ABSTRACT
BACKGROUND: Tumor mutational burden (TMB) is a potential biomarker to predict tumor response to immuno-oncology agents in patients with metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A multi-site cohort study evaluated patients diagnosed with stage IV NSCLC between 2012 and 2019 who had received comprehensive genomic profiling (CGP) and any NSCLC-related treatment at 9 U.S. cancer centers. Baseline characteristics and clinical outcomes were compared between patients with TMB <10 and TMB ≥10. RESULTS: Among the 667 patients with CGP results, most patients received CGP from Foundation Medicine (64%) or Caris (20%). Patients with TMB ≥10 (vs. TMB <10) were associated with a positive smoking history. TMB was associated with ALK (p = 0.01), EGFR (p < 0.01), and TP53 (p < 0.05) alterations. TMB >10 showed a significant association towards longer overall survival (OS) (HR: 0.43, 95% CI: 0.21-0.88, p = 0.02) and progression-free survival (PFS) (HR: 0.43, 95% CI: 0.21-0.85, p = 0.02) in patients treated with first-line immunotherapy and tested by Foundation Medicine or Caris at treatment initiation. CONCLUSIONS: TMB levels greater than or equal to 10 mut/Mb, when tested by Foundation Medicine or Caris at treatment initiation, were significantly associated with improved OS and PFS among patients treated with first-line immunotherapy-containing regimens. Additional prospective research is warranted to validate this biomarker along with PD-L1 expression.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , B7-H1 Antigen/genetics , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/therapy , Cohort Studies , ErbB Receptors/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/therapy , Mutation , Prospective Studies , Receptor Protein-Tyrosine Kinases/genetics , Survival AnalysisABSTRACT
OBJECTIVES: Stereotactic body radiotherapy (SBRT) is being increasingly used for the treatment of patients with lung cancer or lung metastasis who are medically unfit to undergo resection. In order to improve accuracy and confidence in targeting tumors, many centers rely on fiducial implantation. We evaluated the migration of a novel fiducial marker specifically designed for lung tissue implanted via electromagnetic navigation bronchoscopy (ENB). METHODS: We retrospectively quantified the individual and group migrations of SuperLock nitinol coil fiducials for 15 patients receiving lung stereotactic body radiotherapy (SBRT), in order to evaluate the reliability of using these fiducials as a target surrogate for cases where tumors cannot be clearly delineated on cone beam CTs (CBCTs). For each fraction, we compared the individual and group migrations of the fiducials between the planning CT and the acquired CBCT. The group migration was defined as the distance between the centroids of the fiducial group and GTV. RESULTS: A total of 16 lung targets were included in our study for these 15 patients (one patient with two targets). Of 55 fiducials placed, we observed a 100% retention rate. The mean individual migration was 1.87 mm (range, 0.63-5.25 mm) with a standard deviation of 1.26 mm. The mean group migration was 1.94 mm (range, 0.03-6.19 mm) with a standard deviation of 1.45 mm. Overall, there was minimal change in the relative locations of the markers with respect to each other, as well as to the target. CONCLUSIONS: We found that the SuperLock nitinol coil fiducial marker positions are stable throughout the radiation treatment, and can be used as a reliable surrogate to target, and to avoid geometric misses during gated treatments.
