BACKGROUND: In the ARIEL4 trial of rucaparib versus standard-of-care chemotherapy in patients with relapsed BRCA-mutated ovarian carcinoma, the primary endpoint was met, showing improved investigator-assessed progression-free survival with rucaparib. Here, we present the final overall survival analysis of the trial and other post-progression outcomes. METHODS: This open-label, randomised, controlled phase 3 trial was done at 64 hospitals and cancer centres in 12 countries, including Brazil, Canada, Czech Republic, Hungary, Israel, Italy, Poland, Russia, Spain, Ukraine, the UK, and the USA. Eligible patients were women aged 18 or older with BRCA1 or BRCA2-mutated ovarian carcinoma and had received at least two previous chemotherapy regimens. Patients had to have evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) criteria and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (2:1) using an interactive response technology and block randomisation (block size of six) and stratified by progression-free interval after the most recent platinum-containing therapy to receive oral rucaparib (600 mg twice daily administered in 28-day cycles) or chemotherapy on the basis of platinum-sensitivity status. In the chemotherapy group, patients with platinum-resistant disease (progression-free interval ≥1 to <6 months) or partially platinum-sensitive disease (progression-free interval ≥6 to <12 months) received weekly paclitaxel (starting dose 60-80 mg/m2 on days 1, 8, and 15). Patients with fully platinum-sensitive disease (progression-free interval ≥12 months) received the investigator's choice of platinum-based chemotherapy (single-agent cisplatin or carboplatin, or platinum-doublet chemotherapy), in 21-day or 28-day cycles. The primary endpoint (previously reported) was investigator-assessed progression-free survival, assessed in the efficacy population (all randomly assigned patients with deleterious BRCA1 or BRCA2 mutations without reversion mutations) and in the intention-to-treat population (all randomly assigned patients). Overall survival was a prespecified secondary endpoint and was analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned study treatment. The cutoff date was April 10, 2022. This study is registered with ClinicalTrials.gov, NCT02855944; enrolment is complete and the study is closed. FINDINGS: Between March 1, 2017, and Sept 24, 2020, 349 eligible patients were randomly assigned to receive rucaparib (n=233) or chemotherapy (n=116). 332 (95%) of 349 patients were white and 17 (5%) patients were other or of unknown race. In the chemotherapy group, 80 (69%) of 116 patients crossed over to receive rucaparib. Median follow-up was 41·2 months (IQR 37·8-44·6). At data cutoff for this final analysis (April 10, 2022), 244 (70%) of 349 patients had died: 167 (72%) of 233 in the rucaparib group and 77 (66%) of 116 in the rucaparib group. Median overall survival was 19·4 months (95% CI 15·2-23·6) in the rucaparib group versus 25·4 months (21·4-27·6) in the chemotherapy group (hazard ratio 1·3 [95% CI 1·0-1·7], p=0·047). No new safety signals were observed, including during crossover to rucaparib. The most common grade 3-4 adverse events across treatment groups included anaemia or decreased haemoglobin (reported in 59 [25%] of 232 patients in the rucaparib group and seven [6%] of 113 in the chemotherapy group), and neutropenia or decreased neutrophil count (in 26 [11%] of 232 in the rucaparib group and 16 [14%] of 113 patients in the chemotherapy group). Serious adverse events were reported in 66 (28%) of 232 patients in the rucaparib group and 14 (12%) of 113 patients in the chemotherapy group. Ten treatment-related deaths were reported in the rucaparib group, two of which were linked to judged to be related to rucaparib (cardiac disorder and myelodysplastic syndrome), and one death related to treatment was reported in the chemotherapy group, with no specific cause linked to the treatment. INTERPRETATION: These data highlight the need for a better understanding of the most appropriate treatment for patients who have progressed on a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, and the optimal sequencing of chemotherapy and PARP inhibitors in advanced ovarian cancer. FUNDING: Clovis Oncology.

• MeSH
• Progression-Free Survival MeSH
• Adult MeSH
• Indoles * therapeutic use   administration & dosage   adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * drug therapy   genetics   pathology   MeSH
• Mutation * MeSH
• Ovarian Neoplasms * drug therapy   genetics   pathology   mortality   MeSH
• Paclitaxel administration & dosage   adverse effects   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors therapeutic use   adverse effects   administration & dosage   MeSH
• BRCA1 Protein * genetics   MeSH
• BRCA2 Protein * genetics   MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity. Both HCC cell lines exhibited heightened sensitivity to the combined treatment. The effect of drugs on the expression of proliferation markers in an olaparib-resistant patient-derived xenograft (PDX) model of ovarian cancer was also investigated. Ovarian tumors displayed reduced tissue growth, as reflected by a drop in proliferation marker Ki-67 levels in response to PARPi combined with CHK1i. No changes were observed in corresponding liver tissues using Ki-67 and pCHK staining, which indicates the absence of metastases and a hepatotoxic effect. Thus, our results indicate that the dual inhibition of PARP and CHK1 may prove to be a promising therapeutic approach in the treatment of primary HCC as well as OC tumors without the risk of liver metastases, especially in patients with olaparib-resistant tumor profiles.

