Electronic Nose Technology to Predict and Assess Pathologic Response After Neoadjuvant Therapy and Recurrence for Non-Small Cell Lung Cancer - Project Summary In patients with locally advanced lung cancer undergoing induction therapy, prediction and assessment of response to therapy prior to surgery remain challenging. Response Evaluation Criteria in Solid Tumors (RECIST) has been used and validated to assess tumor response. However, the area under the curve for predicting response using RECIST even with radiomics remains moderate. Although circulating tumor DNA and proteins (e.g. CA125, CA15.3, Cyfra 21-1) demonstrate moderate to high specificity for therapy response, the sensitivity of these biomarkers remains variable. Therefore, even when the tumor responded completely to induction therapy, surgical resection of the affected lobe is necessary. A more-accurate prediction of therapy response could facilitate reevaluating current treatment strategies by tailoring induction therapy or even omitting surgery. Additionally, survival after curative-intent therapy is predominantly related to the development of recurrence. Although we and others have identified clinical risk factors associated with recurrence, such as maximum standardized uptake value, histologic subtype, lymphovascular invasion, many risk factors can only be determined only after histopathologic assessment of the resection specimen, which precludes the use of more- aggressive neoadjuvant treatment. In addition, the median time to recurrence detection is approximately 9 months. This may delay treatment of recurrent disease, contributing to the dismal prognosis for these patients. This proposal aims to investigate the use of volatile organic compounds (VOCs) in exhalates, through electronic nose (E-nose) technology, to predict and assess response to induction therapy and identify recurrence after curative-intent treatment of lung cancer. VOCs are metabolic by-products of cellular metabolic processes that are altered by the genetic changes in cancer cells. VOCs are delivered in the bloodstream and exchanged in the alveoli on the basis of diffusion gradients. The close relationship between VOCs, the genomic profile and presence of tumor would allow for the prediction of response to induction therapy and recurrence through noninvasive analysis of exhalates through E-nose. This technology can detect the variations in concentrations and composition of the produced VOCs in relation to the amount of viable tumor remaining after treatment. We will collect 4 breath samples from 20 patients receiving induction therapy for stage II-IIIB non-small cell lung cancer. We will compare the baseline VOC profiles of responders (complete or major) to those of non- responders, as well as the baseline and post-surgical VOC profiles of patients who recurred and those who did not. The longitudinal samples will be evaluated to assess the percentage response to therapy and evolution of recurrence. The performance of the E-Nose will be compared to that of radiologic assessment and histopathologic assessment. This proposal has the potential to directly improve health care and precision oncology by providing a reevaluation of therapy response and recurrence assessment. Moreover, it may identify new biomarkers and metabolic pathways which can be explored in future research.
