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新诊断胰腺癌患者恶病质的炎症标志物和患者报告症状的预测模型

A predictive model of inflammatory markers and patient-reported symptoms for cachexia in newly diagnosed pancreatic cancer patients.

作者信息

Fogelman David R, Morris J, Xiao L, Hassan M, Vadhan S, Overman M, Javle S, Shroff R, Varadhachary G, Wolff R, Vence L, Maitra A, Cleeland C, Wang X S

机构信息

Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd Unit 426, Houston, TX, 77030, USA.

Department of Biostatistics, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

出版信息

Support Care Cancer. 2017 Jun;25(6):1809-1817. doi: 10.1007/s00520-016-3553-z. Epub 2017 Jan 22.

Abstract

BACKGROUND

Cachexia is a frequent manifestation of pancreatic cancer, can limit a patient's ability to take chemotherapy, and is associated with shortened survival. We developed a model to predict the early onset of cachexia in advanced pancreatic cancer patients.

METHODS

Patients with newly diagnosed, untreated metastatic or locally advanced pancreatic cancer were included. Serum cytokines were drawn prior to therapy. Patient symptoms were recorded using the M.D. Anderson Symptom Inventory (MDASI). Our primary endpoint was either 10% weight loss or death within 60 days of the start of therapy.

RESULTS

Twenty-seven of 89 patients met the primary endpoint (either having lost 10% of body weight or having died within 60 days of the start of treatment). In a univariate analysis, smoking, history symptoms of pain and difficulty swallowing, high levels of MK, CXCL-16, IL-6, TNF-a, and low IL-1b all correlated with this endpoint. We used recursive partition to fit a regression tree model, selecting four of 26 variables (CXCL-16, IL-1b, pain, swallowing difficulty) as important in predicting cachexia. From these, a model of two cytokines (CXCL-16 > 5.135 ng/ml and IL-1b < 0.08 ng/ml) demonstrated a better sensitivity and specificity for this outcome (0.70 and 0.86, respectively) than any individual cytokine or tumor marker.

CONCLUSIONS

Cachexia is frequent in pancreatic cancer; one in three patients met our endpoint of 10% weight loss or death within 60 days. Inflammatory cytokines are better than conventional tumor markers at predicting this outcome. Recursive partitioning analysis suggests that a model of CXCL-16 and IL-1B may offer a better ability than individual cytokines to predict this outcome.

摘要

背景

恶病质是胰腺癌的常见表现,会限制患者接受化疗的能力,并与生存期缩短相关。我们开发了一种模型来预测晚期胰腺癌患者恶病质的早期发生。

方法

纳入新诊断的、未经治疗的转移性或局部晚期胰腺癌患者。在治疗前采集血清细胞因子。使用MD安德森症状量表(MDASI)记录患者症状。我们的主要终点是治疗开始后60天内体重减轻10%或死亡。

结果

89例患者中有27例达到主要终点(治疗开始后60天内体重减轻10%或死亡)。在单因素分析中,吸烟、疼痛和吞咽困难的既往症状、高水平的MK、CXCL-16、IL-6、TNF-α以及低水平的IL-1β均与该终点相关。我们使用递归划分来拟合回归树模型,从26个变量中选择4个(CXCL-16、IL-1β、疼痛、吞咽困难)作为预测恶病质的重要变量。由此,两种细胞因子(CXCL-16>5.135 ng/ml且IL-1β<0.08 ng/ml)的模型对该结果的敏感性和特异性(分别为0.70和0.86)优于任何单个细胞因子或肿瘤标志物。

结论

恶病质在胰腺癌中很常见;三分之一的患者达到了我们设定的治疗开始后60天内体重减轻10%或死亡的终点。炎症细胞因子在预测该结果方面优于传统肿瘤标志物。递归划分分析表明,CXCL-16和IL-1B的模型在预测该结果方面可能比单个细胞因子具有更好的能力。

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