Title:
A dose escalation study with intensity modulated radiation therapy (IMRT) in T2N0, T2N1, T3N0 squamous cell carcinomas (SCC) of the oropharynx, larynx and hypopharynx using a simultaneous integrated boost (SIB) approach.

Abstract:
The simultaneous integrated boost (SIB) technique with dose per fraction slightly higher than 2Gy offers the advantages of shortening the treatment time and increasing the biologically equivalent dose to the tumor. This study was designed to evaluate the feasibility of a dose-escalating radiotherapy treatment by using a SIB-IMRT approach in patients with early and moderately advanced head and neck cancers.
Fifty-seven consecutive patients with pharyngo-laryngeal T2N0 or T2N1, or laryngeal T3N0 SCC were included. The therapeutic PTVs were treated according to three consecutive dose levels i.e., 69 Gy in 30 fractions of 2.3 Gy (dose level I), 72 Gy in 30 fractions of 2.4 Gy (dose level II) or 75 Gy in 30 fractions of 2.5 Gy (dose level III). The prophylactic PTVs received a dose of 55.5 Gy delivered in 30 fractions of 1.85 Gy. The primary endpoint of the study was acute toxicity assessed during treatment and during the first 3 months following the completion of radiotherapy. The secondary endpoints included loco-regional control, disease-free survival, overall survival and late toxicity at 2 years of follow-up. The study design allowed patients to be enrolled in the second dose level group if no more than 10% of grade 4 acute toxicity was observed on the first dose level group within 3 months after the completion of IMRT, and so on for the third level group.
Forty-four men and 13 women were included in the trial. The majority of them presented with oropharyngeal cancer (53%) and laryngeal cancer (33%). Only 3 patients developed grade 4 acute mucositis during treatment, one in each dose level. Thirty-two patients (56%) experienced grade 3 toxicity, mostly dermatitis and mucositis, without any significant difference between the groups. Late grade 1 and 2 xerostomia was seen in 53% and 33% of patients, respectively. Transient grade 4 late toxicity was observed in 16% of all patients and was equally distributed among the groups. The 2-year loco-regional control was 82% for all 3 groups (79% dose level I, 88% dose level II, 79% dose level III). The 2-year overall survival was 89% for dose level I and II, and 95% for dose level III.
This dose escalation SIB-IMRT protocol was safe and effective as the sole treatment of early and moderately advanced SCC of head and neck. No toxicity difference was observed between the groups.