• MeSH
• Apoptosis drug effects   MeSH
• Hep G2 Cells MeSH
• Checkpoint Kinase 1 metabolism   antagonists & inhibitors   MeSH
• Phthalazines * pharmacology   MeSH
• Carcinoma, Hepatocellular * drug therapy   pathology   metabolism   MeSH
• Liver drug effects   pathology   metabolism   MeSH
• Humans MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Liver Neoplasms * drug therapy   pathology   metabolism   MeSH
• Ovarian Neoplasms * drug therapy   pathology   metabolism   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors pharmacology   therapeutic use   MeSH
• Piperazines * pharmacology   MeSH
• DNA Damage drug effects   MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Combined Chemotherapy Protocols pharmacology   therapeutic use   adverse effects   MeSH
• Pyrazoles pharmacology   MeSH
• Pyrimidines MeSH
• Drug Synergism * MeSH
• Cell Survival drug effects   MeSH
• Xenograft Model Antitumor Assays * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Poly (ADP ribose) polymerase inhibitors (PARPis) are a treatment option for patients with advanced high-grade serous or endometrioid ovarian carcinoma (OC). Recent guidelines have clarified how homologous recombination deficiency (HRD) may influence treatment decision-making in this setting. As a result, numerous companion diagnostic assays (CDx) have been developed to identify HRD. However, the optimal HRD testing strategy is an area of debate. Moreover, recently published clinical and translational data may impact how HRD status may be used to identify patients likely to benefit from PARPi use. We aimed to extensively compare available HRD CDx and establish a worldwide expert consensus on HRD testing in primary and recurrent OC. METHODS: A group of 99 global experts from 31 different countries was formed. Using a modified Delphi process, the experts aimed to establish consensus statements based on a systematic literature search and CDx information sought from investigators, companies and/or publications. RESULTS: Technical information, including analytical and clinical validation, were obtained from 14 of 15 available HRD CDx (7 academic; 7 commercial). Consensus was reached on 36 statements encompassing the following topics: 1) the predictive impact of HRD status on PARPi use in primary and recurrent OC; 2) analytical and clinical validation requirements of HRD CDx; 3) resource-stratified HRD testing; and 4) how future CDx may include additional approaches to help address unmet testing needs. CONCLUSION: This manuscript provides detailed information on currently available HRD CDx and up-to-date guidance from global experts on HRD testing in patients with primary and recurrent OC.

• MeSH
• Delphi Technique MeSH
• Homologous Recombination MeSH
• Consensus * MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Ovarian Neoplasms * genetics   diagnosis   drug therapy   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors * therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Poznatky o molekulárních subtypech karcinomu endometria (EC) vedly v posledních několika letech k velkým změnám v klasifikačním systému, v prognostických skupinách a ve svém důsledku v terapeutických postupech u pacientek s pokročilým, metastatic­kým a recidivujícím karcinomem endometria. Nejvýznamnějším posunem v obtížně léčitelné kohortě pacientek s pokročilým, metastatickým a recidivujícím EC od dob konvenční chemoterapie je jednoznačně kombinace checkpoint inhibitoru pembrolizumabu s antiangiogenním preparátem lenvatinibem, nezávislá na přítomnosti mikrosatelitové nestability (MSI) nádorových buněk. Ve skupině MSI-high karcinomů se jako velmi úspěšné jeví podání dostarlimabu v monoterapii. iPARP byly vyšetřovány v mnoha terapeutických designech a je evidentní, že jejich léčebné využití bude u pacientek s EC s deficitem v homologní rekombinaci, bez ohledu na BRCA status. Mechanizmus účinku iPARP je u pacientek s EC založený na frekventní přítomnosti PTEN mutace a mutace TP53, jež souvisí právě s deficitem v homologní rekombinaci. iPARP mají jednak vlastní cytotoxický účinek a jednak senzitizují buňky EC k účinkům checkpoint inhibitorů. Ve sdělení je sumarizována současná evidence o preklinickém výzkumu a klinickém využití iPARP u pacientek s pokročilým, metastatickým a rekurentním EC. Nově je v České republice olaparib schválen k podávání v udržovací léčbě v kombinaci s durvalumabem u pacientek s primárně pokročilým nebo rekurentním EC (mismatch repair proficientním - pMMR), které neprogredovaly na I. linii systémové terapie v kombinaci paclitaxel, karboplatina a durvalumab.

