133MO - Differentiation of malignant and benign lung nodules using epigenetically modified nucleosomes in plasma

Background

Recent lung cancer screening trials indicate that low-dose computed tomography (LDCT) has been successful in reducing mortality in high-risk patients. Nonetheless, the high frequency of false-positives leads to expense and possible harm, emphasizing the necessity for complementary biomarkers. To address this, we aimed to enhance the accuracy of lung cancer screening by utilizing a lung cancer-specific immunoassay panel for epigenetically modified nucleosomes in plasma to help differentiate between benign and malignant nodules.

Methods

During the years 2021 and 2022, a total of 806 individuals who had a positive result from LDCT screening and underwent surgery or biopsy were included in the study. Plasma samples from these participants were analyzed for nucleosomes containing histone modifications including H3K27Me3, H3K36Me3, or the H3.1 histone isoform by quantitative immunoassay (Nu.Q®, Belgian Volition SRL). Among these individuals, 648 were diagnosed with either lung cancer or a pre-cancerous lesion, while 158 were diagnosed with a benign lesion based on pathological reports. Logistic regression was used to analyze the assay data, and a simple algorithm was developed to predict whether a nodule was benign or malignant. The algorithm was created using samples collected in 2021 (n=561) as a training set and validated using samples collected in 2022 (n=245).

Results

The plasma epigenetic nucleosome assay for detecting lung cancer showed a diagnostic sensitivity of 92% and a specificity of 82% using a simple regression algorithm, trained on data from the 2021 group. The AUC for differentiating between cancerous and benign nodules was 88%. When the assay was applied to data from 2022, it achieved an AUC of 77% for distinguishing between cancer and benign nodules, with a sensitivity of 60% and a specificity of 84%. The validation test revealed that the algorithm correctly identified patients with stage I cancer and carcinoma in situ in 58% and 61% of cases, respectively.

Conclusions

This large validation study indicates that the epigenetic nucleosome assay has predictive, diagnostic, and prognostic value and could reduce the false-positive rate of LDCT.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Belgian Volition.

Disclosure

P. Chen: Financial Interests, Institutional, Funding: volition. D. Pamart, T. Bygott: Financial Interests, Personal, Full or part-time Employment: Volition. M. Herzog: Financial Interests, Personal, Full or part-time Employment: Belgian Volition; Financial Interests, Personal, Stocks/Shares: VolitionRx; Non-Financial Interests, Member: ASCO. J. Micallef: Financial Interests, Personal, Officer, Chief Scientific Officer: VolitionRx Ltd; Financial Interests, Personal, Stocks/Shares: VolitionRx Ltd. J. Chen: Financial Interests, Institutional, Local PI: Volition. All other authors have declared no conflicts of interest.