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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.

Objective: To determine the impact on overall survival (OS) and patient-reported outcomes (PROs) of combining atezolizumab with standard therapy for newly diagnosed stage III/IV ovarian cancer., Methods: The placebo-controlled double-blind randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial (NCT03038100) assigned eligible patients to 3-weekly atezolizumab 1200 mg or placebo for 22 cycles with platinum-based chemotherapy and bevacizumab. Coprimary endpoints were progression-free survival (already reported) and OS in the PD-L1-positive and intent-to-treat (ITT) populations, tested hierarchically. Prespecified PRO analyses focused on disease-related abdominal pain and bloating symptoms (European Organisation for Research and Treatment of Cancer QLQ-OV28), functioning, and health-related quality of life (HRQoL) (QLQ-C30)., Results: After 38 months' median follow-up, the OS hazard ratio in the PD-L1-positive population was 0.83 (95% CI, 0.66-1.06; p = 0.13); median OS was not estimable with atezolizumab versus 49.2 months with placebo. The hazard ratio for OS in the ITT population was 0.92 (95% CI, 0.78-1.09; median 50.5 versus 46.6 months, respectively). At week 9, similar proportions of patients in both arms of the neoadjuvant cohort showed ≥10-point improvement from baseline in abdominal pain and bloating, functioning, and HRQoL. In the primary surgery cohort, similar proportions of patients in each arm had improved, stable, or worsened physical and role function and HRQoL from baseline over time. Neither cohort showed differences between arms in treatment-related symptoms or overall side-effect bother., Conclusions: Incorporation of atezolizumab into standard therapy for newly diagnosed ovarian cancer does not significantly improve efficacy or impose additional treatment burden for patients., Clinicaltrials: gov registration: NCT03038100., Competing Interests: Declaration of Competing Interest Sandro Pignata: Personal fees (Roche, AstraZeneca, MSD, PharmaMar, GSK, Clovis, Incyte); Research funding to institution (Roche, MSD, AstraZeneca, Clovis, GSK). Michael Bookman: Administrative and per-capita funding for conduct of the clinical trial paid to institution; Consultation fees paid to institution for ad hoc advisory boards (Merck Sharp & Dohme, AstraZeneca, Genentech/Roche, Clovis Oncology, Seattle Genetics, Aravive, AbbVie) and Data Monitoring Committee (Immunogen). Jalid Sehouli: Research funding (Roche Pharma, AstraZeneca, Bayer, Clovis Oncology, GSK, Lilly, Tesaro); Honoraria (Tesaro, GSK, PharmaMar, AstraZeneca, Clovis Oncology, Bayer, Roche, PharmaMar, Vifor Pharma, Hexal AG, Novartis Pharma); Consulting (Tesaro, Merck/Pfizer, PharmaMar, Clovis Oncology, AstraZeneca, Roche Pharma, GSK, MSD, Eisai, Novocure, Oncoinvent). Richard T. Penson: Institutional research funding as principal investigator (Array BioPharma Inc., AstraZeneca., Eisai Inc., Genentech, Inc., Regeneron, Sanofi-Aventis US LLC, Vascular Biogenics Ltd); Royalties (BMJ Publishing, UptoDate, Elsevier Ltd., Wolters Kluwer Health, Wiley Blackwell); Consulting fees for advisory boards (AstraZeneca, Eisai, GSK Inc., ImmunoGen Inc., Merck & Co., Mersana, Novacure, Roche Pharma, Sutro Biopharma, Vascular Biogenics Ltd); serves on Data and Safety Monitoring Boards (AstraZeneca, EQRx, Roche Pharma). Sakari Hietanen: Consultancy fees (AstraZeneca, Eisai, MSD, GSK); Speaker bureau (AstraZeneca, GSK). Radoslaw Madry: Licences/payments (AstraZeneca); Consulting fees (Roche, MSD, AstraZeneca); Honoraria (GSK, AstraZeneca, Roche); Support for attending meetings and/or travel (AstraZeneca, Roche); Participation on Data Safety Monitoring or Advisory Boards (GlaxoSmithKline, AstraZeneca); Receipt of equipment, materials, drugs, medical writing, gifts, or other services (AstraZeneca). Lyndsay Willmott: Honoraria for speaker bureau (AstraZeneca, Clovis, Eisai, Immunogen, GSK, Merck, Seagen); Honoraria for advisory bureau (Genentech); Participation on advisory boards (AstraZeneca, Clovis, Eisai, Genentech, GSK, Immunogen, Seagen). Tashanna Myers: Personal honorarium for lecture (Immunogen); Honorarium to institution for advisory board (Immunogen). Alain Lortholary: Personal honoraria (AstraZeneca, Clovis Oncology, Tesaro/GSK, Roche, MSD, Novartis). Jessica Thomes-Pepin: Consulting fees for advisory board (Immunogen). Carol Aghajanian: Clinical trial funding to institution (AbbVie, AstraZeneca, Clovis, Genentech/Roche); Consulting fees for advisory boards (AbbVie, Roche/Genentech, Eisai/Merck, AstraZeneca/Merck, Repare Therapeutics); Participation on an advisory board (Blueprint medicine [unrecompensed]); Membership of the Board of Directors (GOG-F [travel cost reimbursement for attending meetings], NRG Oncology [unpaid]). Carolyn McCourt: Royalties (UpToDate). Ashley Stuckey: Royalties (UpToDate). Xiaohua Wu: Honorarium for advisory board (Roche). Larry J. Copeland: DMC membership (Corcept Therapeutics, Inc.); Personal fees for advisory boards (Celsion Corporation, Corcept Therapeutics, Inc., Elevar Therapeutics, GSK Inc., Immunogen, Myriad Genetics, Inc., Rubius Therapeutics, Sorrento Therapeutics, Toray Industries, Inc., VBL Therapeutics, Inc., OncoNova, Inc., Inx Med); Research funding to institution (AbbVie, Advaxis, Agenus, Ajinomoto, Array BioPharm, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Deciphera Pharma, Eisai, EMD Serono Inc., ERGOMED Clinical Research, Exelixis, Genentech/Roche, Genmab, GSK, Inc., Hoffmann-La Roche, Immunogen, Incyte Corporation, Iovance Biotherapeutics, InVentive Health Clinical, Jansen R&D, Leap Therapetuics, Ludwig Institute for Pharmaceuticals, Merck, Mersana Therapeutics, Inc., Novocure, Novartis Pharmaceuticals, OncoQuest, PRA International, Regeneron Pharmaceuticals, Seattle Genetics, Serono, Sutro Biopharm, Tesaro (GSK), Arcus Biosciences, Inc., Sumitomo Dainippon Pharma Oncology, Cerulean Pharma, Karyopharm, BeiGene USA, Inc., Ovagene, Pfizer Inc., PharmaMar USA Inc.,Precision Therapeutics, Inc., Sanofi, Stemcentrx, Inc., TRACON Pharm, Verastem, Inc.). Yvette He: Employee contracted to provide statistical support to Roche (Parexel). Luciana Molinero, Sheetal Patel, and Victor K. Khor: Employees (Roche/Genentech); Share holders (Roche). Yvonne G. Lin: Employee (Roche/Genentech); Participation on Advisory Board (Intervenn Biosciences, unpaid); Leadership position/committee member (SGO Membership Committee); Share holder (Roche). Kathleen N. Moore: Research funding to institution (PTC Therapeutics, Lilly, Clovis, Genentech, GSK, Verastem), Personal royalties (UptoDate), Personal consulting fees for advisory boards (Aadi, Alkemeres, Aravive, AstraZeneca, Blueprint pharma, Caris, Clovis, Eisai, Genentech/Roche, GSK, Hengrui, Immunogen, Inxmed, IMab, Iovance, Lilly, Merck, Mereo, Mersana, Myriad, Novartis, Novocure, Onconova, OncXerna, Pannavance, Tarveda, VBL Therapeutics, Verastem); Personal honoraria for lectures/presentations/speaker bureau (AstraZeneca, GSK, Immunogen, PRIME, RTP, Medscape, Great Debates and Updates); Support for attending meetings and/or travel (AstraZeneca); Leadership role (GOG Partners Associate director). All authors: Medical writing and article processing charges (F. Hoffmann-La Roche)., (Copyright © 2023. Published by Elsevier Inc.)