Knowledge of molecular subtypes of endometrial cancer (EC) has led to major changes in the classification system, prognostic groups and, as a result, in therapeutic procedures in patients with advanced, metastatic and recurrent endometrial cancer (EC) in the last few years. The most significant shift in the difficult-to-treat cohort of patients with advanced, metastatic and recurrent EC since conventional chemotherapy is clearly the combination of the checkpoint inhibitor pembrolizumab with the antiangiogenic agent lenvatinib, independent of the presence of microsatellite instability (MSI) of tumor cells. In the MSI-high group of carcinomas, the administration of dostarlimab monotherapy appears to be very successful. iPARPs have been investigated in many therapeutic designs and it is evident that their therapeutic use will be in EC patients with homologous recombination deficiency, regardless of BRCA status. The mechanism of action of iPARP in EC patients is based on the frequent presence of PTEN mutation and TP53 mutation, which is related to the deficit in homologous recombination. iPARPs have both their own cytotoxic effect and sensitize EC cells to the effects of checkpoint inhibitors. The article summarizes the current evidence on preclinical research and clinical use of iPARP in patients with advanced, metastatic and recurrent EC. In the Czech Republic, olaparib is newly approved for administration in maintenance therapy in combination with durvalumab in patients with primarily advanced or recurrent EC (mismatch repair proficient - pMMR) who have not progressed on first-line systemic therapy in combination with paclitaxel, carboplatin and durvalumab.

• MeSH
• Molecular Targeted Therapy MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   therapeutic use   MeSH
• Immune Checkpoint Inhibitors therapeutic use   MeSH
• Humans MeSH
• Endometrial Neoplasms * diagnosis   drug therapy   genetics   pathology   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors administration & dosage   pharmacology   therapeutic use   MeSH
• Antineoplastic Agents, Immunological administration & dosage   therapeutic use   MeSH
• Antineoplastic Protocols MeSH
• Genes, Tumor Suppressor MeSH
• Check Tag
• Humans MeSH

Na základě genetických a morfologických znaků je triple negativní karcinom prsu považován za heterogenní onemocnění, čímž se nabízí otázka, jestli nám nemůže molekulární subtypizace ovlivnit volbu terapie a tím i prodloužit život pacientů, protože triple negativní karcinom prsu se řadí mezi prognosticky nejméně příznivé nádory vůbec.

Analysis of genetics and morphology has shown that triple negative breast cancer is a heterogeneous disease, which brings us to question, if molecular subtyping of triple negative breast cancer can change therapy approach and prolong life of patients, because triple negative breast cancer has one of the worst prognosis of all tumors.

• MeSH
• Chemotherapy, Adjuvant MeSH
• Ki-67 Antigen adverse effects   MeSH
• Genetic Phenomena drug effects   MeSH
• Immunotherapy methods   MeSH
• Humans MeSH
• Antibodies, Monoclonal MeSH
• Poly(ADP-ribose) Polymerase Inhibitors pharmacology   therapeutic use   MeSH
• Prognosis MeSH
• Triple Negative Breast Neoplasms * drug therapy   genetics   classification   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Review MeSH

Tato kazuistika představuje případ pacientky, která byla léčena pro pokročilý ovariální karcinom. Standardně podstoupila cytoredukční výkon (primary debulking surgery) následovaný šesti cykly kombinované chemoterapie na bázi platinového derivátu spolu s paklitaxelem. Protože u pacientky v rámci genetického vyšetření byla zjištěna germinální mutace v genu homologní rekombinace BRCA1, byla indikována udržovací neboli maintenance terapie olaparibem. Vzhledem k hematotoxicitě musela být počáteční dávka upravena, ale i na snížené dávce je pacientka v dlouhodobé remisi.

This case report presents the case of a patient who was treated for advanced ovarian carcinoma. She underwent standard cytoreductive surgery (primary debulking surgery) followed by six cycles of combination chemotherapy based on a platinum derivative along with paclitaxel. Since a mutation in the BRCA1 homologous recombination gene was detected in the patient during genetic testing, maintenance therapy with olaparib was indicated. Due to hematotoxicity the initial dose had to be adjusted, but even at a reduced dose, the patient remains in long-term remission of disease.

