IMRT is currently routine practice for HNSCC due to its ability to decrease toxicities as compared to conventional 3DRT. For the first time we reported randomized data (Bourhis, ASCO 2017) showing that dose escalation with IMRT could still maintain lower toxicity in the context of concurrent chemo-radiotherapy (CRT). Indeed, despite a higher total dose delivered with IMRT, side effects were lower as compared to 3DRT. We present updated results of this randomized trial integrating p16 and smoking information.
patients were randomized between 70 Gy/35F in 7 weeks with conventional RT (arm A) versus 75 Gy/35F with IMRT (arm B). A sequential boost of 2.5Gy × 10 after 50Gy/25F was given to initial tumor volume in arm B. In both arms, patients (pts) received 3 cycles of cisplatin at 100 mg/m2 during RT. To detect a hazard ratio (HR) of 0.56 in LRC, inclusion of 310 pts was required to observe 109 loco-regional progressions and achieve 85% power at 2-sided significance level of 0.05.
Between 2005 and 2015, 188 pts were randomized (closed prematurely because of slow accrual): 82% were males, median age 58 years, 85% had oropharynx and 73% stage IVa. The initial characteristics were well balanced between arms. P16 status was known for 137 (86%) of 160 oropharyngeal cancers with p16+ in 53 (39%), 90% were > 10 pack-year smokers. The median follow-up was 60 months. Acute and late xerostomia were markedly improved in IMRT arm. The 1-year grade 0-1 salivary toxicity (RTOG) was 34% vs 81% (p < 0.0001) in arm A and B respectively. However, the increase of dose with IMRT did not transfer in a higher LRC probability with an adjusted HR of 1.15 [0.66-2.00] (p = 0.62). PFS, overall survival (OS) were not significantly different between the 2 arms. Better LRC, PFS or OS were found in p16+ than in p16- cancers and no interaction were observed between p16 and treatment arms.
Dose escalation with IMRT did not improve LRC in LA-HNSCC patients treated with concomitant CRT, regardless of p16 status. This trial adds to the body of evidence to support the use of IMRT in LA-HNSCC.
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J. Bourhis: Consulting or advisory role: Merck Serono, MSD Oncology, AstraZeneca, BMS. All other authors have declared no conflicts of interest.