Tumor Volume Changes During and after Radiation Therapy as a Predictor for Local Recurrence in Locally Advanced Non-Small Cell Lung Cancer

Abstract

Prediction of tumor response during the treatment course may allow for individualized adaptive radiotherapy. We hypothesized that primary tumor volume change during and immediately following radiation therapy is predictive of local recurrence, thus providing information on which patients may benefit from treatment adaptation. Forty-one patients with locally advanced non-small cell lung cancer (Stage III = 38, Stage II = 3) were treated with definitive radiotherapy using conventional fractions of 1.8 or 2 Gy. Doses ranged from 54 to 70 Gy with a median dose of 66 Gy. All patients were previously enrolled on imaging protocols and underwent multiple 4D fan beam CT scans during radiotherapy. Thirty-six patients also received chemotherapy (29 concurrent, 5 sequential). The primary tumor was contoured on fan beam CT scans acquired pre-treatment, during treatment, and up to 3 months following treatment. A competing risk model was used to determine if there was a relationship between the primary tumor recurrence and percent reduction in tumor size per day. The median overall survival for all patients was 1.74 years. The median follow-up time for living patients was 6.45 years (range: 3.41 to 6.96 years). Median initial primary tumor size was 75.7cc (range: 4.7cc to 622.0cc). Twenty patients (49%) had LR at the primary tumor site, and 23 patients (56%) had distant metastases. During radiotherapy, the average percent reduction of tumor per day was 1.34% (range: -0.25% to 2.72%). Tumors that decreased in size less than 1.4% a day had a hazard ratio of 2.15 for local recurrence compared to those that decreased in size more than 1.4% a day (p = 0.0075). Although larger initial tumor size was associated with an increased risk of primary tumor recurrence (p = 0.0064), there was no relationship between initial tumor size and daily percentage change in tumor size (Pearson correlation coefficient of -0.29). The change in tumor size was not associated with the rates of distant metastases (p = 0.45). Scans taken at 3 months follow-up were also analyzed as tumors continued to shrink in size after treatment, albeit slower at an average rate of 0.81% per day (range: 0.08% to 1.28%). The average volume at 3 months was 21.5cc (range: 0.53cc to 188.3cc). There was no relationship between the change in tumor size at 3 months following treatment and local control (p = 0.18). An increased rate of tumor volume change is associated with a significantly lower rate of primary tumor recurrence and may provide an efficient and easily accessible early measure of radiation response.