• Keywords
• olaparib,
• MeSH
• Cytoreduction Surgical Procedures MeSH
• Genes, BRCA1 MeSH
• Homologous Recombination MeSH
• Remission Induction MeSH
• Middle Aged MeSH
• Humans MeSH
• Ovarian Neoplasms * surgery   drug therapy   classification   mortality   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors pharmacology   therapeutic use   MeSH
• Maintenance Chemotherapy MeSH
• Germ-Line Mutation genetics   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Terapie léky ze skupiny inhibitorů poiy(ADP-ribóza) polymerázy (PARP) je nejmodernějším krokem v léčbě ovariálního karcinomu. Až u poloviny karcinomů vaječníků lze nalézt defekt homologní rekombinace, jednoho ze způsobů opravy DNA. Proto se tento nádor stal modelem pro vývoj látek, které terapeuticky zasahují na úrovni reparace DNA. Buňky s poruchou homologní rekombinace musí využívat jiné cesty opravy DNA. Tyto cesty se tak stávají terapeutickým cílem. Proteiny rodiny PARP, především PARP1, hrají významnou roli v opravě jednovláknových zlomů DNA mechanismem nahrazování jednotlivých bází (base excision repair). Inhibice PARP vede ke kumulaci jednovláknových zlomů DNA, a následně, v důsledku kolapsu replikační vidlice, i k nahromadění dvouvláknových zlomů DNA. Tyto zlomy jsou ale opravovány jiným reparačním mechanismem - právě homologní rekombinací. Vyřazení dalšího z mechanismů opravy DNA inhibicí proteinu PARP olaparibem vede ke zvýšení citlivosti nádorových buněk k chemoterapii, nebo přímo k tzv. syntetické letaLitě. Tato léčba byla donedávna vyhrazena pacientkám s prokázanou germinální nebo somatickou mutací genů BRCA1 a BRCA2. Data o účinnosti PARP inhibitoru niraparibu však dovolila standardní použití u všech pacientek s pokročilým ovariálním karcinomem bez ohledu na mutační status. Prezentovaná kazuistika předkládá popis průběhu onemocnění u pacientky bez prokázané germinální nebo somatické mutace genů BRCA1 nebo BRCA2 s pokročilým high-grade serózním karcinomem ovaria, jíž byl po primární adjuvantní léčbě chemoterapií podáván perorální PARP inhibitor - niraparib - v udržovací léčbě. Přes vyšší toxicitu v úvodu léčby bylo, i za použití techniky deeskalace a reeskalace dávky, dosaženo dlouhodobého přežití bez známek onemocnění se zachováním vynikající kvality života.

Therapy with drugs from the group of poiy(ADP-ribose) polymerase (PARP) inhibitors is the latest step in the treatment of ovarian cancer. Defects in homologous recombination, one of the DNA repair pathways, can be found in up to half of ovarian cancers. Therefore, this tumor has become a model for the development of agents that therapeutically intervene at the level of DNA repair. Cells with defects in homologous recombination must use other DNA repair pathways. These pathways thus become therapeutic targets. PARP family proteins, particularly PARP1, play an important role in the repair of single-stranded DNA breaks by base excision repair. Inhibition of PARP leads to the accumulation of single-stranded DNA breaks and subsequently, due to replication fork collapse, to the accumulation of double-stranded DNA breaks. However, these breaks are repaired by another repair mechanism - homologous recombination. Knocking out another DNA repair mechanism by inhibiting the PARP protein with olaparib leads to i ncreased sensitivity of cancer cells to chemotherapy or directly to so-called synthetic lethality. Until recently, this treatment was reserved for patients with proven germline or somatic mutations in the BRCA1 and BRCA2 genes. However, data on the efficacy of the PARP inhibitor niraparib allowed standard use in all patients with advanced ovarian cancer regardless of mutational status. The present case report describes the course of disease in a patient without a proven germline or somatic mutation of the BRCA1 or BRCA2 genes with advanced high-grade serous ovarian cancer who was treated with the oral PARP inhibitor niraparib as maintenance therapy after primary adjuvant chemotherapy. Despite higher toxicity in the initial treatment, long-term disease-free survival with preservation of an excellent quality of life was achieved, even using dose de-escalation and re-escalation techniques.

