bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2026–02–08
eight papers selected by
Lara Paracchini, Humanitas Research
  1. Clinical Validation of a Cell-Free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection-Reply.
  2. Serous Ovarian Cancer Following Opportunistic Bilateral Salpingectomy.
  3. BRCA1 and BRCA2 carriers: Perceptions of endometrial cancer risk.
  4. Opportunistic Salpingectomy for Prevention of Tubo-Ovarian Carcinoma: The European Society of Gynaecological Oncology Consensus Statements.
  5. Evaluation of homologous recombination testing in ovarian carcinoma.
  6. Ultra-deep duplex sequencing reveals unique features of somatic evolution in the normal tissues of a family with Li-Fraumeni syndrome.
  7. Leveraging multi-modal foundation models for analysing spatial multi-omic and histopathology data.
  8. Longitudinal ctDNA monitoring for post-surgical disease surveillance in patients with stage I-IIIB melanoma.
  1. Cancer Discov. 2026 Feb 06. 16(2): 190-191
    Clinical Validation of a Cell-Free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection-Reply.
    Peter J Mazzone, Peter B Bach, Robert B Scharpf, Victor E Velculescu, Luke R G Pike.
      
    DOI:  https://doi.org/10.1158/2159-8290.CD-25-2046
  2. JAMA Netw Open. 2026 Feb 02. 9(2): e2557267
    Serous Ovarian Cancer Following Opportunistic Bilateral Salpingectomy.
    Ramlogan Sowamber, Alice J Mei, Paramdeep Kaur, Julianne McLeod, Emily McKay, Alex Lukey, Jamie Bakkum-Gamez, Natalia Buza, Paul A Cohen, Kyle Devins, Rhonda Farrell, Christine Garcia, Blake Gilks, Ellen Goode, Anjelica Hodgson, Brooke Howitt, Pei Hui, Jutta Huvila, Anthony Karnezis, Kianoosh Keyhanian, Mary Kinloch, Martin Köbel, Felix K F Kommoss, Lawrence Kushi, Janice S Kwon, Kara Long-Roche, Anais Malpica, Jessica N McAlpine, Dianne Miller, Esther Oliva, Andrea Palicelli, Aleksandra Paliga, Carlos Parra-Herran, Celeste Leigh Pearce, Sharnel Perera, Jurgen M Piek, Haiyan Qiu, Joseph Rabban, Robert Rome, Miranda Steenbeek, Rebecca Stone, Aline Talhouk, Kristin M Tischer, Britton Trabert, Penelope M Webb, John R Zalcberg, David G Huntsman, Gillian E Hanley.
      
    DOI:  https://doi.org/10.1001/jamanetworkopen.2025.57267
  3. Gynecol Oncol. 2026 Jan 30. pii: S0090-8258(26)00238-6. [Epub ahead of print]206 23-31
    BRCA1 and BRCA2 carriers: Perceptions of endometrial cancer risk.
    Mark E Sherman, Laura Pacheco-Spann, Susan Friedman, Diane Rose, William D Foulkes, Christopher C DeStephano, Kristina A Butler, Kathryn J Ruddy, Zhihui Fang, Lauren E Haydu.
       OBJECTIVE: To survey knowledge, preferred information sources, and risk tolerance for EC among BRCA1 and BRCA2 pathogenic variant (PV) carriers.
    METHODS: Electronic survey of 332 anonymous women. Descriptive statistics presented.
    RESULTS: Participants included non-Hispanic White (89.3%) United States residents (91.7%), with mean age of 45 years; 50.6% were BRCA 1 and 45.7% were BRCA 2 carriers; 56.7% had undergone risk-reducing surgery, including hysterectomy in 44.3%. Most cited reasons for hysterectomy were physician recommendation and EC risk. Among women with intact uteri, 42.2% or participants indicated that they would undergo hysterectomy if EC risk was ≥15%. When queried about specific EC risk factors, responses of "don't know" (if risk is increased or decreased) were given for 30.9%-75.5%, and specifically for BRCA1: 55.2% and for BRCA2: 72.6%. Participants expressed preferences for sources of information about EC risk (decreasing order) as gynecologic oncologists; medical oncologists; genetic counselors and gynecologists. Respondents indicated that providers recommended hysterectomy for 36.0%, against hysterectomy for 15.7% or gave conflicting information for 16.6%.
