SIB-IMRT with concomitant chemotherapy-cetuximab after induction chemotherapy for locally-advanced-head-and-neck squamous cell carcinomas

Abstract

Purpose. To determine tolerability and efficacy of induction chemotherapy (I-CHT) followed by simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) with concurrent chemotherapy/cetuximab (C-CHT) for locally-advanced squamous-head-and-neck carcinoma (LA-SHNC). Methods and materials. Nineteen patients (13M/6F) with LA-SHNC (stage III:3-IV:16) were enrolled in a prospective study between March'07 and September'10, including 6 oral cavity/5 oropharynx/5 hypopharynx/2 larynx/1 paranasal sinuses. Four P16-HPV were identified. Two-cycles of Docetaxel/CDDP/Capecitabine, followed by SIB-IMRT andweekly CDDP/Cetuximabwere prescribed. Staging studies included PET-CT with thermoplastic mask, used for to delimited target volumes. Weekly Cone-beam-IGRT was used. The prescribed SIB-IMRT doses to GTV, CTV and PTV were 73.6 Gy (2.24 Gy/f), 56.2 Gy (1.7 Gy/f) and 51.2 Gy (1.6 Gy/f), respectively, in 30 daily fractions. Survival, patterns of failure and acute/late toxicity were analyzed. Local recurrences were identified on MRI and/or PET/CT, and contoured (V-recur) on the original planning-CT. Local failure was classified according to the location of V-recur respect the 95% isodose line GTV prescription (IDL) as “in-field”, “marginal” and “outside” when >95%, 20-95% or <20% of V-recur was within the 95% IDL, respectively. Data from DVH of target and organs-at-risk volume were analyzed. Results. Eighteen patients received 2-cycles of I-CHT. All patients received the prescribed SIB-IMRT dose, median of C-CHT 6- cycles. After complete treatments, objective response was 95% (79%complete/16%partial). Highest toxicity during I-CHT was grade3-4 (31%). During SIB-IMRT,most frequent grade >3 toxicity wasmucositis/dysphagia (32%). No treatment-related dead was observed. Two osteonecrosis were observed. None other late toxicity grade >2 was observed. After 37 months (18-56) median follow-up, 6 patients (31%) relapsed: 1 distant and 5 local (4 “in fied”/1 “marginal”). Three-year D-DFS, L-DFS, DFS, and OS were 94%, 69%, 54%, and 66%, respectively. Univariate study determinate worse OS in undifferentiated SHNC type (p = 0.028), and no complete response after treatments (p = 0.001). Tumor location was predictor of local control: better in oropharyngeal and laryngeal (p = 0.001). Multivariate analysis showed cervical esophagus V50 > 7% (p = 0.001) as predictor of acute mucositis/dysphagia ≥grade3 (p = 0.005). Conclusion. SIB-IMRT with C-CHT after I-CHT is feasible and well tolerated schedule that shortens the overall treatment time in radical treatment of LA-HNSC, achieving encouraging local and distant control rates. A larger population of patients is needed.