• Keywords
• niraparib,
• MeSH
• Homologous Recombination drug effects   MeSH
• Quality of Life MeSH
• Middle Aged MeSH
• Humans MeSH
• Ovarian Neoplasms * drug therapy   genetics   mortality   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors pharmacology   therapeutic use   MeSH
• Disease-Free Survival MeSH
• Recurrence MeSH
• Maintenance Chemotherapy * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Asi u čtvrtiny mužů s metastatickým kastračně rezistentním karcinomem prostaty (mCRPC) můžeme nalézt mutaci v některém z genů, které se účastní oprav DNA pomocí homologní rekombinace. Proteinovou skupinu poly-adenozindifosfát-ribózo-polymeráz (PARP) můžeme zablokovat pomocí tzv. PARP inhibitorů a opravy DNA tak neproběhnou. Prvním PARP inhibitorem, schváleným pro léčbu mCRPC progredujícího po léčbě abirateronem nebo enzalutamidem, je olaparib. Navíc v kombinaci s abirateronem jej můžeme použít již v první linii, kdy mCRPC progreduje na standardní hormonální léčbě.

About a quarter of men with metastatic castration-resistant prostate cancer (mCRPC) have a mutation in one of the genes involved in DNA repair through homologous recombination. The protein group poly (ADP-ribose) polymerase (PARP) can be blocked using so-called PARP inhibitors and DNA repair will not be done. The first PARP inhibitor approved for the treatment of mCRPC progressing after treatment with abiraterone or enzalutamide is olaparib. In addition, in combination with abiraterone, we can use it already in the first line, when mCRPC progresses on standard hormonal treatment.

• Keywords
• olaparib,
• MeSH
• Abiraterone Acetate administration & dosage   MeSH
• Progression-Free Survival MeSH
• Clinical Studies as Topic MeSH
• Drug Therapy, Combination methods   MeSH
• Humans MeSH
• Neoplasm Metastasis drug therapy   MeSH
• Prostatic Neoplasms, Castration-Resistant drug therapy   genetics   complications   MeSH
• Prostatic Neoplasms * drug therapy   genetics   complications   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors * administration & dosage   pharmacology   MeSH
• Antineoplastic Agents administration & dosage   MeSH
• Statistics as Topic MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Pokročilý karcinom prostaty (KP) má relativně často změny v genech, které se účastní opravy DNA. V tom případě můžeme opravu zlomů DNA zablokovat pomocí inhibitorů poly(adenosindifosfát-ribóza)polymerázy (PARP). Nejvíce dat máme o účinnosti inhibitoru PARP olaparibu, který je možné podat pacientům s metastatickým kastračně rezistentním KP (mCRPC) a pozitivitou mutace BRCA1/2 po předchozí léčbě abirateronem nebo enzalutamidem. Druhou indikaci představuje kombinace olaparibu s abirateronem v 1. linii léčby mCRPC (bez nutnosti genetického testování), pokud není klinicky indikována chemoterapie. Talazoparib můžeme podat v kombinaci s enzalutamidem pacientům s mCRPC, u kterých také není indikována chemoterapie. Testování nádorových mutací není vyžadováno. Obdobně také niraparib v kombinaci s abirateronem můžeme použít u pacientů s mCRPC a mutacemi genu BRCA1/2, u kterých nezvažujeme chemoterapii. Výsledky v léčbě mCRPC má ještě rukaparib, který v České republice zatím není možné mužům s KP podávat.

Advanced prostate cancer (PC) relatively often has alterations in genes involved in DNA repair. In that case, we can block the repair of DNA breaks using poly-adenosine diphosphate-ribose-polymerase (PARP) inhibitors. The most studied PARP inhibitor is olaparib, which can be given to patients with metastatic castration-resistant PC (mCRPC) and a positive BRCA1/2 mutation after previous treatment with abiraterone or enzalutamide. The next indication is the combination of olaparib with abiraterone in the firstline treatment of mCRPC (without the need for genetic testing), if chemotherapy is not clinically indicated. Talazoparib can be given in combination with enzalutamide to patients with mCRPC who are also not indicated for chemotherapy. Tumor mutation testing is not required. Similarly, we can also use niraparib in combination with abiraterone in patients with mCRPC and BRCA1/2 gene mutations, if chemotherapy is not considered. Also rucaparib has results in the treatment of mCRPC, but is not yet available for men with PC in the Czech Republic.

• Keywords
• talazoparib, Niraparib,
• MeSH
• Phthalazines therapeutic use   MeSH
• Indazoles therapeutic use   MeSH
• Clinical Studies as Topic methods   MeSH
• Humans MeSH
• Prostatic Neoplasms * drug therapy   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors * therapeutic use   MeSH
• Piperidines therapeutic use   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Hyperthermic Intraperitoneal Chemotherapy methods   MeSH
• Humans MeSH
• Minimally Invasive Surgical Procedures methods   MeSH
• Antibodies, Monoclonal pharmacology   therapeutic use   MeSH
• Ovarian Neoplasms * therapy   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors pharmacology   therapeutic use   MeSH
• Radiotherapy methods   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Review MeSH