The first data on rare sarcomas in Asian patients was recently presented in three studies at the ESMO Asia 2016 Congress in Singapore.
Just half of patients with advanced angiosarcoma received chemotherapy even though it improved overall survival. CIC-rearranged sarcomas are shown to have a much worse prognosis than BCOR-rearranged sarcomas and clinical features are identified to aid accurate diagnoses.
Angiosarcoma is the focus of two studies conducted by the newly formed Asian Sarcoma Consortium (ASC) (Abstract 501O_PR, Abstract 502O_PR). Treatment is challenging since the disease tends to be infiltrative, making surgery with clear margins difficult, while radiation is a poor option for tumors on the scalp and face. Chemotherapy has demonstrated activity in angiosarcoma but long-term remission is rare.
Both studies retrospectively included patients attending eight sites in six countries during 1990 to 2016. The first study outlines the epidemiology, real-world treatment, and clinical outcomes of angiosarcoma in Asia. The median age of the 423 patients was 67 years, about 60 percent had cutaneous angiosarcoma (they were more likely to be older, male, and have localized disease), while 40 percent had visceral angiosarcoma.
In the localized setting, only about 60 percent of patients underwent surgery, but this was significantly lower in the cutaneous (55%) than visceral (75%) cohort. In those who underwent surgery, negative margins were only achieved in approximately 70 percent of cases. Close to half of patients who underwent surgery relapsed. Median relapse free survival was just 12.3 months with no statistical difference between the cutaneous (12.9 months) versus visceral (9.5 months) groups. Patients were more likely to relapse if they were more than 65 years old or had positive surgical margins.
In the advanced setting, only about half of patients received chemotherapy. Median overall survival was 9.5 months with no significant difference between cutaneous (11.5 months) and visceral (8.3 months) groups. ECOG (Eastern Cooperative Oncology Group) performance status was an independent predictor of survival. However, after adjusting for ECOG performance status, overall survival was significantly better in patients who received chemotherapy than those who did not.
"This is one of the largest studies in angiosarcoma and we found that overall prognosis was poor," said lead author Richard Quek, MD, Deputy Head and Senior Consultant, National Cancer Centre Singapore. "In patients with localized disease, negative surgical margin was prognostic for relapse free survival yet it was only achieved in 70 percent of patients. Neoadjuvant (pre-operative) treatment, be it chemotherapy or radiation, might enhance resectability of these tumors and thereby improve survival outcomes.
"In patients with advanced disease we demonstrated that, after adjusting for ECOG performance status, chemotherapy was associated with improved overall survival. But only half of our patients actually received chemotherapy, hence it would be important to understand the reasons behind this low treatment rate," Quek continued. "Could these be physician-related factors? And if so, is more sarcoma-related continuing medical education needed to enhance care for our patients?"
The second angiosarcoma study outlined the clinical characteristics and treatment of 277 patients with advanced metastatic or unresectable disease. The median age was 64 years. The predictors of better prognosis were younger age, female sex, and cutaneous (rather than visceral) disease. Use of chemotherapy gradually increased over the 20-year period, with a preference for paclitaxel and liposomal doxorubicin over other treatments. Progression-free survival in patients receiving at least one line of chemotherapy was 3.8 months. Overall survival was 8.3 months but was significantly higher in patients who received at least one line of palliative chemotherapy (11.5 months) than those who did not (4.4 months).
"It's the first time we have data on expected survival for Asian patients with advanced metastatic or unresectable angiosarcoma," said lead author Tom Chen, MD, Attending Physician, National Taiwan University Hospital, Taipei, Taiwan. "This data will help us to develop clinical trials and new treatments for Asian angiosarcoma patients."
The third study focused on Ewing sarcoma-like small round cell sarcomas (Abstract 503O_PR). Ewing sarcoma is molecularly characterized by a EWSR1 gene alteration or FUS rearrangement. Small round cell sarcomas without these molecular characteristics are designated "Ewing sarcoma-like" disease. Recent molecular genetic studies have identified CIC-rearranged sarcoma (CIC-DUX4, CIC-DUX4L, CIC-FOXO4) and BCOR-rearranged sarcoma (BCOR-CCNB3, BCOR-MAML3, ZC3H7B-BCOR) among these Ewing sarcoma-like small round cell sarcomas. The recently presented study describes the clinical characteristics and treatment outcomes of these two sarcomas.
The study included 17 patients with CIC sarcoma, of whom 12 were male. Median age was 22 years, all cases were soft tissue tumors, and 59 percent of patients had local pain. The seven BCOR sarcoma patients were all male. Median age was 14 years and cases included bone and soft tissue tumors.
The 5-year overall survival rate was 28.2 percent for CIC sarcoma and 100 percent for BCOR sarcoma. Metastases were present in 71 percent of CIC patients at the initial visit and none of the BCOR patients. Only 29 percent of CIC patients responded to chemotherapy compared to 75 percent of BCOR patients.
"CIC-rearranged sarcomas have a much worse prognosis than BCOR-rearranged sarcomas," said lead author Makoto Endo, MD, PhD, Attending Physician, National Cancer Centre, Tokyo, Japan. "CIC and BCOR sarcomas were previously classified as the same tumor. Our research will help us to make a precise diagnosis and should improve the management of these patients."
Commenting on the studies, Thomas Brodowicz, MD, Program Director, Bone and Soft Tissue-Sarcoma Unit, Medical University Vienna, Austria, said: "The two studies on angiosarcoma show that immediate progression-free survival and overall survival are low, which reflects the aggressiveness of this disease. It would be useful to have a more detailed breakdown of the patients-- for example, the treatment and outcomes of primary angiosarcoma versus secondary, which forms at the site of radiation treatment for a previous cancer. It would also be helpful to know whether paclitaxel is more effective when taken every 3 weeks or weekly, which has an antiangiogenic effect that could be beneficial in angiosarcoma."
"The study by Dr. Endo provides practice-changing information," he concluded. "It shows that Ewing sarcoma-like small round cell sarcomas can be further categorized by their specific mutations, which have a strong prognostic impact. This should help us to tailor treatment."