bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2023‒10‒29
eight papers selected by
Lara Paracchini, Humanitas Research

  1. Ann Oncol. 2023 Oct 20. pii: S0923-7534(23)04324-7. [Epub ahead of print]
    Keywords:  HBOC; breast; cancer; hereditary; ovarian; screenings; ultrasound
  2. Nat Commun. 2023 10 24. 14(1): 6756
      High grade serous ovarian carcinoma (HGSOC) is a highly heterogeneous disease that typically presents at an advanced, metastatic state. The multi-scale complexity of HGSOC is a major obstacle to predicting response to neoadjuvant chemotherapy (NACT) and understanding critical determinants of response. Here we present a framework to predict the response of HGSOC patients to NACT integrating baseline clinical, blood-based, and radiomic biomarkers extracted from all primary and metastatic lesions. We use an ensemble machine learning model trained to predict the change in total disease volume using data obtained at diagnosis (n = 72). The model is validated in an internal hold-out cohort (n = 20) and an independent external patient cohort (n = 42). In the external cohort the integrated radiomics model reduces the prediction error by 8% with respect to the clinical model, achieving an AUC of 0.78 for RECIST 1.1 classification compared to 0.47 for the clinical model. Our results emphasize the value of including radiomics data in integrative models of treatment response and provide methods for developing new biomarker-based clinical trials of NACT in HGSOC.
  3. Br J Cancer. 2023 Oct 21.
      BACKGROUND: Most studies examining post-menopausal menopausal hormone therapy (MHT) use and ovarian cancer risk have focused on White women and few have included Black women.METHODS: We evaluated MHT use and ovarian cancer risk in Black (n = 800 cases, 1783 controls) and White women (n = 2710 cases, 8556 controls), using data from the Ovarian Cancer in Women of African Ancestry consortium. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MHT use with ovarian cancer risk, examining histotype, MHT type and duration of use.
    RESULTS: Long-term MHT use, ≥10 years, was associated with an increased ovarian cancer risk for White women (OR = 1.38, 95%CI: 1.22-1.57) and the association was consistent for Black women (OR = 1.20, 95%CI: 0.81-1.78, pinteraction = 0.4). For White women, the associations between long-term unopposed estrogen or estrogen plus progesterone use and ovarian cancer risk were similar; the increased risk associated with long-term MHT use was confined to high-grade serous and endometroid tumors. Based on smaller numbers for Black women, the increased ovarian cancer risk associated with long-term MHT use was apparent for unopposed estrogen use and was predominately confined to other epithelial histotypes.
    CONCLUSION: The association between long-term MHT use and ovarian cancer risk was consistent for Black and White women.
  4. Cancer Discov. 2023 Oct 24.
      People with Li-Fraumeni syndrome harbor a germline pathogenic variant in the TP53 tumor suppressor gene; face a near 100% lifetime risk of cancer; and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for a range of clinical applications, including early cancer detection. Here, we provide a proof-of-principle for a multi-modal liquid biopsy assay that integrates a targeted gene panel, shallow whole genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a longitudinal cohort of 89 Li-Fraumeni syndrome patients. Multi-modal analysis increased our detection rate in patients with an active cancer diagnosis over uni-modal analysis; and was able to detect cancer-associated signal in carriers prior to diagnosis with conventional screening (PPV = 67.6%, NPV = 96.5%). While adoption of liquid biopsy into current surveillance will require further clinical validation, this study provides a framework for individuals with Li-Fraumeni syndrome.
  5. medRxiv. 2023 Oct 02. pii: 2023.09.30.23296390. [Epub ahead of print]
      Background: Circulating tumor DNA (ctDNA) has emerged as an accurate real-time biomarker of disease status across most solid tumor types. Most studies evaluating the utility of ctDNA have focused on time points weeks to months after surgery, which for many cancer types, is significantly later than decision-making time points for adjuvant treatment. In this systematic review, we summarize the state of the literature on the feasibility of using ctDNA as a biomarker in the immediate postoperative period.Methods: We performed a systematic review evaluating the early kinetics, defined here as three days, of ctDNA in patients who underwent curative-intent surgery across several cancer types.
    Results: Among the 2057 studies identified, we evaluated eight cohort studies with ctDNA levels measured within the first three days after surgery. Across six different cancer types, all studies showed an increased risk of cancer recurrence in patients with a positive early postoperative ctDNA level.
    Discussion: While ctDNA clearance kinetics appear to vary based on tumor type, across all studies-detectable ctDNA after surgery was predictive of recurrence, suggesting early post-operative timepoints could be feasibly used for determining minimal residual disease. However, larger studies need to be performed to better understand the precise kinetics of ctDNA clearance across different cancer types as well as to determine optimal postoperative time points.
    Synopsis: This systematic review analyzed the use of ctDNA as a biomarker for minimal residual disease detection in the early postoperative setting and found that ctDNA detection within three days after surgery is associated with an increased risk of recurrence.
  6. Methods Cell Biol. 2023 ;pii: S0091-679X(23)00053-5. [Epub ahead of print]180 49-67
      Transforming growth factor β (TGFβ) is exquisitely regulated under physiological conditions but its activity is highly dysregulated in cancer. All cells make TGFβ and have receptors for the ligand, which is sequestered in the extracellular matrix in a latent form. Ionizing radiation elicits rapid release of TGFβ from these stores, so-called activation, over a wide range of doses and exposures, including low dose (<1Gy) whole-body irradiation, creating an extraordinarily potent signal in the irradiated tissue or tumor. Hence, accurate evaluation of TGFβ activity is complicated because of its ubiquitous distribution as a latent complex. Here we describe conditions for assays that reveal TGFβ activity in situ using either tissue preparations or functional imaging.
    Keywords:  Activation; Immunostaining; Latency; Radiation; TGFβ