Osteoblastc progression during EGFR tyrosine kinase inhibitor therapy in mutated non-small cell lung cancer: A potental blunder

Aims and background: Bone flare reacton as a sign of response to antneoplastc treatment has been redefined, including the onset of new osteoblastc lesions. If misunderstood as skeletal progression, this finding could lead to erroneous therapy discontnuaton, changing the disease clinical course. We aim to describe this clinical phenomenon in patents with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene-actvatng mutatons treated with tyrosine kinase inhibitor (TKI). Methods: We retrospectvely reviewed the computed tomography scans of 43 EGFR-mutated patents with NSCLC treated with EGFR-TKI, analyzing the bone response in terms of increase in the quantty and/or density of lesions, and assessing objectve tumor response to treatment. Results: Osteoblastc reacton was detected in 10 cases (23%), showing different paterns: dimensional or density increase of known osteosclerotc metastases (patern A, n = 4); response of previously lytc lesions (patern B, n = 2); onset of new osteosclerotc lesions (patern C, n = 4). Seven patents had partal response to TKI treatment, with response rate of 70%, vs 50% of patents with bone metastases without this reacton. No difference in terms of median overall survival or progression-free survival emerged between patents with or without osteoblastc reacton. Conclusions: The correct clinico-radiologic interpretaton of osteoblastc reacton is crucial to avoid waste of therapeutc lines when TKI treatment has not yet exhausted its potental effectveness. Clinical implicatons of ambiguous radiologic findings as described in this study deserve further discussion