ABSTRACT
Aim: The main purpose of the present study was to investigate the labor market affiliation of ALK+ NSCLC patients in long-term treatment as well as overall survival and incidence/prevalence. Materials & methods: Nationwide retrospective study of all patients with ALK+ NSCLC in Denmark diagnosed between 2012 and 2018. Results: During the study period ALK+ NSCLC patients had a median overall survival of 44.0 months and a 7.8-fold increase in disease prevalence. Six months prior to diagnosis, 81% of ALK+ NSCLC patients ≤60 years of age were employed. At the end of the 18-month follow-up period, 36% were employed. Conclusion: ALK+ NSCLC patients have prolonged survival following diagnosis, but a large fraction of patients lose affiliation with the labor market.
The purpose of this study was to examine the employment status and survival of patients with ALK+ NSCLC who are undergoing long-term treatment. The researchers conducted a study analyzing data from all such patients diagnosed between 2012 and 2018 in Denmark. The results showed that ALK+ NSCLC patients had a median overall survival of 44.0 months and a that the number of patients increased almost eightfold during the study period. Prior to diagnosis, 81% of ALK+ NSCLC patients who were 60 years of age or younger were employed. However, at the end of the 18-month follow-up period, only 36% of these patients were still employed. In conclusion, ALK+ NSCLC patients tend to have prolonged survival after diagnosis. However, a considerable proportion of these patients lose their affiliation with the labor market, indicating the impact of the disease on employment status.
ALK+ NSCLC patients have prolonged survival following diagnosis, but a large fraction of patients lose affiliation with the labor market following diagnosis. #alkpositive #lcsm.
ABSTRACT
BACKGROUND: Real-world clinical outcomes of anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients vary. This study aimed to investigate the treatment and clinical outcomes of all ALK+ NSCLC patients in Denmark in the period 2011-2018, regardless of disease stage. MATERIALS AND METHODS: A national pathology database with complete coverage was used to identify ALK+ NSCLC patients diagnosed between 2011 and 2018. Clinical data were obtained through retrospective chart reviews. Overall survival (OS) and duration of treatment (DOT) were analyzed using Kaplan-Meier methodologies. RESULTS: A total of 209 ALK+ NSCLC patients were included. The cohort had a slight overrepresentation of female patients (56.5%) with a mean age of 61.6 years. Most patients were adenocarcinoma cases (97%) and presented with an ECOG performance status of 0-1 (79%). Stage IIIb-IVb patients comprised 70% of the cohort. The use of ALK-tyrosine kinase inhibitors (TKIs) as first-line treatment increased over time, with the 1st generation ALK-TKI crizotinib being the predominant treatment in the 1st line. In 1st line treatment, 2nd generation ALK-TKIs had a median DOT more than twice the median DOT of crizotinib (25.1 and 9.1 months, respectively). The median OS for the entire cohort was 44.0 months. Patients with stage I-IIIA disease had a median OS that had not been reached, while those with stage IIIb-IVb disease had a median OS of 31.8 months. Patients with stage IIIb-IVb disease receiving an ALK-TKI as 1st line treatment had a median OS of 42.5 months with immature follow-up. Brain metastases at diagnosis or choice of 1st line treatment did not statistically significantly impact OS. CONCLUSION: This study gives insights into the treatment and outcome of ALK+ NSCLC patients in Denmark and provides a real-world confirmation of the superior disease control provided by 2nd generation ALK-TKIs as compared to the 1st generation ALK-TKI crizotinib.
Subject(s)
Anaplastic Lymphoma Kinase , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Protein Kinase Inhibitors , Female , Humans , Middle Aged , Anaplastic Lymphoma Kinase/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Crizotinib/therapeutic use , Denmark/epidemiology , Lung Neoplasms/drug therapy , Lung Neoplasms/epidemiology , Lung Neoplasms/metabolism , Protein Kinase Inhibitors/therapeutic use , Retrospective StudiesABSTRACT
Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients. Combining fragmentation features, clinical risk factors, and CEA levels, followed by CT imaging, detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites distinguished individuals with small cell lung cancer from those with non-small cell lung cancer with high accuracy (AUC = 0.98). A higher fragmentation score represented an independent prognostic indicator of survival. This approach provides a facile avenue for non-invasive detection of lung cancer.
Subject(s)
Circulating Tumor DNA/metabolism , DNA Fragmentation , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Apoptosis , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Diagnosis, Differential , Early Detection of Cancer , Female , Genome, Human , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Models, Biological , Neoplasm Metastasis , Neoplasm Staging , Small Cell Lung Carcinoma/diagnosis , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/pathology , Young AdultABSTRACT
BACKGROUND: Prior studies have shown that AHRR (cg05575921) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival (in some lung cancer subtypes). It is unknown if AHRR (cg05575921) hypomethylation is associated with reduced survival among lung cancer patients. METHODS: In bisulfite treated leukocyte DNA from 465 lung cancer patients from the Copenhagen prospective lung cancer study, we measured AHRR (cg05575921) methylation. 380 died during max follow-up of 4.4 years. Cox proportional hazard models were used to analyze survival as a function of AHRR (cg05575921) methylation. RESULTS: We observed the expected inverse correlation between cumulative smoking and AHRR methylation, as methylation (%) decreased (Coefficient -0.03; 95% confidence interval, -0.04- -0.02, p = 8.6x10-15) for every pack-year. Cumulative smoking > 60 pack-years was associated with reduced survival (hazard ratio and 95% confidence interval 1.48; 1.05-2.09), however, AHRR (cg05575921) methylation was not associated with survival when adjusted for sex, body mass index, smoking status, ethnicity, performance status, TNM Classification, and histology type of lung cancer. CONCLUSION: AHRR (cg05575921) methylation is linked to smoking but does not provide independent prognostic information in lung cancer patients.
