Department of Thoracic Surgery, Hyogo Cancer Center, Akashi City, Hyogo, Japan.
J Thorac Cardiovasc Surg. 2013 Mar;145(3):839-46. doi: 10.1016/j.jtcvs.2012.03.036. Epub 2012 Apr 11.
Pulmonary large cell neuroendocrine carcinoma is a rare high-grade malignant tumor. Because large cell neuroendocrine carcinoma is rare, the optimal treatment, including perioperative chemotherapy, has not been defined. We retrospectively analyzed the correlation among the effectiveness of perioperative chemotherapy in treating large cell neuroendocrine carcinoma, pathologic stage, and immunoreactivity to neuroendocrine markers.
A total of 63 patients with pulmonary large cell neuroendocrine carcinoma undergoing surgical resection from 2001 to 2009 were included. The resected tumors were immunohistochemically stained with the 3 neuroendocrine markers synaptophysin, chromogranin A, and neural cell adhesion molecule. We categorized patients who were positive for all 3 markers as the triple-positive group and those who were negative for 1 or 2 markers as the non-triple-positive group.
Perioperative chemotherapy resulted in better overall survival than surgery alone (P = .042). Multivariate analysis of survival revealed that perioperative chemotherapy was a significant independent prognostic factor (hazard ratio, 0.323; 95% confidence interval, 0.112-0.934; P = .0371). Among the patients who received perioperative chemotherapy, the non-triple-positive group had a significantly greater 5-year survival rate than the triple-positive group (P = .0216). Moreover, among the non-triple-positive group, a significantly greater 5-year survival rate was observed for the patients who underwent surgery with chemotherapy than for those who underwent surgery without chemotherapy (P = .0081). In contrast, no difference was found in 5-year survival between patients with chemotherapy and those without chemotherapy when the tumors were triple positive.
Our results suggest that perioperative chemotherapy might benefit the survival of patients with pulmonary large cell neuroendocrine carcinoma, in particular when the tumors are not immunoreactive to all 3 neuroendocrine markers.
肺大细胞神经内分泌癌是一种罕见的高级别恶性肿瘤。由于大细胞神经内分泌癌较为罕见，因此，包括围手术期化疗在内的最佳治疗方案尚未确定。我们回顾性分析了围手术期化疗对大细胞神经内分泌癌的疗效、病理分期和神经内分泌标志物免疫反应之间的相关性。
共纳入 2001 年至 2009 年间接受手术切除的 63 例肺大细胞神经内分泌癌患者。切除的肿瘤用 3 种神经内分泌标志物突触素、嗜铬粒蛋白 A 和神经细胞黏附分子进行免疫组织化学染色。我们将所有 3 种标志物均为阳性的患者归类为三重阳性组，将 1 种或 2 种标志物为阴性的患者归类为非三重阳性组。
围手术期化疗的总生存率优于单纯手术（P =.042）。生存的多变量分析显示，围手术期化疗是一个显著的独立预后因素（风险比，0.323；95%置信区间，0.112-0.934；P =.0371）。在接受围手术期化疗的患者中，非三重阳性组的 5 年生存率显著高于三重阳性组（P =.0216）。此外，在非三重阳性组中，接受化疗联合手术的患者 5 年生存率显著高于未接受化疗的患者（P =.0081）。相比之下，当肿瘤对所有 3 种神经内分泌标志物均无免疫反应时，接受化疗的患者与未接受化疗的患者的 5 年生存率无差异。
我们的结果表明，围手术期化疗可能使肺大细胞神经内分泌癌患者受益，特别是当肿瘤对所有 3 种神经内分泌标志物均无免疫反应时。
