The PET-boost trial: isotoxic homogeneous or FDG-directed dose escalation in stage II-III NSCLC
Cooke, S. De Ruysscher, D Reymen, B. Lambrecht, M. Persson, G. F. Dieleman, E. Lewensohn, R. Van Diessen, J. Sikorska, K.
Cooke, S.
De Ruysscher, D
Reymen, B.
Lambrecht, M.
Persson, G. F.
Dieleman, E.
Lewensohn, R.
Van Diessen, J.
Sikorska, K.
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Abstract
Purpose or Objective
The randomized phase II PET-boost trial(NCT01024829)
aimed to improve freedom from local failure(FFLF) by
boosting either the whole primary tumor(PT) or the high
FDG uptake region inside the PT(> 50%SUVmax) in non-small
cell lung cancer (NSCLC) patients. Here we report on the
primary endpoint FFLF at 1 year, and secondary endpoint
overall survival(OS).
Material and Methods
Eligible patients had stage II-III NSCLC with a primary
tumor ≥4 cm, SUVmax ≥5.0 and WHO PS ≤ 2. For each
patient, before randomization, a treatment plan
(24x2.75Gy) was made for both arms with a simultaneously
integrated boost to the whole PT (armA) or to the PT
50%SUVmax area (armB). The boost dose (up to 5.4 Gy per
fraction) was maximized by normal tissue constraints while
the mean lung dose of the two plans was normalized. In
case dose escalation of ≥3 Gy per fraction was not possible,
patients were not randomized. Response was assessed with
(PET/)CT at 3, 6, 12 and 18 months. All CT-scans were
centrally reviewed by a dedicated radiologist. Local failure
was defined as 20% growth from nadir (akin to RECIST). The
trial was powered(one sided α=0.05;β=0.80) to detect an
increase of FFLF at 1 year from 70% (historical rate) to 85%,
requiring 82 randomized patients in each arm. Results
Between Apr 2010 and Sep 2017, 150 patients were
included in 7 institutions. The trial was closed after
randomization of 107 patients (initial target 164): 54 to
armA and 53 to armB. Patient characteristics are
summarized in Table1. Median FU for FFLF was 12.6
months (IQR 5.2-24.6).
Median escalated prescribed dose to the PTVwhole tumor
(armA) was 3.25 Gy per fraction (IQR 3.13-3.40), and
median total dose was 78.0 Gy (IQR 75.0-81.6). Median
prescribed dose to the PTV50%SUVmax (armB) was 3.50 Gy per
fraction (IQR 3.35-3.90), and median total dose was 84.0
Gy (IQR 80.4-93.6). 72% of patients received concurrent
chemo-radiotherapy.
Central review showed that the PT was non-measurable in
27% of CT-scans (96/352), mainly due to inflammation,
fibrosis and/or atelectasis. If lesions remained stable over
time, this was scored as no local failure. In the first year,
22 patients died without known local failure, 16 were lost
to CT follow-up and 8 were not-evaluable. The 1-year FFLF
rate in evaluable patients was 97% (95% CI 91-100) in armA,
and 91% (95% CI 82-100) in armB. The 1- and 3-year OS
rates were 77% and 37% in armA, and 62% and 33% in armB,
respectively. Conclusion
In this randomized phase II trial, dose escalation to the
primary tumor as a whole or 50%SUVmax in NSCLC patients
led to respectively 97% and 91% FFLF at 1 year in central
CT review. Many scans were not evaluable (27%), likely due
to the effect of high dose radiation. Predefined FFLF
increase from 70% to 85% was achieved in both arms,
however the trial did not reach predefined sample size.
In locally advanced non-resectable NSCLC a homogeneous
boost, sparing central structures as much as possible,
should be considered in future research.
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Cooke S, De Ruysscher D, Reymen B, Lambrecht M, Persson GF, Faivre-Finn C, et al. OC-0609: The PET-boost trial: isotoxic homogeneous or FDG-directed dose escalation in stage II-III NSCLC. Radiotherapy and Oncology . 2020 Nov;152:S345–6.