Alessandro Di Federico: Lung adenocarcinomas with Mucinos Histology
Alessandro Di Federico, Medical Oncologist and Ph.D. student at the University of Bologna, shared a post on X:
“Mucinous lung adenocarcinoma (LUAD-Muc) is a WHO-recognized rare subtype of LUAD. Our study in Annals of Oncology aimed to characterize clinicopathologic, genomic, immunophenotypic and transcriptional features differentiating these tumors form other LUADs.
UAD-Muc represented ~10% of LUAD and had:
– Low cigarette use history (pack-years)
– Low PD-L1 & TMB
– Low brain but high bilateral lung mets
– High prevalence of KRAS & ALK but low EGFR, BRAF, & MET driver alterations
– shorter mOS from diagnosis
In addition, LUAD-Muc was enriched in NKX2-1 ( the TTF-1 gene), STK11, SMARCA4, & GNAS muts, but depleted in TP53 muts. Interestingly, co-mutational patterns involving genes such as KRAS, STK11, KEAP1, and SMARCA4 (among others) differed from those found in non-mucinous LUAD.
LUAD-Muc were also characterized by low intratumoral immune cells, including those expressing CD8, PD-1, both CD8 and PD-1, and FOXP3.
Consistently with the features observed, patients with LUAD-Muc had worse ORR, PFS, & OS to immune checkpoint inhibitors with and without chemotherapy, and worse OS to KRAS G12C inhibitors (sotorasib or adagrasib).
Even among hard-to-treat molecular subgroups, such as LUADs with STK11, KEAP1, and/or SMARCA4 muts, LUAD-Muc were invariably associated with worse outcomes to immunotherapy.
Among LUAD-Muc, cases harboring KRAS muts seemed to achieve improved outcomes to immunotherapy compared to KRAS wild-type ones, while no difference was observed among patients treated with chemo-immunotherapy.
Take a look at the paper for many more analyses and details!
This work was possible thanks to the guidance of Jia Luo, to my mentor at the Dana-Farber’s Lowe Center for Thoracic Oncology Mark Awad, and to many great collaborators across institutions: Andrea De Giglio, Arielle Elkrief, Natalie Vokes, Biagio Ricciuti, Adam J Schoenfeld and many more!”
Authors: A. Di Federico, L. Hong, A. Elkrief, R. Thummalapalli, A.J. Cooper, B. Ricciuti1, S. Digumarthy, J.V. Alessi, P. Gogia, F. Pecci, M. Makarem, M.M. Gandhi, E. Garbo, A. Saini, A. De Giglio, V. Favorito, S. Scalera, L. Cipriani, D. Marinelli, D. Haradon, T. Nguyen, J. Haradon, E. Voligny, V. Vaz, F. Gelsomino, F. Sperandi, B. Melotti, M. Ladanyi, J. Zhang, D.L. Gibbons, J.V. Heymach, M. Nishino, J. Lindsay, S.J. Rodig, K. Pfaff, L.M. Sholl, X. Wang, B.E. Johnson, P.A. Jänne, N. Rekhtman, M. Maugeri-Saccà, R.S. Heist, A. Ardizzoni, M.M. Awad, K.C. Arbour, A.J. Schoenfeld, N.I. Vokes, J. Luo
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