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Ovarian cancer (OC) presents daunting lethality rates worldwide, with frequent late-stage diagnosis and chemoresistance, highlighting the need for improved prognostic approaches. Venous thromboembolism (VTE), a major cancer mortality factor, is partially driven by endothelial dysfunction (ED). ED's pro-inflammatory state fosters tumour progression, suggesting a VTE-independent link between ED and cancer. Given this triad's interplay, ED markers may influence OC behaviour and patients' prognosis. Thus, the impact of ED-related genes and single-nucleotide polymorphisms (SNPs) on OC-related VTE and patient thrombogenesis-independent prognosis was investigated. NOS3 upregulation was linked to lower VTE incidence (χ2, p = 0.013), while SELP upregulation was associated with shorter overall survival (log-rank test, p = 0.048). Dismissing patients with VTE before OC diagnosis, SELP rs6136 T allele carriers presented lower progression-free survival (log-rank test, p = 0.038). Nevertheless, due to the SNP minor allele underrepresentation, further investigation is required. Taken together, ED markers seem to exhibit roles that depend on the clinical context, such as tumour-related thrombogenesis or cancer prognosis. Validation with larger cohorts and more in-depth functional studies are needed for data clarification and potential therapeutic strategies exploitation to tackle cancer progression and thrombosis in OC patients. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is a leading cause of death among gynaecological malignancies. The haemostatic system, which controls blood flow and prevents clotting disorders, paradoxically drives OC progression while increasing the risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) have emerged as crucial in understanding VTE pathogenesis. Exploring the connection between cancer and thrombosis through these RNAs could lead to novel biomarkers of cancer-associated thrombosis (CAT) and OC, as well as potential therapeutic targets for tumour management. Thus, this study examined the impact of eight plasma miRNAs targeting the tissue factor (TF) coagulation pathway—miR-18a-5p, -19a-3p, -20a-5p, -23a-3p, -27a-3p, -103a-3p, -126-5p and -616-3p—in 55 OC patients. Briefly, VTE occurrence post-OC diagnosis was linked to shorter disease progression time (log-rank test, p = 0.024) and poorer overall survival (OS) (log-rank test, p < 0.001). High pre-chemotherapy levels of miR-20a-5p (targeting coagulation factor 3 (F3) and tissue factor pathway inhibitor 2 (TFPI2)) and miR-616-3p (targeting TFPI2) predicted VTE after OC diagnosis (χ2, p < 0.05). Regarding patients' prognosis regardless of VTE, miR-20a-5p independently predicted OC progression (adjusted hazard ratio (aHR) = 6.13, p = 0.005), while miR-616-3p significantly impacted patients' survival (aHR = 3.72, p = 0.020). Further investigation is warranted for their translation into clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: The exploration of prognostic biomarkers in ovarian cancer (OC) persists due to the daunting challenge of therapy resistance and poor patient outcomes. Dysregulated components of haemostasis are recognized as pivotal players in OC pathogenesis, contributing to tumour growth, metastasis, and the onset of cancer-associated thrombosis (CAT). Drawing upon the concept of immunothrombosis, which elucidates the intricate crosstalk among immune cells, platelets, and endothelial cells, this study investigated the expression of haemostasis-related genes in peripheral blood entities (particularly platelets and immune cells). The aim was to uncover prognostic markers, potential therapeutic targets for cancer management, and CAT predictors. Lower pre-chemotherapy F3 and F8 expression levels were significantly associated with increased CAT susceptibility post tumour diagnosis. The latter was also associated with shorter progression-free and overall survival. These findings point out the prognostic potential of these genes in OC in the context of immunothrombosis. Validation in larger cohorts is essential for clinical translation. Ovarian cancer (OC) is the deadliest gynaecological malignancy. Identifying new prognostic biomarkers is an important research field. Haemostatic components together with leukocytes can drive cancer progression while increasing the susceptibility to venous thromboembolism (VTE) through immunothrombosis. Unravelling the underlying complex interactions offers the prospect of uncovering relevant OC prognostic biomarkers, predictors of cancer-associated thrombosis (CAT), and even potential targets for cancer therapy. Thus, this study evaluated the expression of F3, F5, F8, F13A1, TFPI1, and THBD in peripheral blood cells (PBCs) of 52 OC patients. Those with VTE after tumour diagnosis had a worse overall survival (OS) compared to their counterparts (mean OS of 13.8 ± 4.1 months and 47.9 ± 5.7 months, respectively; log-rank test, p = 0.001). Low pre-chemotherapy F3 and F8 expression levels were associated with a higher susceptibility for OC-related VTE after tumour diagnosis (χ2, p < 0.05). Regardless of thrombogenesis, patients with low baseline F8 expression had a shorter progression-free survival (PFS) than their counterparts (adjusted hazard ratio (aHR) = 2.54; p = 0.021). Among those who were not under platelet anti-aggregation therapy, low F8 levels were also associated with a shorter OS (aHR = 6.16; p = 0.006). Moving forward, efforts should focus on external validation in larger cohorts. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann–Whitney U test, p = 0.037; Χ2 test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients. [ABSTRACT FROM AUTHOR]

Abstract Background Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD). Methods In this study, we evaluated DPYD promoter methylation through quantitative methylation-specific PCR and screened DPYD for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29 patients Results Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However, DPYD promoter methylation and large DPYD intragenic rearrangements were absent in all cases analyzed. Conclusions Our results indicate that DPYD promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity.