Background: The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment., Methods: Patients received maintenance olaparib capsules (400 mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort. The co-primary endpoints were investigator-assessed progression-free survival (PFS; modified Response Evaluation Criteria in Solid Tumors v1.1) in BRCAm and sBRCAm cohorts. Secondary endpoints included health-related quality of life (HRQoL) and tolerability., Results: 177 patients received olaparib. At the primary data cut-off (17 April 2020), the median follow-up for PFS in the BRCAm cohort was 22.3 months. The median PFS (95% CI) in BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts was 18.0 (14.3-22.1), 16.6 (12.4-22.2), 19.3 (14.3-27.6) and 16.4 (10.9-19.3) months, respectively. Most patients with BRCAm reported improvements (21.8%) or no change (68.7%) in HRQoL and the safety profile was as expected., Conclusions: Maintenance olaparib had similar clinical activity in PSR OC patients with sBRCAm and those with any BRCAm. Activity was also observed in patients with a non-BRCA HRRm. ORZORA further supports use of maintenance olaparib in all patients with BRCA-mutated, including sBRCA-mutated, PSR OC., Competing Interests: Declaration of Competing Interest Sandro Pignata: Honoraria from AstraZeneca, Merck Sharp & Dohme (MSD), Roche, Pfizer, GlaxoSmithKline (GSK) and Clovis Pharma; and research funding from Roche, MSD, AstraZeneca and Pfizer. Amit Oza: Principal investigator of investigator-initiated studies with AstraZeneca; institutional grant funding from AstraZeneca; and steering committee member (non-compensated) for AstraZeneca, Clovis Oncology and GSK. Geoff Hall: Research funding from IQVIA. Beatriz Pardo: Research funding from AstraZeneca, GSK, Clovis and MSD. Radoslaw Madry: Advisory board participation for AstraZeneca, Roche and GSK; and personal fees from AstraZeneca, Roche and GSK. David Cibula: Advisory board participation for AstraZeneca, Roche, Genmab, SOTIO, Merck and GSK. Jaroslav Klat: Reports no disclosures. Ana Montes: Reports no disclosures. Rosalind Glasspool: Principal investigator for trials sponsored by AstraZeneca, Clovis, Tesaro, Immunogen, Pfizer and Lilly; research funding from Clovis, Boehringer Ingelheim and Lilly/Ignyta; institution research funding from Tesaro; institutional fees from Novartis and personal fees from AstraZeneca, MSD, Clovis, Tesaro, GSK, Immunogen and SOTIO. Nicoletta Colombo: Personal fees from AstraZeneca, MSD, Roche, Tesaro, GSK, Clovis Oncology, PharmaMar, Pfizer, Amgen, Novartis, BIODCAD and Immunogen. Imre Pete: Reports no disclosures. Ana Herrero Ibáñez: Consulting/advisory board participation for GSK; speakers’ bureau participation for Clovis, GSK, MSD and PharmaMar; and research funding from AstraZeneca and Roche. Margarita Romeo Marín: Institution research funding from AstraZeneca, GSK, Clovis and Pfizer. Personal fees from MSD and GSK. Rumya Ilieva: Reports no disclosures. Constanta Timcheva: Principal investigator of clinical trials of AstraZeneca, Roche, Novartis, Pfizer and Merck; and member of advisory boards of Astellas, Servier and Novartis. Massimo Di Maio: Principal investigator of clinical trials of Roche, Merck, BeiGene, Novartis, Pfizer and Exelixis; member of advisory boards of AstraZeneca, Roche, Novartis, Pfizer, Eisai, Astellas, Janssen, Merck and Amgen; institutional research funding from Tesaro – GlaxoSmithKline. Christopher Blakeley: AstraZeneca employment and stock ownership. Rosie Taylor: AstraZeneca contractor. Alan Barnicle: AstraZeneca employment and stock ownership. Andrew Clamp: Research funding from AstraZeneca; and honoraria from AstraZeneca, Clovis Oncology, GSK/Tesaro and Eisai., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The ESO-ESSO-ESTRO Multidisciplinary Course in Oncology is intended to fill the gap of the undergraduate fragmented oncology education, to provide insight into all theoretical and practical aspects of oncology, and to encourage future professional choices towards an oncology discipline. Students are exposed to (a) preclinical cancer topics; (b) natural history of the disease; (c) laboratory diagnostic tests; (d) medical, radiation, surgical, and palliative treatment; and (e) direct or through multidisciplinary patients' approach. Students are obliged to attend (i) all theoretical lectures, (ii) clinical case presentations, (iii) laboratories and ward visits, and (iv) to prepare and present a specific project under supervision. Participation is limited to 24 medical students who are selected through a competitive application process. Between 2016 and 2019, 96 students from 29 countries have attended. Data analysis derived from a given questionnaire demonstrates that most of the participants have declared that (1) they have achieved their expectations and objectives, (2) they have highly rated both clinical and non-clinical teaching oncological topics, and (3) they have been stimulated in developing a professional career in the field of oncology., (© 2021. American Association for Cancer Education.)

Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition., Design: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts' consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines., Results: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive., Conclusion: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer., Competing Interests: Disclosure IV: Consulting (2019-2021): Aksebio (2021); Amgen (Europe) GmbH (2019); AstraZeneca (2019-2022); BMS (2021); Clovis Oncology Inc. (2019-2019); Carrick Therapeutics (2019); Deciphera Pharmaceuticals (2020-2021); Eisai (2021); Elevar Therapeutics (2020); F. Hoffmann-La Roche Ltd (2019-2021); Genmab (2019-2021); GSK (2019-2021); Immunogen Inc. (2019-2022); Jazzpharma (2021-2022); Karyopharm (2021); Mersana (2020); Millennium Pharmaceuticals (2019); MSD (2019-2022); Novocure (2020-2022); Novartis (2021); Octimet Oncology NV (2019); Oncoinvent AS (2019-2022); Sotio a.s. (2019-2022); Verastem Oncology (2020); Zentalis (2020). Contracted research: Oncoinvent AS (2019-2020); Genmab (2019-2021). Corporate sponsored research: Amgen (2019-2020); Roche (2019-2020). AG-M: Consulting (2019-2021): Amgen (Europe) (2019); AstraZeneca (2019-2021); Clovis Oncology Inc. (2019-2021); Eisai (2021); F. Hoffmann-La Roche Ltd (2019-2021); Genmab (2019-2020); GSK (2019-2021); Immunogen Inc. (2019-2021); Mersana (2020); MSD (2019-2021); Novocure (2020); Novartis (2021); Oncoinvent AS (2019-2021); Sotio (2019-2021). Contracted research: La Roche (2019-2021); GSK (2019-2021).IR-C: Consulting (2019-2021): Amgen (2019-2021); AstraZeneca (2019-2021); Clovis Oncology Inc. (2019-2021); Eisai (2021); F. Hoffmann-La Roche Ltd (2019-2021); Genmab (2019-2020); GSK (2019-2021); Mersana (2020-2021); Merck Serono (2020-2021); MSD (2019-2021); Novocure (2021); Novartis (2021); OnxEo (2020-2021); Pharmamar (2019-2021); Deciphera (2019-2021). Contracted research: BMS (2019-2021); MSD (2019-2021).PH: Honoraria: Amgen, AstraZeneca, GSK, Roche, Sotio, Stryker, Zai Lab, MSD, Clovis. Advisory board: AstraZeneca, Roche, GSK, Clovis, Immunogen, MSD/Merck. Research funding (institute): AstraZeneca, Roche, GSK, Genmab, Immunogen, Clovis. NC: Consulting: AstraZeneca; BIOCAD; Clovis Oncology; Eisai; GlaxoSmithKline; Immunogen; Mersana; MSD; Oncxerna; Pharmamar; Pfizer; Roche; Tesaro. Promotional speaker: AstraZeneca; Clovis; Eisai; GlaxoSmithKline; MSD; Novartis; Tesaro. PP: AstraZeneca (2019-2021); Exact Science (2019-2021); GSK (2019-2021); HEDERADx (2021); MSD (2019-2021); Novartis (2020); Onco DNA (2019-2021); Pfizer (2019-2021); Predilife (2019-2021); Seqone (2019-2021).DL: Consulting (2019-2021): Amgen (2020); AstraZeneca (2019-2021); Clovis Oncology Inc. (2019-2021); Eisai (2021); F. Hoffmann-La Roche Ltd (2019-2020); Genmab (2019-2021); GSK (2019-2021); Immunogen Inc. (2019-2021); MSD (2019-2021); Novartis (2021); Merck Serono (2020-2021); Pharmamar (2019-2021). Contracted research: MSD (2019-2021); GSK (2019-2021); Clovis Oncology (2019-2021). MRM: Consulting and lectures: AstraZeneca; Biocad; GSK; Karyopharm; Merck; Roche; Zailab. Contracted research: Apexigen; AstraZeneca; GSK; Ultimovacs. Other: Karyopharm & Sera Prognistics (Member of Board of Directors); Deciphera (Trial Chair). BB: Consulting (2019-2021): F. Hoffmann-La Roche (2019-2020); AstraZeneca (2019-2020); Merck Serono (2019-2020); Pharmaswiss (2019-2020); GSK (2019); Novartis (2019-2021). Contracted research: AstraZeneca (2020-2021); F. Hoffmann-La Roche (2019-2020). RM: Consulting (2019-2021): AstraZeneca (2019-2021); F. Hoffmann-La Roche Ltd (2019-2020); GSK (2019-2021). JDB: Consulting (2020-2021): AstraZeneca. Contracted research: Clovis Oncology (2019); Aprea (2019-21); Tailor Bio (2020-21); Other: Co-founder and shareholder Inivata (2019-2021); Co-founder and shareholder Tailor Bio (2019-2021). MGEMA: Consulting (2019-2020): MSD. Contracted research: Pfizer (2020); AstraZeneca (2020). RB: Consulting and lectures (2019-2021): AbbVie; AstraZeneca; Bayer; BMS; Boehringer-Ingelheim; Janssen; Illumina; Lilly; MSD; Novartis; Qiagen; Pfizer; Roche. Other (2019-2021): Testifying Advisor for MSD in GBA-assessment for Pembrolizumab, Advisor for Durvalumab. Co-Founder and CSO for Targos Molecular Pathology, Kassel/Germany until April 2021. DL: Consulting (2019-2021): AstraZeneca (2019-2021); BMS (2019); Boehringer Ingelheim (2019); Montis Biosciences (2021); MSD (2019-2021). Contracted research: Montis Biosciences (2021)., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Human papillomavirus infection is one of the most common sexually transmitted diseases. Long-term exposure to the HPV leads to development of high-grade squamous intraepithelial lesions that can eventually transform into cervical cancer. The aim of the study was to assess the HPV genotype distribution in patients with abnormal pap smear and provide prospective study., Material and Methods: We obtained material from 674 women who registered to Specialist Medical Practice in the years 2008-2020. The sample for the molecular test was collected using combi brush and forwarded to the independent, standardized laboratory. HPV detection was done using PCR followed by DNA enzyme immunoassay and reverse hybridization line probe assay for virus genotyping. Sequence analysis was performed to characterize virus genotypes in HPV - positive samples., Results: We found that 53% of patients tested positive for HPV. The percentage decreased with age. The following HPV types were the most common: HPV - 16 (24.5%), HPV - 53 (13.1%), HPV - 31 (10.3%), HPV - 51 (9.7%), HPV - 56 (9.5%). To our knowledge, this study is the largest assessment of HPV genotypes in Poland., Conclusions: Our results suggest that type-specific, high-risk HPV DNA - based screening should focus on HPV types 16, 31, 51, 56.

