Abstract
AB042. Deep dive into the NEJM study suggesting health consequences after thymectomy
Frank Detterbeck1, Henry Kaminski2
1Division of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT, USA;
2Department of Neurology & Rehabilitation Medicine, George Washington University, Washington, DC, USA
Correspondence to: Frank Detterbeck, MD. Division of Thoracic Surgery, Department of Surgery, Yale School of Medicine, BB205, 330 Cedar St, New Haven, CT 06520-8062, USA. Email: Frank.detterbeck@yale.edu.
Background: A recent study raised questions about health consequences of thymectomy in adults. International Thymic Malignancy Interest Group (ITMIG) members need a thorough understanding of this.
Methods: The study hypothesis was that thymectomy leads to worse survival and increased subsequent cancer, autoimmune disease, and infection (due to immune compromise). The primary analysis compared patients undergoing thymectomy to matched controls undergoing cardiac surgery, with endpoints of survival, subsequent cancer, autoimmune disease, or infection. The secondary analysis aimed to correlate the primary findings with an increase in severity of subsequent cancers—by analyzing unmatched patient subsets (n=75) who developed cancer or autoimmune disease after thymectomy vs. cardiac surgery. A tertiary analysis assessed immune function markers in an unmatched subset in whom blood was available (n=19/22).
Results: The primary analysis suggested that thymectomy was associated with worse survival and more cancers, but not autoimmune disease or infection. However, confidence in interpretation and attribution of the effect to thymectomy is weakened by questions regarding the comparator selection, matching process, the approach to confirmatory subset analyses and the time period when differences became manifest. The secondary analysis suggests that thymectomy is associated with more aggressive cancers and multiplicity of autoimmune diseases than the comparator cohort. However, the thymectomy and cardiac surgery cohorts were unmatched; differences in age and sex and ambiguities regarding endpoint definitions create uncertainly in interpretation and effect attribution. Interpretation of the tertiary analysis is hampered by the limited cohort of unmatched patients; however, evidence of diminished immune function was seen after thymectomy vs. controls, and in patients who developed cancer vs. those who didn’t.
Conclusions: The NEJM study suggested that thymectomy may have health consequences, which is consistent with basic science data (reviewed separately) that immune compromise associated with thymic involution may be linked to the incidence of cancer, autoimmune disease and infections with increasing age. However, the questions regarding the structure of the NEJM study as discussed in this abstract leave uncertainties how clearly the observations can be attributed to thymectomy.
Keywords: Thymectomy; cancer; autoimmunity; infection; immunology
Acknowledgments
Funding: None.
Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-24-ab042/coif). H.K. reports serving as a consultant for UCB Pharmaceuticals, Curie.bio, Samsung, Canopy Immunotherapeutics and EMD Serono, and an unpaid consultant for Care Constitution. H.K. has equity interest in Mimivax, LLC and is principal investigator for the Rare Disease Network, MGNet supported by NIH grant U54NS115054. H.K. also reports unrestricted educational grant to George Washington University from Argenix. The other author has no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Because the study involves a review of a published paper, IRB approval is not applicable.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
doi: 10.21037/med-24-ab042
Cite this abstract as: Detterbeck F, Kaminski H. AB042. Deep dive into the NEJM study suggesting health consequences after thymectomy. Mediastinum 2024;8:AB042.
