Histological response to radiotherapy is an early event in myxoid liposarcoma

Lam, S.W.; Silva, T.M.; Traast-Kooistra, J.; Briaire-de Bruijn, I.; Akker, B. van den; Bakker, P.A.C.; ... ; Bovée, J.V.M.G. (2023)

Article / Letter to editor

Compared to other sarcomas, myxoid liposarcoma (MLS) is exceptionally sensitive to radiation therapy, but the underlying mechanism remains unknown. The objective was to assess the tissue-based changes in MLS during and after neoadjuvant radiotherapy in 26 patients of the DOREMY trial. Morphological assessment was performed on biopsies pre-treatment, after 8 fractions, 16 factions, and after surgical resection and included percentage of viable tumor cells, hyalinization, necrosis, and fatty maturation. Furthermore, immunohistochemistry was performed for apoptosis (cleaved caspase-3), anti-apoptosis (Bcl-2), activity of mTOR signaling (phospho-S6), hypoxia (CAIX), proliferation (Ki67), inflammation (CD45 and CD68), and microvessel density (CD34 Chalkley count). A pronounced reduction in vital tumor cells was observed early with a drop to 32.5% (median) tumor cells (IQR 10–93.8%) after 8 fractions. This decreased further to 10% (IQR 5–30%) after 16 fractions and 7.5% (IQR 5–15%) in the surgical specimen. All but one patient had an excellent response with < 50% remaining tumor cells. Inversely, treatment response was mainly observed as hyalinization and less often as fatty maturation. Additionally, a decrease of inflammatory cells was noticed especially during the first eight fractions. Microvessel density remained stable over time. Immunohistochemical markers for apoptosis, anti-apoptosis, activity of mTOR signaling, proliferation, and hypoxia did not show any marked changes within the remaining tumor cells during and after radiotherapy. As a modest dose of neoadjuvant radiotherapy induces profound tissue changes in MLS, mainly during the first 8 fractions, current findings might suggest that in a carefully selected patient population further deintensification of radiotherapy might be explored.

• Myxoid liposarcoma
• Radiotherapy
• Personalized medicine

• All authors: Lam, S.W.; Silva, T.M.; Traast-Kooistra, J.; Briaire-de Bruijn, I.; Akker, B. van den; Bakker, P.A.C.; Lansu, J.; Haas, R.L.M.; Bovée, J.V.M.G.
• Date: 2023-08-12
• Journal: Virchows Archiv
• Volume: 483
• Issue: 4
• Pages: 487 - 495
• DOI: doi:10.1007/s00428-023-03615-5
• Link: https://link.springer.com/article/10.1007/s00428-023-03615-5