Objective: DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer., Methods: In this open-label, parallel-group, phase 2 trial (ClinicalTrials.gov number NCT02107950), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3-6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint)., Results: Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42-1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20-0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa., Conclusions: DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity., Competing Interests: Declaration of Competing Interest BM: Honoraria for speeches and advisory role from Roche, Pfizer, BMS, Astellas, Novartis, Bayer, MSD, Merck Serono, Sanofi, Servier, AstraZeneca, Amgen, Janssen, Eisai, E. Lilly, Pierre Farbre, and travel support from BMS and Merck Serono. LG: Research funding from Lytix and Phosplatin, consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, OmniSEQ, The Longevity Labs, Inzen, and the Luke Heller TECPR2 Foundation. LP: Personal fees from SOTIO a.s., Daiichi Sankyo, and Beckman Coulter. PK: Consulting/advisory honoraria from SOTIO a.s. HIBH, JF, TH, MH: Employees of SOTIO a.s. JB: Employee of and holds stock in SOTIO a.s. RS: Employee of and holds stock in SOTIO a.s., and holds a patent for HHP killing of tumor cells. The other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Most patients with ovarian cancer will relapse after receiving frontline platinum-based chemotherapy and eventually develop platinum-resistant or platinum-refractory disease. We report results of avelumab alone or avelumab plus pegylated liposomal doxorubicin (PLD) compared with PLD alone in patients with platinum-resistant or platinum-refractory ovarian cancer., Methods: JAVELIN Ovarian 200 was an open-label, parallel-group, three-arm, randomised, phase 3 trial, done at 149 hospitals and cancer treatment centres in 24 countries. Eligible patients were aged 18 years or older with epithelial ovarian, fallopian tube, or peritoneal cancer (maximum of three previous lines for platinum-sensitive disease, none for platinum-resistant disease) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1:1) via interactive response technology to avelumab (10 mg/kg intravenously every 2 weeks), avelumab plus PLD (40 mg/m 2 intravenously every 4 weeks), or PLD and stratified by disease platinum status, number of previous anticancer regimens, and bulky disease. Primary endpoints were progression-free survival by blinded independent central review and overall survival in all randomly assigned patients, with the objective to show whether avelumab alone or avelumab plus PLD is superior to PLD. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02580058. The trial is no longer enrolling patients and this is the final analysis of both primary endpoints., Findings: Between Jan 5, 2016, and May 16, 2017, 566 patients were enrolled and randomly assigned (combination n=188; PLD n=190, avelumab n=188). At data cutoff (Sept 19, 2018), median duration of follow-up for overall survival was 18·4 months (IQR 15·6-21·9) for the combination group, 17·4 months (15·2-21·3) for the PLD group, and 18·2 months (15·8-21·2) for the avelumab group. Median progression-free survival by blinded independent central review was 3·7 months (95% CI 3·3-5·1) in the combination group, 3·5 months (2·1-4·0) in the PLD group, and 1·9 months (1·8-1·9) in the avelumab group (combination vs PLD: stratified HR 0·78 [repeated 93·1% CI 0·59-1·24], one-sided p=0·030; avelumab vs PLD: 1·68 [1·32-2·60], one-sided p>0·99). Median overall survival was 15·7 months (95% CI 12·7-18·7) in the combination group, 13·1 months (11·8-15·5) in the PLD group, and 11·8 months (8·9-14·1) in the avelumab group (combination vs PLD: stratified HR 0·89 [repeated 88·85% CI 0·74-1·24], one-sided p=0·21; avelumab vs PLD: 1·14 [0·95-1·58], one-sided p=0·83]). The most common grade 3 or worse treatment-related adverse events were palmar-plantar erythrodysesthesia syndrome (18 [10%] in the combination group vs nine [5%] in the PLD group vs none in the avelumab group), rash (11 [6%] vs three [2%] vs none), fatigue (ten [5%] vs three [2%] vs none), stomatitis (ten [5%] vs five [3%] vs none), anaemia (six [3%] vs nine [5%] vs three [2%]), neutropenia (nine [5%] vs nine [5%] vs none), and neutrophil count decreased (eight [5%] vs seven [4%] vs none). Serious treatment-related adverse events occurred in 32 (18%) patients in the combination group, 19 (11%) in the PLD group, and 14 (7%) in the avelumab group. Treatment-related adverse events resulted in death in one patient each in the PLD group (sepsis) and avelumab group (intestinal obstruction)., Interpretation: Neither avelumab plus PLD nor avelumab alone significantly improved progression-free survival or overall survival versus PLD. These results provide insights for patient selection in future studies of immune checkpoint inhibitors in platinum-resistant or platinum-refractory ovarian cancer., Funding: Pfizer and Merck KGaA, Darmstadt, Germany., Competing Interests: Declaration of interests EP-L reports personal fees from AstraZeneca, Clovis Oncology, Incyte, Pfizer, Roche, and Tesaro; non-financial support from AstraZeneca, Roche, and Tesaro; and is the chair of ARCAGY-Research. KF reports grants and personal fees from Pfizer during the conduct of the study; and grants and personal fees from AstraZeneca, Chugai Pharma, Eisai, Genmab, Merck & Co, Taiho Pharmaceutical, and Zeria Pharmaceutical; grants from GSK, Immunogen, Lilly, OncoTherapy, and Regeneron; and personal fees from Daiichi Sankyo, Janssen, Kyowa Hakko Kirin, Mochida, Nippon Kayaku, and Novartis outside the submitted work. JAL reports serving as a consultant or advisor for Artios Pharma, AstraZeneca, Clovis Oncology, Eisai, GSK, Merck & Co, and Pfizer; has received research funding from AstraZeneca and Merck & Co; has received honoraria from AstraZeneca, Clovis Oncology, Eisai, and GSK; and has participated in an independent monitoring committee for Regeneron. RK reports personal fees from Clovis Oncology, Eisai, GSK, Incyte, and Roche; has received non-financial support from GSK; and grants from Merck & Co. I-LR-C reports personal fees from AstraZeneca, Clovis Oncology, GSK, Merck KGaA, Mersana Therapeutics, and Roche; received grants from Bristol Myers Squibb and GSK; and has received reimbursement for travel and accommodation expenses from AstraZeneca and GSK. KY reports serving as a consultant or advisor for AstraZeneca, Chugai Pharma, Eisai, Novartis, and Takeda; and received honoraria from AstraZeneca, Eisai, Pfizer, Takeda, and Taiho Pharmaceutical. SB reports personal fees from AstraZeneca, Clovis Oncology, Genmab, Immunogen, Merck KGaA, Mersana Therapeutics, Pfizer, Roche, and Tesaro; and has received grants from AstraZeneca, GSK, Merck & Co, and Tesaro. AL reports grants from Pfizer during the conduct of the study; serving as a consultant or advisor for AstraZeneca, BIOCAD, Clovis Oncology, GSK/Tesaro, Merck KGaA, Merck & Co, and Zentalis Pharmaceuticals; and has received reimbursement for travel and accommodation expenses from AstraZeneca, Clovis Oncology, and GSK/Tesaro. AVT has received honoraria and grants from AstraZeneca. KHJ reports personal fees from AstraZeneca, Celgene, Novartis, Roche, and Takeda Pharmaceuticals. FZ reports employment at and holds stock in Pfizer. RAS reports employment at Pfizer at the time when the study was conducted. CW reports employment at and holds stock in Pfizer. SSD reports employment at Pfizer. BJM reports serving as a consultant or advisor for and has received honoraria from Agenus, Akeso Bio, Aravive, AstraZeneca, Clovis Oncology, Eisai, Elevar Therapeutics, Genmab/Seattle Genetics, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Merck & Co, Mersana Therapeutics, Myriad Pharma, Novocure, Pfizer, Puma Biotechnology, Roche/Genentech, Tesaro/GSK, and VBL Therapeutics; is a member of a speakers' bureau for AstraZeneca, Clovis Oncology, Eisai, Merck & Co, Roche/Genentech, and Tesaro/GSK; and reports employment at McKesson/US Oncology. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: A phase II study (ClinicalTrials.gov identifier: NCT00628251) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy., Patients and Methods: In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician's choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population., Results: Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% v 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; P = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; P = .013; median, 13.4 v 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy., Conclusion: Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.

