Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1929e1931
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Journal of Cranio-Maxillo-Facial Surgery journal homepage: www.jcmfs.com
Prognostic factors and survival rates for parotid duct carcinoma patients Shuang Shi a, 1, Qigen Fang b, 1, Fayu Liu b, Ming Zhong c, Changfu Sun b, * a
Department of Pediatric Dentistry, School of Stomatology, China Medical University, Shenyang, PR China Department of Oral Maxillofacial Surgery, School of Stomatology, China Medical University, No.117, Nanjing North Street, Heping District, Shenyang, Liaoning 110002, PR China c Department of Oral Pathology, School of Stomatology, China Medical University, Shenyang, PR China b
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 3 January 2014 Accepted 5 August 2014 Available online 13 August 2014
Objective: To investigate the survival rates of patients diagnosed with parotid duct carcinoma (PDC) and analyze the associated risk factors. Methods: This study included 38 patients with PDC and the following information was collected for each patient: gender, age, tumor size, TNM classification, neck node metastasis, HouseeBrackmann grade, neural invasion, use of postoperative radiation therapy and survival data. The KaplaneMeier method and the Cox model were used to determine prognostic factors for disease-specific survival (DSS) and recurrence-free survival (RFS) rates. Results: Of the 38 patients, 36 (94.7%) were male. Mean age at initial diagnosis was 59.9 years (range: 43 e79). A total of 32 (84.2%) patients had T3/T4 tumors, and 29 (76.3%) patients had a preoperative House eBrackmann grade of Ⅰ/Ⅱ. A correlation analysis showed that tumor stage was significantly associated with HouseeBrackmann grade (Spearman r ¼ 0.521, p ¼ 0.001). The 5-year DSS and RFS rates were 45% and 30%, respectively. Using Cox-regression analysis, node metastasis and the preoperative House eBrackmann grade were the independent predictors of both RFS and DSS. Postoperative radiation could decrease disease recurrence, but did not improve disease-specific survival. Conclusion: Parotid duct carcinoma is an aggressive tumor. Node status and preoperative House eBrackmann grade are key prognostic factors. © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Keywords: Salivary duct carcinoma Parotid duct carcinoma HouseeBrackmann grade Prognosis Survival analysis
1. Introduction Salivary duct carcinoma (SDC) was first identified by Kleinsasser et al. (1968) and its histological picture strongly resembled that of breast ductal carcinoma. SDC is an aggressive neoplasm characterized by nerve infiltration and lymph metastasis. It usually arises in the parotid gland, followed by the submandibular gland and minor salivary glands. SDC has a poor prognosis and is predominantly found in males (Thompson, 2012; Ettl et al., 2012; Wee et al., 2012). Due to the low incidence of SDC, only a few articles have reported clinical results which we will briefly summarize here. A previous study of 26 SDC patients who had undergone surgical excision revealed distant metastasis in 16 patients and 20 patients
* Corresponding author. Tel.: þ86 24 22894773; fax: þ86 24 86602310. E-mail address: [email protected] (C. Sun). 1 The first two authors made the same contribution.
died (Lewis et al., 1996). In a similar study, where all patients but one underwent surgery, 14 (58.3%) patients died from their tumors, four patients (15.4%) had a localeregional recurrence and 10 (38.5%) had distant metastasis (Guzzo et al., 1997). Jaehne et al. (2005) described 50 cases: local disease recurrence was observed in 48% of the patients, distant disease metastasis developed in 48% of the patients and recurrent lymph node disease was observed in four patients (8%). Salvoaara et al. (2013) studied 25 cases; all patients underwent surgery and seven (28%) patients showed recurrence of disease within a median follow-up time of 15 months. Finally, a study by Kim et al. (2012) focused on postoperative radiotherapy: treatment failures occurred in 15 (42.9%) of the 35 patients and distant metastasis developed in the majority of patients (93.3%). In these studies, 56e77% of cases indicated pathological nodal involvement at the time of diagnosis and the 5-year disease-specific survival (DSS) rate ranged from 11.5% to 55.1%. No clear survival estimates or descriptions of prognostic indicators have been reported. Moreover, immunohistochemical analyses are becoming increasingly important.
