Chemoradiation or Altered Fractionation for T2N0M0 Glottic Cancer

Abstract

T2 glottic squamous cell carcinoma (SCC) though amenable to larynx preservation, have a poorer prognosis than T1 tumors. We tested the hypothesis that two treatment intensification approaches improve outcome: [A] concurrent chemoradiation (CCRT) versus radiotherapy RT only and [B] altered RT fractionation (either accelerated fractionation (AFX) using 2.25Gy/fraction, or hyperfractionation (HFX) at <2Gy/fraction twice daily) versus standard fractionation (SFX) using 2Gy/fraction. This is an institutional review board-approved retrospective study of 180 patients with T2N0M0 SCC treated at 70 centers from 2000-2015. We analyzed [A] CCRT (14.4% of patients) versus RT only, and [B] AFX, HFX, and SFX (14.6%, 14.6% and 70.7% of patients respectively). We calculated rates of acute and late toxicity (by Chi Squared or Fisher’s Exact Tests for univariate analysis (UVA) and logistic regression for multivariate analysis (MVA); overall survival (OS), progression-free survival (PFS), and locoregional recurrence-free survival (LRFS) (by the Kaplan-Meier method for UVA and the Cox Proportional Hazards Model for MVA). SFX included patients who had CCRT. Summarized in Table 1. [A] CCRT gave a better OS versus RT only (76.9 vs 61.0%, p = 0.83 on UVA but p=0.04 on MVA ), higher PFS (88.5 vs 83.1%) and LRFS (88.5% vs 83.8%) neither of which were significant. CCRT had higher acute grade 2-4 toxicity (80.8% vs. 54.5%, p = 0.01and 0.02 on UVA and MVA respectively) . [B] AFX and HFX had significantly higher OS than SFX: 75.0%, 70.8% and 62.1% respectively, p = 0.01 and 0.18 on UVA and MVA respectively; with no increased acute toxicity. The only other treatment factor that affected overall survival was treatment duration: 71.4% for <50 days and 53.6% for ≤50 days p = 0.03 on UVA. Late toxicity was not affected by CCRT, AFX nor HFX but was increased by current or past use of alcohol on MVA (p = 0.02 ). The varied approaches reported here reflects a lack of consensus. Altered fractionation, though used in <30% of patients, may be preferred to CCRT because of its lower Grade 2- 4 acute toxicity rate. To find an optimal treatment of T2N0M0 SCC glottis, we recommend a randomized study of concurrent chemotherapy and altered fractionation.Abstract MO_2_2471; Table1Results for [A] Concurrent chemoradiation (CCRT) [B] Altered fractionation[A] CCRTNo CCRT (%)CCRT (%)§ p value¶ P valuemax. acute toxicity rategrade 0-145.519.20.010.02grade 2-454.580.8max. late toxicity rategrade 0-187.588.51.00.41grade 2-412.511.5OS61.076.90.830.04PFS83.188.50.690.32LRFS83.888.50.740.36[B] Altered fractionationSFXAFXHFXP value*P value†max. acute toxicity rategrade 0-140.545.837.50.830.12grade 2-459.554.262.5max. late toxicity rategrade 0-186.890.085.00.930.13grade 2-413.210.015.0OS62.175.070.80.010.18PFS84.587.579.20.990.75LRFS85.387.579.20.990.79§=univariate analysis; ¶=multivariate analysis; max = maximum Open table in a new tab