    CONCLUSIONS: Many carriers have limited knowledge of EC risk and do not receive consistent counseling about hysterectomy.
    Keywords:  BRCA; Endometrial cancer; Mutation; Risk-reducing surgery
    DOI:  https://doi.org/10.1016/j.ygyno.2026.01.235
  4. JAMA. 2026 Feb 02.
    Opportunistic Salpingectomy for Prevention of Tubo-Ovarian Carcinoma: The European Society of Gynaecological Oncology Consensus Statements.
    Jurgen M Piek, Jolijn Schauwaert, Laura Burney Ellis, Ignacio Zapardiel, François Planchamp, Kata Koblos, Joanna Kacperczyk-Bartnik, Sarah J Bowden, Houssein El Hajj, Mihaela Grigore, Miranda P Steenbeek, Nicolò Bizzarri, Maria Kyrgiou, Murat Gültekin.
       Importance: The fallopian tube epithelium has been demonstrated to be an important source of tubo-ovarian carcinoma. Therefore, removal of the fallopian tubes during unrelated pelvic or abdominal surgery (opportunistic salpingectomy) can potentially lower future ovarian cancer risk.
    Objectives: To assess current evidence on the efficacy, risks, and long-term outcomes of opportunistic salpingectomy and to develop consensus statements for the European Society of Gynaecological Oncology.
    Evidence Review: An international working group of 14 individuals including a patient representative was formed to develop consensus statements on opportunistic salpingectomy. The MEDLINE database was used to conduct a literature review of English-language studies from January 1, 2000, through March 1, 2025, evaluating opportunistic salpingectomy for reduction of tubo-ovarian carcinoma, complication rates, additional surgical time, and impact on ovarian function. Statements were subsequently drafted collaboratively based on the review of the literature and adapted in an iterative process in conference call meetings with opportunity for anonymous and nonanonymous feedback. The anonymous voting was binary (agree/disagree) for each potential statement. Final statements reached consensus with more than 75% agreement.
    Findings: In the literature review, 230 studies were identified, of which 129 were deemed relevant to consensus statement development. Consensus was achieved on 18 statements, with grades of recommendation ranging from B to D and levels of evidence from II to V. Opportunistic salpingectomy is significantly associated with a lower risk of subsequent tubo-ovarian carcinoma, with no adverse short-term impact on ovarian function. The procedure appears safe across surgical approaches, with little additional operative time. Existing evidence does not indicate harm to ovarian function or premature menopause, although long-term evidence is not available. Salpingectomy is feasible during both gynecological and nongynecological procedures and should be considered in women undergoing gynecological surgery and, where possible, in women undergoing selected nongynecological pelvic or abdominal surgeries.
    Conclusions and Relevance: Existing evidence demonstrates that opportunistic salpingectomy is significantly associated with a lower risk of developing tubo-ovarian carcinoma. Clinicians should include this prevention intervention in preoperative counseling of eligible women.
    DOI:  https://doi.org/10.1001/jama.2025.24510
  5. Virchows Arch. 2026 Feb 07.
    Evaluation of homologous recombination testing in ovarian carcinoma.
    Vera M Witjes, Joanne A de Hullu, Angela van Remortele, Lilian Vreede, Efraim H Rosenberg, Saskia A G M Cillessen, Floris H Groenendijk, Elisabeth M P Steeghs, Laura Moonen, Arjen R Mensenkamp, Arja Ter Elst, Wendy W J de Leng, Nicoline Hoogerbrugge, Marjolijn J L Ligtenberg.
