Journal of Cancer 2017, Vol. 8
Ivyspring International Publisher
Research Paper
2269
Journal of Cancer
2017; 8(12): 2269-2276. doi: 10.7150/jca.19611
Importance of maintaining body weight for prevention of distant metastasis of nasopharyngeal carcinoma: An alternative workflow for cancer-risk assessment Wenna Zhang1,2*, Yupei Chen2*, Lei Chen2*, Xu Liu2, Ying Sun2, Yanming Li1, and Jun Ma2 1. 2.
Department of respiratory and critical care medicine, Beijing Hospital, National Center of Gerontology, No. 1 Dahua Road, Dongdan, Beijing 100730, P.R. China. State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P.R. China.
* These authors contributed equally to this work. Corresponding author: Prof. Jun Ma, State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, P.R. China. Telephone: +86-20-87343469; Fax: +86-20-87343295; E-mail: [email protected] and Prof. Yanming Li, Department of respiratory and critical care medicine, Beijing Hospital, National Center of Gerontology, No. 1 Dahua Road, Dongdan, Beijing 100730, P.R. China. E-mail: [email protected] © Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Received: 2017.02.11; Accepted: 2017.04.25; Published: 2017.07.20
Abstract Purpose: To design an alternative workflow for cancer-risk assessment to predict distant metastasis (DM) of nasopharyngeal carcinoma (NPC). Methods: We enrolled 234 patients with non-disseminated NPC and a family history of cancer who underwent intensity-modulated radiotherapy and concurrent chemo-radiotherapy with/without induction chemotherapy in our primary cohort. We conducted univariate and multivariate analyses of the associated prognostic factors, built a nomogram model for distant-metastasis–free survival (DMFS), and confirmed the prognostic value of weight-loss ratio (WTratio). The secondary cohort included 97 patients with available pre-DNA levels who were treated at our cancer center. We performed internal validation with the primary cohort and external validation with the secondary cohort, and compared the new DMFS model with the current 7th TNM staging system. Results: In the primary cohort, 95.9% patients experienced weight loss. The N group (N2-3 vs. N0-1, P = 0.037) and pre-DNA level (P = 0.02) were independent prognostic factors for DMFS in NPC patients. Smoking (P = 0.051) and WTratio (P = 0.052) showed a significant trend for DMFS. WTratio was an independent prognostic factor for DMFS (P = 0.03). Smoking, WTratio, N group, and pre-DNA level were merged to build a risk-score model for DMFS using a nomogram, which could predict survival after internal and external validation. Conclusions: Maintaining body weight during treatment is essential to prevent DM of NPC. Compared with the current 7th TNM staging system, the new DMFS model might better predict DM of NPC. The alternative workflow designed could be applied for prognostic analysis of other cancers. Key words: nasopharyngeal carcinoma; weight-loss ratio; meta-analysis; nomogram; prognosis
1. Introduction Nasopharyngeal carcinoma (NPC), also known as “Canton cancer” for its high prevalence in southern China, arises from the nasopharynx epithelium [1].
Worldwide, NPC accounted for only 0.6% of all cancers diagnosed in 2012[2]. Due to the anatomical constraints and high radiosensitivity of NPC, http://www.jcancer.org
Journal of Cancer 2017, Vol. 8
2270
2. Materials and Methods 2.1 Patient selection This study was reviewed and approved by the Ethics Committee of Sun Yat-sen University Cancer Center (SYSUCC). A total of 253 patients with a family history of cancer who received IMRT and concurrent chemo-radiotherapy (CCRT) with or without induction chemotherapy were treated at the SYSUCC between October 2009 and February 2012. We excluded 11 patients who received docetaxel during radiotherapy and eight patients whose basic information was not available. Finally, 234 patients were enrolled in the primary cohort to build the nomogram and conduct the internal validation. The secondFigure 1. Flow chart of the study. Abbreviations: RT, radiotherapy; DMFS, distant-metastasis–free survival; RCT, ary cohort included 97 patients randomized control trial; AJCC/UICC, American Joint Committee on Cancer/International Union Against Cancer with available data on the pre-DNA levels, who were radiotherapy alone was previously the mainstay treated at the SYSUCC as a part of a multi-center treatment, but it showed a poor overall 5-year randomized control trial (RCT) [12] for external survival rate of approximately 50% [3]. With the validation. A flow chart of the research process is combination of population screening and the presented in Figure 1. application of intensity-modulated radiotherapy 2.2 Data collection (IMRT) and platinum-based chemotherapy, tumor We extracted data from the medical records of control and long-term survival of NPC has improved patients, including sex, age, smoking, EBV infection tremendously; however, this effect was not evident state, pre-treatment serum LDH level, albumin titer, for distant metastasis [2]. weight before/after treatment, and family history of Our previously published meta-analysis [4] cancer at diagnosis. We restaged all patients confirmed that plasma Epstein-Barr virus (EBV) DNA