Long Term Outcome of Definitive Chemo-IMRT for Locally Advanced Nasopharyngeal Cancer Patients using Helical Tomotherapy

Abstract

To evaluate treatment outcome of definitive chemo-IMRT using Helical Tomotherapy (HT) for patients with nasopharyngeal cancer (NPC). In this analysis, contiguous 132 patients with NPC treated with definitive chemo-IMRT from 2006 to 2015 were analyzed. Until 2007, chemotherapy underwent with alternating method (N=38), then followed by concurrent chemoradiation (CRT; n=91) with (n=86) or without (n=24) adjuvant chemotherapy (AC). As for IMRT method, 70/54 Gy for involved/prophylactic site in 35 fractions was delivered by SIB method until 2011. After that 2-step method was used, in which a 46 Gy in 23 fractions for the entire neck followed by boost up to 70 Gy in 35 fractions. Patient characteristics was as follows; Male: Female = 98: 34, median age 54.5 y.o (11-76), PS 0: 1: 2: 3 = 30: 99: 2: 1, T-factor 1: 2: 3: 4 = 52: 27: 27: 26, N-factor 0: 1: 2: 3 = 14: 47: 53: 18, Clinical Stage (CS; UICC v.8) I: II: III: IVA = 6: 29: 56: 41, WHO Histological Type (HT) I: II-III: unknown = 31: 100: 1. Median follow-up time was 60 months (1.9 – 136 M). Median radiation dose was 70 Gy (95%CI = 67.5-70.1) and median cisplatin dose of concurrent use and total were 240 mg/m2 (95%CI = 207.4-225.9) and 310 mg/m2 (95%CI = 301.2-349.7). At last follow-up, 100 patients lived with (N=12) or without disease (N=88), and 32 patients died for disease (N=22) or other reason (N=10). The 5-y rates of Overall Survival (OS), Progression-Free Survival (PFS), Loco-reginal Recurrence-Free Survival (LRFS) and Distant Metastasis-Free Survival (DMFS) was 75.2% (95%C.I. 67.2-83.1), 64.2% (95%C.I. 55.6-72.8), 79.9% (95%C.I. 72.4-87.4), and 86.9% (95%C.I. 80.7-93.1), respectively. By univariate analyses, Significant factors of OS was elderly (P=0.006), T4 (P=0.0007), N3 (P=0.048), CS-IVA (P=0.0018), HT-I (P=0.001), no adjuvant (p=0.013), and lower CDDP dose (p=0.0091), respectively ; for PFS it was elderly (P=0.002), T4 (P=0.003), N3 (P=0.013), CS-IVA (P=0.0033), HT-I (P=0.003), and lower CDDP (p=0.044), respectively. For LRFS it was elderly (P=0.006), T4(P=0.0025), N3 (P=0.01), and CS-IV (P=0.0025), respectively. Both adjuvant (p=0.06) and higher CDDP(P=0.06) showed only tendency for poorer DMFS. By multivariate analysis, prognostic factor was only elderly (HR=2.84; P=0.018) for OS, while there was a tendency for T4 (HR=4.62; P=0.053). For PFS it was elderly (HR=2.26; P=0.018), T4 (HR=6.63; P=0.0067), and N3 (HR=5.37; P=0.014), respectively. For LRFS it was N3 (HR=9.12; P=0.034), while there was a tendency for T4 (HR=10.8; P=0.052). For DMFS, they were N3 (HR=5.78; P=0.049) and adjuvant (HR=5.272; P=0.026). Grade 2 xerostomia at 6M, 1Y, and 2Y was 61%, 22% and 17%, respectively. Two patients required gastrostomy due to late dysphagia. Seven (5.3%) brain necrosis and 3 (2.3%) cranial nerve palsy developed. Matured analysis of definite chemo-IMRT using HT for NPC was quite acceptable. Adjuvant chemotherapy seemed to be efficacious especially for DM.