ABSTRACT
INTRODUCTION: Immune checkpoint inhibitors are highly effective in treating various cancers. We analyzed the significance of the KRAS/STK11 co-mutation in relation to the efficacy of immune checkpoint inhibitors in pan-cancer patient cohort. METHODS: We analyzed data from open-access research: MSK-IMPACT (molecular profiling data from patients receiving systemic antitumor therapy) and MSK-TMB (molecular profiling data from patients receiving immune checkpoint inhibitors). In both studies, high throughput sequencing was used for molecular profiling. RESULTS: A total of 10,336 patients receiving antitumor therapy (MSK-IMPACT study) and 1661 patients receiving immune checkpoint inhibitors (MSK-TMB study) were included in the analysis. Co-mutation STK11/KRAS was found in 156 (1.5%) and 46 (2.8%) patients in the two studies, respectively. Most patients with the STK11/KRAS co-mutation had non-small cell lung cancer (83% and 85% in the two studies, respectively). Among non-small cell lung cancer patients, the STK11 mutation was associated with a worse outcome for patients receiving systemic antitumor therapy, but not immune checkpoint inhibition therapy (HR for OS 1.90 [95% CI 1.36-2.65] and 1.44 [95% CI 0.88-2.37]). Co-mutation STK11/KRAS was also not associated with patient outcome in any of the studies (HR for OS 0.93 [95% CI 0.56-1.52] and 1.09 [95% CI 0.54-2.19]). High tumor mutational burden was associated with better outcome in the cohort of patients receiving immune checkpoint inhibitors. An analogous analysis among patients in the pan-cancer cohort (excluding patients with non-small cell lung cancer) showed STK11 mutations and high tumor mutational burden have a predictive role for the efficacy of immune checkpoint inhibitors, but not STK11/KRAS co-mutation. CONCLUSIONS: Co-mutation STK11/KRAS is common among patients with non-small cell lung cancer and is not an independent predictive marker for the efficacy of immune checkpoint inhibitors. Further studies are required to clarify the role of STK11 mutations in immune checkpoint inhibitor treatment response.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins p21(ras) , Humans , AMP-Activated Protein Kinase Kinases , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/therapeutic use , Proto-Oncogene Proteins p21(ras)/geneticsABSTRACT
BACKGROUND: The bulk of relevant studies compare individual or very few sports and on small samples of athletes. This requires extensive analysing postural stability in various sports. RESEARCH QUESTION: The main objective of our study was to identify the features of postural stability in a normal vertical stance in athletes of various kinds. METHODS: This study compares postural stability in a normal bipedal stance with eyes open (EO) and eyes closed (EC) conditions among athletes (n = 936, age: 6-47 years) from different sports and performance level. Postural stability was measured through the center of pressure (COP) sway area (AS) and velocity (VCP) while standing quietly in a normal bipedal position with EO and EC on a stabiloplatform (50 Hz). RESULTS: The order of VCP-EO increase in athletes compared to Control was as follows: Shooting (-11.3 %, p < .0001) < Football (-10.4 %, p < .0001) < Boxing (-8.7 %, p < .0001) < Cross-Country Skiing (-7.2 %, p < .0001) < Gymnastics (-7.0 %, p < .0001) < Running (-6.9 %, p < .0001) < Team Games Played with Hands (-6.8 %, p < .0001) < Wrestling (-6.3 %, p < .0001) < Tennis (-5.5 %, p = .0004) < Alpine Skiing (-5.4 %, p = .002) < Rowing (-5.0 %, p = .194) < Speed Skating (-4.7 %, p = .004) < Figure Skating (-3.6 %, p = .034) < Control. SIGNIFICANCE: Practicing any kind of sport was associated with increased postural stability in normal bipedal stance. This is the first study that provides reference values of COP sway and velocity with and without visual control on a stable force platform for different sport groups.
Subject(s)
Postural Balance , Soccer , Adolescent , Adult , Athletes , Child , Gymnastics , Humans , Middle Aged , Standing Position , Young AdultABSTRACT
The effects of different factors-such as age, sex, performance level, and athletic shoe features-on postural balance in athletes remain unclear. The main objective of our study is to identify the features of postural stability in athletes of different age, sex, performance level, and using different types of athletic shoes. This study assessed postural stability in athletes (n = 936, 6-47 years) in a normal bipedal stance with eyes open (EO) and eyes closed (EC). Postural stability was evaluated based on the center of pressure (COP), sway area (AS), and velocity (VCP) while standing on a stabiloplatform. Children (6-12 years) and teen athletes (13-17 years) showed reduced AS-EO (p < 0.01) and VCP-EO (p < 0.01) compared to control (n = 225, 7-30 years). In male and female athletes aged 18+, only VCP-EC was lower versus control. In females (13-17 and 18+), VCP-EO and EC were lower than in males (p < 0.05). Only in the Shooting group, the athletes' performance levels had an effect on VCP-EO (p = 0.020). Long use of rigid athletic shoes with stiff ankle support was associated with reduced posture stability. Postural stability in athletes was mostly influenced by the athlete's age, and, to a lesser extent, by their sex, performance level, and athlete shoe features.