Background: Niraparib is a poly(ADP-ribose) polymerase inhibitor approved in the USA and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to treatment-emergent adverse event (TEAE) was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was carried out to identify clinical parameters that predict dose reductions., Patients and Methods: All analyses were carried out on the safety population, comprising all patients who received at least one dose of study drug. Patients were analyzed according to the study drug consumed (i.e., as treated). A predictive modeling method (decision trees) was used to identify important variables for predicting the likelihood of developing grade ≥3 thrombocytopenia within 30 days after the first dose of niraparib and determine cut-off points for chosen variables., Results: Following dose modification, 200 mg was the most commonly administered dose in the ENGOT-OV16/NOVA trial. Baseline platelet count and baseline body weight were identified as risk factors for increased incidence of grade ≥3 thrombocytopenia. Patients with a baseline body weight <77 kg or a baseline platelet count <150 000/µl in effect received an average daily dose ∼200 mg (median = 207 mg) due to dose interruption and reduction. Progression-free survival in patients who were dose reduced to either 200 or 100 mg was consistent with that of patients who remained at the 300 mg starting dose., Conclusions: The analysis presented suggests that patients with baseline body weight of <77 kg or baseline platelets of <150 000/µl may benefit from a starting dose of 200 mg/day., Clinicaltrials.gov Id: NCT01847274.

