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恶病质指数作为癌症恶病质的潜在生物标志物和弥漫性大 B 细胞淋巴瘤的预后指标。

Cachexia index as a potential biomarker for cancer cachexia and a prognostic indicator in diffuse large B-cell lymphoma.

机构信息

Division of Hematology-Oncology, Department of Internal Medicine, Institute of Health Science, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Republic of Korea.

Department of Radiology, Institute of Health Science, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Republic of Korea.

出版信息

J Cachexia Sarcopenia Muscle. 2021 Dec;12(6):2211-2219. doi: 10.1002/jcsm.12837. Epub 2021 Oct 21.

Abstract

BACKGROUND

Cancer cachexia is known to adversely affect the clinical course in patients with malignant lymphoma. The cachexia index (CXI) is a potential biomarker of cancer cachexia, and its implications for the prognosis and treatment outcome of lung cancer and aggressive lymphoma has been assessed in previous studies.

METHODS

A total of 267 patients diagnosed with diffuse large B-cell lymphoma who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy were retrospectively reviewed. The CXI was calculated as the skeletal muscle index (SMI) × serum albumin/neutrophil-lymphocyte ratio (NLR). Although previous studies measured the SMI using the muscles of the L3 vertebral level, the present study used both the L3 vertebral muscles and the pectoralis muscles (PM) at the T4 vertebral level to measure the SMI. Depending on the type of muscles used, the CXI was termed the L3-CXI or PM-CXI. Using sex-specific cutoff values for CXI, the patients were categorized as follows: (i) high-CXI group (high L3-CXI and high PM-CXI), (ii) intermediate-CXI group (high L3-CXI and low PM-CXI), and (iii) low-CXI group (low L3-CXI and low PM-CXI).

RESULTS

Complete responses to R-CHOP were obtained in 145/173 (83.8%), 25/36 (69.4%), and 27/57 (47.4%) patients in the high-CXI, intermediate-CXI, and low-CXI groups, respectively (P < 0.001). Treatment-related anaemia (15.6%, 30.6%, and 26.3%, P = 0.038), thrombocytopenia (21.4%, 36.1%, and 43.9%, P < 0.001), febrile neutropenia (23.7%, 44.4%, and 36.8%, P = 0.022), and any nonhaematologic toxicity (31.2%, 44.4%, and 54.4%, P = 0.001) of Grade 3 or more were more common in the lower CXI groups than in the higher-CXI groups. Early treatment discontinuation for reasons other than lymphoma progression also occurred more frequently in the low-CXI group (24/57, 42.1%) compared with the intermediate-CXI (5/36, 13.9%) and high-CXI (18/173, 10.4%) groups (P < 0.001). Median overall survival in the high-CXI, intermediate-CXI, and low-CXI groups was not reached, 50.6 months, and 14.5 months, respectively (p < 0.001). Multivariable analysis showed that low CXI was an independent negative prognostic factor for overall survival (hazard ratio 2.103, 95% confidence interval 1.278-3.460, P = 0.003).

CONCLUSIONS

We suggest that in patients with diffuse large B-cell lymphoma, the CXI is a biomarker for cancer cachexia that can predict survival, treatment response, treatment-related toxicity, and compliance with R-CHOP. Patients were more clearly stratified by this new CXI category compared with the classifications described in previous studies.

摘要

背景

癌症恶病质已知会对恶性淋巴瘤患者的临床病程产生不利影响。恶病质指数(CXI)是癌症恶病质的潜在生物标志物,其对肺癌和侵袭性淋巴瘤的预后和治疗结果的影响已在先前的研究中进行了评估。

方法

回顾性分析了 267 例接受利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松(R-CHOP)免疫化疗治疗的弥漫性大 B 细胞淋巴瘤患者。CXI 计算为骨骼肌指数(SMI)×血清白蛋白/中性粒细胞-淋巴细胞比值(NLR)。尽管先前的研究使用 L3 椎体水平的肌肉测量 SMI,但本研究使用 L3 椎体肌肉和 T4 椎体水平的胸肌(PM)来测量 SMI。根据肌肉类型的不同,CXI 被称为 L3-CXI 或 PM-CXI。使用 CXI 的性别特异性截断值,将患者分为以下几类:(i)高-CXI 组(高 L3-CXI 和高 PM-CXI)、(ii)中-CXI 组(高 L3-CXI 和低 PM-CXI)和(iii)低-CXI 组(低 L3-CXI 和低 PM-CXI)。

结果

高-CXI、中-CXI 和低-CXI 组患者对 R-CHOP 的完全缓解率分别为 145/173(83.8%)、25/36(69.4%)和 27/57(47.4%)(P<0.001)。治疗相关贫血(15.6%、30.6%和 26.3%,P=0.038)、血小板减少症(21.4%、36.1%和 43.9%,P<0.001)、发热性中性粒细胞减少症(23.7%、44.4%和 36.8%,P=0.022)和任何≥3 级的非血液学毒性(31.2%、44.4%和 54.4%,P=0.001)在较低 CXI 组中更为常见。由于淋巴瘤进展以外的其他原因,早期治疗中断在低-CXI 组(24/57,42.1%)也比中-CXI 组(5/36,13.9%)和高-CXI 组(18/173,10.4%)更为常见(P<0.001)。高-CXI、中-CXI 和低-CXI 组的中位总生存期分别为未达到、50.6 个月和 14.5 个月(P<0.001)。多变量分析显示,低 CXI 是总生存期的独立不良预后因素(危险比 2.103,95%置信区间 1.278-3.460,P=0.003)。

结论

我们建议在弥漫性大 B 细胞淋巴瘤患者中,CXI 是一种可以预测生存、治疗反应、治疗相关毒性和对 R-CHOP 治疗依从性的癌症恶病质生物标志物。与先前研究中描述的分类相比,该新 CXI 类别更能清楚地对患者进行分层。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdae/8718032/f28c58ed0f45/JCSM-12-2211-g002.jpg

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