Phase 2 Study Evaluates Response-Based Adaptive Radiotherapy for NSCLC

Personalized response-based adaptive radiation therapy (RT) with concurrent chemotherapy provided excellent tumor control while minimizing rates of high-grade toxicities in patients with locally advanced non-small cell lung cancer (NSCLC), showed a study published in the International Journal of Radiation Oncology, Biology–Physics.

The phase 2 study was conducted at the University of Michigan, and it included 47 patients who had received a diagnosis of stage IIA-III unresectable NSCLC.

“Local failure rates after treatment for locally advanced NSCLC remain high,” the researchers said. “Efforts to improve local control with uniform dose-escalation or dose-escalation to mid-treatment PET-avid residual disease have been limited by heightened toxicity.”

Therefore, the researchers sought to improve local tumor control and reduce toxicity by using functional imaging, fluorodeoxyglucose-positron emission tomography (FDG-PET) and ventilation/perfusion single photon emission computerized tomography (V/Q SPECT).

Imaging was conducted before treatment and again during treatment to help predict treatment outcomes and how well the lung functions during treatment. Blood and urine samples were also collected to investigate any markers that might determine the patient’s risk of developing adverse effects from radiation to the lungs.

The primary endpoint of the study was grade ≥2 lung and esophageal toxicities. Time to local progression, tumor response, and overall survival were secondary endpoints.

Patients enrolled in the study were a median age of 66 years, mostly white (91%) men (66.4%), and 60% formerly smoked. The patients received concurrent chemoradiation with personalized RT over 30 fractions incorporating FDG-PET and V/Q SPECT.

Based on mid-treatment FDG-PET, the final 9 fractions were adapted up to a total of 80.4 Gy. Patients who did not progress then went onto receive consolidative carboplatin/paclitaxel or durvalumab (Imfinzi).

The study showed that response-based adaptive RT reduced the rates of high-grade esophagitis and pneumonitis. At 1 year after treatment, the rates of grade 2 and grade 3 pneumonitis were 21.3% and 2.1%, respectively. There was no difference in pneumonitis rates among patients who received and did not receive adjuvant durvalumab (P=0.74).

Grade 2 esophagitis was seen in 66% of the patients. However, there were no grade 3 esophageal-related toxicities.

Moreover, the 1- and 2-year local control rates were 94.5% and 87.5%, respectively. Overall survival was 82.8% at the 1-year mark and 62.3% at 2 years.

“Response-based adaptive dose-escalation accounting for tumor change and normal tissue function during treatment provided excellent local control, comparable toxicity to standard chemoradiation, and did not increase toxicity with adjuvant immunotherapy,” the researchers said.

Source: IJROBP