Target Volume Dynamics During Radiation Therapy in Lung Cancer - Identifying the Window of Opportunity

Abstract

To assess the dynamic changes in the target volume (TV) during the course of radical radiotherapy in Lung Cancer. We studied 83 consecutive patients with lung cancer treated with radical intent from January 2012 till December 2017.These patients received concurrent CTRT or Neoadjuvant Chemotherapy followed by Radiotherapy (RT) or RT alone. Radiotherapy was delivered to a total dose of 60-66Gy either with conventional fractionation or hypofractionation, using 3DCRT or IMRT technique. The gross tumor volume was contoured on the CBCTs and volume changes were computed from baseline planning scan for assessing the impact of treatment. Seventy-eight patients were found to be eligible for volume analysis (NSCLC = 69, SCLC = 9, CTRT = 38, NACT = 9, no chemotherapy = 31, conventional fractionation = 51, hypo fractionated RT = 27, 3DCRT = 38, IMRT = 40). The mean tumor volume at the beginning of radiotherapy was 105.62cc (range 4-689cc). The weekly mean percentage change in the volume of primary disease from pre-RT volume were 5.4% after week 1, 13.5% after week 2, 18.8% after week 3, 26.2% after week 4, 25.4% after week 5 and 31.5 % after week 6 (Pearson correlation coefficient - 0.607-1; moderate to strong relationship). Mean change in volume from week 1 to week 2 was 7.3%, week 2 to week 3 was 7.9%, week 3 to week 4 was 7.8%, week 4 to week 5 was 1% and week 5 to week 6 was 6.4 %. The weekly changes in volume with conventional fraction were 2.1%, 11%,17.2%,26.2%,25.3% and 31.5%, from week 1 till week 6; and with hypofractionation were 11.73%,17.63% and 23.87% from baseline till week 1, week 2 and after week 3 respectively. Weekly percentage changes seen with conventional fractionation were as follows: 8.4% for week 1-2; 7.2% for week 2-3; 7.8% for week 3-4; 1% for week 4-5 and 6.4% for week 5-6. For the entire cohort, at a median follow up of 36 months, 2-year overall survival (OS) rate was 65% and at 3-years was 56%. The 2-year PFS was 42% and 3 year was 30% with median PFS of 16 months. In patients with stable target volume, median PFS was 22 months compared to 14 months in patients with early volume reduction; early target increase and late decrease showed a similar PFS of 12 months (p value = 0.913, using log rank test). Also, patients with volume change at week 3 had statistically significant longer PFS compared to rest. Patients with a 20% volume change at week 4 had statistically significant longer OS. Patients with more than 10% and 30% volume change at week 4 had a trend towards better LRC (0.08) and OS (0.09) respectively. We observed that the maximum change in volume during treatment was seen at 3rd-4th week. This has implications, particularly for adaptive re-planning which may be done at mid treatment to reduce the doses delivered to normal tissue without compromising on the dose received by the target volume. We also observed significant correlation between various outcome parameters and volume changes during radiation for lung cancer.