Leiomyosarcoma survival across anatomical sites identifies high- and low-risk patient groups to inform clinical trial design
Ailsa J Oswald, Rashi Krishna, Xiangfei Yan, Patricia Roxburgh, Robert L HollisAbstract
Background
Leiomyosarcoma, the commonest subtype of soft tissue sarcoma, affects a wide range of anatomical sites. Few multi-site analyses of leiomyosarcoma have been performed to characterise differences across anatomical sites, and to identify patient or tumour characteristics independently associated with survival. Such information is critical to inform future design of pan-site trials necessary due to the rarity of leiomyosarcoma.
Methods
We analysed a study cohort of 11,751 patients with leiomyosarcoma across a range of anatomical sites.
Results
The uterus(36.3%), limbs(16.6%), superficial trunk(10.8%) and retroperitoneum (9.2%) were the most common anatomical sites. Median follow-up time was 8.4 years. Uterine tumours accounted for a greater proportion in black patients(P-adj<0.001), while the skin(P-adj<0.001) and limbs(P-adj<0.001) were more common sites in the white population. Marked differences in age, grade and stage at diagnosis were observed across anatomical sites. Multivariable analysis identified site, grade, race, marital status and household income as independently associated with outcome: individuals of black race, widowed patients, and those with the lowest income demonstrated significantly shorter survival. The uterus, urinary tract and trunk were among the highest risk sites, while the limbs, head and neck, and male reproductive tract were associated with more favourable outcomes after adjustment. ATRX mutations were enriched(P-adj<0.0001) within uterine cases compared to other sites in a pooled analysis of publicly available sequencing.
Conclusion
Major disparities in outcome are clear across leiomyosarcoma subgroups defined by anatomical site and patient characteristics. Future trials may wish to account for the intrinsic aggressiveness of tumours arising at different anatomical locations.