TY - JOUR
T1 - 18F-FDG-PET guided vs whole tumour radiotherapy dose escalation in patients with locally advanced non-small cell lung cancer (PET-Boost)
T2 - Results from a randomised clinical trial
AU - Cooke, Saskia A.
AU - de Ruysscher, Dirk
AU - Reymen, Bart
AU - Lambrecht, Maarten
AU - Fredberg Persson, Gitte
AU - Faivre-Finn, Corinne
AU - Dieleman, Edith M. T.
AU - Lewensohn, Rolf
AU - van Diessen, Judi N. A.
AU - Sikorska, Karolina
AU - Lalezari, Ferry
AU - Vogel, Wouter
AU - van Elmpt, Wouter
AU - Damen, Eugène M. F.
AU - Sonke, Jan-Jakob
AU - Belderbos, José S. A.
N1 - Funding Information: We are grateful for funding by the European Commission's Seventh Framework Programme (ARTFORCE, grant agreement no 257144) and the Dutch Cancer Society (KWF) (project no 2010-4675). The content of this report is the sole responsibility of the authors and does not necessarily reflect the official views of the EC or KWF. Professor Sonke is supported by a grant from Elekta AB. Professor Faivre-Finn is supported by a grant from the NIHR Manchester Biomedical Research Centre. We thank the patients and their families; all investigators, involved physicians, physicists, RTTs, planners, site staff and data managers. We also thank Pietje Muller as study project coordinator, and the members of the independent monitoring committee. Further acknowledgments to Harry Bartelink and Gunnar Westman for their invaluable contributions. Funding Information: We are grateful for funding by the European Commission’s Seventh Framework Programme (ARTFORCE, grant agreement no 257144) and the Dutch Cancer Society (KWF) (project no 2010-4675). Funding Information: Professor Sonke is supported by a grant from Elekta AB. Funding Information: Professor Faivre-Finn is supported by a grant from the NIHR Manchester Biomedical Research Centre. Publisher Copyright: © 2023 Elsevier B.V.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - Background and purpose: We aimed to assess if radiation dose escalation to either the whole primary tumour, or to an 18F-FDG-PET defined subvolume within the primary tumour known to be at high risk of local relapse, could improve local control in patients with locally advanced non-small-cell lung cancer. Materials and methods: Patients with inoperable, stage II-III NSCLC were randomised (1:1) to receive dose-escalated radiotherapy to the whole primary tumour or a PET-defined subvolume, in 24 fractions. The primary endpoint was freedom from local failure (FFLF), assessed by central review of CT-imaging. A phase II ‘pick-the-winner’ design (alpha = 0.05; beta = 0.80) was applied to detect a 15 % increase in FFLF at 1-year. ClinicalTrials.gov:NCT01024829. Results: 150 patients were enrolled. 54 patients were randomised to the whole tumour group and 53 to the PET-subvolume group. The trial was closed early due to slow accrual. Median dose/fraction to the boosted volume was 3.30 Gy in the whole tumour group, and 3.50 Gy in the PET-subvolume group. The 1-year FFLF rate was 97 % (95 %CI 91–100) in whole tumour group, and 91 % (95 %CI 82–100) in the PET-subvolume group. Acute grade ≥ 3 adverse events occurred in 23 (43 %) and 20 (38 %) patients, and late grade ≥ 3 in 12 (22 %) and 17 (32 %), respectively. Grade 5 events occurred in 19 (18 %) patients in total, of which before disease progression in 4 (7 %) in the whole tumour group, and 5 (9 %) in the PET-subvolume group. Conclusion: Both strategies met the primary objective to improve local control with 1-year rates. However, both strategies led to unexpected high rates of grade 5 toxicity. Dose differentiation, improved patient selection and better sparing of central structures are proposed to improve dose-escalation strategies.
AB - Background and purpose: We aimed to assess if radiation dose escalation to either the whole primary tumour, or to an 18F-FDG-PET defined subvolume within the primary tumour known to be at high risk of local relapse, could improve local control in patients with locally advanced non-small-cell lung cancer. Materials and methods: Patients with inoperable, stage II-III NSCLC were randomised (1:1) to receive dose-escalated radiotherapy to the whole primary tumour or a PET-defined subvolume, in 24 fractions. The primary endpoint was freedom from local failure (FFLF), assessed by central review of CT-imaging. A phase II ‘pick-the-winner’ design (alpha = 0.05; beta = 0.80) was applied to detect a 15 % increase in FFLF at 1-year. ClinicalTrials.gov:NCT01024829. Results: 150 patients were enrolled. 54 patients were randomised to the whole tumour group and 53 to the PET-subvolume group. The trial was closed early due to slow accrual. Median dose/fraction to the boosted volume was 3.30 Gy in the whole tumour group, and 3.50 Gy in the PET-subvolume group. The 1-year FFLF rate was 97 % (95 %CI 91–100) in whole tumour group, and 91 % (95 %CI 82–100) in the PET-subvolume group. Acute grade ≥ 3 adverse events occurred in 23 (43 %) and 20 (38 %) patients, and late grade ≥ 3 in 12 (22 %) and 17 (32 %), respectively. Grade 5 events occurred in 19 (18 %) patients in total, of which before disease progression in 4 (7 %) in the whole tumour group, and 5 (9 %) in the PET-subvolume group. Conclusion: Both strategies met the primary objective to improve local control with 1-year rates. However, both strategies led to unexpected high rates of grade 5 toxicity. Dose differentiation, improved patient selection and better sparing of central structures are proposed to improve dose-escalation strategies.
KW - 18F-FDG-PET
KW - Dose escalation
KW - Hypofractionation
KW - Locally advanced non-small cell lung cancer
KW - Radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=85147888863&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.radonc.2023.109492
DO - https://doi.org/10.1016/j.radonc.2023.109492
M3 - Article
C2 - 36706958
SN - 0167-8140
VL - 181
JO - Radiotherapy and oncology
JF - Radiotherapy and oncology
M1 - 109492
ER -