http://dx.doi.org/10.1016/j.jcms.2014.08.001 1010-5182/© 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
1930
S. Shi et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1929e1931
In order to better understand the development of malignant tumors of the salivary glands, and to attempt to predict their clinical course, tumor research is now focusing on molecular methods. Therefore, cell proliferation rate (Ki-67), mutation of oncogenes and overexpression of growth factor-binding receptors such as HER2/neu, p16 and p53 have been identified as important factors to consider in the genesis of salivary gland tumors (Mlika et al., 2012; Jaehne et al., 2005). In this study, we investigated the survival rates of patients diagnosed with parotid duct carcinoma (PDC) and analyzed the associated risk factors. 2. Materials and methods Our study was approved by the institutional research committee of the China Medical University and all participants signed an informed consent agreement. Patients diagnosed with parotid SDC between 2005 and 2012 at the Oral Maxillofacial Head and Neck Tumour Center of the China Medical University were included in this study. These patients had not received any previous treatment for parotid SDC. The following information was collected for each patient: age, sex, preoperative HouseeBrackmann grade, TNM stage, nerve invasion, radiological and surgical records and survival data. The KaplaneMeier method and the Cox model were used to determine prognostic factors for disease-specific survival (DSS) and recurrence-free survival (RFS) rates. The following factors were included in the evaluation: gender, age, tumor size, TNM classification, neck node metastasis, HouseeBrackmann grade, neural invasion and use of postoperative radiation therapy. Statistical analysis was conducted using SPSS 13.0. A p < 0.05 was considered to be significant. 3. Results A total of 38 patients (36 male and two female) were included in the study (Table 1) and the mean age was 59.9 years (range: 43e79). Using the UICC 2002 staging system, patient's tumors were classified as follows: two tumors were stage T1, four tumors were stage T2, six tumors were stage T3 and 26 tumors were stage T4. Of the 30 patients who received selective neck dissection, 14 cases had positive neck node metastasis. Pathological examinations revealed nerve invasion in 26 patients. Analysis of the preoperative HouseeBrackmann grade indicated that 19 patients had a grade of Ⅰ, 10 patients had a grade of Ⅱ, six patients had a grade of Ⅲ and the remaining patients had a grade of Ⅳ. The mean follow-up time was 39.1 months (range: 15e84). After discharge from the hospital, 14 patients received postoperative radiotherapy. Our follow-up revealed that 18 patients had developed a recurrence: 13 cases recurred locally, three cases recurred regionally and two cases had lung metastasis. Sixteen patients had died due to the disease. The 5-year DSS and RFS rates were 45% and 30%, respectively. We performed a correlation analysis which showed that tumor stage was significantly associated with the HouseeBrackmann grade (Spearman r ¼ 0.521, p ¼ 0.001). The univariate analysis revealed that node metastasis and preoperative HouseeBrackmann grade were associated with RFS (all p < 0.05). Node metastasis, facial nerve invasion and preoperative HouseeBrackmann grade were significantly associated with DSS (all p < 0.05). The Cox model revealed that node metastasis and preoperative HouseeBrackmann grade were independent prognosis factors for RFS, while node metastasis, nerve invasion and preoperative HouseeBrackmann grade were independent prognosis factors for DSS (Table 2).
