bims-ovdlit 2022-09-25 papers

Issue of 2022–09–25
five papers selected by
Lara Paracchini, Humanitas Research

Curr Opin Biomed Eng. 2022 Jun;pii: 100381. [Epub ahead of print]22

A review of co-registered transvaginal photoacoustic and ultrasound imaging for ovarian cancer diagnosis.

Ovarian cancer is the deadliest of all gynecological malignancies. When ovarian cancer is detected at an early, localized stage, surgery and chemotherapy can cure 70%-90% of patients, compared with 20% or fewer when it is diagnosed at later stages. Clearly, early detection is critical, yet the lack of early symptoms and effective screening tools means that only 20-25% of ovarian cancers are diagnosed early. Photoacoustic imaging (PAI) is an emerging modality that uses a short-pulsed laser to excite tissue. The resulting photoacoustic waves are used to image tissue optical contrast, which is directly related to tissue microvasculature and thus to cancer growth. When co-registered with transvaginal ultrasound (US), PAI offers great promise in diagnosing earlier stage ovarian cancers and distinguishing benign processes from malignant ovarian masses. In this article, we review the limitations of the current imaging tools for early ovarian cancer diagnosis and present recent advances in co-registered PAI/US.

Keywords: Ovarian cancer; Photoacoustic imaging; Transvaginal ultrasound

DOI: https://doi.org/10.1016/j.cobme.2022.100381

Clin Lab Med. 2022 Sep;pii: S0272-2712(22)00034-8. [Epub ahead of print]42(3): 485-496

When Tissue Is the Issue: Expanding Cell-Free DNA "Liquid Biopsies" to Supernatants and Nonplasma Biofluids.

Vera Paulson, Eric Q Konnick, Christina H Lockwood.

While tissue biopsy remains the gold standard for tumor biomarker testing, assays using plasma-derived cfDNA, aka circulating-tumor DNA (ctDNA), have recently demonstrated validity in the setting of limited tissue or recurrent disease. Tumor-derived cfDNA is also present in nonplasma biofluids and supernatants procured through interventional procedures. Evaluation of cfDNA extracted from these fluids may have benefits at nearly every stage of cancer patient management, from diagnosis and prognosis to monitoring disease progression and predicting therapeutic response. This review will focus on preanalytical, analytical, and postanalytical variables that must be considered when analyzing "liquid biopsies" outside the plasma compartment.

Keywords: Biofluid; Cell-free DNA (cfDNA); Cerebrospinal fluid (CSF); Circulating tumor DNA (ctDNA); Liquid biopsy; Preanalytical variables; Supernatant; Urinary tumor DNA (utDNA)

DOI: https://doi.org/10.1016/j.cll.2022.05.005

Front Oncol. 2022 ;12 951292

Incidence of pelvic high-grade serous carcinoma after isolated STIC diagnosis: A systematic review of the literature.

Valerie Catherine Linz, Amelie Löwe, Josche van der Ven, Annette Hasenburg, Marco Johannes Battista.

Objective: Serous tubal intraepithelial carcinoma (STIC) is a precursor lesion of pelvic high-grade serous carcinoma (HGSC). Information on treatment and outcome of isolated STIC is rare. Therefore, we reviewed systematically the published literature to determine the incidence of subsequent HGSC in the high- and low-risk population and to summarize the current diagnostic and therapeutic options.
Methods: A systematic review of the literature was conducted in MEDLINE-Ovid, Cochrane Library and Web of Science of articles published from February 2006 to July 2021. Patients with an isolated STIC diagnosis and clinical follow-up were included. Study exclusion criteria for review were the presence of synchronous gynaecological cancer and/or concurrent non-gynaecological malignancies.
Results: 3031 abstracts were screened. 112 isolated STIC patients out of 21 publications were included in our analysis with a pooled median follow-up of 36 (interquartile range (IQR): 25.3-84) months. 71.4% of the patients had peritoneal washings (negative: 62.5%, positive: 8%, atypic cells: 0.9%). Surgical staging was performed in 28.6% of all STICs and did not show any malignancies. 14 out of 112 (12.5%) patients received adjuvant chemotherapy with Carboplatin and Paclitaxel. Eight (7.1%) patients developed a recurrence 42.5 (IQR: 33-72) months after isolated STIC diagnosis. Cumulative incidence of HGSC after five (ten) years was 10.5% (21.6%). Recurrence occurred only in BRCA1 carriers (seven out of eight patients, one patient with unknown BRCA status).
Conclusion: The rate of HGSC after an isolated STIC diagnosis was 7.1% with a cumulative incidence of 10.5% (21.6%) after five (ten) years. HGSC was only observed in BRCA1 carriers. The role of adjuvant therapy and routine surveillance remains unclear, however, intense surveillance up to ten years is necessary.
Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021278340.

Keywords: high-grade serous carcinoma (HGSC); incidence; outcome; peritoneal carcinomatosis; precursor; serous tubal intraepithelial carcinoma (STIC); treatment

DOI: https://doi.org/10.3389/fonc.2022.951292

Int J Mol Sci. 2022 Sep 10. pii: 10503. [Epub ahead of print]23(18):

Combined PARP and Dual Topoisomerase Inhibition Potentiates Genome Instability and Cell Death in Ovarian Cancer.

Inken Flörkemeier, Julia S Hillmann, Jörg P Weimer, Jonas Hildebrandt, Nina Hedemann, Christoph Rogmans, Astrid Dempfle, Norbert Arnold, Bernd Clement, Dirk O Bauerschlag.

Although ovarian cancer is a rare disease, it constitutes the fifth leading cause of cancer death among women. It is of major importance to develop new therapeutic strategies to improve survival. Combining P8-D6, a novel dual topoisomerase inhibitor with exceptional anti-tumoral properties in ovarian cancer and compounds in preclinical research, and olaparib, a PARP inhibitor targeting DNA damage repair, is a promising approach. P8-D6 induces DNA damage that can be repaired by base excision repair or homologous recombination in which PARP plays a major role. This study analyzed benefits of combining P8-D6 and olaparib treatment in 2D and 3D cultures with ovarian cancer cells. Measurement of viability, cytotoxicity and caspase activity were used to assess therapy efficacy and to calculate the combination index (CI). Further DNA damage was quantified using the biomarkers RAD51 and γH2A.X. The combinational treatment led to an increased caspase activity and reduced viability. CI values partially show synergisms in combinations at 100 nM and 500 nM P8-D6. More DNA damage accumulated, and spheroids lost their membrane integrity due to the combinational treatment. While maintaining the same therapy efficacy as single-drug therapy, doses of P8-D6 and olaparib can be reduced in combinational treatments. Synergisms can be seen in some tested combinations. In summary, the combination therapy indicates benefits and acts synergistic at 100 nM and 500 nM P8-D6.

Keywords: PARP inhibitor; dual topoisomerase inhibitor; ovarian cancer

DOI: https://doi.org/10.3390/ijms231810503