Dose Escalation by Boosting Radiation Dose Within the Primary Tumor on the Basis of a Pre-treatment FDG-PET-CT Scan in Stage IB, II and III NSCLC: a Randomized Phase II Trial
A randomized phase II study will be conducted in patients with inoperable stage IB, II or
III non-small cell lung cancer (NSCLC). The patients will be randomized to receive the
standard 66 Gy given in 24 fractions of 2.75 Gy with an integrated boost to the primary
tumor as a whole (Arm A) or with an integrated boost to the 50% SUVmax area of the primary
tumor (of the pre-treatment FDG-PET scan) (Arm B). Both treatment arms may be combined with
chemotherapy (concurrent or sequential). Patients fulfilling the eligibility criteria will
be registered in the study, and an initial radiotherapy treatment planning will be
performed. When an integrated boost to the primary tumor as a whole up to 72 Gy is not
possible because of dose constraints, the patient will receive 66 Gy or lower according to
the normal tissue tolerance (see below). They will not be randomized, but will be followed
in the trial. As such, it will be clear which proportion of patients can receive an
integrated boost and what the outcome is when dose-escalation is not possible.
Stage IB-II patients receive radiotherapy alone, and stage III patients combined
chemotherapy and radiation. The patients may have received induction chemotherapy up to two
cycles before registration in this trial. The statistical calculations have been performed
to deal with this patient heterogeneity.
The primary objective of this study is to determine the local progression-free survival
(LPFS)at 1 year.
Secondary objectives will be
- Toxicity as a function of radiotherapy dose and volume of the tissue irradiated.
- Overall survival.
- Quality of life
- PET imaging of hypoxia using [18F]HX4, single injection and then PET CT scanning two
and four hours post injection.
- Dynamic Contrast-Enhanced CT imaging
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Local progression-free survival at 1 year
José Belderbos, MD, PhD
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)