Dr. Rajkumar Venkatramani
A novel risk-based treatment strategy for young patients with soft-tissue synovial sarcoma was associated with favorable outcomes compared with historical controls in the ARST0332 trial (Abstract 10012). Rajkumar Venkatramani, MD, of Baylor College of Medicine, presented the results during the Pediatric Oncology II Oral Abstract Session on Monday, June 1.
Soft-tissue synovial sarcoma, the second most common soft-tissue sarcoma in childhood, is considered more chemosensitive than other non-rhabdomyosarcoma soft-tissue sarcomas (NRSTS), and there is no clear standard of care. The primary objectives of the trial were evaluation of outcomes in patients treated according to a risk-based strategy and assessment of the feasibility of neoadjuvant chemotherapy plus radiation for patients with intermediate- and high-risk unresected NRSTS. The strategy assessed in the trial used radiation therapy less frequently and at lower doses.
The 129 patients evaluated in the trial (median age 14.6; 51% female) were assigned to four treatment arms based on disease features that included Pediatric Oncology Group (POG) grade and diagnosis of either nonmetastatic or metastatic disease (Fig. 1). Patients considered low risk underwent gross tumor resection prior to study entry and were assigned to groups A and B. Group A had a low tumor grade and was treated with observation, whereas group B had a high tumor grade and received 55.8 Gy of adjuvant radiation. Patients considered intermediate risk with a tumor diameter greater than 5 cm and patients considered high risk with metastatic disease who had a low-grade tumor underwent gross resection and were assigned to group C, which received ifosfamide/doxorubicin and 55.8 Gy of radiation. Patients considered intermediate and high risk with nonmetastatic or metastatic disease, respectively, whose tumor was unresectable were assigned to group D, and received neoadjuvant ifosfamide/doxorubicin chemotherapy, 45 Gy of radiation, surgery at week 13, and a radiation therapy boost based on margins.
Event-free survival at 3 years was 83% (95% CI [68%, 92%]) in the low-risk group, 79% (95% CI [65%, 88%]) in the intermediate-risk group, and 16% (95% CI [4%, 35%] in the high-risk group. Three-year overall survival was 97% (95% CI [82%, 99%]) in the low-risk group, 93% (95% CI [83%, 97%]) in the intermediate-risk group, and 29% (95% CI [11%, 49%]) in the high-risk group.
Dr. Steven G. DuBois
Other than POG grade, no other factors were predictive of outcome, including age, gender, invasiveness, primary site, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, or mitoses per 10 high-powered fields. Combined neoadjuvant chemoradiation proved to be a feasible treatment strategy. According to Dr. Venkatramani, the results from the trial suggest that POG grade 2 synovial sarcoma can be treated as a low-grade tumor, and POG grade 3 synovial sarcoma with a diameter of 5 cm or smaller can be safely managed with wide resection alone.
After presenting the trial results, Dr. Venkatramani said that “the outcome for synovial sarcoma remains poor, and new therapies are needed.”
Discussant Steven Dubois, MD, of the University of California, San Francisco, said that the trial is
“the largest pediatric synovial series reported to date, and it really benefits from pathology central review of diagnosis and the grade of the tumor, which is important given the cooperative group nature of the study and the rarity of the disease.”
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