Impact of Total Radiation Dose on the Treatment Outcomes in Radiotherapy and Concomitant Superselective Intra-arterial High Dose Cisplatin for Locally Advanced Maxillary Sinus Cancer

Abstract

The purpose of this study is to analyze the relationship between the total radiation dose and the treatment outcomes in radiotherapy and concomitant superselective intra-arterial high dose cisplatin (RADPLAT) for locally advanced maxillary sinus cancer. We have evaluated 54 patients with locally advanced maxillary sinus cancer, who were treated with RADPLAT from March 2004 to February 2019. There were 45 males and 9 females. The median age was 68 years (range 38 to 87 years). T stage was T2 in 2 case, T3 in 10 cases, T4a in 31 cases, and T4b in 11 cases. All patients had no nodal involvement. There were 53 patients who had squamous cell carcinomas, and one with undifferentiated carcinoma. Thirty-four patients received three-dimensional conformal radiotherapy (3DCRT) until 2015, and 20 patients received intensity modulated radiotherapy (IMRT) using volumetric modulated arc therapy since 2016. Median prescribed dose to the local lesion was 66 Gy (range 50 to 66 Gy) in 3DCRT group and 66 Gy (range 60 to 70 Gy) in IMRT group. All patients were irradiated at 2 Gy/fraction. All patients did not receive either prophylactic neck irradiation or volume reduction surgery before RADPLAT. Superselective intra-arterial infusions of high-dose cisplatin (100-120 mg/m2) was performed with median 6 cycles per week (range 1 to 10 cycles) in combination with simultaneous intra-venous infusions of sodium thiosulfate to neutralize cisplatin toxicity. Superselective intra-arterial infusions were performed during or before radiotherapy in all patients. The median follow-up period was 30.3 months (range 2.9 to 193 months). The 3-year local control rate and overall survival rate in all patients were 70.7%, and 86.2%, respectively. The 3-year local control rate were 88.5% in IMRT group, which had a slightly better control rate than 3DCRT group (64.0%) (p = 0.149). However, the patients who were treated with 70 Gy of IMRT (n = 14) tended to have excellent local control rate (91.7%) than patients treated with 66 Gy of IMRT or 3DCRT (72.1%, n = 27) and 60 Gy or lower of 3DCRT (49.2%, n = 13). There was no difference in total dose of cisplatin between the three groups. The 3-year overall survival rate was 100 % in patients treated 70 Gy, 90.0% in patients with 66 Gy, and 82.0% in patients with 60 Gy or lower (p = 0.655). There were no treatment-related deaths. Acute grade 3 mucositis developed in 5 patients in IMRT group and 9 patients in 3DCRT group. No late grade 3 or higher eye disorders except for cataract developed in IMRT group, while blindness occurred in 4 patients in 3DCRT group. The patients who had received 70 Gy using IMRT showed excellent local control rate without increasing adverse events. The total dose may have an impact on local control rate and survival rate in radiotherapy with concomitant superselective intra-arterial high dose cisplatin.