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Risk-Based Treatment of Pediatric and Young Adult Synovial Sarcoma


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In a report from the Children’s Oncology Group ARST0332 study published in the Journal of Clinical Oncology, Venkatamani et al found that risk-based treatment of pediatric and young adult patients with synovial sarcoma produced favorable outcomes in those with nonmetastatic disease. Outcomes in those with metastatic disease remained poor.

Study Details

The study enrolled 138 evaluable newly diagnosed patients aged < 30 years between 2007 and 2012. Risk was determined using tumor grade, maximum tumor diameter, resectability, surgical margins, and nonmetastatic vs metastatic status.

Patients categorized as low-risk (n = 46) received surgery alone (group A, n = 41, 29.7%) or with adjuvant radiotherapy at 55.8 Gy (group B, n = 5, 3.6%). Patients categorized as intermediate risk with no metastases (n = 71) and high-risk (n = 21, all with metastases) received either surgery and adjuvant chemoradiotherapy with ifosfamide/doxorubicin and radiotherapy at 55.8 Gy (group C, n = 23, 16.7%) or neoadjuvant chemoradiotherapy with ifosfamide/doxorubicin and radiotherapy at 55.8 Gy, surgery, radiotherapy boost based on margins, and adjuvant ifosfamide/doxorubicin (group D, n = 69, 50%).   

Key Findings

At a median follow-up of 6.8 years (range = 0.01–10.98 years), estimated 5-year event-free survival by risk group was 81.9% (95% CI = 69–94.8) among low-risk patients, 69.8% (95% CI = 57.6%–82.0%) among intermediate-risk patients, and 7.62% (95% CI = 0.0%–22.0%) among high-risk patients (overall P < .0001).

Estimated 5-year overall survival was 97.7% (95% CI = 92.7%–100%) among low-risk patients, 88.8% (95% CI = 80.5%–97.1%) among intermediate-risk patients, and 12.5% (95% CI = 0.0%–28.7%) among high-risk patients (overall P <.0001).

Estimated 5-year event-free and overall survival were 64% and 89.5% among intermediate-risk patients in group C and 71.2% and 86.5% among intermediate-risk patients in group D.

By treatment group, estimated 5-year event-free survival (overall P = .0142) and overall survival (overall P = .0004) were 84.5% and 100% in group A, 60.0% and 80.0% in group B, 64.1% and 89.5% in group C, and 53.6% and 66.3% in group D.

After adjustment for features that defined risk category, no other patient or disease characteristics—including age, sex, tumor site, tumor invasiveness, and tumor depth—improved the risk stratification model.

No deaths due to toxicity were observed. Four unexpected grade 4 adverse events were observed in group D.

The investigators concluded, “The risk-based treatment strategy used in ARST0332 produced favorable outcomes in patients with nonmetastatic synovial sarcoma relative to historical controls despite using radiotherapy less frequently and at lower doses. The outcome for metastatic synovial sarcoma remains unsatisfactory and new therapies are urgently needed.”

Rajkumar Venkatramani, MD, of Texas Children’s Cancer Center, Texas Children’s Hospital, Baylor College of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the NCTN Operations Center and NCTN Statistics & Data Center and St. Baldrick’s Foundation. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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