Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation

Purpose : The ability to prescribe treatment based on relative risks for normal tissue injury has important implications for oncologists. In non-small-cell lung cancer, increasing the dose of radiation may improve local control and survival. Changes in plasma transforming growth factor beta (TGF beta) levels during radiotherapy (RT) may identify patients at low risk for complications in whom higher doses of radiation could be safely delivered. Patient and Methods: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved nodes to a dose of 73.6 Gy (1.6 Gy twice daily). If the plasma TGF beta level was normal after 73.6 Gy, additional twice daily RT was delivered to successively higher total doses. The maximum-tolerated dose was defined as the highest radiation dose at which less than or equal to one grade 4 (life-threatening) late toxicity and less than or equal to two grade 3 to 4 (severe life-threatening) late toxicities occurred. Results: Thirty-eight patients were enrolled. Median follow-up was 16 months. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGF beta levels. Fourteen patients whose TGF beta levels were normal after 73.6 Gy were escalated to 80 Gy (n = 8) and 86.4 Gy (n = 6). In the 86.4-Gy group, dose-limiting toxicity was reached because there were two (33%) grade 3 late toxicities. Conclusion: It is feasible to use plasma TGF beta levels to select patients for RT dose escalation for non-small-cell lung cancer. The maximum-tolerated dose using this approach is 86.4 Gy.