Y. Liang, Y. Que, B. Zhao, W. Xiao, X. Zhang, Z. Zhou, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China; Y. Liang, B. Zhao, Z. Zhou, Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China; T. Hou, Department of Oncology, the Second Xiangya Hospital, Central South University, Changsha, P.R. China Y. Que, W. Xiao, X. Zhang, Department of Medical Melanoma and Sarcoma, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
Clin Orthop Relat Res. 2019 Oct;477(10):2287-2295. doi: 10.1097/CORR.0000000000000767.
Several studies have examined the Controlling Nutritional Status (CONUT) score, which is a screening tool for nutritional status and an effective biomarker for patient survival after cancer treatment. However, its role in soft-tissue sarcoma (STS) remains unknown. Because of the lack of predictive markers for survival in patients with STS, we aimed to determine the CONUT score's association with survival.
QUESTIONS/PURPOSES: (1) Is there a relationship between the CONUT score and clinicopathologic characteristics such as tumor size, tumor location, pathological grade, and advanced stage based on the American Joint Committee on Cancer (AJCC) guidelines? (2) Is the CONUT score associated with disease-free survival (DFS) and overall survival (OS) in patients treated surgically for STS, even when compared with other systemic inflammatory response markers?
Between 1999 and 2016, 769 patients underwent R0 resection for STS at our institution. Adequate medical records and available followup data were required for inclusion in this study. Exclusion criteria were synchronous inflammatory diseases, unplanned excision, and neoadjuvant therapy. There were 658 patients (86%) who fulfilled all criteria. The minimum followup time was 24 months (median, 103 months; range, 61-147 months). The median age of the patients was 43 years (range, 5-85 years), and 265 patients (40%) were women. All patients had Stage I to IV tumors according to the 8 edition of the AJCC staging system. The grade classification was determined to be G1 in 130 patients (20%), G2 in 304 (46%), and G3 in 201 (31%). The CONUT score was calculated based on the serum albumin concentration, total peripheral lymphocyte count, and total cholesterol concentration. The score ranged from 0 to 12, with higher scores indicating worse nutritional status. The patients were classified into two groups according to a receiver operating characteristic curve analysis: the high (≥ 2) and low (0 or 1) CONUT score groups. There were 435 patients in the low CONUT score group and 223 in the high CONUT score group. We tested for an association between the CONUT scores and gender, age, tumor diameter, tumor depth, tumor grade, and AJCC stage using the chi-square and Fisher's exact methods. We also compared the strength of the association between postoperative survival and the CONUT scores, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) using multivariate Cox proportional hazard model analyses.
High CONUT scores were associated with large tumor size (odds ratio [OR], 1.47; 95% CI, 1.06-2.04; p = 0.020), deep tumor location (OR, 1.66; 95% CI, 1.17-2.36; p = 0.004), high tumor grade (OR, 2.54; 95% CI, 1.56-4.14; p = 0.001), and advanced AJCC stage (OR, 1.86; 95% CI, 1.14-3.02; p < 0.001). The low CONUT score group exhibited a higher 5-year OS rate and longer OS than the high CONUT score group (82% versus 65%; odds ratio, 2.45; 95% CI, 1.27-4.72; p < 0.001; 81 versus 64 months, Z = -2.56; p < 0.001). A multivariate analysis indicated that an elevated CONUT score was an independent predictor of OS (hazard ratio [HR], 1.86; 95% CI, 1.47-4.14; p < 0.001) and DFS (HR, 1.63; 95% CI, 1.26-2.11; p < 0.001), but the NLR and PLR were not. In an individual subgroup analysis, the CONUT scores were associated with OS and DFS in the tumor diameter (< 5 or ≥ 5 cm) subgroup, tumor depth (superficial or deep) subgroup, tumor grade (G1 and G2) subgroup, and AJCC stage (I/II or III/IV) subgroup, but not in the G3 subgroup (p = 0.051 and p = 0.065).
