The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress.
Dr. Saskia A. Cooke
“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.
In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.
“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.
PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.
“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.
The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.
For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.
“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.
The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.
The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.
With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.
With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.
The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).
“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.
In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.
“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.
The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.
“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.
The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.