bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2025–02–02
five papers selected by
Lara Paracchini, Humanitas Research



  1. BJS Open. 2024 Dec 30. pii: zrae161. [Epub ahead of print]9(1):
       BACKGROUND: Ovarian cancer is the leading cause of death among gynaecological cancers. The identification of the fallopian tube epithelium as the origin of most ovarian cancers introduces a novel prevention strategy by removing the fallopian tubes during an already indicated abdominal surgery for another reason, also known as an opportunistic salpingectomy. This preventive opportunity is evidence based, recommended and established at the time of gynaecologic surgery in many countries worldwide. To expand interest among surgeons in performing a salpingectomy during non-gynaecological surgery, the aim of this review is to identify knowledge gaps during those surgeries.
    METHODS: A scoping review was performed following the PRISMA-Scoping Review (ScR) checklist. PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL) database and Cochrane Library were systematically searched from inception to November 2024. Trial registers were searched for ongoing trials. All studies reporting original data on salpingectomy during non-gynaecological surgery were included. Outcomes were provided narratively.
    RESULTS: Eighteen studies were identified reporting on the implementation, surgical feasibility, patients' perspectives, physicians' knowledge and cost-effectiveness of an opportunistic salpingectomy during non-gynaecological surgery. Population-level data indicate that an opportunistic salpingectomy is rarely performed in non-gynaecological surgeries. High success rates and no complications of an opportunistic salpingectomy were observed during bariatric surgery and cholecystectomies. However, performing an additional salpingectomy appeared more time-consuming. Patients had strong interest in information on and willingness to undergo opportunistic salpingectomy. Cost-effectiveness analysis encourages opportunistic salpingectomy use, as models show reduced ovarian cancer incidence and mortality rate while being cost-effective.
    CONCLUSIONS: Opportunistic salpingectomy during non-gynaecologic surgery appears to be a promising method to prevent ovarian cancer. Implementing such a strategy will require education of multiple surgical disciplines, training and resolution of organizational issues.
    DOI:  https://doi.org/10.1093/bjsopen/zrae161
  2. Clin Cancer Res. 2025 Jan 29.
      LINE-1 retrotransposons, comprising 17% of the genome, drive cancer instability through hypomethylation. The DIAMOND assay, targeting LINE-1 hypomethylation with bisulfite sequencing of cell free DNA, achieved AUCs of 88% to 100% across six cancer types, surpassing mutation-based diagnostics and suggesting utility in early cancer detection and management.
    DOI:  https://doi.org/10.1158/1078-0432.CCR-24-4051
  3. PLoS Med. 2025 Jan;22(1): e1004514
       BACKGROUND: There is indication that the fallopian tubes might be involved in ovarian cancer pathogenesis and their removal reduces cancer risk. Hence, bilateral salpingectomy during hysterectomy or sterilization, so called opportunistic salpingectomy (OS), is gaining wide acceptance as a preventive strategy. Recently, it was discussed whether implementation of OS at other gynecologic surgery, e.g., cesarean section, endometriosis excision or myomectomy and even at non-gynecologic abdominal surgery such as cholecystectomy or appendectomy for women with completed family could be feasible. This modeling analysis evaluated the clinical and economic potential of OS at gynecologic and abdominal surgeries.
