Wait-and-See Treatment Strategy and Genomic Alternations Associated with Progression in Lung Adenocarcinoma with Pleural Dissemination
28 Pages Posted: 9 May 2019More...
Background: To evaluate the feasibility of postoperative wait-and-see strategy, as well as identify genomic alternations of progression for lung adenocarcinoma with pleural dissemination (pM1a).
Methods: 131 patients diagnosed with malignant pleural dissemination either unexpectedly found during primary tumor resection or recurred post-surgery were retrospectively selected. We evaluated survival difference among three postoperative initial treatments: chemotherapy, targeted therapy and wait-and-see strategy. Whole-exome sequencing were performed on 26 patients with dramatic progression or gradual progression, aiming to identify markers associated with progression pattern.
Findings: In the entire cohort, the wait-and-see group showed significantly longer progression-free survival (PFS) than chemotherapy group (P < 0.001) but similar PFS with targeted group (P = 0.984). This pattern persisted in EGFR-positive patients. However, in patients with EGFR-negative/ unknown, PFS was significantly extended in wait-and-see group compared to the other two strategies. Furthermore, better overall survival was seen in patients who received chemotherapy or targeted therapy after wait-and-see than those received initial chemotherapy or targeted therapy. Results from WES analysis demonstrated that high genomic instability index (GIS) and chromosome 18q loss were enriched in metastasis tumors, and high GIS was significantly associated with poor PFS (P = 0.029).
Interpretation: These findings suggest wait-and-see is a feasible treatment strategy for pM1a patients. Dramatic and gradual progression may be attributed to high and low level of genomic instability, respectively.
Funding Statement: This work was supported by Project of National Natural Science Foundation (grant numbers 81673031, 81872510 to WZ Zhong).
Declaration of Interests: The authors have no conflict of interest to declare.
Ethics Approval Statement: This study was approved by the Ethics and Scientific Committees of Guangdong Provincial People’s Hospital (No. GDREC2016175H(R2)).
Keywords: Lung adenocarcinoma, pleural dissemination, wait-and-see, genome instability, progression
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