Confirmation of Recurrent Lung Cancer Following Resection Using Liquid Biopsy, a Proof-of-Concept Real-World Study.

Appropriate management requires timely and accurate confirmation of non-small cell lung cancer (NSCLC) recurrence in patients who have had curative-intent surgical resection. We assessed the association between circulating tumor DNA (ctDNA) identified using amplicon sequencing and evidence of recurrence on CT surveillance. A prospective cohort study of NSCLC patients with early-stage disease undergoing curative-intent resection was conducted. Surveillance was performed post-operatively at pre-defined intervals with both liquid biopsy and chest CT imaging. Amplicon panel next-generation sequencing was performed on DNA and RNA from tumor tissue and on plasma cell-free DNA for tumor-informed ctDNA detection. Resected tumors from 78 NSCLC patients were analyzed. Alterations were detected on the DNA assay for 65 tumors and only on the RNA assay for 4 tumors. Of the 65 patients with alterations detected on the tumor DNA assay, 29 completed post-operative liquid biopsy testing. Four of those 29 patients had evidence of recurrence on imaging, of whom two had biopsy confirmation of recurrence and detectable ctDNA at the 12-month follow-up. Molecular confirmation of NSCLC recurrence can be provided through amplicon sequencing of plasma cell-free DNA in cases with imaging evidence of recurrence. Invasive tissue diagnosis may be avoidable in patients with ctDNA confirmation of recurrence that is suspected based on imaging. Further study of ctDNA assessment technologies in the setting of suspected recurrence is necessary to inform post-operative lung cancer surveillance guidelines.

Selective utilization of circulating tumor DNA testing enables disease monitoring in endometrial and ovarian carcinomas.

OBJECTIVE: Biomarkers reflecting real-time response to therapy and recurrence are lacking. We assessed the clinical value of detecting cell-free circulating tumor DNA (ctDNA) mutations in endometrial cancer (EC) and ovarian cancer (OC) patients. METHODS: EC/OC patients undergoing primary surgery were consented for tissue banking and 2-year serial blood draws. Tumor tissue DNA and plasma ctDNA underwent next generation sequencing using a targeted gene panel to identify somatic mutations. RESULTS: Of 44 patients (24 EC, 17 OC, 2 synchronous endometrial and ovarian carcinomas [SEOC] and 1 endocervical adenocarcinoma [EA]) at least one somatic mutation was identified in tumor tissue in 40 (91%, 20/24 EC, all OC/SEOC/EA), and in preoperative plasma ctDNA in 12 (27%) patients (6/24 [25%] EC and 6/17 [35%] OC). Detection of preoperative ctDNA mutations was associated with advanced stage, higher preoperative CA125, and disease recurrence. In 5/12 (42%) patients with preoperative ctDNA mutations, examination/imaging suggested clinical stage I however final pathology revealed stage II/III. In 11 patients where serial timepoints were assessed during treatment for ctDNA and CA125, ctDNA clearance preceded normalization of CA125. Thirteen patients developed recurrent disease (4 EC, 8 OC, 1 EA); 8 in whom ctDNA mutations were detected postoperatively, and 4 followed through time of recurrence with ctDNA mutations identified 2-5 months prior to clinical/radiologic/biomarker progression in 3. CONCLUSION: ctDNA can reflect larger tumor volume/metastases, treatment response and recurrence in EC and OC. Careful patient selection is critical to direct resources to patients most likely to benefit, considering disease burden and risk group.