EMSY, a BRCA2-associated protein, is amplified and overexpressed in various sporadic cancers. This is the first study assessing the clinical impact of its expression and polymorphisms on ovarian cancer (OvCa) outcome in the context of the chemotherapy regimen used. In 134 frozen OvCa samples, we assessed EMSY mRNA expression with Reverse Transcription-quantitative PCR, and also investigated the EMSY gene sequence using SSCP and/or PCR-sequencing. Clinical relevance of changes in EMSY mRNA expression and DNA sequence was evaluated in two subgroups treated with either taxane/platinum (TP, n=102) or platinum/cyclophosphamide (PC, n=32). High EMSY expression negatively affected overall survival (OS), disease-free survival (DFS) and sensitivity to treatment (PS) in the TP-treated subgroup (p-values: 0.001, 0.002 and 0.010, respectively). Accordingly, our OvCa cell line studies showed that the EMSY gene knockdown sensitized A2780 and IGROV1 cells to paclitaxel. Interestingly, EMSY mRNA expression in surviving cells was similar as in the control cells. Additionally, we identified 24 sequence alterations in the EMSY gene, including the previously undescribed: c.720G>C, p.(Lys240Asn); c.1860G>A, p.(Lys620Lys); c.246-76A>G; c.421+68A>C. In the PC-treated subgroup, a heterozygous genotype comprising five SNPs (rs4300410, rs3814711, rs4245443, rs2508740, rs2513523) negatively correlated with OS (p-value=0.009). The same SNPs exhibited adverse borderline associations with PS in the TP-treated subgroup. This is the first study providing evidence that high EMSY mRNA expression is a negative prognostic and predictive factor in OvCa patients treated with TP, and that the clinical outcome may hinge on certain SNPs in the EMSY gene as well., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to disclose.

Purpose: The aim of this study was to evaluate whether body weight changes in patients undergoing chemotherapy for epithelial ovarian cancer (EOC) influence progression-free survival (PFS) and overall survival (OS)., Methods: An analysis of 190 patients diagnosed with ovarian cancer after first-line chemotherapy was conducted. Changes in body weight were assessed by comparing measurements at baseline to those of the third and sixth cycles of chemotherapy. PFS and OS were calculated with the Kaplan-Meier method and multivariate Cox model., Results: Significant reduction in body weight in advanced EOC was observed with no changes in early EOC. Significant differences in PFS were observed in advanced EOC patients that lost more than 5 % of their body weight (6 months), maintained weight (13 months), or gained more than 5 % of their body weight (15 months). Similarly, significant differences in OS were noted in advanced EOC at the following time points: 24.3, 42.4, and 66.2 months. No effect was reported for early EOC patients. The multivariate Cox analysis showed significant body weight changes from the first to the sixth chemotherapy cycle for PFS (HR = 0.97; 95 % CI 0.95-0.99) and OS (HR = 0.94; 95 % CI 0.91-0.97) as well as from the first to the third chemotherapy cycle for OS (HR = 0.93; 95 % CI 0.88-0.98)., Conclusions: Body weight changes can be recognized as a prognostic factor for PFS and OS in advanced EOC patients undergoing chemotherapy. Weight loss is associated with poorer survival while weight gain improved outcomes.

An increasing number of patients with diagnosed synchronous or metachronous neoplasms that arc gene as well as non-gene dependent which are associated with the development of new oncological treatment, and environmental factors, prompted the authors of this study to conduct an analysis in a narrow group of patients with multiple cancers and simultaneous BRCA1I mutations (confirmed by genetic analysis). BRCA1 mutation, as well as multiple cancers were found in seven patients treated between 2007 and 2013. The patients diagnosed with a second cancer shared a uniquely common trait - a 5382insC mutation. The study describes four patients that did not carry a BRCA 1/2 mutation, yet were diagnosed with multiple cancers. A brief review of literature was performed concerning multiple cancers in women.

The authors present two cases of benign tumors one located on the outer surface of the vulva, and the second extending beyond the vagina. The first, originating from the right pudendal lip, a lipoma measuring 23 cm in greatest diameter, weighing 6.6 kg, and the second a pedunculated, uterine smooth muscle myoma with a pedicle of 6.5 cm, maximum diameter 18 cm, weight 700 grams, which caused significant metroptosis. Operative procedures in each case were free of complications.

A case report of a 50-cm diameter and 20-kg mass of benign ovarian tumor. Total abdominal hysterectomy with a bilateral salpingooophorectomy was performed with full patient recovery. Fibrothecomas can remain long asymptomatic and can grow to giant sizes.