Abstract Introduction Langerhans' cell histiocytosis is a proliferative histiocytic disorder of unknown cause originating from dendritic cells. Case presentation The authors report a case of Langerhans' cell histiocytosis in a 48-year-old man with multisystemic disease presentation, including liver involvement. Conclusion Hepatic involvement is an uncommon feature in this rare disease and there is no consensus on the most effective therapeutic approach.

Burnout is a professional syndrome associated with stress caused by overwork. Our aim was to calculate the prevalence of burnout and stress on medical residents of Oncology, Haematology and Radiotherapy in Portugal, as well as to determine predictors of burnout and stress. An anonymous questionnaire was applied (n = 118). Statistical analysis consisted of a descriptive and inferential analysis. The prevalence of burnout and stress was calculated to be 45.2 and 50%, respectively. The dimensions that generated higher levels of stress were ‘dealing with patients’ and ‘overwork’. Burnout was directly related with stress dimension ‘overwork’. The prevalence of burnout in Portuguese oncological residents is high as in other European countries and in the U.S. Therefore, interventional strategies can be designed. [ABSTRACT FROM PUBLISHER]

MGMT downregulation in high-grade gliomas (HGG) has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP) or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA). By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation) and genetic (monosomy, locus deletion) changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD). Methods: In this study, we evaluated DPYD promoter methylation through quantitative methylation-specific PCR and screened DPYD for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29 patients Results: Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However, DPYD promoter methylation and large DPYD intragenic rearrangements were absent in all cases analyzed. Conclusions: Our results indicate that DPYD promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity. [ABSTRACT FROM AUTHOR]

