Department of Radiation Oncology, Shaoxing People's Hospital, 312000, Shaoxing, Zhejiang, China.
Department of Thoracic Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
Strahlenther Onkol. 2022 Dec;198(12):1094-1104. doi: 10.1007/s00066-022-01977-4. Epub 2022 Jul 20.
Small cell lung cancer (SCLC) is characterized by a high risk of brain metastasis and poor survival. This study aims to assess the prognostic role of lactate dehydrogenase (LDH) in limited-stage small cell lung cancer (LS-SCLC) treated with thoracic radiotherapy (TRT) and prophylactic cranial irradiation (PCI).
This study retrospectively evaluated 197 consecutive patients who underwent TRT and PCI for LS-SCLC between November 2005 and October 2017. Both pretreatment and maximal serum LDH levels (mLDH) during treatment were checked, and an increased LDH level was defined as more than 240 IU/ml. Clinical factors were tested for associations with intracranial progression-free survival (IPFS) and overall survival (OS) after PCI. The Kaplan-Meier method was used to calculate survival rates, and multivariate Cox regression analyses were carried out to identify variables associated with survival.
Of the total patients, 28 had higher pretreatment LDH levels and mLDH levels were increased in 95 patients during treatment. In patients in the normal and elevated mLDH groups, the 1‑, 2‑, and 5‑year IPFS rates were 96.7% vs. 90.1%, 91.7% vs. 73.8%, and 87.8% vs. 61.0% (P < 0.01), respectively. Compared to those with normal LDH levels, patients with increased mLDH levels had a higher cumulative risk of intracranial metastasis (hazard ratio [HR] 3.87; 95% confidence interval [CI] 1.73-8.63; P < 0.01) and worse overall survival (HR 2.59; 95% CI 1.67-4.04; P < 0.01). The factors LDH level at baseline or changes between pretreatment level and maximum level during treatment failed to predict brain metastases or OS with statistical significance. In the multivariate analyses, both mLDH during treatment (HR 3.53; 95% CI 1.57-7.92; P = 0.002) and patient age ≥ 60 (HR 2.46; 95% CI 1.22-4.94; P = 0.012) were independently associated with worse IPFS. Factors significantly associated with worse OS included mLDH during treatment (HR 2.45; 95% CI 1.56-3.86; P < 0.001), IIIB stage (HR 1.75; 95% CI 1.06-2.88; P = 0.029), and conventional radiotherapy applied in TRT (HR 1.66; 95% CI 1.04-2.65; P = 0.034).
The mLDH level during treatment predicts brain metastasis and survival in LS-SCLC patients treated with TRT and PCI, which may provide valuable information for identifying patients with poor survival outcomes and possible candidates for treatment intensification.
小细胞肺癌（SCLC）的特点是脑转移风险高且生存预后差。本研究旨在评估乳酸脱氢酶（LDH）在接受胸部放疗（TRT）和预防性颅脑照射（PCI）的局限期小细胞肺癌（LS-SCLC）患者中的预后作用。
本研究回顾性评估了 2005 年 11 月至 2017 年 10 月期间接受 TRT 和 PCI 治疗的 197 例 LS-SCLC 连续患者。检查了治疗前和治疗过程中最大血清 LDH 水平（mLDH），并将升高的 LDH 水平定义为超过 240IU/ml。检测了临床因素与 PCI 后颅内无进展生存期（IPFS）和总生存期（OS）的相关性。采用 Kaplan-Meier 法计算生存率，采用多因素 Cox 回归分析确定与生存相关的变量。
在所有患者中，28 例患者治疗前 LDH 水平升高，95 例患者在治疗过程中 mLDH 水平升高。在 mLDH 正常和升高的患者中，1、2 和 5 年的 IPFS 率分别为 96.7%比 90.1%、91.7%比 73.8%和 87.8%比 61.0%（P<0.01）。与 LDH 水平正常的患者相比，mLDH 水平升高的患者颅内转移的累积风险更高（风险比 [HR] 3.87；95%置信区间 [CI] 1.73-8.63；P<0.01），整体生存情况更差（HR 2.59；95%CI 1.67-4.04；P<0.01）。基线时 LDH 水平或治疗前水平与治疗过程中最大水平之间的变化等因素无法预测脑转移或 OS，差异无统计学意义。在多因素分析中，治疗过程中的 mLDH（HR 3.53；95%CI 1.57-7.92；P=0.002）和患者年龄≥60 岁（HR 2.46；95%CI 1.22-4.94；P=0.012）与较差的 IPFS 独立相关。与较差 OS 显著相关的因素包括治疗过程中的 mLDH（HR 2.45；95%CI 1.56-3.86；P<0.001）、IIIb 期（HR 1.75；95%CI 1.06-2.88；P=0.029）和 TRT 中应用常规放疗（HR 1.66；95%CI 1.04-2.65；P=0.034）。
治疗过程中的 mLDH 水平可预测 LS-SCLC 患者接受 TRT 和 PCI 治疗后的脑转移和生存情况，可为识别生存结局较差的患者和可能需要强化治疗的患者提供有价值的信息。