Aim of the Study: To evaluate an association between food products consumption, dietary intake and the incidence of selected gastrointestinal symptoms (nausea, vomiting, diarrhea and constipation) in cancer patients undergoing chemotherapy., Material and Methods: Fifty six women receiving chemotherapy for ovarian cancer were eligible for the study. Anthropometrical measurements were assessed. The dietary intake was evaluated by 24-hours food records. The association between the consumption of selected food products and gastrointestinal symptoms incidences was assessed by modified semi-quantitative food frequency questionnaire including 77-different food items that was developed and applied in cancer patients undergoing chemotherapy., Results: BMI values indicated 9%, 45%, 30% and 16% of patients as underweight, normal weight, overweight and obese respectively. Only 23% and 32% of patients never experienced nausea and constipation when 43% and 45% never experienced vomiting and diarrhea. Nausea was promoted by oils, constipation by chocolate and chocolate products and diarrhea by dairy products, stone fruit and apple. Significant inverse correlations were found between vomiting and the intake of energy, fat, protein, carbohydrates, B groups vitamins, vitamin D, phosphorus and zinc. The difference in energy intake between marginal values of vomiting incidence exceeded 400 kcal., Conclusions: Dietary intake as well as specific food products influence on gastrointestinal side effect of chemotherapy in cancer patients. The dietary approach based on either exclusion or limited intake of selected food products and improvement of diet could reduce and prevent chemotherapy induced gastrointestinal symptoms therefore should be taken under consideration in clinical practice., Competing Interests: The authors declare no conflict of interest.

Objective: Despite the considerable disease burden of ovarian cancer, there were no cost studies in Central and Eastern Europe. This study aimed to describe treatment patterns, health care utilization, and costs associated with treating ovarian cancer in Hungary, Poland, Serbia, and Slovakia., Method: Overall clinical practice for management of epithelial ovarian cancer was investigated through a 3-round Delphi panel. Experts completed a survey based on the chart review (n = 1542). The survey was developed based on clinical guidelines and the International Federation of Gynecology and Obstetrics Annual Report. Means, ranges, and outlier values were discussed with the experts during a telephone interview. Finally, consensus estimates were obtained in face-to-face workshops. Based on these results, overall cost of ovarian cancer was estimated using a Markov model., Results: The patients included in the chart review were followed up from presurgical diagnosis and in each phase of treatment, that is, surgical staging and primary surgery, chemotherapy and chemotherapy monitoring, follow-up, and palliative care. The 5-year overall cost per patient was €14,100 to €16,300 in Hungary, €14,600 to €15,800 in Poland, €7600 to €8100 in Serbia, and €12,400 to €14,500 in Slovakia. The main components were chemotherapy-associated costs (68%-74% of the total cost), followed by cost of primary treatment with surgery (15%-21%) and palliative care (3%-10%)., Conclusions: Patients with ovarian cancer consume considerable health care resources and incur substantial costs in Central and Eastern Europe. These findings may prove useful for clinicians and decision makers in understanding the economic implications of managing ovarian cancer in Central and Eastern Europe and the need for innovative therapies.

Angiogenesis is a dynamic process which leads to a development of cancer and metastases. The most recognized and dominant prognostic factor is vascular endothelial growth factor (VEGF) and its receptors. VEGF was identyfied in 1989. There are three receptors for VEGF: VEGFR1 (VEGF receptor 1) and VEGFR2 that play the role in angiogenesis and development of ascites, and VEGFR3 is critical for lymphangiogenesis. There is bevacizumab--a new drug, monoclonal antibody that can block connection VEGF to its receptors. The first notification of activity of bevacizumab in ovarian cancer was in 2005. The aim of the article is to show some clinical trials in ovarian cancer and their results. The bevacizumab was registered in November 2011 in first line with standard chemotherapy in ovarian cancer. There is a new weapon against this disease.

BRCA1 dysfunction may occur by different mechanisms that are rarely evaluated concomitantly. We aimed to analyze BRCA1 germline mutations, loss of heterozygosity (LOH) and promoter methylation in unselected ovarian carcinomas in the context of their clinicopathologic characteristics and other molecular changes. BRCA1 mutations were analyzed in 257 carcinomas using single-strand conformation polymorphism (SSCP), heteroduplex, and sequencing methods. LOH at the BRCA1 locus was screened for in 180 cancers. Methylation analysis was performed for 241 tumors using quantitative methylation specific PCR (qMSP). BRCA1 alterations, comprising germline mutations, allelic loss, and/or aberrant promoter methylation, were found in 77.6% (125/161) of ovarian carcinomas. Patients with germline mutations were younger than non-carriers (P < 0.0001). Germline mutations and LOH were associated with advanced stages (P=0.009, P < 0.0001), high tumor grade (P=0.005, P < 0.0001), and TP53 mutations (P=0.003, P < 0.0001, for mutations and LOH, respectively). LOH was also associated with the serous histological type (P=0.004) and PIK3CA amplification (P=0.003). Aberrant promoter methylation was associated with LOH (P=0.017) and absence of germline mutations (P=0.037). The high frequency of LOH at the BRCA1 locus suggests that LOH may be an important mechanism of BRCA1 deficiency in ovarian carcinomas. Tumors with various BRCA1 alterations have a similar phenotype of high-grade, high-stage carcinomas with frequent TP53 mutations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Survivin is an inhibitor of apoptosis and a regulator of mitotic progression. TP53 protein is a negative transcriptional regulator of survivin. The aim of our study was to evaluate the clinical significance of survivin expression in advanced stages ovarian cancer with respect to the TP53 status., Methods: Survivin and TP53 expression was evaluated immunohistochemically in 435 archival samples of ovarian carcinomas (244 patients were treated with platinum/cyclophosphamide-PC/PAC; 191-with taxane-platinum (TP) agents). Univariate and multivariate statistical analyses were performed in patients groups divided according to the administered chemotherapeutic regimen, and in subgroups with and without TP53 accumulation (TP53+ and TP53-, respectively)., Results: Nuclear and cytoplasmic survivin expression was observed in 92% and 74% of the carcinomas, respectively. In patients treated with TP, high nuclear survivin expression decreased the risk of disease recurrence and death, and increased the probability of high platinum sensitivity (p < 0.01), but only in the TP53(+) group, and not in the TP53(-) group., Conclusions: It appears that TP53 status determines the clinical importance of nuclear survivin expression in taxane-platinum treated ovarian cancer patients.

