Osteoblastic progression during EGFR tyrosine kinase inhibitor therapy in mutated non-small cell lung cancer: a potential blunder.

AIMS AND BACKGROUND: Bone flare reaction as a sign of response to antineoplastic treatment has been redefined, including the onset of new osteoblastic lesions. If misunderstood as skeletal progression, this finding could lead to erroneous therapy discontinuation, changing the disease clinical course. We aim to describe this clinical phenomenon in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene-activating mutations treated with tyrosine kinase inhibitor (TKI). METHODS: We retrospectively reviewed the computed tomography scans of 43 EGFR-mutated patients with NSCLC treated with EGFR-TKI, analyzing the bone response in terms of increase in the quantity and/or density of lesions, and assessing objective tumor response to treatment. RESULTS: Osteoblastic reaction was detected in 10 cases (23%), showing different patterns: dimensional or density increase of known osteosclerotic metastases (pattern A, n = 4); response of previously lytic lesions (pattern B, n = 2); onset of new osteosclerotic lesions (pattern C, n = 4). Seven patients had partial response to TKI treatment, with response rate of 70%, vs 50% of patients with bone metastases without this reaction. No difference in terms of median overall survival or progression-free survival emerged between patients with or without osteoblastic reaction. CONCLUSIONS: The correct clinico-radiologic interpretation of osteoblastic reaction is crucial to avoid waste of therapeutic lines when TKI treatment has not yet exhausted its potential effectiveness. Clinical implications of ambiguous radiologic findings as described in this study deserve further discussion.

Are interstitial lung abnormalities associated with COPD? A nested case-control study.

PURPOSE: In this study, we tested the association between COPD and interstitial lung abnormality (ILA), notably in relation to the presence of computed tomography (CT) signs of lung fibrosis. PATIENTS AND METHODS: COPD cases were selected from participants undergoing lung cancer screening (Multicentric Italian Lung Detection trial) for airflow obstruction (n=311/2,303, 13.5%) and 146 consecutive patients with clinical COPD. In all, 457 COPD cases were selected and classified according to the stages of Global Initiative for Chronic Obstructive Lung Disease. A nested matching (case:control = 1:2) according to age, sex, and smoking history was operated between each COPD case and two control subjects from Multicentric Italian Lung Detection trial without airflow obstruction. Low-dose CT scans of COPD cases and controls were reviewed for the presence of ILA, which were classified into definite or indeterminate according to the presence of signs of lung fibrosis. RESULTS: The frequency of definite ILA was similar between COPD cases and controls (P=0.2), independent of the presence of signs of lung fibrosis (P=0.07). Combined definite and indeterminate ILA was homogeneously distributed across Global Initiative for Chronic Obstructive Lung Disease stages (P=0.6). Definite ILA was directly associated with current smoker status (odds ratio [OR] 4.05, 95% confidence interval [CI]: 2.2-7.4) and increasing pack-years (OR 1.01, 95% CI: 1-1.02). Subjects with any fibrotic ILA were more likely to be older (OR 1.17, 95% CI: 1.10-1.25) and male (OR 8.58, 95% CI: 1.58-68.9). CONCLUSION: There was no association between COPD and definite ILA. However, low-dose CT signs of lung fibrosis were also observed in COPD, and their clinical relevance is yet to be determined.

Hypersensitivity pneumonitis. High resolution CT findings with pathological correlations. A pictorial essay.

The diagnosis of HP is based upon the association of antigen exposure history, compatible clinical and radiological findings and high titres of precipitating serum antibodies to specific antigens. The manifestations of HP are usually divided into three typesacute, sub-acute and chronicbut a significant overlap exists. The clinical spectrum probably reflects different factors, specific to the subject, as well as the frequency and degree of exposure. The aim of this pictorial essay is to present the more common presentations of HP.