TY - JOUR
T1 - A multicentric randomized controlled phase III trial of adaptive and 18F-FDG-PET-guided dose-redistribution in locally advanced head and neck squamous cell carcinoma (ARTFORCE)
AU - de Leeuw, Anna Liza M.P.
AU - Giralt, Jordi
AU - Tao, Yungan
AU - Benavente, Sergi
AU - France Nguyen, Thanh Vân
AU - Hoebers, Frank J.P.
AU - Hoeben, Ann
AU - Terhaard, Chris H.J.
AU - Wai Lee, Lip
AU - Friesland, Signe
AU - Steenbakkers, Roel J.H.M.
AU - Tans, Lisa
AU - Heukelom, Jolien
AU - Kayembe, Mutamba T.
AU - van Kranen, Simon R.
AU - Bartelink, Harry
AU - Rasch, Coen R.N.
AU - Sonke, Jan Jakob
AU - Hamming-Vrieze, Olga
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/7
Y1 - 2024/7
N2 - Background and purpose: This multicenter randomized phase III trial evaluated whether locoregional control of patients with LAHNSCC could be improved by fluorodeoxyglucose-positron emission tomography (FDG-PET)-guided dose-escalation while minimizing the risk of increasing toxicity using a dose-redistribution and scheduled adaptation strategy. Materials and methods: Patients with T3-4-N0-3-M0 LAHNSCC were randomly assigned (1:1) to either receive a dose distribution ranging from 64-84 Gy/35 fractions with adaptation at the 10th fraction (rRT) or conventional 70 Gy/35 fractions (cRT). Both arms received concurrent three-cycle 100 mg/m2 cisplatin. Primary endpoints were 2-year locoregional control (LRC) and toxicity. Primary analysis was based on the intention-to-treat principle. Results: Due to slow accrual, the study was prematurely closed (at 84 %) after randomizing 221 eligible patients between 2012 and 2019 to receive rRT (N = 109) or cRT (N = 112). The 2-year LRC estimate difference of 81 % (95 %CI 74–89 %) vs. 74 % (66–83 %) in the rRT and cRT arm, respectively, was not found statistically significant (HR 0.75, 95 %CI 0.43–1.31, P=.31). Toxicity prevalence and incidence rates were similar between trial arms, with exception for a significant increased grade ≥ 3 pharyngolaryngeal stenoses incidence rate in the rRT arm (0 versus 4 %, P=.05). In post-hoc subgroup analyses, rRT improved LRC for patients with N0-1 disease (HR 0.21, 95 %CI 0.05–0.93) and oropharyngeal cancer (0.31, 0.10–0.95), regardless of HPV. Conclusion: Adaptive and dose redistributed radiotherapy enabled dose-escalation with similar toxicity rates compared to conventional radiotherapy. While FDG-PET-guided dose-escalation did overall not lead to significant tumor control or survival improvements, post-hoc results showed improved locoregional control for patients with N0-1 disease or oropharyngeal cancer treated with rRT.
AB - Background and purpose: This multicenter randomized phase III trial evaluated whether locoregional control of patients with LAHNSCC could be improved by fluorodeoxyglucose-positron emission tomography (FDG-PET)-guided dose-escalation while minimizing the risk of increasing toxicity using a dose-redistribution and scheduled adaptation strategy. Materials and methods: Patients with T3-4-N0-3-M0 LAHNSCC were randomly assigned (1:1) to either receive a dose distribution ranging from 64-84 Gy/35 fractions with adaptation at the 10th fraction (rRT) or conventional 70 Gy/35 fractions (cRT). Both arms received concurrent three-cycle 100 mg/m2 cisplatin. Primary endpoints were 2-year locoregional control (LRC) and toxicity. Primary analysis was based on the intention-to-treat principle. Results: Due to slow accrual, the study was prematurely closed (at 84 %) after randomizing 221 eligible patients between 2012 and 2019 to receive rRT (N = 109) or cRT (N = 112). The 2-year LRC estimate difference of 81 % (95 %CI 74–89 %) vs. 74 % (66–83 %) in the rRT and cRT arm, respectively, was not found statistically significant (HR 0.75, 95 %CI 0.43–1.31, P=.31). Toxicity prevalence and incidence rates were similar between trial arms, with exception for a significant increased grade ≥ 3 pharyngolaryngeal stenoses incidence rate in the rRT arm (0 versus 4 %, P=.05). In post-hoc subgroup analyses, rRT improved LRC for patients with N0-1 disease (HR 0.21, 95 %CI 0.05–0.93) and oropharyngeal cancer (0.31, 0.10–0.95), regardless of HPV. Conclusion: Adaptive and dose redistributed radiotherapy enabled dose-escalation with similar toxicity rates compared to conventional radiotherapy. While FDG-PET-guided dose-escalation did overall not lead to significant tumor control or survival improvements, post-hoc results showed improved locoregional control for patients with N0-1 disease or oropharyngeal cancer treated with rRT.
KW - 18F-FDG PET
KW - Adaptive radiotherapy
KW - Chemoradiation
KW - Dose escalation
KW - Dose painting
KW - Head and neck cancer
KW - Oropharynx cancer
KW - RCT
KW - SCCHN
UR - http://www.scopus.com/inward/record.url?scp=85191890443&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2024.110281
DO - 10.1016/j.radonc.2024.110281
M3 - Article
C2 - 38636708
AN - SCOPUS:85191890443
SN - 0167-8140
VL - 196
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
M1 - 110281
ER -