    METHODS AND FINDINGS: A state transition model representing all relevant health states (healthy, healthy with hysterectomy or tubal ligation, healthy with other gynecologic or non-gynecologic abdominal surgery, healthy with hysterectomy and salpingectomy, healthy with salpingectomy, healthy with hysterectomy and salpingo-oophorectomy, ovarian cancer and death) was developed and informed with transition probabilities based on inpatient case numbers in Germany (2019). Outcomes for women aged 20-85 years were simulated over annual cycles with 1,200,000 million individuals. We compared four strategies: (I) OS at any suitable abdominal surgery, (II) OS only at any suitable gynecologic surgery, (III) OS only at hysterectomy or sterilization, and (IV) no implementation of OS. Primary outcome measures were prevented ovarian cancer cases and deaths as well as the incremental cost-effectiveness ratio (ICER). Volume of eligible interventions in strategy I was 3.5 times greater than in strategy III (286,736 versus 82,319). With strategy IV as reference, ovarian cancer cases were reduced by 15.34% in strategy I, 9.78% in II, and 5.48% in III. Setting costs for OS to €216.19 (calculated from average OS duration and operating room minute costs), implementation of OS would lead to healthcare cost savings as indicated by an ICER of €-8,685.50 per quality-adjusted life year (QALY) gained for strategy I, €-8,270.55/QALY for II, and €-4,511.86/QALY for III. Sensitivity analyses demonstrated stable results over a wide range of input parameters with strategy I being the superior approach in the majority of simulations. However, the extent of cancer risk reduction after OS appeared as the critical factor for effectiveness. Preventable ovarian cancer cases dropped to 4.07% (I versus IV), 1.90% (II versus IV), and 0.37% (III versus IV) if risk reduction would be <27% (hazard ratio [HR] > 0.73). ICER of strategies I and II was lower than the 2× gross domestic product per capita (GDP/C) (€94,366/QALY, Germany 2022) within the range of all tested parameters, but strategy III exceeded this threshold in case-risk reduction was <35% (HR > 0.65). The study is limited to data from the inpatient sector and direct medical costs.
    CONCLUSIONS: Based on our model, interdisciplinary implementation of OS in any suitable abdominal surgeries could contribute to prevention of ovarian cancer and reduction of healthcare costs. The broader implementation approach demonstrated substantially better clinical and economic effectiveness and higher robustness with parameter variation. Based on a lifetime cost saving of €20.89 per capita if OS was performed at any suitable abdominal surgery, the estimated total healthcare cost savings in Germany could be more than €10 million annually.
    DOI:  https://doi.org/10.1371/journal.pmed.1004514
  4. Cancer Pathog Ther. 2025 Jan;3(1): 16-29
      Cancer is an evolutionary process involving the accumulation of diverse somatic mutations and clonal evolution over time. Phylogenetic inference from samples obtained from an individual patient offers a powerful approach to unraveling the intricate evolutionary history of cancer and provides insights that can inform cancer treatment. Somatic copy number alterations (CNAs) are important in cancer evolution and are often used as markers, alone or with other somatic mutations, for phylogenetic inferences, particularly in low-coverage DNA sequencing data. Many phylogenetic inference methods using CNAs detected from bulk or single-cell DNA sequencing data have been developed over the years. However, there have been no systematic reviews on these methods. To summarize the state-of-the-art of the field and inform future development, this review presents a comprehensive survey on the major challenges in inference, different types of methods, and applications of these methods. The challenges are discussed from the aspects of input data, models of evolution, and inference algorithms. The different methods are grouped according to the markers used for inference and the types of the reconstructed trees. The applications include using phylogenetic inference to understand intra-tumor heterogeneity, metastasis, treatment resistance, and early cancer development. This review also sheds light on future directions of cancer phylogenetic inference using CNAs, including the improvement of scalability, the utilization of new types of data, and the development of more realistic models of evolution.
    Keywords:  Chromosomal instability; Clonal evolution; Copy number change; Phylogenetic inference; Somatic mutation
    DOI:  https://doi.org/10.1016/j.cpt.2024.04.003
  5. JNCI Cancer Spectr. 2025 Jan 28. pii: pkaf008. [Epub ahead of print]
      Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants and associated with a high lifelong cancer risk. We analysed the German LFS registry that contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (non-functional, partially-functional) and a novel (clusters A, B, C) classification of variants into different groups. Partially-functional and cluster B or C variants were enriched in patients not meeting clinical testing criteria. Time to first malignancy was longer in carriers of partially-functional variants (Hazard Ratio [HR] = 0.38; 95% CI, 0.22 to 0.66). Variants grouped within clusters B (HR = 0.45; 95% CI, 0.28 to 0.71) or C (HR = 0.34; 95% CI, 0.19 to 0.62) were associated with later cancer onset than NULL variants. These findings can be used to risk-stratify patients and inform care.
    Keywords:   TP53 ; Li-Fraumeni syndrome; genotype-phenotype correlation
    DOI:  https://doi.org/10.1093/jncics/pkaf008