bims-preonc 2025-01-05 papers

Issue of 2025–01–05
five papers selected by
Ankita Daiya, OneCell Diagnostics Inc.

Oral Oncol. 2024 Dec 31. pii: S1368-8375(24)00466-4. [Epub ahead of print]161 107148

The role of ctDNA from liquid biopsy in predicting survival outcomes in HPV-negative head and neck cancer: A meta-analysis.

Nivedita Kaorey, Kyle Dickinson, Venkata Ramana Agnihotram, Anthony Zeitouni, Nader Sadeghi, Julia V Burnier.

The incidence of head and neck cancer (HNC) is on the rise, making it a significant clinical challenge. Human papillomavirus (HPV)-related and HPV-negative HNC exhibit distinct etiopathogenesis and prognoses, requiring targeted approaches for effective management. Conventional tissue biopsies are essential for confirming the diagnosis and locating solid tumors. However, they have limitations in detecting microscopic disease, tracking treatment response, and capturing the dynamic heterogeneity of the mutational profile within the tumor. Liquid biopsy using circulating tumor DNA (ctDNA) analysis has emerged as a promising non-invasive tool to overcome the drawbacks of conventional biopsy for comprehensive molecular profiling. This meta-analysis aims to colligate available evidence on the clinical utility of ctDNA analysis in predicting survival outcomes, specifically in HPV-negative HNC. Our systematic search of six electronic databases identified eight publications (N = 886 patients) meeting the inclusion criteria. The included studies reported data from HPV-negative HNC patients, employing ctDNA analysis to report survival outcomes. Our findings reveal a significant association between mutation or methylation in ctDNA and worsened survival outcomes in HPV-negative HNC cases. The presence of ctDNA mutations in TP53 and methylation of SEPT9 and SHOX2 was linked to reduced overall survival, disease-free survival, and progression-free survival. Subgroup analyses demonstrated consistent associations across different survival outcomes, ctDNA detection methods, and blood collection tubes used. Our study underscores the need for future research endeavors prioritizing larger, well-designed prospective studies with standardized methodologies to further elucidate the role of ctDNA analysis in guiding personalized treatment approaches and optimizing patient care in this specific HNC cohort.

Keywords: Biomarkers; HPV-negative; Head and neck cancer; Liquid biopsy; Survival outcomes; circulating tumor DNA; ctDNA

DOI: https://doi.org/10.1016/j.oraloncology.2024.107148

Hematol Oncol Clin North Am. 2024 Dec 27. pii: S0889-8588(24)00147-3. [Epub ahead of print]

Emergence of Circulating Tumor DNA as a Precision Biomarker in Lung Cancer Radiation Oncology and Beyond.

Ayesha Hashmi, Lilli J Greiner, Pradeep S Chauhan, Jeffrey J Szymanski, Sean Park, Kenneth Olivier, Dawn Owen, Aadel A Chaudhuri.

Circulating tumor DNA (ctDNA) is emerging as a transformative biomarker in the management of non-small cell lung cancer (NSCLC). This review focuses on its role in detecting minimal residual disease (MRD), predicting treatment response, and guiding therapeutic decision-making in radiation oncology and immunotherapy. Key studies demonstrate ctDNA's prognostic value, particularly in identifying relapse risk and refining patient stratification for curative-intent and consolidative treatments. Future research is essential to standardize ctDNA assays, optimize integration into clinical workflows, and expand its clinical utility. This biomarker holds substantial promise by enabling non-invasive, real-time monitoring and improving outcomes for patients with NSCLC and beyond.

Keywords: Circulating tumor DNA; Immunotherapy; Liquid biopsy; Minimal residual disease; Non-small cell lung cancer; Oligometastatic disease; Radiation therapy; Treatment monitoring

DOI: https://doi.org/10.1016/j.hoc.2024.11.002

Brief Bioinform. 2024 Nov 22. pii: bbae677. [Epub ahead of print]26(1):

Precise identification of somatic and germline variants in the absence of matched normal samples.

Somatic variants play a crucial role in the occurrence and progression of cancer. However, in the absence of matched normal controls, distinguishing between germline and somatic variants becomes challenging in tumor samples. The existing tumor-only genomic analysis methods either suffer from limited performance or insufficient interpretability due to an excess of features. Therefore, there is an urgent need for an alternative approach that can address these issues and have practical implications. Here, we presented OncoTOP, a computational method for genomic analysis without matched normal samples, which can accurately distinguish somatic mutations from germline variants. Reference sample analysis revealed a 0% false positive rate and 99.7% reproducibility for variant calling. Assessing 2864 tumor samples across 18 cancer types yielded a 99.8% overall positive percent agreement and a 99.9% positive predictive value. OncoTOP can also accurately detect clinically actionable variants and subclonal mutations associated with drug resistance. For the prediction of mutation origins, the positive percent agreement stood at 97.4% for predicting somatic mutations and 95.7% for germline mutations. High consistency of tumor mutational burden (TMB) was observed between the results generated by OncoTOP and tumor-normal paired analysis. In a cohort of 97 lung cancer patients treated with immunotherapy, TMB-high patients had prolonged PFS (P = .02), proving the reliability of our approach in estimating TMB to predict therapy response. Furthermore, microsatellite instability status showed a strong concordance (97%) with polymerase chain reaction results, and leukocyte antigens class I subtypes and homozygosity achieved an impressive concordance rate of 99.3% and 99.9% respectively, compared to its tumor-normal paired analysis. Thus, OncoTOP exhibited high reliability in variant calling, mutation origin prediction, and biomarker estimation. Its application will promise substantial advantages for clinical genomic testing.

