Neoadjuvant chemotherapy and surgery versus surgery for organ preservation of T3 and T4a nasal and paranasal sinus squamous cell carcinoma (NPNSCC) ECOG-ACRIN EA3163.

PURPOSE Neoadjuvant chemotherapy for structure preservation (SP) in nasal and paranasal sinus squamous cell carcinoma (NPNSCC) has been described in single-institution but not randomized studies. EA3163 was a randomized study investigating whether cytoreductive neoadjuvant chemotherapy would improve SP or overall survival (OS). PATIENTS AND METHODS Patients with T3/T4a and select T4b NPNSCC requiring orbital or base of skull (BOS) resection were randomized to surgery (Arm A), versus surgery preceded by docetaxel/cisplatin x3 cycles (Arm B). Degree of anticipated SP (orbit and BOS) was required preoperatively and post-chemotherapy. SP was noted at surgery. Co-primary objectives were SP rate (orbit/BOS) and OS. 82 patients needed to be accrued for 81% power with 0.1 one-sided alpha using Fisher's exact test for SP rate and 83% with 0.1 one-sided alpha using log-rank test for OS. RESULTS Among 23 evaluable patients, overall SP rate was 30%: 15% in Arm A (N=2/13, 95%CI: 1.9-45.4%), 50% in Arm B (N=5/10, 95%CI: 18.7-81.3%) (p=0.17). Among 18 patients with pathologic T3/T4a disease, overall SP rate was 39%: 18% in Arm A (N=2/11, 95%CI: 2.3-51.8%), 71% in Arm B (N=5/7, 95%CI: 29.0-96.3%) (p=0.049). Orbit and BOS-specific preservation rates were 38% (95%CI: 8.5-75.5%) vs 83% (95%CI: 35.9-99.6%), and 33% (95%CI: 9.9-65.1%) vs 67% (95%CI: 29.9-92.5%) in Arm A vs B, respectively. The most common grade ≥3 toxicities included mucositis, anemia, nausea and lymphopenia (all >10%). No grade 5 events were reported. CONCLUSIONS These results support neoadjuvant chemotherapy as an effective intervention for SP in T3/T4a NPNSCC and deserve further evaluation.