Induction Chemotherapy for Chemoselection in Advanced Sinonasal Mucosal Melanoma

Objective Sinonasal mucosal melanoma (SNMM) is a locally aggressive tumor. The mainstay of treatment in SNMM is surgical resection with negative margins. The role of induction chemotherapy is poorly understood. The aim of this study is to assess the role of induction chemotherapy for surgically treated patients with SNMM.

Methods We retrospectively reviewed 18 patients with stage III (N = 8) and IV (n = 10) SNMM treated between 1995 and 2016 in MD Anderson Cancer Center. Indications for induction chemotherapy were distant metastasis, poor performance status, and locally advanced disease (orbit, brain, or palate invasion). SNMM patients were treated with two to four cycles of dacarbazine (DTIC) 200 mg/m² days 1 to 5, vincristine 1 mg/m² days 1 and 4 every 21 days. IFN-α, initiated day 8, was administered 3 × 106 IU/d in five cases. Response to induction chemotherapy was defined according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was disease-specific survival. Our secondary outpoints were overall and disease-free survival and organ (i.e., palate, eye, and brain) preservation.

Results The median follow-up was 29 months (range: 3–169 months). Three patients (16%) had distant metastasis (M1). Complete response (CR) was documented in three patients (16%), partial response (PR) in eight (44%) patients, and stable disease (SD)/disease progression (PD) in seven patients. Patients with CR/PR underwent subsequent definitive radiotherapy (5/11, 46%) or surgery (6/11, 54%). Patients with SD/PD received concurrent chemoradiation (2/7, 28%), additional chemotherapy with cisplatin, vinblastine, IFN-α and IL-12 (1 patient), radiotherapy (1 patient), and surgery (1 patient). One patient with SD after induction chemotherapy was treated with concurrent radiation and vemurafenib, followed by surgery. None of the surgically treated patients required orbital exenteration. Five-year overall survival for patients with CR/SD was 39% compared with 8% for patients with SD/PD (HR: 2.79, 95% CI: 0.75–10.35, reference for HR = CR/SD).

Conclusion The overall response rate was 61%. Patients with advanced disease who respond to induction chemotherapy may have better survival than patients who have no response. In patients with SNMM, induction chemotherapy may be a strategy for selecting patients for definitive treatment in patients with locally advanced disease.