according to the 7th edition of the American Joint assays, including pre-treatment EBV DNA (pre-DNA) Committee on Cancer/International Union Against level, post-treatment EBV DNA (post-DNA) level, and Cancer (AJCC/UICC) staging system [13]. Patients the EBV DNA clearance rate, are highly prognostic of were categorized into two groups according to their long-term survival and distant metastasis in patients family history of cancer: an NPC group, including with NPC. Other risk factors such as smoking [5], patients with a positive history of both NPC and other family history of cancer [6], serum lactate dehydrocancers, and a non-NPC group, including patients genase (LDH) level [7], and lymph node staging [8] without a family history of cancer. The normal serum are also associated with NPC prognosis. The common LDH enzyme activity was defined as 109.0–245.0 side effects of treatments of cancer patients include IU/L, and elevated LDH activity was defined as weight loss and malnutrition, which lead to poor >245.0 IU/L. The normal serum albumin level was treatment tolerance, prolonged hospital stay, and defined as 35.0–55.0 g/L, and patients with an poor outcomes [9-11]. However, despite extensive albumin level < 35.0 g/L were considered to have a efforts to improve the outcome of patients with NPC, low albumin level. The cutoff values of pre-DNA, distant metastasis remains the main failure pattern in weight loss, and WTratio were calculated using NPC. Therefore, this meta-analysis aimed to (1) survival receiver-operating characteristic (ROC) determine the weight-loss ratio (WTratio) in a larger curves. All patients were treated with radical population and confirm the prognostic value of the radiotherapy using IMRT with or without platinumWTratio, and (2) build a nomogram model for distant based chemo-radiotherapy. metastasis in order to predict the prognosis of NPC. http://www.jcancer.org
Journal of Cancer 2017, Vol. 8
2271
Table 1. Characteristics of the study and results of the univariate analysis Factors
Primary cohort No. (%) DMFS(%) P value Age (years) 0.423 ⩾46 106 (45.3) 84.9
Ivyspring International Publisher
Research Paper
2269
Journal of Cancer
2017; 8(12): 2269-2276. doi: 10.7150/jca.19611
Importance of maintaining body weight for prevention of distant metastasis of nasopharyngeal carcinoma: An alternative workflow for cancer-risk assessment Wenna Zhang1,2*, Yupei Chen2*, Lei Chen2*, Xu Liu2, Ying Sun2, Yanming Li1, and Jun Ma2 1. 2.
Department of respiratory and critical care medicine, Beijing Hospital, National Center of Gerontology, No. 1 Dahua Road, Dongdan, Beijing 100730, P.R. China. State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P.R. China.
* These authors contributed equally to this work. Corresponding author: Prof. Jun Ma, State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, P.R. China. Telephone: +86-20-87343469; Fax: +86-20-87343295; E-mail: [email protected] and Prof. Yanming Li, Department of respiratory and critical care medicine, Beijing Hospital, National Center of Gerontology, No. 1 Dahua Road, Dongdan, Beijing 100730, P.R. China. E-mail: [email protected] © Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Received: 2017.02.11; Accepted: 2017.04.25; Published: 2017.07.20
Abstract Purpose: To design an alternative workflow for cancer-risk assessment to predict distant metastasis (DM) of nasopharyngeal carcinoma (NPC). Methods: We enrolled 234 patients with non-disseminated NPC and a family history of cancer who underwent intensity-modulated radiotherapy and concurrent chemo-radiotherapy with/without induction chemotherapy in our primary cohort. We conducted univariate and multivariate analyses of the associated prognostic factors, built a nomogram model for distant-metastasis–free survival (DMFS), and confirmed the prognostic value of weight-loss ratio (WTratio). The secondary cohort included 97 patients with available pre-DNA levels who were treated at our cancer center. We performed internal validation with the primary cohort and external validation with the secondary cohort, and compared the new DMFS model with the current 7th TNM staging system. Results: In the primary cohort, 95.9% patients experienced weight loss. The N group (N2-3 vs. N0-1, P = 0.037) and pre-DNA level (P = 0.02) were independent prognostic factors for DMFS in NPC patients. Smoking (P = 0.051) and WTratio (P = 0.052) showed a significant trend for DMFS. WTratio was an independent prognostic factor for DMFS (P = 0.03). Smoking, WTratio, N group, and pre-DNA level were merged to build a risk-score model for DMFS using a nomogram, which could predict survival after internal and external validation. Conclusions: Maintaining body weight during treatment is essential to prevent DM of NPC. Compared with the current 7th TNM staging system, the new DMFS model might better predict DM of NPC. The alternative workflow designed could be applied for prognostic analysis of other cancers. Key words: nasopharyngeal carcinoma; weight-loss ratio; meta-analysis; nomogram; prognosis
1. Introduction Nasopharyngeal carcinoma (NPC), also known as “Canton cancer” for its high prevalence in southern China, arises from the nasopharynx epithelium [1].
