Extending the EXOTIC Database to Allow the Recognition of Potential Causes of Exon 20-Mutated NSCLC

To the Editor:

We read with great interest the Letter to the Editor by Zandwijk et al.¹ regarding our recent publication on the EXOTIC real-world database focusing on molecular epidemiology and clinical outcomes of exon 20-mutated NSCLC.² We are particularly thankful to the authors for their innovative suggestion to expand the EXOTIC consortium to include data on occupational data, residential history, and radiological features in an effort to identify potential causative environmental factors for this challenging disease entity. In fact, such discussions have been recently launched within the members of the Consortium, after important announcements on the potential etiologic correlation between air pollution (in the form of particulate matter 2.5 [PM2.5] nanoparticle exposure) and alveolar transformation in non and never smokers with classical activating EGFR mutations.³ These new data have revived the interest to further study causality in other subsets of oncogene-addicted NSCLC, including those with exon 20 mutations. Interestingly, in the EXOTIC registry, 76% of patients were never or past smokers.² The correlation between asbestos exposure, PM2.5 concentration levels, and exon 20-mutated NSCLC remains largely unknown, and scarce preclinical data have been reported to date,^4,5 none of which focuses on exon 20 mutations in particular. The fact that this subgroup of patients bears a worse prognosis as compared with classical EGFR mutations renders the necessity to identify potential causal factors even more urgent.

In the EXOTIC consortium, we have launched an initiative to identify environmental factors that may synergize with EGFR mutations to provoke neoplastic transformation in light or never smokers. These environmental factors include occupational exposure including—but not restricted to—asbestos and other occupational hazardous dusts, residential data to compare with PM2.5 exposure, and any history of pulmonary fibrosis and radiological evidence of chronic pneumonitis or presence of asbestos plaques. Recuperation of this information is expected to be challenging and time consuming, as most of the data will be collected retrospectively, across a large number of institutions in Europe and a considerable number of patients are deceased, further limiting retrieval of data. On these grounds, establishing international collaborations might again be the key factor: The EXOTIC consortium would be happy to collaborate with networks from other continents (including of course Australia) in an effort to maximize available data that are necessary to establish those correlations. In this context, we would be happy to receive any expression of interest to expand our database on a global level.

CRediT Authorship Contribution Statement

Giannis Mountzios: Conception and design, Statistical analysis, Data curation, Manuscript writing, Final approval of the manuscript.