FDG PET/CT for Evaluating Early Response to Neoadjuvant Chemotherapy in Pediatric Patients with Sarcoma: A Prospective Single-Center Trial
Introduction: This is a prospective, single-center trial (UCLA-IRB#10-000246) in pediatric patients with high-grade bone or soft tissue sarcoma. The aim was to evaluate FDG-PET/CT as a tool for early response assessment to neoadjuvant chemotherapy (neo-CTX).Methods: Bone or soft tissue sarcoma patients with i) baseline FDG PET/CT within four weeks prior to the start of neo-CTX (PET1), ii) early interim FDG PET/CT (six weeks after the start of neo-CTX (PET2), iii) evaluation of neo-CTX response
... f neo-CTX response by histology or MRI, and iv) definitive therapy after neo-CTX (surgery or radiation) were included. Semi-quantitative PET parameters (SUVmax, SUVmean, SUVpeak, MTV and TLG) and their changes from PET1 to PET2 (ΔPET) were calculated. Patients with necrosis ≥90% in the excised tumor tissue after surgery or with complete disappearance of the soft tissue component on MRI after neo-CTX were considered responders. The primary endpoint was to evaluate the predictive value of FDG PET/CT parameters at baseline and early during neo-CTX for overall survival (OS) and time to progression (TTP). The secondary outcome was to evaluate if FDG PET/CT can predict the response to neo-CTX assessed by percentage of necrosis in the resected tumor or post-treatment MRI. Primary and secondary outcomes were also evaluated in a sub-population of patients with bone involvement only.Results: Thirty-four consecutive patients were enrolled (10 females; 24 males; median age=15.1 years). 17/34 patients (50%) had Osteosarcoma, 13/34 (38%) Ewing Sarcoma, 2/34 (6%) synovial sarcoma and 2/34 (6%) embryonal liver sarcoma. Median follow-up was 39 months (range 16-84). Eight of 34 patients (24%) died, 9/34 (27%) were alive with disease and 17/34 (50%) had no evidence of residual/recurrent disease. Fifteen of 34 (44.1%) and 19/34 (55.9%) were responders and non-responders, respectively. PET2-parameters were associated with longer TTP (p <0.02). ΔMTV was associated with tissue response to neo-CTX (p=0.047). None of the PET1, PET2 or ΔPET parameters were associated with OS. Conclusion: FDG PET/CT performed six weeks after the start of neo-CTX can serve as an early interim biomarker for TTP and pathologic response but not for OS in pediatric bone and soft tissue sarcoma patients.