Pathomechanism of burn shock is associated with an important endocrine disorder and cytokines storm. As a result of the burns are released to bloodstream kinins such as: histamine, serotonin and bradykinin and also inflammatory mediators such as: tromboxans, prostacyclins, prostaglandins and leukotrienes. Arises temporary endothelial failure. Comes to the escape of liquid blood to the tissues and a sudden decrease in the quantity of the fluid in the vessels and appear symptoms of burn shock. Offset of fluids by vascular wall to the extravascular space described mathematically with Landis-Starling law. Treatment of burn shock relies on intensive fluid therapy to fill vessels. Fluid rules are based on infusion crystalloids, colloids, hypersaline or plasma. Effect of fluid resuscitation after severe burn are edemas of whole body. Severe burn receives up to 25 000 ml of fluids intravenous in the first 48 hours after injury. The quantity of water defaulting tissue after 48 hours is even 13 000-18 500 ml which is 300-400% of the volume of blood flow. From 3rd day after burn this may produce symptoms of acute circulatory insufficiency or polycompartment syndrom. Enforces this restrictive fluid treatment and removing significant quantities of water from the bloodstream. In East Poland Burn Center and Reconstructive Surgery we remove even 300-350 ml fluid/h by ultrafiltration during CVVHD CiCa. Additional application hemodynamic monitoring such Vigileo-Flotrac has considerably reduce the amount of complications such as: intra-abdominal hypertension IAH, acute heart syndrome, cerebral edema and pulmonary edema.

Procedures aimed at the treatment of precancerous lesions and ectopia on the uterine cervix are frequently linked to lesions of anatomical structures. The application of hyaluronic acid (Cicatridine vaginal ovules) promotes accelerated healing of the uterine cervix and acquisition of a normal shape in the uterine cervix canal. Local application of hyaluronic acid in the vagina following radiotherapy due to cancer in the uterine cervix or endometrium favourably affects the healing of post-irradiation lesions in the vagina and improves quality of life. Over 90% of patients responded positively to the application of hyaluronic acid in the form of a cream on dystrophic lesions in the vulva. Hyaluronic acid aids the healing process of post-procedural wounds in the uterine cervix, following radiotherapy applied due to cancer of the uterine cervix, endometrium and in vulvar dystrophy.

Advances in cancer treatment of young patients have resulted in markedly improved survival rates and quality of life. However infertility remains to be one of adverse effects of anticancer therapy. Female patients who receive high-dose abdominal and/or pelvic irradiation or chemotherapy based on alkylating agents are at highest risk of developing ovarian failure. Among women whose fertility was not impaired during oncologic treatment, there is a significantly increased number of premature labors. High-dose irradiation also predisposes to low-birthweight infants. Neither chemotherapy nor radiotherapy increase a risk of congenital malformations.

Objective: The aim of this study was to evaluate selected clinical, histological and diagnostic factors as prognostics of time and location of endometrial cancer recurrence. We also attempted to design a more efficient follow-up protocols for patients with recurrent endometrial cancer., Methods: A retrospective review of 196 patients with recurrent endometrial cancer treated at the Department of Gynecologic Oncology, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, was done. Recurrence was analyzed by site, presence or absence of symptoms and methods of detection. We focused our attention on the impact of specific disease characteristics on pattern and risk of recurrence., Results: Vast majority of recurrences (88%) occurred within the first 3 years after the primary treatment, whereas 71% within the first two years after the completion of the treatment. More than half of the patients (55%) were symptomatic when relapse occurred, while no statistically significant differences were found in time to relapse between the symptomatic and the asymptomatic group. Disease-free time observed when vaginal relapse occurred was significantly shorter compared to distant sites (p = 0.049). Histological maturity of primary tumor seems to be a prognostic of disease-free time (p = 0.039). Also patients with histological type I and II seem to have different courses of the disease (p = 0.064). Among recurrent endometrial cancer cases, pelvic examination, abdominal or pelvic ultrasound and chest x-ray could detect 95% of relapses., Conclusions: A follow-up program in the first three years after the primary treatment of endometrial cancer is useful in detecting recurrent disease. There is no reason to use an intensive program of follow-up in patients with low risk primary disease. Pelvic examination, vaginal and abdominal ultrasound, chest x-ray are good and not expensive methods in relapse detection. There is no clinical justification for the routine use of the Pap smear in the follow-up of patients with endometrial cancer.

Both ghrelin and obestatin are derived from preproghrelin by post-translational processing. The two peptides are secreted into the blood but circulating levels of these peptides have not been assessed in women with ovarian tumours. Therefore, the purpose of this study was to evaluate peripheral blood concentrations of active and total ghrelin and obestatin in patients with benign ovarian tumours and those with ovarian cancer. The studies were conducted on 22 patients operated due to benign ovarian tumours, and 31 patients operated due to ovarian cancer. A control group consisted of 32 women, 24 to 65 years of age. Both in women with benign ovarian tumours and those with ovarian cancer blood concentrations of active ghrelin and obestatin were higher than in the control group (active ghrelin: 90 +/- 4, 84 +/- 4 and 56 +/- 9 pg/ml, respectively, obestatin: 660 +/- 36; 630 +/- 30 and 538 +/- 31 ng/ml (x +/- SE), respectively). In contrast, total ghrelin concentrations in blood were similar in the studied groups. The alterations resulted in increased values of active to total ghrelin concentration ratio in the peripheral blood of patients with benign ovarian tumours or with ovarian cancer (0.79 +/- 0.02 and 0.93 +/- 0.05, respectively vs 0.58 +/- 0.02 in the control group). Due to the absence of any convincing proof for the presence of a functional GHS-R-1a receptor for ghrelin in human ovaries it did not seem probable that the observed elevated levels of active ghrelin and obestatin were directly linked to development of ovarian tumours.