Risk factors and outcome of children and young adults with initially unresected nonrhabdomyosarcoma soft tissue sarcoma: An analysis from the International Soft Tissue Sarcoma Consortium.
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
BACKGROUND: The role of neoadjuvant therapy in children, adolescents, and young adults (CAYA) with initially unresectable nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) remains controversial, with recommendations varying by cooperative group. The International Soft Tissue Sarcoma Consortium (INSTRuCT) is a collaboration among North American and European study groups (Children's Oncology Group [COG], Cooperative Weichteilsarkom Studiengruppe [CWS], and European Paediatric Soft Tissue Sarcoma Study Group [EpSSG]). The prognostic value of tumor characteristics and outcome for CAYA with initially unresected localized NRSTS was analyzed. METHODS: The INSTRuCT database was searched for all CAYA whose initial surgical intervention was biopsy only or surgery resulting in gross residual disease (R2). Study data from the COG (ARST0332), EpSSG (NRSTS-2005), International Society of Paediatric Oncology Malignant Mesenchymal Tumour Committee (MMT-95), and CWS (CWS-91, -96, and -2002P) were included. All patients received preoperative chemotherapy, which was often alkylator and/or anthracycline based. Neoadjuvant radiation (RT) was protocol specified for all ARST0332 subjects and for higher risk NRSTS-2005 subjects but not for subjects in the CWS or MMT-95 studies, where the use and timing of RT were more variable. RESULTS: Outcomes were analyzed for 661 patients aged <21 years enrolled in the ARST0332 (n = 113), MMT-95 (n = 144), NRSTS-2005 (n = 221), and CWS-91, -96, and -2002P (n = 183) studies between 1988 and 2016. The median age was 12 years (range, 0-21 years). Tumors were most commonly >5 cm (n = 484; 73%), located in the extremity (n = 354; 55%), T2 (n = 360; 55%), and N0 (n = 572; 87%). A greater percentage of patients with tumors of ≤5 cm were enrolled in European versus North American studies. Five-year event-free survival (EFS) for the entire cohort was 57.6% (95% CI, 53.5%-61.4%). EFS-independent prognostic factors were histology (synovial sarcoma most favorable and malignant peripheral nerve sheath tumor least favorable; p < .0001), invasiveness (p = .002), and primary site (extremity most favorable; p = .02). Patients in studies with protocol-specified neoadjuvant RT (ARST0332 and NRSTS-2005) achieved higher R0/R1 delayed resection margins (98% and 96%, respectively) compared to those in studies with more variable RT incorporation (CWS and MMT-95) (81% and 46%, respectively) (p < .0001). In restricting the outcome analysis to those who were event free at Week 24 only, in an attempt to minimize bias in the heterogeneous treatment strategies across trials, there was a trend toward improved survival for patients treated with chemotherapy + RT (pre- or postoperative) versus chemotherapy alone (EFS, p = .075; overall survival, p = .058). EFS for subjects with large (>5-cm) synovial sarcoma treated in the recent ARST0332 and NRSTS-2005 studies was more favorable when compared to earlier CWS and MMT-95 protocols. CONCLUSIONS: Outcomes were more favorable with the combination of chemotherapy and RT (pre- or postoperative) versus no RT for initially unresected NRSTS. Patients with large synovial sarcoma may benefit from contemporary trial designs incorporating more of a risk-based directed neoadjuvant chemotherapy and RT approach. Higher R0 margin status rates were achieved in protocols with specified preoperative RT, which resulted in improved outcomes.