Using changes in plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation for non-small cell lung cancer

Purpose: The ability to prescribe treatment based upon 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 β (TGFβ) levels during radiotherapy may identify patients at low risk for complications in whom higher doses of radiation could be safely delivered. Materials and methods: Patients with locally advanced or medically inoperable non-small cell lung cancer received 3 dimensional conformal radiotherapy to the primary tumor and radiographically involved nodes to a dose of 73.6 Gy (1.6 Gy twice daily). If the plasma TGFβ level was normal after 73.6 Gy, additional twice daily radiotherapy was delivered to successively higher total doses. The maximum tolerated dose was defined as the highest radiation dose at which ≤1 Grade 4 (life threatening) late toxicity and ≤2 Grade 3–4 (severe-life threatening) late toxicity occurred. Results: Thirty-eight patients were enrolled. Median follow-up is 16 months. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy due to persistently abnormal TGFβ levels. Fourteen patients whose TGFβ 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 as there were 2 (33%) Grade 3 late toxicities. Conclusion: It is feasible to use plasma TGFβ levels to select patients for RT dose escalation for nonsmall cell lung cancer. The maximum tolerated dose using this approach is 86.4 Gy.