High CONUT scores were independently associated with aggressive tumor behavior and unfavorable survival for patients with low-grade, but not high-grade, resected STS. If these findings can be substantiated in larger studies, the CONUT score might be useful for predicting survival and help to develop new treatment strategies for nutrition interventions.
Level III, therapeutic study.
已有多项研究对控制营养状态（CONUT）评分进行了研究，该评分是一种用于评估营养状态的筛查工具，也是癌症治疗后患者生存的有效生物标志物。然而，其在软组织肉瘤（STS）中的作用尚不清楚。由于缺乏预测 STS 患者生存的标志物，我们旨在确定 CONUT 评分与生存的相关性。
问题/目的：（1）CONUT 评分与肿瘤大小、肿瘤位置、病理分级和根据美国癌症联合委员会（AJCC）指南确定的晚期肿瘤等临床病理特征之间是否存在关联？（2）CONUT 评分与接受手术治疗的 STS 患者的无病生存（DFS）和总生存（OS）相关，与其他全身性炎症反应标志物相比如何？
1999 年至 2016 年间，我们机构对 769 例 STS 患者进行了 R0 切除。本研究需要有充分的病历和可获得的随访数据。排除标准为同时患有炎症性疾病、计划外切除和新辅助治疗。符合所有标准的患者有 658 例（86%）。最小随访时间为 24 个月（中位数，103 个月；范围，61-147 个月）。患者的中位年龄为 43 岁（范围，5-85 岁），265 例（40%）为女性。所有患者均根据第 8 版 AJCC 分期系统分期为 I 至 IV 期肿瘤。分级分类为 G1 级 130 例（20%），G2 级 304 例（46%），G3 级 201 例（31%）。CONUT 评分根据血清白蛋白浓度、总外周血淋巴细胞计数和总胆固醇浓度计算。评分范围为 0 至 12，得分越高表示营养状态越差。根据受试者工作特征曲线分析，将患者分为两组：低 CONUT 评分组（0 或 1）和高 CONUT 评分组（≥ 2）。低 CONUT 评分组有 435 例患者，高 CONUT 评分组有 223 例患者。我们使用卡方检验和 Fisher 确切概率法检验 CONUT 评分与性别、年龄、肿瘤直径、肿瘤深度、肿瘤分级和 AJCC 分期之间的相关性。我们还使用多变量 Cox 比例风险模型分析比较了术后生存与 CONUT 评分、中性粒细胞与淋巴细胞比值（NLR）和血小板与淋巴细胞比值（PLR）之间的相关性。
高 CONUT 评分与肿瘤直径较大（优势比 [OR]，1.47；95%置信区间 [CI]，1.06-2.04；p = 0.020）、肿瘤位置较深（OR，1.66；95%CI，1.17-2.36；p = 0.004）、肿瘤分级较高（OR，2.54；95%CI，1.56-4.14；p = 0.001）和 AJCC 晚期（OR，1.86；95%CI，1.14-3.02；p < 0.001）相关。低 CONUT 评分组的 5 年 OS 率和 OS 时间均高于高 CONUT 评分组（82%比 65%；OR，2.45；95%CI，1.27-4.72；p < 0.001；81 比 64 个月，Z = -2.56；p < 0.001）。多变量分析表明，升高的 CONUT 评分是 OS（风险比 [HR]，1.86；95%CI，1.47-4.14；p < 0.001）和 DFS（HR，1.63；95%CI，1.26-2.11；p < 0.001）的独立预测因子，但 NLR 和 PLR 不是。在亚组分析中，CONUT 评分与肿瘤直径（< 5 或 ≥ 5 cm）亚组、肿瘤深度（表浅或深部）亚组、肿瘤分级（G1 和 G2）亚组和 AJCC 分期（I/II 或 III/IV）亚组的 OS 和 DFS 相关，但在 G3 亚组中无关（p = 0.051 和 p = 0.065）。
高 CONUT 评分与低级别、但不是高级别的 STS 患者的侵袭性肿瘤行为和不利生存相关。如果这些发现能在更大的研究中得到证实，CONUT 评分可能有助于预测生存，并有助于制定新的营养干预治疗策略。
III 级，治疗性研究。