Table 1 Patient information. Case Age Sex T stage Nerve HouseeBrackmann Postoperative Results invasion grade radiotherapy 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38
47 45 67 79 60 79 78 53 53 56 43 73 60 76 50 54 55 59 52 48 72 59 70 54 78 70 57 54 55 73 72 56 57 50 58 45 48 61
M M M M M M M M M M M M M M F M M M M M M M M M M M M M M M M M M M M M M F
T2 T4 T4 T3 T4 T4 T4 T4 T3 T1 T4 T4 T2 T4 T4 T4 T4 T4 T3 T4 T3 T4 T4 T1 T4 T4 T4 T4 T2 T4 T4 T3 T4 T4 T3 T4 T4 T2
No Yes Yes No Yes Yes Yes Yes No No Yes Yes No Yes Yes Yes Yes Yes No Yes No Yes Yes No Yes Yes Yes Yes No Yes Yes No Yes Yes No Yes Yes No
Ⅰ Ⅰ Ⅱ Ⅰ Ⅰ Ⅰ Ⅳ Ⅱ Ⅰ Ⅰ Ⅲ Ⅳ Ⅰ Ⅱ Ⅲ Ⅲ Ⅲ Ⅱ Ⅰ Ⅱ Ⅲ Ⅰ Ⅰ Ⅰ Ⅰ Ⅱ Ⅳ Ⅱ Ⅰ Ⅰ Ⅱ Ⅰ Ⅰ Ⅲ Ⅰ Ⅱ Ⅱ Ⅰ
Yes No No No No Yes No Yes No No Yes No No Yes Yes No No Yes No No No Yes Yes No Yes No No Yes Yes No No No No No No Yes Yes No
Alive Alive Alive Dead Alive Alive Dead Alive Alive Alive Dead Dead Alive Alive Dead Dead Dead Dead Alive Alive Dead Alive Alive Alive Alive Dead Dead Dead Alive Alive Dead Alive Alive Dead Alive Dead Dead Alive
M: male, F: female.
4. Discussion In this study we investigated the survival rates of patients diagnosed with parotid duct carcinoma (PDC) and analyzed the associated risk factors. Our study was based on results from 38 patients who were diagnosed between 2005 and 2012. One of the first factors that we examined from this cohort was age and we were surprised to discover that elderly patients had a similar prognosis to younger patients. This is in contrast to the results reported by Jayaprakash et al. (2014), who found that SDC
Table 2 Survival analysis of the patients with parotid duct carcinoma. Variables
Sex Age (
Contents lists available at ScienceDirect
Journal of Cranio-Maxillo-Facial Surgery journal homepage: www.jcmfs.com
Prognostic factors and survival rates for parotid duct carcinoma patients Shuang Shi a, 1, Qigen Fang b, 1, Fayu Liu b, Ming Zhong c, Changfu Sun b, * a
Department of Pediatric Dentistry, School of Stomatology, China Medical University, Shenyang, PR China Department of Oral Maxillofacial Surgery, School of Stomatology, China Medical University, No.117, Nanjing North Street, Heping District, Shenyang, Liaoning 110002, PR China c Department of Oral Pathology, School of Stomatology, China Medical University, Shenyang, PR China b
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 3 January 2014 Accepted 5 August 2014 Available online 13 August 2014
Objective: To investigate the survival rates of patients diagnosed with parotid duct carcinoma (PDC) and analyze the associated risk factors. Methods: This study included 38 patients with PDC and the following information was collected for each patient: gender, age, tumor size, TNM classification, neck node metastasis, HouseeBrackmann grade, neural invasion, use of postoperative radiation therapy and survival data. The KaplaneMeier method and the Cox model were used to determine prognostic factors for disease-specific survival (DSS) and recurrence-free survival (RFS) rates. Results: Of the 38 patients, 36 (94.7%) were male. Mean age at initial diagnosis was 59.9 years (range: 43 e79). A total of 32 (84.2%) patients had T3/T4 tumors, and 29 (76.3%) patients had a preoperative House eBrackmann grade of Ⅰ/Ⅱ. A correlation analysis showed that tumor stage was significantly associated with HouseeBrackmann grade (Spearman r ¼ 0.521, p ¼ 0.001). The 5-year DSS and RFS rates were 45% and 30%, respectively. Using Cox-regression analysis, node metastasis and the preoperative House eBrackmann grade were the independent predictors of both RFS and DSS. Postoperative radiation could decrease disease recurrence, but did not improve disease-specific survival. Conclusion: Parotid duct carcinoma is an aggressive tumor. Node status and preoperative House eBrackmann grade are key prognostic factors. © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Keywords: Salivary duct carcinoma Parotid duct carcinoma HouseeBrackmann grade Prognosis Survival analysis
