What question did this study set out to answer?

This study aims to characterize the genomic and immunologic features of lung cancer in lung transplant recipients.

May 20, 2026

A22-06 Molecular Landscape of Lung Cancer Arising in Lung Transplant Recipients

Key Points

This study aims to characterize the genomic and immunologic features of lung cancer in lung transplant recipients.
Retrospective review of lung transplant recipients from 2016 to 2024 at a high-volume center
Collection of clinical data including transplant type, histology, and outcomes
Analysis of genomic testing results using next-generation sequencing and PD-L1 expression
45 out of 1,202 lung transplant recipients (3.7%) developed lung cancer after a median of 3.3 years post-transplant
Genomic alterations were found in 33% of patients tested, with no actionable targets identified
Median survival after lung cancer diagnosis was 6.6 months, with 87% mortality by analysis.

Abstract

Abstract Rationale Lung cancer (LC) is an increasingly recognized complication after lung transplantation (LT), representing a leading cause of late mortality in this population. Post-transplant LC management remains challenging due to limited functional reserve, immunosuppression, and the predominance of advanced-stage presentation. While targeted and immune-based therapies have transformed outcomes in the general population, the molecular characteristics of LC arising after LT—and their therapeutic relevance—remain poorly defined. This study characterizes the genomic and immunologic landscape of LC developing in LT recipients. Methods We retrospectively reviewed all LT recipients at a single high-volume transplant center between 2016 and 2024. Clinical data, transplant type, histology, stage, and outcomes were collected for patients who developed LC. Molecular testing results, including next-generation sequencing (NGS) and programmed death-ligand 1 (PD-L1) expression, were analyzed to identify genomic alterations and immunologic profiles. Results Among 1,202 LT recipients, 45 (3.7%) developed LC at a median of 3.3 years post-transplant. The majority were male (80%) and White (83%), and most had a prior smoking history (91%). LC occurred after single LT in 43 (95.6%) and double LT in 2 (4.4%). Non-small cell LC (NSCLC) accounted for 37 cases, small cell LC (SCLC) for 5, and mixed histology for 2. Eighty percent of tumors arose in the native lung, and 56% presented at an advanced stage. NGS was performed in 15 patients (33%), revealing genomic alterations in KRAS, BRAF, TP53, NF1, MTAP, and others; however, none were actionable with current FDA-approved therapies. PD-L1 expression 1% was identified in 8 of 11 tested samples. Median survival following LC diagnosis was 6.6 months, and 87% had died at analysis. Conclusions LC after LT frequently arises in the native lung and often presents at an advanced stage. Only one-third of cases underwent molecular testing, which revealed diverse but currently non-actionable genomic alterations. Broader application of NGS and incorporation of molecular profiling into multidisciplinary transplant oncology care may enhance future therapeutic opportunities. Collaborative, multicenter studies are needed to establish standardized molecular testing and management pathways for post-transplant malignancies. This abstract is funded by: None

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