KRAS G12C Mutant Non-Small Cell Lung Cancer Linked to Female Sex and High Risk of CNS Metastasis: Population-based Demographics and Survival Data From the National Swedish Lung Cancer Registry.

BACKGROUND: Real-world data on demographics related to KRAS mutation subtypes are crucial as targeted drugs against the p.G12C variant have been approved. METHOD: We identified 6183 NSCLC patients with reported NGS-based KRAS status in the Swedish national lung cancer registry between 2016 and 2019. Following exclusion of other targetable drivers, three cohorts were studied: KRAS-G12C (n = 848), KRAS-other (n = 1161), and driver negative KRAS-wild-type (wt) (n = 3349). RESULTS: The prevalence of KRAS mutations and the p.G12C variant respectively was 38%/16% in adenocarcinoma, 28%/13% in NSCLC-NOS and 6%/2% in squamous cell carcinoma. Women were enriched in the KRAS-G12C (65%) and KRAS-other (59%) cohorts versus KRAS-wt (48%). A high proportion of KRAS-G12C patients in stage IV (28%) presented with CNS metastasis (vs. KRAS-other [19%] and KRAS-wt [18%]). No difference in survival between the mutation cohorts was seen in stage I-IIIA. In stage IV, median overall survival (mOS) from date of diagnosis was shorter for KRAS-G12C and KRAS-other (5.8 months/5.2 months) vs. KRAS wt (6.4 months). Women had better outcome in the stage IV cohorts, except in KRAS-G12C subgroup where mOS was similar between men and women. Notably, CNS metastasis did not impact survival in stage IV KRAS-G12C, but was associated with poorer survival, as expected, in KRAS-other and KRAS-wt. CONCLUSION: The KRAS p.G12C variant is a prevalent targetable driver in Sweden and significantly associated with female sex and presence of CNS metastasis. We show novel survival effects linked to KRAS p.G12C mutations in these subgroups with implications for clinical practice.

Patterns of care and outcomes in immigrants with non-small cell lung cancer. A population-based study (Sweden).

OBJECTIVES: While studies have found lower cancer risks and better cancer survival in immigrant populations, it is debated whether cancer care is offered on equal terms to all residents regardless of background. Our aim was to study patterns of care and outcomes in immigrants in a country with a tax-financed universal health care system. MATERIAL AND METHODS: We used a population-based database to compare clinical presentation, management and mortality between Swedish-born and immigrant patients with non-small cell lung cancer (NSCLC). Analyses were adjusted for potential confounders. RESULTS: We identified 40,075 patients diagnosed with NSCLC of which 84% were born in Sweden, 7% in Nordic and 9% in Non-Nordic countries. Non-Nordic immigrants were to a higher extent male, smokers, younger at diagnosis, had a better performance status and a higher educational level. No differences were seen regarding comorbidity burden or stage at diagnosis. Non-Nordic immigrants more often underwent positron emission tomography (PET) (aHR 1.32; 95% CI 1.19-1.45) and were more often discussed in a multidisciplinary team setting (aHR 1.30; 95% CI 1.17-1.44). There were no differences in treatment modalities following adjustment for age, with the exception of concurrent chemoradiotherapy in stage IIIA disease which was more common in Non-Nordic immigrants (aOR 1.34; 95% CI 1.03-1.74). Both overall and cause specific survival in non-metastatic disease were higher among Non-Nordic immigrants. Overall mortality in stage I-II: HR 0.81; 95% CI 0.73-0.90 and stage IIIA: HR 0.75; 95% CI 0.65-0.86. Following full adjustments, cause-specific mortality in stage I-II was aHR 0.86, 95% CI 0.75-0.98. CONCLUSION: Taken together, only minor differences in management and outcomes were observed between Swedish-born and immigrant patients. We conclude that lung cancer care is offered on equal terms. If anything, outcomes were better in Non-Nordic immigrants with early stage NSCLC.

Highly elevated systemic inflammation is a strong independent predictor of early mortality in advanced non-small cell lung cancer.

BACKGROUND: Ample evidence support inflammation as a marker of outcome in non-small cell lung cancer (NSCLC). Here we explore the outcome for a subgroup of patients with advanced disease and substantially elevated systemic inflammatory activity. METHODS: The source cohort included consecutive patients diagnosed with NSCLC between January 2016 - May 2017 (n = 155). Patients with active infection were excluded. Blood parameters were examined individually, and cut-offs (ESR > 60 mm, CRP > 20 mg/L, WBC > 10 × 109, PLT > 400 × 109) were set to define the group of hyperinflamed patients. A score was developed by assigning one point for each parameter above cut-off (0-4 points). RESULTS: High systemic inflammation was associated with advanced stage and was seldom present in limited NSCLC. However, the one year survival of patients in stage IIIB-IV (n = 93) with an inflammation score of ≥2 was 0% compared to 33% and 50% among patients with a score of 1 and 0 respectively. The effect of a high inflammation score on overall survival remained significant in multi-variate analysis adjusted for confounding factors. The independent hazard ratio of an inflammation score ≥ 2 in multi-variate analysis (HR 3.43, CI 1.76-6.71) was comparable to a change in ECOG PS from 0 to 2 (HR 2.42, CI 1.13-5.18). CONCLUSION: Our results show that high level systemic inflammation is a strong independent predictor of poor survival in advanced stage NSCLC. This observation may indicate a need to use hyperinflammation as an additional clinical parameter for stratification of patients in clinical studies and warrants further research on underlying mechanisms linked to tumor progression.

