bims-tumhet 2023-11-05 papers

Issue of 2023–11–05
six papers selected by
Sergio Marchini, Humanitas Research

Ann Oncol. 2023 Oct 26. pii: S0923-7534(23)04325-9. [Epub ahead of print]

Reply to the Letter to the Editor 'There is no place for ovarian cancer screening in hereditary breast-ovarian cancer syndromes (in regard to "ESMO Clinical Practice Guideline on risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes")' by Tjalma, W.

ESMO Guidelines Committee

Keywords: BRCA; ESMO Clinical Practice Guideline; hereditary breast and ovarian cancer syndromes; risk reduction

DOI: https://doi.org/10.1016/j.annonc.2023.10.119

Exp Mol Med. 2023 Nov 01.

Cancer signature ensemble integrating cfDNA methylation, copy number, and fragmentation facilitates multi-cancer early detection.

Cell-free DNA (cfDNA) sequencing has demonstrated great potential for early cancer detection. However, most large-scale studies have focused only on either targeted methylation sites or whole-genome sequencing, limiting comprehensive analysis that integrates both epigenetic and genetic signatures. In this study, we present a platform that enables simultaneous analysis of whole-genome methylation, copy number, and fragmentomic patterns of cfDNA in a single assay. Using a total of 950 plasma (361 healthy and 589 cancer) and 240 tissue samples, we demonstrate that a multifeature cancer signature ensemble (CSE) classifier integrating all features outperforms single-feature classifiers. At 95.2% specificity, the cancer detection sensitivity with methylation, copy number, and fragmentomic models was 77.2%, 61.4%, and 60.5%, respectively, but sensitivity was significantly increased to 88.9% with the CSE classifier (p value < 0.0001). For tissue of origin, the CSE classifier enhanced the accuracy beyond the methylation classifier, from 74.3% to 76.4%. Overall, this work proves the utility of a signature ensemble integrating epigenetic and genetic information for accurate cancer detection.

DOI: https://doi.org/10.1038/s12276-023-01119-5

Front Oncol. 2023 ;13 1258228

Overcoming the challenges of drug development in platinum-resistant ovarian cancer.

Ramez N Eskander, Kathleen N Moore, Bradley J Monk, Thomas J Herzog, Christina M Annunziata, David M O'Malley, Robert L Coleman.

The definition of "platinum-resistant ovarian cancer" has evolved; it now also reflects cancers for which platinum treatment is no longer an option. Standard of care for platinum-resistant ovarian cancer is single-agent, non-platinum chemotherapy with or without bevacizumab, which produces modest response rates, with the greatest benefits achieved using weekly paclitaxel. Several recent phase 3 trials of pretreated patients with prior bevacizumab exposure failed to meet their primary efficacy endpoints, highlighting the challenge in improving clinical outcomes among these patients. Combination treatment with antiangiogenics has improved outcomes, whereas combination strategies with immune checkpoint inhibitors have yielded modest results. Despite extensive translational research, there has been a lack of reliable and established biomarkers that predict treatment response in platinum-resistant ovarian cancer. Additionally, in the platinum-resistant setting, implications for the time between the penultimate dose of platinum therapy and platinum retreatment remain an area of debate. Addressing the unmet need for an effective treatment in the platinum-resistant setting requires thoughtful clinical trial design based on a growing understanding of the disease. Recent cancer drug approvals highlight the value of incorporating molecular phenotypes to better define patients who are more likely to respond to novel therapies. Clinical trials designed per the Gynecologic Cancer InterGroup recommendations-which advocate against relying solely upon the platinum-free interval-will help advance our understanding of recurrent ovarian cancer response where platinum rechallenge in the platinum-resistant setting may be considered. The inclusion of biomarkers in clinical trials will improve patient stratification and potentially demonstrate correlations with biomarker expression and duration of response. With the efficacy of antibody-drug conjugates shown for the treatment of some solid and hematologic cancers, current trials are evaluating the use of various novel conjugates in the setting of platinum-resistant ovarian cancer. Emerging novel treatments coupled with combination trials and biomarker explorations offer encouraging results for potential strategies to improve response rates and prolong progression-free survival in this population with high unmet need. This review outlines existing data from contemporary clinical trials of patients with platinum-resistant ovarian cancer and suggests historical synthetic benchmarks for non-randomized trials.

Keywords: and targeted therapy; bevacizumab; biomarker; folate receptor alpha; mirvetuximab soravtansine; platinum-resistant ovarian cancer

DOI: https://doi.org/10.3389/fonc.2023.1258228

Curr Med Imaging. 2023 Oct 31.

CT Findings of Stage IA Ovarian Cancer: Comparison between Borderline Tumor and Stage IC Ovarian Cancer.

Li Cui, Xing Hua Zhu, Lu Yao Fan, Li Zhang, Zhiyong Shen.

BACKGROUND: Ovarian cancer is a common gynecological malignant tumor in women. Most patients have reached the advanced stage when they visit the hospital. In order to diagnose ovarian cancer at an early stage, treat it at an early stage, and improve the survival rate of patients, this study has used the imaging computed tomography (CT) method to diagnose stage IA ovarian cancer.
PURPOSE: The purpose of this work was to study CT features of stage IA ovarian cancer, and compare the borderline tumor and stage IC ovarian cancer at the same time so as to improve the CT diagnosis of early ovarian cancer.
METHODS: We retrospectively collected clinical and CT data of patients with stage I ovarian cancer and borderline ovarian tumor admitted to Nantong Tumor Hospital from 2013 to 2021. Altogether, 23 cases of patients (borderline ovarian tumor, 9 cases; stage IA ovarian cancer, 5 cases; stage IC ovarian cancer, 9 cases) were involved. CT characteristics of these patients were analyzed in terms of the tumor diameter, cystic solid structure, solid component, septation, enhancement, peritoneal thickening, ascites, and abdominal lymph nodes.
RESULTS: CT features of stage IA ovarian cancer included large tumor size (average diameter: 15 cm), cystic solid structure (4/5; 80%), septation (4/5; 80%), and enhanced cystic wall, septum, or solid components of the tumor on contrast-enhanced CT (5/5; 100%) no peritoneal thickening (0/5; 0%), no ascites (0/5; 0%), and no abdominal lymph node enlargement (0/5; 0%). The tumor structure did not differ significantly between stage IA and IC ovarian cancers (p > 0.05), while intraperitoneal ascites did (χ2 = 0.031; p < 0.05). Stage IA and borderline ovarian tumors did not differ significantly in ovarian tumor structure (p > 0.05).
CONCLUSION: CT features of stage IA ovarian cancer included large tumor size, cystic solid structure, septation, and enhanced cystic wall and solid parts in the tumors. No pelvic or abdominal metastasis was observed.

Keywords: borderline ovarian tumor; computed tomography; ovarian cancer; stage IA; stage IC

DOI: https://doi.org/10.2174/0115734056251322231024071757