bims-ovdlit 2023-07-16 papers

Issue of 2023–07–16
three papers selected by
Lara Paracchini, Humanitas Research

Cancers (Basel). 2023 Jun 30. pii: 3445. [Epub ahead of print]15(13):

Development of the NOGGO GIS v1 Assay, a Comprehensive Hybrid-Capture-Based NGS Assay for Therapeutic Stratification of Homologous Repair Deficiency Driven Tumors and Clinical Validation.

The worldwide approval of the combination maintenance therapy of olaparib and bevacizumab in advanced high-grade serous ovarian cancer requires complex molecular diagnostic assays that are sufficiently robust for the routine detection of driver mutations in homologous recombination repair (HRR) genes and genomic instability (GI), employing formalin-fixed (FFPE) paraffin-embedded tumor samples without matched normal tissue. We therefore established a DNA-based hybrid capture NGS assay and an associated bioinformatic pipeline that fulfils our institution's specific needs. The assay´s target regions cover the full exonic territory of relevant cancer-related genes and HRR genes and more than 20,000 evenly distributed single nucleotide polymorphism (SNP) loci to allow for the detection of genome-wide allele specific copy number alterations (CNA). To determine GI status, we implemented an %CNA score that is robust across a broad range of tumor cell content (25-85%) often found in routine FFPE samples. The assay was established using high-grade serous ovarian cancer samples for which BRCA1 and BRCA2 mutation status as well as Myriad MyChoice homologous repair deficiency (HRD) status was known. The NOGGO (Northeastern German Society for Gynecologic Oncology) GIS (GI-Score) v1 assay was clinically validated on more than 400 samples of the ENGOT PAOLA-1 clinical trial as part of the European Network for Gynaecological Oncological Trial groups (ENGOT) HRD European Initiative. The "NOGGO GIS v1 assay" performed using highly robust hazard ratios for progression-free survival (PFS) and overall survival (OS), as well a significantly lower dropout rate than the Myriad MyChoice clinical trial assay supporting the clinical utility of the assay. We also provide proof of a modular and scalable routine diagnostic method, that can be flexibly adapted and adjusted to meet future clinical needs, emerging biomarkers, and further tumor entities.

Keywords: BRCA1; BRCA2; DNA repair; HRD; HRR; LOH; OS; PAOLA-1; PARP inhibition; PARPi; PFS; breast cancer; diagnostics; genomic instability; homologous repair deficiency; molecular pathology; ovarian cancer; somatic mutation

DOI: https://doi.org/10.3390/cancers15133445

J Am Soc Cytopathol. 2023 May 23. pii: S2213-2945(23)00045-5. [Epub ahead of print]

Fallopian tube cytology as a diagnostic tool for adnexal malignancy: the CytoSaLPs score.

Victoria Psomiadou, Sofia Lekka, Theodoros Panoskaltsis, Helen Tsouma, Natasa Novkovic, Helen J Trihia, Olympia Tzaida, Dimitrios Korfias, Panagiotis Giannakas, Christos Iavazzo, Christos Papadimitriou, Nikolaos Vlahos, George Vorgias.

INTRODUCTION: During the past decade, the theory that high-grade extrauterine pelvic tumors originate from the fallopian tube has been strongly suggested. Our study aims to illuminate the possible role of tubal cytology as an accessory identification tool for gynecologic extrauterine malignancies, allowing in the long term the implementation of population-level cytologic tube evaluation during all benign gynecologic surgeries that do not result in salpingectomy.
MATERIALS AND METHODS: We ex vivo collect salpingeal epithelial cells from the fibria directly from fresh fallopian tube specimens from women undergoing salpingectomy for any indication. The cytomorphologic characteristics of the salpingeal cells are subsequently evaluated and categorized into malignant and non-malignant. Finally, the ipsilateral adnexa are examined with the SEE-FIM (Sectioning and Extensively Examining the FIMbriated End) protocol and the pathology reports are corelated with the cytologic findings. Our research protocol is ongoing and is designed to include a total of 300 patients in order to confirm the sensitivity and specificity of salpingeal cytology as a method in the early diagnosis of extrauterine gynecologic malignancies.
RESULTS: So far, we have obtained 343 salpingeal brushings from a total of 214 patients. The sensitivity of cytology regarding distinguishing malignant from non-malignant tumors is 69.64% (95% CI: 55.90%-81.22%), and its specificity 75.96% (95% CI: 70.59%-80.79%). Cytology's positive predictive value (PPV) is 16.33% (95% CI: 12.57%-20.67%), while the negative predictive value (NPP) reached 92.77% (95% CI: 89.56%-95.04%). In general, the diagnostic accuracy of the cytologic evaluation reaches 74.93% (95% CI: 66.99%-79.43%).
CONCLUSIONS: Salpingeal cytomorphologic evaluation appears to be a promising method for early detection of adnexal cancer.

Keywords: Adnexal malignancy; Fallopian tube cytology; Gynecological oncology; Ovarian cancer early diagnosis; Tubo-ovarian carcinoma

DOI: https://doi.org/10.1016/j.jasc.2023.05.003

Nature. 2023 Jul;619(7969): 259-268

Practical recommendations for using ctDNA in clinical decision making.

Stacey A Cohen, Minetta C Liu, Alexey Aleshin.

The continuous improvement in cancer care over the past decade has led to a gradual decrease in cancer-related deaths. This is largely attributed to improved treatment and disease management strategies. Early detection of recurrence using blood-based biomarkers such as circulating tumour DNA (ctDNA) is being increasingly used in clinical practice. Emerging real-world data shows the utility of ctDNA in detecting molecular residual disease and in treatment-response monitoring, helping clinicians to optimize treatment and surveillance strategies. Many studies have indicated ctDNA to be a sensitive and specific biomarker for recurrence. However, most of these studies are largely observational or anecdotal in nature, and peer-reviewed data regarding the use of ctDNA are mainly indication-specific. Here we provide general recommendations on the clinical utility of ctDNA and how to interpret ctDNA analysis in different treatment settings, especially in patients with solid tumours. Specifically, we provide an understanding around the implications, strengths and limitations of this novel biomarker and how to best apply the results in clinical practice.

DOI: https://doi.org/10.1038/s41586-023-06225-y