Therapeutic Ratio of Hypofractionation in Early Glottic Cancer: A Topic Worth Revisiting?

Michael T. Scott, MD, MBA; Austin Dosch, MD; Nagy Elsayyad, MD; Matthew C. Abramowitz, MD; Arnold M. Markoe, MD; Deukwoo Kwon, PhD; W. Zhao, MD, MS; and Michael A. Samuels, MD
Published: Tuesday, Sep 29, 2015
Michael T. Scott, MD, MBA

Michael T. Scott, MD, MBA



The optimal fractionation for early glottic cancer is unclear. Prospective randomized data showing superiority of 2.25 Gy versus 2 Gy/fraction derive from only 1 trial. We analyzed our single-institutional experience to address the therapeutic ratio of 2.25 Gy vs. 2 Gy.

Materials and Methods

One hundred patients with T1-T2 glottic carcinoma received radiation therapy (RT) between 2003-2013. Their records underwent retrospective analysis. Median age was 64 years. Seventy-six had T1 tumors; 24 had T2. Forty-eight received 2 Gy daily (conventional RT--CRT) and 52 received 2.25 Gy daily (hypofractionated RT--HRT). Median CRT dose was 66 Gy and HRT dose was 63 Gy. Logistic regression, t-test, log-rank test, and Cox proportional hazards regression were used and two-sided p-value was reported. Recurrence-free survival (RFS) was estimated using Kaplan-Meier method.


Median follow-up was 28.8 months overall, with 54.7 months for CRT and 16.1 months for HRT, after excluding from local control analysis 9 patients with follow-up <3 months. CRT patients had less grade 2 dysphagia (P = 0.014), grade >2 hoarseness (P = 0.001), grade >2 mucositis (P < 0.001), and required less frequent administration of opiates (P = 0.004). Rates of grade >2 radiation dermatitis (P = 0.421), grade >2 laryngeal edema (P = 0.549), and weight loss (P = 0.655) during treatment were similar. Complete response (CR) was 91.7% in the CRT group vs. 90.4% for HRT. RFS was comparable at 24 months (86.7% vs 86.6%, P = 0.988) and at 60 months (82.8% vs 78.8%, P = 0.655) in CRT and HRT patients. P-value of log-rank test for RFS was 0.797. Univariate analysis for the 76 T1 patients upheld the significance for all of the above findings, including CR and RFS, except grade 2 dysphagia (P = 0.156).


Our retrospective data suggest that treatment of early glottic cancer with 2.25 Gy/fraction may result in greater acute toxicity than 2 Gy/fraction without improved efficacy.


Early stage glottic cancers are a common malignancy of the head and neck, and may be treated effectively with radiotherapy (RT), surgery, or laser microsurgery.1 RT provides local control rates of 80-95%.2-10 Historically, conformal RT (CRT) used 2 Gy per fraction for 33 fractions. Some retrospective data have demonstrated that hypofractionated regimens (>2 Gy) with a shorter overall treatment time (OTT) improved local control. However, most reports used <2 Gy as the control.2-4, 11-13 Few retrospective studies have evaluated 2 Gy vs. 2.25 Gy.

In 2006, Yamazaki published a prospective randomized trial demonstrating superior local control of 92% with HRT versus 77% with CRT.14 A limited discussion of toxicity indicated no significant differences in acute mucosal, skin or chronic adverse reactions. There are many differences in the techniques used in this study and in typical United States practice (beam energy, field size, dose prescription point, dose range). Biologic or cultural differences between a Japanese patient cohort and one from the United States may affect tumor control or toxicity outcomes. Since 2006, the Japanese randomized trial has not been replicated. For these reasons, the outcome and toxicity results from that study may not apply to patients treated in the United States at the University of Miami, we noted greater toxicity with HRT without apparent local control benefit compared to CRT. Therefore, we decided to re-examine this topic.

Materials and Methods

Patient and Tumor Characteristics

Retrospective data collection and analysis was approved by our Institutional Review Board. One hundred patients with histologically proven T1-2N0M015 glottic carcinoma treated with RT at the University of Miami between 2003-2013 were identified. Patient and tumor characteristics are summarized in Table 1.

Table 1: Patient and Tumor Characteristics

Table 1: Patient and Tumor Characteristics


Treatment Characteristics

Table 2: Treatment Characteristics

Table 2: Treatment Characteristics

* excluding 9 pts whose follow-up duration is less than 3 months

Treatment was delivered with 6 MV photons to opposed lateral or slightly oblique fields. A few patients prior to 2006 also received an additional anterior field. In both eras, patients were treated to an isodose line (usually 98% or 95%) with fields ranging from 5x5 to 6x6 cm. Bolus was used on some anterior commissure cases in the CRT era but not in the HRT era.

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