Risk of long-term complications after TGF-β1-guided very-high-dose thoracic radiotherapy

被引:68
作者
Anscher, MS
Marks, LB
Shafman, TD
Clough, R
Huang, H
Tisch, A
Munley, M
Herndon, JE
Garst, J
Crawford, J
Jirtle, RL
机构
[1] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Bioinformat & Biostat, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Med Med Oncol, Durham, NC 27710 USA
来源
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2003年 / 56卷 / 04期
关键词
transforming growth factor-beta; dose escalation; lung cancer; late complications;
D O I
10.1016/S0360-3016(03)00184-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To report the incidence of late complications in long-term survivors of very-high-dose thoracic radiotherapy (RT) treated on a prospective clinical trial. Methods and Materials: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved lymph nodes to a dose of 73.6 Gy at 1.6 Gy twice daily. If the plasma transforming growth factor-beta1 (TGF-beta1) level was normal after 73.6 Gy, additional twice-daily RT was delivered to successively higher total doses until the maximal tolerated dose was reached. Patients within a given dose level were followed for 6 months before escalation to the next dose level was permitted. Late complications were defined according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: Thirty-eight patients were enrolled between 1996 and 1999. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGF-beta1 levels. Fourteen patients received dose escalation (80 Gy in 8; 86.4 Gy in 6). Grade 3 or greater late complications occurred in 4 of 24, 1 of 8, and 2 of 6 patients treated to 73.6, 80, and 86.4 Gy, respectively. The corresponding patient numbers with late Grade 4-5 toxicity were 3 of 24, 0 of 6, and 0 of 8. Overall, 7 (18%) of the 38 patients developed Grade 3-5 late toxicity. Nonpulmonary complications predominated (4 of 7). Five (71%) of seven serious complications developed within 11 months after RT; however, the remaining two complications (29%) occurred very late (at 43 and 62 months). The 5-year actuarial risk of late Grade 3-5 complications was 33%. Conclusion: Long-term survivors of very-high-dose RT for non-small-cell lung cancer have a significant risk of severe treatment-related complications. At these high dose levels, the predominant toxicity may no longer be pulmonary. All Grade 4-5 complications occurred in patients whose dose was limited to 73.6 Gy because of a persistently elevated TGF-beta1. Thus, persistently elevated plasma TGF-beta1 levels toward the end of RT may identify patients at greatest risk of severe complications. (C) 2003 Elsevier Inc.
引用
收藏
页码:988 / 995
页数:8
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