Dose escalation of radiotherapy (RT) for locally advanced head and neck carcinomas treated with concomitant chemotherapy (CT) and RT: Results of the GORTEC 2004-01 randomized trial.

Abstract

6015 Background: Concomitant CT-RT is a well established standard of care (SoC) in locally advanced (LA) squamous cell carcinomas of the head and neck (SCCHN). While there is a well established dose effect relationship for RT alone in these cancers, it is not known whether this also applies to concomitant CT-RT. Methods: Patients were randomized between 75 Gy/7 weeks (Arm A) versus 70 Gy/35F in 7 weeks (Arm B). A sequential boost of 10 times 2.5 Gy after 50Gy/25F was given to the initial gross tumor volume (GTV) in Arm A. IMRT was used for arm A and 3D conformal RT for arm B. In both arms, patients (pts) received during RT 3 cycles of cisplatin at 100 mg/m2. Inclusion criteria were pts fit for receiving high dose cisplatin, non metastatic, non operated stage III-IV SCC of oral cavity, oro/hypopharynx. A 1:1 randomization was done by minimization on centers, N & T stages & GTV uni/bilateral. To detect a hazard ratio (HR) of 0.56 in locoregional (LR) control, inclusion of 310 pts was required to observe 109 LR progressions and achieve 85% power at 2-sided significance level of 0.05. Results: Between 2005 and 2015, 188 pts were randomized: 82% males, median age 58 years, 85% oropharynx. The accrual rate was slower than expected, due to the fact that IMRT became a SoC and was only allowed in arm A. As a consequence the trial was discontinued after inclusion of 188 patients. The majority of pts had stage IVa (73% vs 72%). All initial characteristics were well balanced between arms. The median follow-up was 4.7 years, not different between arms. Acute and late xerostomia were markedly improved in arm A (IMRT arm). The 1-year grade 0-1 salivary toxicity (RTOG) was 81% and 34% (p< 0.0001) in arm A and B respectively. At 3 years these rates were 92% vs 53% (p=0.0003). The increase of the dose to the GTV with IMRT did not transfer in a higher LR control probability with an adjusted HR of 0.88 [95%CI 0.51-1.52] (p=0.63). PFS, overall survival were not significantly different between the 2 arms. Conclusions: The dose escalation of RT to the GTV did not improve LR control in patients treated with concomitant CT-RT. This trial adds some new evidence level 1 in favor of IMRT in LA SCCHN. Clinical trial information: NCT00158678.