Predictive value and molecular correlates of MYC immunohistochemistry and copy number gain in non-small cell lung carcinomas treated with immunotherapy.

OBJECTIVES: Accurately predicting which patients diagnosed with non-small cell lung cancer (NSCLC) will respond to immunotherapy remains a clinical challenge. This study aims to determine the associations between MYC immunoreactivity, MYC copy number gain (CNG), driver mutations and survival following immunotherapy treatment, to provide insight into whether clinical MYC assessment may have predictive value. MATERIALS AND METHODS: MYC copy number status was determined in 82 patients with NSCLC treated with immunotherapy, and MYC immunohistochemistry (IHC) was performed on 80 of these cases. MYC staining in ≥ 40 % of tumor cells was considered positive. Driver gene alterations, PD-L1 status and survival outcomes were assessed through retrospective chart review. Overall survival (OS) and progression free survival (PFS) were calculated from the date of immunotherapy initiation. RESULTS: Nine (11 %) of 82 cases had MYC CNG and 56 (70 %) of the 80 immunostained cases were positive for MYC. MYC CNG was significantly associated with STK11 mutation (P=0.023), whereas positive MYC IHC was significantly associated with KRAS mutation (P=0.0076) and current/former smoking (P=0.0007). MYC CNG and positive MYC IHC were not significantly associated with each other (P=0.42), or with PD-L1 ≥ 1 % (MYC CNG: P=0.10; MYC IHC: P=0.09). Positive MYC IHC and PD-L1 ≥ 1 % were both significant predictors of OS (MYC: HR 2.7, 95 % CI 1.1-6.4, P=0.026; PD-L1: HR 0.33, 95 % CI 0.15-0.72, P=0.0055). MYC IHC positive/PD-L1 < 1 % cases had the shortest OS (median 230 versus 918 days, P=0.00069) and PFS (median 84 versus 254 days, P=0.0087). MYC CNG was not associated with OS or PFS. CONCLUSION: We find that positive MYC IHC is an independent predictor of shorter OS after immunotherapy treatment, with MYC positive/PD-L1 < 1 % status predictive of particularly poor immunotherapy response. We identify positive MYC IHC as a feature of possible relevance to NSCLC treatment selection and of interest for future therapy development.

Sex Differences in All-Cause Inpatient Mortality Risk in Gastric Cancer: Nationwide Inpatient Population-Based Study.

Objective The purpose of this study is to evaluate the differences in demographic characteristics, comorbidities, and hospital outcomes in gastric cancer inpatients by sex and evaluate the risk factors for in-hospital mortality in gastric cancer inpatients by sex. Methods We conducted a cross-sectional study using the nationwide inpatient sample (NIS, 2019). Our sample included 22,415 adult inpatients (age ≥18 years) hospitalized with a primary discharge diagnosis of gastric cancer that was identified by the international classification of diseases, 10th revision (ICD-10) codes of C16.x. Independent univariate binomial logistic regression models were used to evaluate the odds ratio (OR) of predictors associated with all-cause in-hospital mortality in gastric cancer inpatients by sex. Results The total number of patients admitted with gastric cancer was 22,415, out of which 62.7% were males and 37.3% were females, with the mean age at the admission of 65.5 years and 66.4 years, respectively. While studying comorbidities, we found that 41.5% percent of all patients had gastric cancer with metastasis, and there existed a significantly higher prevalence in males (42.2% vs. 40.4% in females). Other important and statistically significant comorbid conditions that were prevalent in these patients include complicated diabetes (12.2%), obesity (12.1%), depression (8%), and alcohol abuse (3.1%). Females between 50-59 years of age were at 2.5 times increased risk of mortality compared to those less than 40 years of age (OR: 2.5; 95% CI: 1.28-4.95). Conclusion Females of the age group 50-59 years are at greater risk of all-cause inpatient mortality due to gastric cancer. Black males are at increased risk of all-cause inpatient mortality compared to White males. Gastric cancer incidence and mortality rates have been down trending with the development of screening and better treatment options, but it still continues to be a major burden on the healthcare system.