      Homologous recombination deficiency (HRD) testing may be used to stratify ovarian carcinoma (OC) patients for PARP inhibitor therapy. In the Netherlands, different NGS-based assays are used to assess genomic instability as a hallmark of HRD. We evaluated the uniformity of HRD testing. Firstly, interlaboratory assessments of 10 tumors were performed in 8 centers. 71 out of the 77 (92%) successful tests were concordant. Results were more consistent in OC with a pathogenic variation (PV) or promoter methylation of a homologous recombination repair (HRR) gene (97%) than in those without (87%). Secondly, concordance between BRCA1/RAD51C promoter methylation and HRD was assessed in 244 samples without a PV in HRR genes. BRCA1/RAD51C promoter methylation was present in 38 out of 100 (38%) samples classified as HRD, and absent in all (n = 144) non-HRD samples (p < 0.001). Lastly, pathology reports from 765 HRD tests were reviewed to evaluate routine diagnostics. Testing was successful in 695 (91%) cases. HRD detection rates were higher in high-grade serous OC compared to other histological subtypes (49% versus 12%, p < 0.001). The five HRD assays varied significantly in HRD detection rates in high-grade serous OC. The results support the applicability of genomic instability analyses to assess HRD, while also highlighting the need to improve harmonization across different assays when HRD is used for therapeutic decision making.
    Keywords:  BRCA; Genomic instability; Homologous recombination deficiency; Ovarian cancer; PARP inhibitors; Quality control
    DOI:  https://doi.org/10.1007/s00428-026-04432-2
  6. bioRxiv. 2026 Jan 13. pii: 2026.01.12.699071. [Epub ahead of print]
    Ultra-deep duplex sequencing reveals unique features of somatic evolution in the normal tissues of a family with Li-Fraumeni syndrome.
    Hunter L Colegrove, Marianne E Dubard-Gault, Henry Marshall, Brendan F Kohrn, Thomas H Smith, Zachary K Norgaard, Fang Yin Lo, Elizabeth K Schmidt, Jacob E Higgins, Charles C Valentine, Desiree A Marshall, John I Clark, Eric Q Konnick, Jesse J Salk, Marshall S Horwitz, Raheleh Rahbari, Alison F Feder, Rosa Ana Risques.
      Li-Fraumeni Syndrome (LFS) is caused by germline pathogenic variants in TP53 which predispose carriers to early onset cancer across multiple tissues. While genomically profiling those cancers has revealed factors contributing to their formation, little is understood about how LFS impacts clonal evolution in healthy tissues preceding cancer. Here, we use ultra-deep duplex sequencing (mean ∼15,000× depth) to investigate somatic mutation and selection in a family carrying the germline TP53 p.R181H pathogenic variant and a cohort of non-carrier controls. In blood samples, the germline variant was associated with more mutations in a panel designed to capture genomewide mutagenesis, and with reduced positive selection on somatic TP53 mutations, despite confounding by chemotherapy treatment in one individual. DNMT3A and TET2 mutations were positively selected and GATA2 mutations were negatively selected across the cohort, independent of the p.R181H status. Extensive multi-tissue sampling of 22 non-cancerous and 6 cancerous samples was also performed at autopsy in one individual with LFS who succumbed to esophageal cancer. Cross-tissue analysis revealed excess mutations in sun-exposed skin, esophagus and chronically-inflamed stomach tissue, and highly parallel emergence of mutations in the p.R248 hotspot of TP53 across most (18/28) tissue samples. Most somatic TP53 mutations in LFS that could be assessed for phase arose on the chromosomal copy lacking the p.R181H variant. Our study reveals how the germline p.R181H variant reshapes baseline somatic mutation and selection in normal tissues and highlights the importance of understanding early somatic evolution in LFS prior to cancer development and treatment.
    DOI:  https://doi.org/10.64898/2026.01.12.699071
  7. Nat Biomed Eng. 2026 Feb 05.
    Leveraging multi-modal foundation models for analysing spatial multi-omic and histopathology data.