Are older patients with non-small cell lung cancer receiving optimal care? A population-based study.

BACKGROUND: Results from studies addressing age-related patterns of cancer care have found evidence of unjustified differences in management between younger and older patients. METHODS: We examined associations between age and clinical presentation, management and mortality in patients diagnosed with non-small cell lung cancer (NSCLC) between 2002 and 2016. Analyses were adjusted for comorbidity and other factors that may have affected management decisions and outcomes. RESULTS: The study population encompassed 40,026 patients with NSCLC. Stage at diagnosis did not differ between age groups ≤ 84. The diagnostic intensity was similar in age groups <80 years. In patients with stage IA-IIB disease and PS 0-2, surgery was more common in the youngest age groups and decreased with increasing age, and was rarely performed in those ≥ 85 years. The use of stereotactic body radiotherapy (SBRT) increased with age (≤69 years 5.4%; ≥85 years 35.8%). In patients with stage IIIA disease and PS 0-2, concurrent chemoradiotherapy was more common in younger patients (≤69 years 55.3%; ≥85 years 2.2%). In stage IA-IIIA disease, no major differences in treatment-related mortality was observed. In stage IIIB-IV and PS 0-2, chemotherapy was more common in patients <80 years. However, 58.1% of patients 80-84 years and 30.3% ≥ 85 years received treatment. In stage IA-IIIA, overall and cause-specific survival decreased with increasing age. No age-differences in survival were observed in patients with stage IIIB-IV NSCLC. CONCLUSION: Treatments were readily given to older patients with metastatic disease, but to a lesser degree to those with early stage disease. Significant differences in cause specific survival were observed in early, but not late stage disease. Our findings underscore the importance of individualized assessment of health status and life expectancy. Our results indicate that older patients with early stage lung cancer to a higher extent should be considered for curative treatment.

Educational level and management and outcomes in non-small cell lung cancer. A nationwide population-based study.

OBJECTIVES: We examined associations between educational level and clinical presentation, patterns of management and mortality in patients with non-small cell lung cancer (NSCLC) in Sweden, a country with a National Health Care System. MATERIALS AND METHODS: We identified 39,671 patients with a NSCLC diagnosis 2002-2016 in Lung Cancer Data Base Sweden (LCBaSe), a population-based research database. In analyses adjusted for comorbidity and other prognostic factors, odds Ratios (OR) and hazard Ratios (HR) were estimated to examine associations between patients' educational level and aspects of management and mortality. RESULTS: Stage at diagnosis and waiting times did not differ between educational groups. In multivariable analysis, the likelihood to undergo PET/CT and assessment in a multidisciplinary team setting were higher in patients with high compared to low education (aOR 1.14; CI 1.05-1.23 and aOR 1.22; CI 1.14-1.32, respectively). In patients with early stage IA-IIB disease, the likelihood to undergo stereotactic radiotherapy was elevated in patients with high education (aOR 1.40; CI 1.03-1.91). Both all-cause (aHR 0.86; CI 0.77-0.92) and cause-specific mortality (aHR 0.83; CI 0.74-0.92) was lower in patients with high compared to low education in early stage disease (IA-IIB). In higher stage NSCLC no differences were observed. Patterns were similar in separate assessments stratified by sex and histopathology. CONCLUSIONS: While stage at diagnosis and waiting times did not differ between educational groups, we found socioeconomic differences in diagnostic intensity, multidisciplinary team assessment, stereotactic radiotherapy and mortality in patients with NSCLC. These findings may in part reflect social gradients in implementation and use of novel diagnostic and treatment modalities. Our findings underscore the need for improved adherence to national guidelines.

The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab.

UNLABELLED: It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination. MATERIAL AND METHODS: Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic influenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal influenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the influenza strains. For the pneumococcal vaccine 14 different serotype-specific anti-capsular antibodies were measured by bead assay xMAP(®). RESULTS: Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI ≥ 40) to the pandemic-like strain A/California7/2009HINI. After the first and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal flu vaccination SPR against influenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported. CONCLUSION: A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to influenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.