Use of circulating interleukin-18 for prognosticating and treating recurrence in early stage non-small cell lung cancer
Inventors
Pass, Harvey I. • Goparaju, Chandra M.
Assignees
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Publication Number
US-12553897-B2
Publication Date
2026-02-17
Expiration Date
Abstract
Provided are methods for aiding in diagnosis and treatment of non-small cell lung cancer (NSCLC) adenocarcinoma. The methods involve determining elevated circulating Interleukin-18 (IL-18) values to aid in the diagnosis and treatment of NSCLC. Medical interventions based on determining circulating IL-18 levels are provided and include additional scanning, surgical resection of tumors, and administration of adjuvant therapy, such as chemotherapy or immune therapy.
Core Innovation
A method is described for prognosticating a likelihood of recurrence of, and treating an individual diagnosed with non-small cell lung cancer (NSCLC) adenocarcinoma, where the treatment occurs following surgical resection of the NSCLC. The method includes determining a level of circulating Interleukin-18 (IL-18) from a preoperative biological sample obtained from the individual, comparing the IL-18 level to a reference value, and predicting recurrence when the level is higher than the reference value of about 33 ng/ml.
Following the prognostic determination, adjuvant therapy is administered to the individual as the treatment. The disclosure ties elevated circulating plasma IL-18 measured from preoperative samples to recurrence risk, including locoregional/systemic recurrence and second-primary events, and describes reference or threshold values for circulating IL-18 used to support predictive performance, including sensitivity and specificity targets and ROC curve/AUC.
The disclosure frames the prognostic decision in the context of early-stage NSCLC adenocarcinoma and surgical management, including after R0 resection, and supports the use of circulating IL-18 as a preoperative biomarker. It also mentions potential adjuvant modalities and IL-18 biology relevant to measurement and interpretation, including measurement approaches such as ELISA in plasma and/or buffy coat, IL-18 neutralizing agents or IL-18 pathway antagonists, limited prognostic utility for squamous histology, and findings relating to tobacco exposure.
Claims Coverage
The independent claim set sets out a prognostic-and-treatment workflow comprising determining circulating IL-18 from a preoperative biological sample and administering adjuvant therapy when the IL-18 level is higher than a reference value of about 33 ng/ml. Dependent claims refine the adjuvant therapy type and add quantitative sensitivity and specificity thresholds for the reference value.
Prognostication using circulating IL-18 above a reference value
Determining a level of circulating Interleukin-18 (IL-18) from a preoperative biological sample obtained from the individual that is higher than a reference value of about 33 ng/ml of the IL-18 to predict a likelihood of recurrence of the NSCLC.
Adjuvant therapy administration following surgical resection
Administering adjuvant therapy to the individual as the treatment following surgical resection of the NSCLC, where the adjuvant therapy is provided in response to the IL-18-based recurrence prediction.
Adjuvant therapy including chemotherapy or immunotherapy
Performing the method with adjuvant therapy that includes chemotherapy or immunotherapy.
Adjuvant therapy including cisplatin
The adjuvant therapy includes administration of cisplatin.
Reference value meeting sensitivity and specificity thresholds
Characterizing the reference value such that it yields sensitivity of at least 80% and specificity of at least 90%.
Reference value meeting higher sensitivity and specificity thresholds
Specifying the reference value such that it yields sensitivity of at least 84% and specificity of at least 95%.
Across the claims, the core inventive coverage is based on measuring circulating IL-18 from a preoperative biological sample and using a reference value (about 33 ng/ml) to predict recurrence likelihood, followed by administering adjuvant therapy after surgical resection. Dependent claims narrow the adjuvant therapy to chemotherapy and/or immunotherapy (including cisplatin) and require reference values that achieve specified sensitivity and specificity thresholds.
Stated Advantages
Predicts a likelihood of recurrence of NSCLC adenocarcinoma using elevated circulating IL-18 measured from preoperative biological samples.
Provides a basis for administering adjuvant therapy following surgical resection.
Supports predictive performance quantified by sensitivity and specificity targets for reference values.
Associates elevated circulating plasma IL-18 with recurrence risk, including locoregional/systemic and second-primary events.
Documented Applications
Prognosticating recurrence likelihood in early-stage NSCLC adenocarcinoma using elevated circulating plasma IL-18 from preoperative samples, including after R0 resection, and using this to guide post-surgical management with adjuvant therapy.
Supporting further diagnostic workup for recurrence risk using elevated circulating IL-18, including when imaging by CT is clear, as described in the disclosure.
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