    Tianyu Liu, Tinglin Huang, Tong Ding, Hao Wu, Peter Humphrey, Sudhir Perincheri, Kurt Schalper, Rex Ying, Hua Xu, James Zou, Faisal Mahmood, Hongyu Zhao.
      Recent advances in pathology foundation models, pre-trained on large-scale histopathology images, have greatly advanced disease-focused applications. At the same time, spatial multi-omic technologies now measure gene and protein expression with high spatial resolution, offering valuable insights into tissue context. Yet, existing models struggle to integrate these complementary data types. Here, to address this challenge, we present spEMO, a computational framework that unifies embeddings from pathology foundation models and large language models for spatial multi-omic analysis. By leveraging multi-modal representations, spEMO surpasses single-modality models across diverse downstream tasks, including spatial domain identification, spot-type classification, whole-slide disease prediction and interpretation, multicellular interaction inference and automated medical reporting. These results highlight spEMO's strength in both biological discovery and clinical applications. Furthermore, we introduce a new benchmark task-multi-modal alignment-to evaluate how effectively pathology foundation models retrieve complementary information. Together, spEMO establishes a powerful step towards holistic, interpretable and generalizable AI for spatial biology and pathology.
    DOI:  https://doi.org/10.1038/s41551-025-01602-6
  8. Clin Cancer Res. 2026 Feb 03.
    Longitudinal ctDNA monitoring for post-surgical disease surveillance in patients with stage I-IIIB melanoma.
    George Ansstas, Karam Khaddour, Sumedha Sudhaman, Karen Lin, Griffin L Budde, Andrew Poklepovic, Bently P Doonan, Meghan J Mooradian, Ryan J Sullivan, Vincent T Ma, Jeremy Rosiecki, Steven Liu, Ronald Drengler, Daniel B Flora, Georgia M Beasley, Kristen E Rhodin, John R Hyngstrom, Elise K Brunsgaard, J Bryce Ortiz, Giby V George, Michael Krainock, Minetta C Liu, Alan Tan.
       PURPOSE: Circulating tumor DNA (ctDNA) has emerged as an important biomarker for early recurrence detection and monitoring disease status during treatment in patients with cancer, including melanoma. We evaluate the prognostic value and impact of post-operative ctDNA detection in patients with stage I-IIIB melanoma using a clinically validated ctDNA assay.
    EXPERIMENTAL DESIGN: We conducted a retrospective analysis of real-world data of patients with stage I-IIIB melanoma, including ctDNA results using a personalized, tumor-informed, 16-plex mPCR-NGS assay. Adjuvant treatment decisions and post-surgical plasma sample collection timepoints were at the physician's discretion. ctDNA results were correlated with clinical outcomes.
    RESULTS: Across 190 patients and a total of 1,578 samples, a median of 7 ctDNA tests (range: 1-33) per patient were performed over a median period of 24.6 months (range: 3.7 - 74.7). ctDNA-positivity at any postoperative timepoint was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR]: 40.63, 95% CI: 19.9 - 82.96, P<0.0001). This finding was also observed in patients specifically with regional or distant recurrence (HR: 39.55, 95% CI: 18.08 - 86.51, P<0.0001). In multivariate analysis, ctDNA-positivity was the most significant prognostic factor associated with RFS when compared with other clinicopathologic factors, including stage, sex, and mitotic rate (HR: 25.36, 95% CI: 9.16-70.3, P<0.001).
    CONCLUSIONS: Our findings highlight the prognostic value of post-surgical, personalized ctDNA detection of recurrence and longitudinal disease surveillance in stage I-IIIB melanoma. The impact of ctDNA on real-world clinical decision-making highlights the need to assess outcomes when cancer management is influenced by ctDNA dynamics.
    DOI:  https://doi.org/10.1158/1078-0432.CCR-25-3643
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