Rodrigues George, Oberije Cary, Senan Suresh, Tsujino Kayoko, Wiersma Terry, Moreno-Jimenez Marta, Kim Tae Hyun, Marks Lawrence B, Rengan Ramesh, De Petris Luigi, Ramella Sara, DeRuyck Kim, De Dios Núria Rodriguez, Warner Andrew, Bradley Jeffrey D, Palma David A
London Health Sciences Centre, London, Ontario, Canada.
MAASTRO Clinic, Maastricht, The Netherlands.
Int J Radiat Oncol Biol Phys. 2015 Jan 1;91(1):133-9. doi: 10.1016/j.ijrobp.2014.09.033.
The clinical benefits and risks of dose escalation (DE) for stage III non-small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database.
An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis.
Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0 months). There was an increase in grades III to V lung toxicity associated with ID (13.0% vs 4.9%, respectively).
No significant overall survival benefits were found with intermediate DE; however, more grade III or greater lung toxicity was observed. The separation of survival curves after 15 months of follow-up suggests that a small overall survival improvement associated with intermediate DE cannot be excluded.
尽管放射肿瘤学组（RTOG）0617方案已得出结果，但III期非小细胞肺癌（NSCLC）剂量递增（DE）的临床益处和风险仍不明确。临床实践存在显著异质性，许多临床医生在0617研究中60至74 Gy的剂量组之间选择了中等剂量水平。本研究通过分析一个大型多机构数据库，调查了该策略是否与任何生存益处/风险相关。
创建了一个接受根治性同步放化疗的III期NSCLC患者个体数据库（13个机构，n = 1274例患者）。根据10 Gy时的肿瘤生物等效剂量（BED 10）将患者分为两组：接受标准剂量（SD；n = 552）的患者，其BED 10为72 Gy≤BED 10≤76.8 Gy（例如60 - 64 Gy/30 - 32分次[fr]），以及接受中等剂量（ID；n = 497）的患者，其BED 10为76.8 Gy < BED 10 < 100.8 Gy（例如>64 Gy/32 fr且<74 Gy/37 fr），低剂量患者（n = 225）被排除在外。然后使用倾向评分对患者进行匹配，得到两组各19
