Kye Young Lee

Abstract

EGFR genotyping is essential step for therapeutic decision of NSCLC patients and it is usually done using lung biopsy tisue. Recently the incidence of peripheral type lung cancer, especially adenocarcinoma, is increasing.  Lung biopsy is invasive and sometimes difficult to get adequate tissue for histologic and molecular diagnosis, even with advanced peripheral lung biopsy technology including navigation bronchoscopy,  radial EBUS and robotic bronchoscopy. Significant number of stage 1 NSCLC patients are usually diagnosed by VATS (video-assisted thoracospic surgery) biopsy. Exosomes are  messengers of cancer cells. It has been proven that exosomes carry oncogenic EGFR mutant DNA in the experiment using EGFR mutated lung cancer cells and BALF obtained from EGFR-mutated NSCLC patients. I have developed an innovative lung cancer diagnostic platform for EGFR mutation testing named as ExoBAL with high accuracy and ultraspeed, avoiding invasive tissue biopsy, even in early stage lung cancer. Turn-around-time (TAT) of ExoBAL is only 1-2 days, while it takes more than 2 weeks when using conventional tissue biopsy. The sensitivity, specificity, and concordance rate of ExoBAL in comparison with tissue biopsy is more than 95% each in advanced stage 3, 4 NSCLC patients who needs argent therapeutic decision between EGFR-TKIs and immunochemotherapy.  In stage IB and II NSCLC, diagnostic sensitivity of ExoBAL shows more than 90% sensitivity. However, in stage IA NSCLC, its sensitivity is decreased to around 70%. ExoBAL can easily detect metabolically active stage 1 tumor, its detecting power for silent and dormant stage 1 tumor is decreased. I called this phenomenon “shedder vs non-shedder”, because active tumor sheds much more amount of tumor exosomes.  This limitation of diagnostic sensitivity in stage 1A NSCLC can be  overcomed by DNA methylation profiling of BALF exosomal DNA.  ExoBAL has great potential  to provide huge benefits to NSCLC patients in the aspect of avoiding invasive tissue biopsy with high accuracy and rapid TAT.

Audience take away :

• I’d like to explain lung biopsy issue in the management of lung cancer patients, especially stage 1 NSCLC.


• Innovative diagnostic method for detecting early stage lung cancer should be developed to reduce lung cancer mortality.


• Exosome-based liquid biopsy is promising because exosomes are the messenger of cancer cells carrying oncogenic mutant DNA. 


• BALF (bronchoalveolar lavage fluid) contains enriched tumor-derived exosomes and ExoBAL shows high  sensitivity and accuracy for EGFR mutation testing in comparison with conventional tissue biopsy.


• ExoBAL provide preoperative tumor evaluation before surgery even  without tissue biopsy and can be applied to neoadjuvant therapy to reduce  post-op recurrence.