Correlation between lung fibrosis and radiation therapy dose after concurrent radiation therapy and chemotherapy for limited small cell lung cancer

PURPOSE: To evaluate the relationship between physician-identified radiographic fibrosis, lung tissue physical density change, and radiation dose after concurrent radiation therapy and chemotherapy for limited small cell lung cancer. MATERIALS AND METHODS: Fibrosis volumes of different severity levels were delineated on computed tomography (CT) images obtained at 1-year follow-up of 21 patients with complete response to concurrent radiation therapy and chemotherapy for limited small cell lung carcinoma. Delivered treatments were reconstructed with a three-dimensional treatment planning system and geometrically registered to the follow-up CT images. Tissue physical density change and radiation dose were computed for each voxel within each fibrosis volume and within normal lung. Patient responses were grouped per radiation and chemotherapy protocol. RESULTS: A significant correlation was noted between fibrosis grade and tissue physical density change and fibrosis grade. For doses less than 30 Gy, the probability of observing fibrosis was less than 2% with conventional fractionation and less than 4% with accelerated fractionation. Physical lung density change also showed a threshold of 30-35 Gy. For doses of 30-55 Gy and cisplatin and etoposide (PE) chemotherapy, fibrosis probability was 2.0 times greater for accelerated fractionation compared with conventional fractionation (P < .005) and was correlated to increasing dose for both fractionation schedules. CONCLUSION: Lung tissue physical density changes correlated well with fibrosis incidence, and both increased with increasing dose greater than a threshold of 30-35 Gy. With concurrent PE chemotherapy, fibrosis probability was twice as great with accelerated fractionation as with once-daily fractionation.