Abstract
The aim of this study was to develop a prognostic classifier and subdivided the M1 stage for nasopharyngeal carcinoma patients with synchronous metastases (mNPC). A retrospective cohort of 347 mNPC patients was recruited between January 2000 and December 2010. Thirty hematological markers and 11 clinical characteristics were collected, and the association of these factors with overall survival (OS) was evaluated. Advanced machine learning schemes of a support vector machine (SVM) were used to select a subset of highly informative factors and to construct a prognostic model (mNPC-SVM). The mNPC-SVM classifier identified ten informative variables, including three clinical indexes and seven hematological markers. The median survival time for low-risk patients (M1a) as identified by the mNPC-SVM classifier was 38.0 months, and survival time was dramatically reduced to 13.8 months for high-risk patients (M1b) (P < 0.001). Multivariate adjustment using prognostic factors revealed that the mNPC-SVM classifier remained a powerful predictor of OS (M1a vs. M1b, hazard ratio, 3.45; 95% CI, 2.59 to 4.60, P < 0.001). Moreover, combination treatment of systemic chemotherapy and loco-regional radiotherapy was associated with significantly better survival outcomes than chemotherapy alone (the 5-year OS, 47.0% vs. 10.0%, P < 0.001) in the M1a subgroup but not in the M1b subgroup (12.0% vs. 3.0%, P = 0.101). These findings were validated by a separate cohort. In conclusion, the newly developed mNPC-SVM classifier led to more precise risk definitions that offer a promising subdivision of the M1 stage and individualized selection for future therapeutic regimens in mNPC patients.
Highlights
Nasopharyngeal carcinoma (NPC) is a distinct malignancy of the head and neck with a high incidence (4%-6%) of distant metastases [1,2,3]
A total of 269 (78.0%) of the 347 patients had died by the last follow-up
The mNPC-support vector machine (SVM) classifier remained a powerful predictor of overall survival (OS) after multivariate adjustment using clinicopathological characteristics
Summary
Nasopharyngeal carcinoma (NPC) is a distinct malignancy of the head and neck with a high incidence (4%-6%) of distant metastases [1,2,3]. The current American Joint Committee on Cancer (AJCC/ UICC) Tumor, Node, and Metastasis (TNM) staging uses “M1” to denote the TNM stage for all patients with distant metastasis. TNM staging ignores the heterogeneity between patients, and this system may exhibit reduced critical accuracy in patients with distant metastases [1, 5, 6]. NPC patients exhibit common clinical characteristics, such as tumor volume and number, and numerous molecular and hematological markers are useful to predict outcomes of NPC patients, especially the microcosmic aspect of patients. Hematological markers are more applicable to clinical practice because of its convenience and availability
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