 95% CI 15·0-28·1) of 162 patients treated with MIRV reported improvement in QLQ-OV28 abdominal and gastrointestinal scores, compared with 23 (15·3%; 10·0-22·1) of 150 patients treated with the investigator's choice of chemotherapy. These differences were not statistically significant (odds ratio 1·5 [95% CI 0·8-2·6]; p=0·26). INTERPRETATION: MIRV did not seem to impair or improve patient quality of life compared with investigator's choice of chemotherapy. The similar quality-of-life outcomes in the two treatment groups, combined with the previously reported higher efficacy of MIRV compared with single-agent chemotherapy, support MIRV as new treatment option for FRα-positive platinum-resistant ovarian cancer. FUNDING: AbbVie.

• MeSH
• chemorezistence * účinky léků   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• epiteliální ovariální karcinom * farmakoterapie   mortalita   patologie   MeSH
• folátový receptor 1 * metabolismus   antagonisté a inhibitory   MeSH
• hodnocení výsledků péče pacientem * MeSH
• humanizované monoklonální protilátky * terapeutické užití   škodlivé účinky   MeSH
• imunokonjugáty * terapeutické užití   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• maytansin * analogy a deriváty   terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• nádory vaječníků * farmakoterapie   patologie   mortalita   metabolismus   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

• Klíčová slova
• osimertinib, durvalumab,
• MeSH
• ftalaziny terapeutické užití   MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   terapeutické užití   MeSH
• nádory endometria farmakoterapie   MeSH
• nádory vaječníků * farmakoterapie   MeSH
• PARP inhibitory terapeutické užití   MeSH
• piperaziny terapeutické užití   MeSH
• protinádorové látky imunologicky aktivní aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• protinádorové látky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• Check Tag
• lidé MeSH

Východiska: Multimodální prehabilitace v onkogynekologii je založena na úzké spolupráci onkologů a onkogynekologů s prehabilitačním týmem. Součástí týmu jsou rehabilitační lékaři, fyzioterapeuti, ergoterapeuti, nutriční terapeut a klinický psycholog. Cílem je dosažení maximálně možného psychosenzomotorického potenciálu před plánovaným radikálním operačním výkonem. Případ: U 66leté pacientky s diagnostikovaným high-grade serózním ovariálním karcinomem IIIC dle FIGO byla po skončení neoadjuvantní chemoterapie indikována 21denní lůžková prehabilitace v režimu 4/7. Prehabilitaci dominovala individuální fyzioterapie a ergoterapie s frekvencí 2× denně po dobu 20–30 min. Byly aplikovány terapeutické programy obsahující prvky kardiorespiračního tréninku, relaxačních metod, svalového i kognitivního tréninku. Terapie byla doplněna i o prvky teleprehabilitace v domácím prostředí. Závěr: Vyhodnocením aplikovaných funkčních testů lze demonstrovat významné zlepšení celkové fyzické kondice, respiračních parametrů i kvality života popisované pacientky.

Background: Multimodal prehabilitation in oncogynecology is based on close collaboration between oncologists, oncogynecologists and the prehabilitation team. The team includes rehabilitation physicians, physiotherapists, occupational therapists, a nutritional therapist and a clinical psychologist. The aim is to achieve the maximum possible psychosensomotor potential before the planned radical surgery. Case: A 66-year-old female patient diagnosed with high-grade serous ovarial carcinoma, stage IIIC according to International Federation of Gynecology and Obstetrics (FIGO) classification, after completion of neoadjuvant chemotherapy, was indicated for 21 days of inpatient prehabilitation in a 4/7 regimen. Prehabilitation was dominated by individual physiotherapy and occupational therapy with a frequency of twice a day for 20–30 minutes. Therapeutic programs containing elements of cardiorespiratory training, relaxation methods, muscular and cognitive training were applied. The therapy was supplemented with elements of telerehabilitation in the home environment. Conclusion: The evaluation of the applied functional tests demonstrates a significant improvement in the overall physical condition, respiratory parameters and quality of life of the patient described.

• Klíčová slova
• HGSC,
• MeSH
• fyzioterapie v předoperační přípravě * MeSH
• kardiorespirační zdatnost MeSH
• kvalita života MeSH
• lidé MeSH
• nádory vaječníků * chirurgie   diagnóza   rehabilitace   MeSH
• senioři MeSH
• telerehabilitace MeSH
• tělesná výkonnost MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Maintenance olaparib demonstrated clinical activity for progression-free survival in patients without a germline BRCA1 and/or BRCA2 mutation (non-gBRCAm) who had platinum-sensitive relapsed ovarian cancer in the phase IIIb, open-label, single-arm, non-comparator, international OPINION trial (NCT03402841). We report final overall survival (OS; secondary endpoint), prespecified secondary endpoint updates and ad hoc OS analysis by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. METHODS: Patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer, ≥2 prior lines of platinum-based chemotherapy, and in response following their last platinum-based chemotherapy received 300 mg olaparib tablets twice daily until disease progression or unacceptable toxicity. RESULTS: 279 patients were enrolled and treated. With a median follow-up in patients censored for OS of 33.1 months (data cut-off September 17, 2021), median OS was 32.7 months (95 % CI 29.5-35.3); the 24-month OS rate was 65.8 %. In ad hoc subgroup analyses, OS rates tended to be higher in patients with HRD-positive tumors; 24-month OS rates were 81.5 %, 74.2 %, 72.0 % and 55.8 % in the sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative subgroups, respectively. Grade ≥ 3 treatment-emergent adverse events were reported in 82 patients (29.4 %), most commonly anemia (13.6 %). Overall, two cases of myelodysplastic syndrome were reported (no new cases since the primary analysis). CONCLUSION: These data provide additional evidence of olaparib as maintenance therapy in patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer, with longer OS observed in those with HRD-positive tumors. The safety profile was consistent with the primary analysis and known safety profile of olaparib, with no new safety findings.

• MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• epiteliální ovariální karcinom * farmakoterapie   genetika   mortalita   MeSH
• ftalaziny * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * farmakoterapie   genetika   MeSH
• nádory vaječníků * farmakoterapie   genetika   mortalita   MeSH
• PARP inhibitory * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• piperaziny * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• protein BRCA1 genetika   MeSH
• protein BRCA2 genetika   MeSH
• senioři MeSH
• udržovací chemoterapie MeSH
• zárodečné mutace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH