Winther-Larsen Anne, Hoffmann Lone, Moeller Ditte S, Khalil Azza A, Knap Marianne M
a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark.
b Department of Medical Physics , Aarhus University Hospital , Aarhus , Denmark.
Acta Oncol. 2015;54(9):1574-81. doi: 10.3109/0284186X.2015.1062135. Epub 2015 Jul 23.
Loco-regional failure (LRF) remains a significant problem in limited disease small cell lung cancer (LD-SCLC) patients treated with definitive chemoradiotherapy. Dose-escalation may be a way forward to reduce the failure rate. However, the risk of toxicity rises with increasing doses. Knowledge on factors associated with LRF could aid the selection of patients for more aggressive treatment. Therefore, the aim of this study is to evaluate factors correlated with LRF in a cohort of LD-SCLC patients treated with definitive chemoradiotherapy. Moreover, factors associated with improved survival were investigated.
We included 147 consecutive LD-SCLC patients treated from 2007 to 2013. Radiotherapy was delivered as either 45 Gy in 1.5-Gy fractions twice daily or 46-50 Gy in 2-Gy fractions once daily. Chemotherapy was etoposide combined with either carboplatin or cisplatin given mainly concomitantly with radiotherapy. Pattern of first failure and survival were evaluated retrospectively. Cumulative LRF (CLRF) and overall survival (OS) were calculated by the Kaplan-Meier method. The impact of covariates on LRF and OS was evaluated by using Cox proportional hazards model.
With a median follow-up time of 42.2 months, 37 patients experienced LRF as first failure. Isolated LRF was seen in 16 patients, but no isolated regional failure was seen. The CLRF rate was 22% at 1-year and 43% at 3-years. N3-stage was an independent prognostic factor correlated with LRF development (p = 0.043). Median OS was 24.1 months (95% CI 19-29 months) and a three-year survival of 34%. Prognostic factors associated with improved OS were staging including a positron emission tomography (PET) scan (p = 0.004) and receiving prophylactic cranial irradiation (PCI) (p = 0.006).
N3-stage was an independent prognostic factor for LRF. Receiving a pretreatment PET scan and receiving PCI were prognostic factors for improved OS. Reduction in LRF may be achieved with dose-escalation in patients with N3-stage. This can be evaluated in prospective dose-escalation trials.
对于接受根治性放化疗的局限期小细胞肺癌(LD-SCLC)患者,局部区域复发(LRF)仍是一个重大问题。增加放疗剂量可能是降低复发率的一种方法。然而,毒性风险会随着剂量增加而上升。了解与LRF相关的因素有助于选择更积极治疗的患者。因此,本研究旨在评估一组接受根治性放化疗的LD-SCLC患者中与LRF相关的因素。此外,还对与生存改善相关的因素进行了研究。
我们纳入了2007年至2013年连续治疗的147例LD-SCLC患者。放疗采用两种方式,一种是每天两次,每次1.5 Gy,共45 Gy;另一种是每天一次,每次2 Gy,共46 - 50 Gy。化疗采用依托泊苷联合卡铂或顺铂,主要与放疗同步进行。回顾性评估首次复发模式和生存情况。采用Kaplan-Meier法计算累积LRF(CLRF)和总生存期(OS)。使用Cox比例风险模型评估协变量对LRF和OS的影响。
中位随访时间为42.2个月,37例患者以LRF作为首次复发。16例患者出现孤立性LRF,但未观察到孤立性区域复发。1年时CLRF率为22%,3年时为43%。N3期是与LRF发生相关的独立预后因素(p = 0.043)。中位OS为24.1个月(95%可信区间19 - 29个月),3年生存率为34%。与OS改善相关的预后因素包括分期,其中正电子发射断层扫描(PET)(p = 0.004)和接受预防性颅脑照射(PCI)(p = 0.006)。
N3期是LRF的独立预后因素。接受治疗前PET扫描和接受PCI是OS改善的预后因素。对于N3期患者,增加放疗剂量可能降低LRF。这可在前瞻性剂量递增试验中进行评估。