Mesenchymal chondrosarcoma: An Australian multi‐centre cohort study

Abstract

Background Mesenchymal chondrosarcoma (MCS) is an ultra‐rare sarcoma that follows a more aggressive course than conventional chondrosarcoma. This study evaluates prognostic factors, treatments (surgery, chemotherapy, and radiation), and outcomes in an Australian setting. Methods We collected demographics, clinicopathological variables, treatment characteristics, and survival status from patients with MCS registered on the national ACCORD sarcoma database. Outcomes include overall survival (OS) and progression‐free survival (PFS). Results We identified 22 patients with MCS between 2001–2022. Median age was 28 (range 10–59) years, 19 (86%) had localised disease at diagnosis of whom 16 had surgery (84%), 11 received radiation (58%), and 10 chemotherapy (53%). Ten (52%) developed recurrence and/or metastases on follow‐up and three patients with initial metastatic disease received surgery, radiation, and chemotherapy. At a median follow‐up of 50.9 (range 0.4–210) months nine patients had died. The median OS was 104.1 months (95% CI 25.8–182.3). There was improved OS for patients with localised disease who had surgical resection of the primary ( p = 0.003) and those with ECOG 0–1 compared to 2–3 ( p = 0.023) on univariate analysis. Conclusions This study demonstrates contemporary Australian treatment patterns of MCS. The role of chemotherapy for localised disease remains uncertain. Understanding treatment patterns and outcomes help support treatment decisions and design of trials for novel therapeutic strategies.

Mesenchymal Chondrosarcoma from Diagnosis to Clinical Trials

“…Many studies suggest that tumors with nested round cell morphology and staghorn vasculature lacking a distinctive cartilaginous component should undergo FISH testing for HEY1-NCOA2 fusion [ 75 , 77 ]. Another well-known diagnostic marker in MCS is the lack of isocitrate dehydrogenase ( IDH ) 1/2 mutations, common in central, periosteal, and dedifferentiated CS [ 7 , 32 ]. Until now, no other markers commonly used in diagnostics are known, and further research is strongly encouraged.…”

“…Surgical resection remains the mainstay of MCS treatment for individuals with localized disease. Compared with other subtypes, MCS represents more aggressive behavior and worse survival outcomes [ 6 , 7 , 8 ]. Surgery should always aim at resection with disease-free margins.…”

“…Unfortunately, due to anatomic constraints, obtaining wide margins is not always possible, and, in some cases, amputation is needed ( Figure 1 ). Therefore, sometimes neoadjuvant or adjuvant therapy has to be considered; non-radical resection results in a high risk of local recurrence [ 7 , 78 ].…”

“…The incidence rate of MCS in men and women is similar [ 4 ]. According to a November 2015 retrospective review of chondrosarcoma subtypes using the SEER database, the mesenchymal subtype effects the largest proportion of African Americans (16.4%) and Asian individuals (about 9.3%) [ 6 , 7 , 8 ].…”

Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions

“…Chondrosarcoma can be classified into lesser-known subtypes such as dedifferentiated, mesenchymal, clear cell, and extra-skeletal myxoid chondrosarcoma [ 13 ]. Dedifferentiated chondrosarcomas develop from lower-grade common chondrosarcoma, while mesenchymal chondrosarcoma is very malignant and has a biomorphic histological model with small, round cell islands that interpenetrate with cartilage and dedifferentiate spindle cells [ 13 , 14 ]. Clear-cell chondrosarcoma is less aggressive and is composed of cells containing a large amount of glycogen in the cytoplasm [ 13 , 15 ].…”