Adaptive radiotherapy effective and tolerable in locally advanced NSCLC
Adaptive radiotherapy (RT) guided by 18F-FDG PET/CT functional imaging improves objective response rate (ORR) and survival in non-small-cell lung cancer (NSCLC) without increasing toxicity compared with conventional RT, a small study conducted in China has shown.
The results, reported at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC 2018), showed significant improvements in ORR, progression-free survival (PFS) and overall survival (OS) in patients with unresectable stage IIIA/IIIB NSCLC who were randomized to receive adaptive RT with concurrent chemotherapy (n=36) vs those who received conventional RT plus concurrent chemotherapy (n=36). [Zhu Y, et al, WCLC 2018, abstract OA01.02]
In the study, patients in the adaptive RT arm received PET/CT-guided simultaneous-integrated boost (SIB) RT (PGTV1+2 69 Gy/30 fractions/6 weeks; PTV1+2 60 Gy/30 fractions/6 weeks) with two concurrent cycles of chemotherapy, while those in the conventional RT arm received PET/CT-guided conventional RT (PTV 60 Gy/30 fractions/ 6 weeks) with two concurrent chemotherapy cycles. Following this, patients in both arms underwent a second PET/CT scan when a radiation dose of PTV 40 Gy was delivered. Patients in the adaptive RT arm then received shrinking field and SIB RT guided by the second PET/CT scan, followed by two cycles of consolidation chemotherapy, while those in the conventional RT arm received two cycles of consolidation chemotherapy alone.
“The primary endpoint of ORR was 77.8 percent in the adaptive RT arm and 52.8 percent in the conventional RT arm [p=0.026],” reported investigator Dr Yaping Xu of Shanghai Pulmonary Hospital Shanghai, China.
“After a median follow-up of 28 months, median PFS was 12.5 months in the adaptive RT group vs 8.2 months in the conventional RT group, demonstrating a significant improvement with the adaptive strategy [p=0.013],” said Xu.
Median OS was 22 months with adaptive RT vs 18.1 months with conventional RT (p=0.045).
“A total of 54 patients experienced recurrence as a first event, including 24 patients [44.4 percent] with locoregional recurrence alone, 17 patients [31.5 percent] with distant metastasis alone, and 13 patients [24.1 percent] with both patterns of failure,” said Xu.
“The number of chemotherapy cycles and the type of RT were found to be significant risk factors for locoregional recurrence,” she continued. “Patients who received adaptive RT had a lower risk than those who received conventional RT, with a hazard ratio of conventional vs adaptive RT of 2.227 [95 percent confidence interval, 1.267 to 3.921; p=0.005].”
In the study, rates of grade ≥2 treatment-related adverse events, including radiation-induced lung injury, radiation-induced oesophagitis, radiation-related myocardial damage and myelosuppression, were similar between the two arms.
“Our results showed that shrinking field and SIB RT guided by 18F-FDG PET/CT functional imaging is safe and feasible in clinical practice, with improvements in ORR, PFS and OS without significantly increasing the risk of RT-related toxicity compared wit conventional RT,” concluded Xu. “A phase III multicentre trial with a larger sample size is needed to confirm the superiority of this adaptive RT strategy in patients with locally advanced NSCLC.”