Yungan Tao1, Anne Auperin2, Pierre Blanchard3, Marc Alfonsi4, Xu-Shan Sun5, Michel Rives6, Yoann Pointreau7, Joël Castelli8, Pierre Graff9, Stéphanie Wong Hee Kam10, Juliette Thariat11, Ovidiu Veresezan12, Steve Heymann13, Sophie Renard-Oldrini14, Cédrik Lafond7, Alexandre Cornely3, Odile Casiraghi3, Pierre Boisselier15, Michel Lapeyre16, Julian Biau17, Jean Bourhis18. 1. Gustave-Roussy Cancer Campus Grand Paris, Villejuif, France. Electronic address: yungan.tao@gustaveroussy.fr. 2. Gustave-Roussy Cancer Campus Grand Paris, Villejuif, France; INSERM 1018, Villefjuif, France. 3. Gustave-Roussy Cancer Campus Grand Paris, Villejuif, France. 4. Institut Sainte Catherine, Avignon, France. 5. Hopital Nord Franche-Comté de Montbéliard & CHRU de Besançon, France. 6. Institut Claudius Regaud, Toulouse, France. 7. Centre Jean Bernard, Le Mans, France. 8. Centre Eugène Marquis, Rennes, France. 9. Institut Claudius Regaud, Toulouse, France; Centre Alexis Vautrin, Nancy, France. 10. AP-HM Hôpital de la Timone, Marseille, France. 11. Centre Antoine Lacassagne, Nice, France; Centre francois Baclesse, Caen, France. 12. Centre Henri Becquerel, Rouen, France. 13. Clinique Sainte Anne, Strasbourg, France. 14. Centre Alexis Vautrin, Nancy, France. 15. Centre Eugène Marquis, Rennes, France; Institut du Cancer de Montpellier, France. 16. Centre Alexis Vautrin, Nancy, France; Centre Jean Perrin, Clermont-Ferrand, France. 17. Centre Jean Perrin, Clermont-Ferrand, France. 18. Gustave-Roussy Cancer Campus Grand Paris, Villejuif, France; CHUV Lausanne, Switzerland. Electronic address: jean.bourhis@chuv.ch.
Abstract
BACKGROUND:Concurrent chemoradiotherapy (CRT) is the standard of care (SoC) in locally advanced (LA) head and neck squamous cell carcinomas (HNSCC). This trial was designed to test whether dose-escalated IMRT and cisplatin could improve locoregional control without increasing complications over 3D-radiotherapy. METHODS: Patients were randomized between 70 Gy/35F in 7 weeks with 3D-RT (Arm A) versus 75 Gy/35F with IMRT (Arm B). Both arms received 50 Gy in 25 fractions followed by a sequential boost of 20 Gy/10F in Arm A and 25 Gy/10F to gross tumor volume in Arm B, as well as 3 cycles of cisplatin at 100 mg/m2 during RT. The primary endpoint was locoregional progression (LRP). RESULTS:188 patients were randomized: 85% oropharynx and 73% stage IVa. P16 status was documented for 137 oropharyngeal tumors with P16+ in 53 (39%) patients; and 90% were smokers. Median follow-up was 60.5 months. Xerostomia was markedly decreased in arm B (p < 0.0001). The 1-year grade ≥2 xerostomia (RTOG criteria) was 63% vs 23% and 3-year 45% vs 11% in arms A and B, respectively. Xerostomia LENT-SOMA scale was also reduced in arm B. Dose-escalated IMRT did not reduce LRP with an adjusted HR of 1.13 [95%CI = 0.64-1.98] (p = 0.68). Survival was not different (adjusted HR: 1.19 [95%CI = 0.78-1.81], p = 0.42). No interaction between p16 and treatment effect was found. CONCLUSION: Dose-escalated IMRT did not improve LRC in LA-HNSCC patients treated with concomitant CRT over standard 3D-RT. This trial reinforces the evidence showing IMRT reduces xerostomia in LA-HNSCC treated with radiotherapy. Clinicaltrial.gov: NCT00158678.
RCT Entities:
BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard of care (SoC) in locally advanced (LA) head and neck squamous cell carcinomas (HNSCC). This trial was designed to test whether dose-escalated IMRT and cisplatin could improve locoregional control without increasing complications over 3D-radiotherapy. METHODS:Patients were randomized between 70 Gy/35F in 7 weeks with 3D-RT (Arm A) versus 75 Gy/35F with IMRT (Arm B). Both arms received 50 Gy in 25 fractions followed by a sequential boost of 20 Gy/10F in Arm A and 25 Gy/10F to gross tumor volume in Arm B, as well as 3 cycles of cisplatin at 100 mg/m2 during RT. The primary endpoint was locoregional progression (LRP). RESULTS: 188 patients were randomized: 85% oropharynx and 73% stage IVa. P16 status was documented for 137 oropharyngeal tumors with P16+ in 53 (39%) patients; and 90% were smokers. Median follow-up was 60.5 months. Xerostomia was markedly decreased in arm B (p < 0.0001). The 1-year grade ≥2 xerostomia (RTOG criteria) was 63% vs 23% and 3-year 45% vs 11% in arms A and B, respectively. Xerostomia LENT-SOMA scale was also reduced in arm B. Dose-escalated IMRT did not reduce LRP with an adjusted HR of 1.13 [95%CI = 0.64-1.98] (p = 0.68). Survival was not different (adjusted HR: 1.19 [95%CI = 0.78-1.81], p = 0.42). No interaction between p16 and treatment effect was found. CONCLUSION: Dose-escalated IMRT did not improve LRC in LA-HNSCCpatients treated with concomitant CRT over standard 3D-RT. This trial reinforces the evidence showing IMRT reduces xerostomia in LA-HNSCC treated with radiotherapy. Clinicaltrial.gov: NCT00158678.