Psychobiological stress response to a lung cancer diagnosis: a prospective study of patients in Iceland and Sweden.

BACKGROUND: A diagnostic work-up leading to a lung cancer diagnosis is a severely stressful experience that may impact tumor progression. Yet, prospective data are scarce on psychological and biological components of stress at the time of lung cancer diagnosis. The aim of this study was to assess pre-to-post diagnosis change in psychological distress and urinary excretion of catecholamines in patients with suspected lung cancer. METHODS: Participants were 167 patients within the LUCASS study, recruited at referral for suspected lung cancer to University Hospitals in Iceland and Sweden. Patients completed questionnaires on perceived distress (Hospital Anxiety and Depression Scale, HADS) before and after diagnosis of lung cancer or a non-malignant origin. A subpopulation of 85 patients also provided overnight urine for catecholamine analysis before and at a median of 24 days after diagnosis but before treatment. RESULTS: A lung cancer diagnosis was confirmed in 123 (73.7%) patients, with a mean age of 70.1 years. Patients diagnosed with lung cancer experienced a post-diagnosis increase in psychological distress (p = 0.010), while patients with non-malignant lung pathology showed a reduction in distress (p = 0.070). Both urinary epinephrine (p = 0.001) and norepinephrine (p = 0.032) levels were higher before the diagnosis among patients eventually diagnosed with lung cancer compared to those with non-malignant lung pathology. We observed indications of associations between pre-to-post diagnosis changes in perceived distress and changes in urinary catecholamine levels. CONCLUSION: Receiving a lung cancer diagnosis is associated with an increase in psychological distress, while elevated catecholamine levels are evident already before lung cancer diagnosis.

Evaluation of NTRK immunohistochemistry as a screening method for NTRK gene fusion detection in non-small cell lung cancer.

PURPOSE: The small molecule inhibitors larotrectinib and entrectinib have recently been approved as cancer agnostic drugs in patients with tumours harbouring a rearrangement of the neurotrophic tropomyosin receptor kinase (NTRK). These oncogenic fusions are estimated to occur in 0.1-3 % of non-small cell lung cancers (NSCLC). Although molecular techniques are most reliable for fusion detection, immunohistochemical analysis is considered valuable for screening. Therefore, we evaluated the newly introduced diagnostic immunohistochemical assay (clone EPR17341) on a representative NSCLC cohort. METHODS: Cancer tissue from 688 clinically and molecularly extensively annotated NSCLC patients were comprised on tissue microarrays and stained with the pan-TRK antibody clone EPR17341. Positive cases were further analysed with the TruSight Tumor 170 RNA assay (Illumina). Selected cases were also tested with a NanoString NTRK fusion assay. For 199 cases, NTRK RNA expression data were available from previous RNA sequencing analysis. RESULTS: Altogether, staining patterns for 617 NSCLC cases were evaluable. Of these, four cases (0.6 %) demonstrated a strong diffuse cytoplasmic and membranous staining, and seven cases a moderate staining (1.1 %). NanoString or TST170-analysis could not confirm an NTRK fusion in any of the IHC positive cases, or any of the cases with high mRNA levels. In the four cases with strong staining intensity in the tissue microarray, whole section staining revealed marked heterogeneity of NTRK protein expression. CONCLUSION: The presence of NTRK fusion genes in non-small cell lung cancer is exceedingly rare. The use of the immunohistochemical NTRK assay will result in a small number of false positive cases. This should be considered when the assay is applied as a screening tool in clinical diagnostics.

The prevalence of chronic airflow obstruction in three cities in the Nordic-Baltic region.

BACK GROUND: Chronic airflow obstruction (CAO) is the primary characteristic of Chronic obstructive pulmonary disease (COPD) but is also seen in chronic asthma. OBJECTIVE: To compare the prevalence of CAO and possible risk factors between Tartu in Estonia, Reykjavik in Iceland and Uppsala in Sweden. METHODS: All participants underwent spirometry testing of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) before and after bronchodilation. CAO was defined as post-bronchodilator FEV1/FVC below lower limit of normal. Information on respiratory diseases and smoking status, was obtained through questionnaires administered by trained interviewers. RESULTS: 1037 men and 956 women participated in the study. The prevalence of CAO was lower in women in Tartu compared to the other centres (4.9% vs. 13.4 and 8.7% in Reykjavik and Uppsala, respectively, p = 0.002) while no difference was found for men. A similar picture was seen for the proportion of participants that had smoked 10 pack years or more which was much lower in Tartu for women than in Reykjavik and Uppsala, respectively (13.2% vs. 33.7 and 29.2%, p < 0.001). (Fig. 1). Of the participants with CAO the majority (57-67%) did not have a previous diagnosis of asthma or COPD. CONCLUSION: The prevalence of CAO was lower in Estonian women than in women from Iceland and Sweden. The reason for this was probably that the Estonian women had smoked less than the female participants from Iceland and Sweden. The majority of those with CAO do not have a diagnosed lung disease.