Utility of chemoradioselection for the optimization of treatment intensity in advanced hypopharyngeal and laryngeal carcinoma

Definitive concomitant chemoradiotherapy (CRT) with high-dose cis-platinum (CDDP) is a current standard protocol for advanced laryngeal and hypopharyngeal cancer sparing surgery for salvage. However, this modality is associated with limited feasibility and frequent sever toxicities. In the present study, a 'chemoradioselection' protocol with minimal toxicity was developed using initial response to CRT as a biomarker for patient selection. Between 2000, March and 2012, September 123 patients with stage III (44), IV (79) laryngeal (64) and hypopharyngeal carcinoma (59) excluding T4 cases were enrolled to this protocol. Two cycles of split (15 mg/m2 ×5 days, 2000-2008) or bolus (80 mg/m2, 2009-present) CDDP was concurrently administered. Tumor responses were evaluated after 40 Gy of CRT and 64 responders (chemoradioselected, CRS) received further CRT up to 70 Gy, while radical surgery was recommended for the 59 non-responders (N-CRS), and 34 underwent surgery (N-CRS-ope). The remaining 25 patients who refused surgery (N-CRS-refu) were treated with continuous CRT. The 5-year overall survival (OS) and disease-specific survival (DSS) were 67, and 77%, respectively. The CRS demonstrated favorable 5-year OS (73%) and laryngo-esophageal dysfunction-free survival (LEDFS, 69%) rates. In contrast, the N-CRS-refu showed significantly lower 5-year OS (47%) compared with CRS (73%) and N-CRS-ope (70%) (P=0.0193), and significantly lower 5-year LEDFS (20%) compared with the CRS (69%) (P<0.0001). On multivariate analyses, including T, N, primary site and planned treatment (CRS + N-CRS-ope) or not (N-CRS-refu), unplanned treatment alone showed a significant correlation with poor OS [hazard ratio (HR), 2.584; 95% confidence interval (CI), 1.313-4.354; P=0.007). Chemoradioselection reflects the biological aggressiveness of each tumor, and is able to segregate patients for functional laryngeal preservation with moderate intensity CRT (150-160 mg/m2 of CDDP) from those who would be better treated with surgery. This strategy may be useful for the optimization of the therapeutic intensity.