Keywords: DNA sequencing; OncoTOP; bioinformatics; biomarker; cancer genomics

DOI: https://doi.org/10.1093/bib/bbae677

Case Rep Oncol Med. 2024 ;2024 6640468

New Germline TP53 Variant Detected After Radiotherapy-Induced Angiosarcoma of the Chest Wall in a Previously Treated Breast Cancer Patient: A Case Report and Review of Li-Fraumeni Syndrome and Radiotherapy-Induced Sarcoma.

Bruna Bianca Lopes David, Sávio Solon Alves Silva, Vanessa Dinoa, Tadeu Diniz, Emilio Pereira, Carolina Bustamante, Bernardo Garicochea.

Li-Fraumeni syndrome (LFS) is one of the most common hereditary cancer predisposition syndromes in Brazil. The high frequency of the syndrome is due to a founding variant (R337H) in the country. LFS is characterized by a wide variety of malignant phenotypes. Despite the great epidemiological importance of the R337H variant, the frequency of other types of pathogenic variants is like other populations, with the majority of these being missense variants. There is strong evidence that radiotherapy is associated with secondary sarcomas, including angiosarcomas, and this finding is especially true for LFS patients. Angiosarcoma is not described as overrepresented in individuals with LFS, except in patients submitted to radiotherapy. Germline testing in all breast cancer patients under 65 will reveal many germline mutations in TP53 without a family history of cancers associated with the syndrome. We present a case of a previously undescribed pathogenic variant in TP53 (c788del, pAns263llefs⁣∗82) in a patient with no family history of cancer, with a previous diagnosis of breast carcinoma treated with radiotherapy, who developed angiosarcoma after a few years leading to germline testing. The presence of angiosarcoma in a radiotherapy bed should raise suspicion for LFS. The recent recommendation of testing breast cancer patients under the age of 65, even without any family history, can be a source of discoveries of new mutations and assist in therapeutic decisions.

Keywords: Li–Fraumeni syndrome; angiosarcoma; breast cancer; radiotherapy; sarcoma

DOI: https://doi.org/10.1155/crom/6640468

Cancer Sci. 2024 Dec 31.

Osimertinib for EGFR-Mutant NSCLC Patients With Acquired T790M and EGFR Amplification After First-Generation EGFR-TKI Resistance.

Yidan Zhang, Yingqi Xu, Jianlin Xu, Hua Zhong, Jinjing Xia, Runbo Zhong.

Third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for patients harboring T790M after first-generation EGFR-TKI resistance. However, the impact of acquired EGFR amplification on the efficacy of third-generation EGFR-TKI against T790M remains uncertain. We aimed to investigate whether the presence of acquired EGFR amplification after first-generation EGFR-TKI resistance influences the efficacy of third-generation EGFR-TKI in patients with advanced non-small-cell lung cancer (NSCLC). We reviewed data from 275 advanced NSCLC patients harboring T790M after first-generation EGFR-TKI resistance. Patients were categorized into two groups based on the presence or absence of acquired EGFR amplification identified through next-generation sequencing (NGS) after first-line EGFR-TKI treatment. We evaluated the efficacy of osimertinib used as a second-line treatment. Among these patients, 59 exhibited acquired EGFR amplification, while 216 did not. The median progression-free survival (PFS) was 12.20 months in the EGFR amplification group and 12.03 months in the non-amplification group (p = 0.011), with median overall survival (OS) of 33.90 months and 23.30 months, respectively (p = 0.164). Multivariate analysis of PFS revealed that acquired EGFR amplification and EGFR 19del were independent prognostic factors for patients with T790M undergoing osimertinib. Additionally, subgroup analysis indicated a prolonged PFS in patients with EGFR 19del compared to those with EGFR 21L858R (p = 0.034) in the EGFR amplification group. Following first-generation EGFR-TKI resistance, advanced EGFR-mutant NSCLC patients harboring both acquired T790M and EGFR amplification are likely to experience enhanced PFS with osimertinib. This phenomenon is particularly noteworthy among individuals with EGFR 19del.

Keywords: EGFR; EGFR amplification; EGFR‐TKI; NSCLC; T790M

DOI: https://doi.org/10.1111/cas.16437