Objectives: Maintenance therapies, including poly (ADP-ribose) polymerase (PARP) inhibitors and/or bevacizumab, have substantially improved the prognosis of patients with advanced ovarian cancer. Owing to the variability in treatment strategies across Europe, a Delphi study was conducted among European experts to understand the heterogeneity of clinical practice and identify key factors driving maintenance treatment decisions for advanced ovarian cancer., Methods: A pragmatic literature review was conducted to identify key questions regarding maintenance treatment strategies in patients with advanced ovarian cancer. Utilizing a Delphi methodology, consensus was assessed among a panel of 16 experts using a questionnaire based on results of the pragmatic literature review., Results: Panelists agreed that BRCA mutation and homologous recombination status should be assessed in parallel at diagnosis, and that first-line platinum chemotherapy may be initiated concurrently. There was a consensus that alternative homologous recombination deficiency tests are acceptable provided they are clinically validated. Panelists agreed that Response Evaluation Criteria in Solid Tumors (RECIST) and CA-125 elimination rate constant K (KELIM) scores can help assess tumor chemosensitivity and guide treatment-related decisions. Panelists defined high-risk disease as International Federation of Gynecology and Obstetrics (FIGO) stage IV disease or stage III with residual disease after initial/interval cytoreduction. Risk of disease progression was a key determinant of choice between PARP inhibitor, bevacizumab, or both in combination, as maintenance therapy in advanced ovarian cancer., Conclusions: Key drivers for selecting advanced ovarian cancer maintenance treatments include tumor mutational status as a key biomarker and clinician perception of the risk for early disease progression., Competing Interests: Competing interests: BY has had consulting positions for MSD, AstraZeneca, GSK-TESARO, Bayer, Roche-Genentech, ECS Progastrin, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, Seagen, Myriad, Menarini, Gilead, and Eisai. APF has had advisory roles for AstraZeneca, GSK-Tesaro, Clovis, PharmaMar, Abilify Pharma, and Eisai; has been a speaker for AstraZeneca, GSK-Tesaro, Clovis, PharmaMar, Karyopharm and Seagen; and has received research grants to their institution from GSK, PharmaMar, AstraZeneca, and Novartis. BS has received grants/research support from AstraZeneca, Roche, MSD, and GSK; honoraria or consultation fees from AstraZeneca, Roche, MSD, GSK, and Eisai; and has participated in company-sponsored speakers bureaus for AstraZeneca, Roche, MSD, GSK, and Eisai. AG has received honoraria from AstraZeneca, GSK, Merck, Roche, and Clovis; and has been a speaker for AstraZeneca, GSK, Merck, and Clovis. CG has received grants from AstraZeneca, MSD, Novartis, GSK, BerGen Bio, Merdannex, Roche, and Verastem; and has received honoraria from AstraZeneca, MSD, GSK, Clovis, Verastrem, Takeda, Eisai, Cor2Ed, and Peer Voice. SP has received honoraria from AstraZeneca, MSD, GSK, Roche, Clovis, Immunogen and AbbVie; and research/funding from AstraZeneca, Roche, MSD, and GSK. DL has had consulting or advisory roles for AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Novocure, Seagen, Sutro; has received research funding to their institution from AstraZeneca, Clovis Oncology, Pharma & Genmab, GSK, Immunogen, Incyte, MSD, Novartis, Pharmamar, Roche, Seagen, alkermes and Corcept; has received travel accommodation/expenses from AstraZeneca, GSK and MSD. MPBG has had advisory roles for AstraZeneca, MSD, GSK, Clovis, PharmaMar, and Eisai; has been a speaker for AstraZeneca, MSD, GSK, Clovis, and PharmaMar; and has received travel accommodation and expenses from AstraZeneca, MSD, GSK, and PharmaMar. IR has had advisory roles for Roche, AstraZeneca, GSK, and Clovis; has received grants/research support from Roche, AstraZeneca, and GSK; has received honoraria from PharmaMar, Roche, AstraZeneca, GSK, MSD, Eisai, and Seagen; and has been a sponsored speaker for PharmaMar, Roche, AstraZeneca, GSK, and MSD. CGr has received funding from AstraZeneca, Meda Pharma, and Roche Diagnostics; honoraria or consultation fees from AstraZeneca, Celgene, Clovis, Eisai, GSK, MSD, PharmaMar, Roche, and Vifor Pharma; and has participated in company-sponsored speakers bureaus for Amgen, AstraZeneca, Eisai, GSK, MSD, PharmaMar, and Roche. TVG has consulted/advised for AstraZeneca, BioNTech, Eisai, GSK, ImmunoGen, Incyte, Karyopharm, MSD/Merck, OncXerna Therapeutics, Seagen, Tubulis, Zentalis; travel, accommodations, and/or expenses paid by AstraZeneca, ImmunoGen, MSD/Merck, PharmaMar; research funding from Amgen, AstraZeneca, and Roche; all payments are institutional. MR has received grants/research support from Neye Foundation, Novo Nordisk Foundation, and AstraZeneca; and has received honoraria or consultation fees from Laegeforeningen/Danish Medical Association, AstraZeneca, and GSK. DCC has received honoraria from Amgen, AZD, GSK, Janssen, Pfizer, and MSD Oncology; has had consulting or advisory roles with Seagen, Genmab, MSD Oncology, and GSK; and has received research funding from Roche and Pfizer. JF has received honoraria from AstraZeneca and GSK. LB has received funding from AstraZeneca, Helse Vest, and the University of Bergen; has been a sponsored speaker for GSK and MSD. AL has received funding from Sanofi, Roche, GSK, BMS, AstraZeneca, Ose Immuno, Lovance, Agenus, Arcagy Gineco, Ability Pharma, Apmonia, Blueprint Medicines Corporation, MSD, Clovis, Merck Serono, Onko+, Zentalis, Kephren, and Medscape. TdlMR has received grants/research support from Seagen, MSD, and Pfizer; honoraria or consultation fees from AstraZeneca, Pfizer, MSD, GSK, Gilead, Clovis Oncology, and Esai; and has participated in company-sponsored speakers bureaus for AstraZeneca, GSK, and MSD. PH has received honoraria from Amgen, AstraZeneca, GSK, Roche, Sotio, Stryker, Zai Lab, MSD, Clovis, Eisai, Mersana, and Exscientia; has participated in advisory boards for AstraZeneca, Roche, GSK, Clovis, Immunogen, MSD, Miltenyi, Novartis, and Eisai; and has received research funding to their institution from AstraZeneca, Roche, GSK, Genmab, DFG, European Union, DKH, Immunogen, Seagen, Clovis, and Novartis. CK has received honoraria or consultation fees from GSK, AstraZeneca, Novartis, PharmaMar, Genomic Health, Roche, Eli Lilly, Merck MSD, Pfizer, and Daiichi Sankyo; has participated in company-sponsored speakers bureaus for GSK, AstraZeneca, Novartis, and Roche; and has received travel support from GSK, AstraZeneca, and Roche. JS-B has received honoraria or consultation fees from AstraZeneca, GSK, and MSD; and has received grants/research support from AstraZeneca, Novartis, Pfizer, and Roche., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)