Importance of radiation dose in achieving improved loco-regional tumor control in limited stage small-cell lung carcinoma: An update

Abstract

Between 1974 and 1986, 576 patients (284 limited and 292 extensive stages) were treated at this institution. To keep multiagent chemotherapy (CT) at a uniform intensity, patients who received (a) combined modality approach of both multiagent chemotherapy and thoracic radiotherapy (RT) and (b) ≥3 cycles of multiagent chemotherapy (≥3 drugs), were chosen for this analysis. Out of 284 patients with limited Stage small-cell lung carcinoma, there were 154 such patients who met these strict criteria, and the treatment methods for the remaining 130 patients were as follows: (a) chemotherapy alone with radiotherapy reserved for local failure (47 pts); (b) radiotherapy alone (20 pts); (c) surgery ± adjuvant chemotherapy or radiotherapy (37 pts); (d) modified chemotherapy plus radiotherapy (26 pts). During the 12-year period, the therapeutic factors have evolved. Radiation-dose was increased from 30–40 Gy (time dose fractionation 49–66) in 1974–1977 to 44–52 Gy (time dose fractionation 73–86) in 1978–1986. The target volume for radiotherapy included the primary lesion with a 2-cm margin of normal lung and the mediastinum. Chemotherapy program also evolved from COP, CAV (1974–1977) to MACC, VCE-VCA, PCE-ACE (1978–1986). Fifty of 154 patients (32%) developed loco-regional recurrence (infield failure) and 98% ( 49 50 ) of these patients exhibited this by 2.5 years. Survival data of 154 patients were as follows: (a) Median survival time (MST) was 12 M; (b) actuarial survival rates at 2 and 5 years were 21% and 8%, respectively. Fifty percent of these patients died within 12 months (MST 12 M) and were not exposed to the full length of the risk period for loco-regional failure. To take into account the duration of exposure to the risk period, actuarial method was employed to measure the probability of loco-regional failure. Loco-regional failure rates at 2.5 years were 37%, 39%, 49%, 79%, and 84% for 50 Gy, 45 Gy, 40 Gy, 35 Gy, and 30 Gy, respectively. The difference between the recurrence rates of 37% and 79% by 50 Gy and 35 Gy was statistically significant, p < 0.05. Although the recurrence rates of 37% and 49% by 50 Gy and 40 Gy were not statistically different, there was a strong trend of a better control rate of loco-regional carcinoma by higher radiation doses. The time to recurrence seems also shorter with lower radiation-dose than that of higher radiation doses. Current radiotherapy schedules using 45 Gy to 50 Gy (time dose fractionation 75–82) are still associated with 37% to 39% of loco-regional failure rates at 3.0 years, and these data urge trials employing radiation-doses higher than 50 Gy or altered fractionation schedules to achieve the best possible rate of loco-regional control of small cell lung carcinoma.