Photo Credit: Magicmine

The following is a summary of “Phase II Trial Assessing Toxicity of Personalized Response-Based Radiation Treatment in Patients with Locally Advanced Non-Small Cell Lung Cancer,” published in the July 2024 issue of Oncology by Edwards et al.

Local failure rates following treatment for locally advanced non-small-cell lung cancer (NSCLC) remain significant. Traditional efforts to enhance local control through uniform dose-escalation or targeted dose-escalation to mid-treatment PET-avid residual disease have been hindered by increased toxicity. This trial aimed to refine response-based adaptive radiation therapy (RT) and reduce toxicity by incorporating FDG-PET and V/Q SPECT imaging during treatment.

In this single-institution Phase II trial (NCT02492867), 47 patients with Stage IIA-III unresectable NSCLC were prospectively enrolled. Patients underwent concurrent chemoradiation with personalized, response-based adaptive RT over 30 fractions, utilizing V/Q SPECT and FDG-PET. The initial 21 fractions (46.2Gy at 2.2 Gy/fraction) targeted the tumor while minimizing exposure to SPECT-defined functional lung. The treatment plan was adapted for the final 9 fractions (2.2-3.8Gy/fraction), reaching a total dose of up to 80.4Gy, based on mid-treatment FDG-PET tumor response, to escalate the dose to the residual tumor while minimizing the impact on the functional lung. Non-progressing patients received either consolidative carboplatin/paclitaxel or durvalumab. The primary endpoint was the incidence of ≥ grade 2 lung and esophageal toxicities. Secondary endpoints included time to local progression, tumor response, and overall survival.

One year post-treatment, grade 2 and grade 3 pneumonitis incidences were 21.3% and 2.1%, respectively, with no significant difference in pneumonitis rates between patients who received adjuvant durvalumab and those who did not (p=0.74). While no patients experienced grade 3 esophageal toxicities, 66.0% experienced grade 2 esophagitis. The 1- and 2-year local control rates were 94.5% (95% CI, 87.4%-100%) and 87.5% (95% CI, 76.7%-100%), respectively. Overall survival was 82.8% (95% CI, 72.6%-94.4%) at 1 year and 62.3% (95% CI, 49.6%-78.3%) at 2 years.

The study concluded that response-based adaptive dose-escalation, which accounts for tumor and normal tissue function changes during treatment, provided excellent local control with toxicity rates comparable to standard chemoradiation. Additionally, this approach did not increase toxicity when combined with adjuvant immunotherapy. This method holds promise for improving treatment outcomes in patients with locally advanced NSCLC.

Source: sciencedirect.com/science/article/abs/pii/S0360301624007491