Worldwide, NPC accounted for only 0.6% of all cancers diagnosed in 2012[2]. Due to the anatomical constraints and high radiosensitivity of NPC, http://www.jcancer.org
Journal of Cancer 2017, Vol. 8
2270
2. Materials and Methods 2.1 Patient selection This study was reviewed and approved by the Ethics Committee of Sun Yat-sen University Cancer Center (SYSUCC). A total of 253 patients with a family history of cancer who received IMRT and concurrent chemo-radiotherapy (CCRT) with or without induction chemotherapy were treated at the SYSUCC between October 2009 and February 2012. We excluded 11 patients who received docetaxel during radiotherapy and eight patients whose basic information was not available. Finally, 234 patients were enrolled in the primary cohort to build the nomogram and conduct the internal validation. The secondFigure 1. Flow chart of the study. Abbreviations: RT, radiotherapy; DMFS, distant-metastasis–free survival; RCT, ary cohort included 97 patients randomized control trial; AJCC/UICC, American Joint Committee on Cancer/International Union Against Cancer with available data on the pre-DNA levels, who were radiotherapy alone was previously the mainstay treated at the SYSUCC as a part of a multi-center treatment, but it showed a poor overall 5-year randomized control trial (RCT) [12] for external survival rate of approximately 50% [3]. With the validation. A flow chart of the research process is combination of population screening and the presented in Figure 1. application of intensity-modulated radiotherapy 2.2 Data collection (IMRT) and platinum-based chemotherapy, tumor We extracted data from the medical records of control and long-term survival of NPC has improved patients, including sex, age, smoking, EBV infection tremendously; however, this effect was not evident state, pre-treatment serum LDH level, albumin titer, for distant metastasis [2]. weight before/after treatment, and family history of Our previously published meta-analysis [4] cancer at diagnosis. We restaged all patients confirmed that plasma Epstein-Barr virus (EBV) DNA according to the 7th edition of the American Joint assays, including pre-treatment EBV DNA (pre-DNA) Committee on Cancer/International Union Against level, post-treatment EBV DNA (post-DNA) level, and Cancer (AJCC/UICC) staging system [13]. Patients the EBV DNA clearance rate, are highly prognostic of were categorized into two groups according to their long-term survival and distant metastasis in patients family history of cancer: an NPC group, including with NPC. Other risk factors such as smoking [5], patients with a positive history of both NPC and other family history of cancer [6], serum lactate dehydrocancers, and a non-NPC group, including patients genase (LDH) level [7], and lymph node staging [8] without a family history of cancer. The normal serum are also associated with NPC prognosis. The common LDH enzyme activity was defined as 109.0–245.0 side effects of treatments of cancer patients include IU/L, and elevated LDH activity was defined as weight loss and malnutrition, which lead to poor >245.0 IU/L. The normal serum albumin level was treatment tolerance, prolonged hospital stay, and defined as 35.0–55.0 g/L, and patients with an poor outcomes [9-11]. However, despite extensive albumin level < 35.0 g/L were considered to have a efforts to improve the outcome of patients with NPC, low albumin level. The cutoff values of pre-DNA, distant metastasis remains the main failure pattern in weight loss, and WTratio were calculated using NPC. Therefore, this meta-analysis aimed to (1) survival receiver-operating characteristic (ROC) determine the weight-loss ratio (WTratio) in a larger curves. All patients were treated with radical population and confirm the prognostic value of the radiotherapy using IMRT with or without platinumWTratio, and (2) build a nomogram model for distant based chemo-radiotherapy. metastasis in order to predict the prognosis of NPC. http://www.jcancer.org
Journal of Cancer 2017, Vol. 8
2271
Table 1. Characteristics of the study and results of the univariate analysis Factors
Primary cohort No. (%) DMFS(%) P value Age (years) 0.423 ⩾46 106 (45.3) 84.9