1. Introduction Salivary duct carcinoma (SDC) was first identified by Kleinsasser et al. (1968) and its histological picture strongly resembled that of breast ductal carcinoma. SDC is an aggressive neoplasm characterized by nerve infiltration and lymph metastasis. It usually arises in the parotid gland, followed by the submandibular gland and minor salivary glands. SDC has a poor prognosis and is predominantly found in males (Thompson, 2012; Ettl et al., 2012; Wee et al., 2012). Due to the low incidence of SDC, only a few articles have reported clinical results which we will briefly summarize here. A previous study of 26 SDC patients who had undergone surgical excision revealed distant metastasis in 16 patients and 20 patients
* Corresponding author. Tel.: þ86 24 22894773; fax: þ86 24 86602310. E-mail address: [email protected] (C. Sun). 1 The first two authors made the same contribution.
died (Lewis et al., 1996). In a similar study, where all patients but one underwent surgery, 14 (58.3%) patients died from their tumors, four patients (15.4%) had a localeregional recurrence and 10 (38.5%) had distant metastasis (Guzzo et al., 1997). Jaehne et al. (2005) described 50 cases: local disease recurrence was observed in 48% of the patients, distant disease metastasis developed in 48% of the patients and recurrent lymph node disease was observed in four patients (8%). Salvoaara et al. (2013) studied 25 cases; all patients underwent surgery and seven (28%) patients showed recurrence of disease within a median follow-up time of 15 months. Finally, a study by Kim et al. (2012) focused on postoperative radiotherapy: treatment failures occurred in 15 (42.9%) of the 35 patients and distant metastasis developed in the majority of patients (93.3%). In these studies, 56e77% of cases indicated pathological nodal involvement at the time of diagnosis and the 5-year disease-specific survival (DSS) rate ranged from 11.5% to 55.1%. No clear survival estimates or descriptions of prognostic indicators have been reported. Moreover, immunohistochemical analyses are becoming increasingly important.
http://dx.doi.org/10.1016/j.jcms.2014.08.001 1010-5182/© 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
1930
S. Shi et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1929e1931
In order to better understand the development of malignant tumors of the salivary glands, and to attempt to predict their clinical course, tumor research is now focusing on molecular methods. Therefore, cell proliferation rate (Ki-67), mutation of oncogenes and overexpression of growth factor-binding receptors such as HER2/neu, p16 and p53 have been identified as important factors to consider in the genesis of salivary gland tumors (Mlika et al., 2012; Jaehne et al., 2005). In this study, we investigated the survival rates of patients diagnosed with parotid duct carcinoma (PDC) and analyzed the associated risk factors. 2. Materials and methods Our study was approved by the institutional research committee of the China Medical University and all participants signed an informed consent agreement. Patients diagnosed with parotid SDC between 2005 and 2012 at the Oral Maxillofacial Head and Neck Tumour Center of the China Medical University were included in this study. These patients had not received any previous treatment for parotid SDC. The following information was collected for each patient: age, sex, preoperative HouseeBrackmann grade, TNM stage, nerve invasion, radiological and surgical records and survival data. The KaplaneMeier method and the Cox model were used to determine prognostic factors for disease-specific survival (DSS) and recurrence-free survival (RFS) rates. The following factors were included in the evaluation: gender, age, tumor size, TNM classification, neck node metastasis, HouseeBrackmann grade, neural invasion and use of postoperative radiation therapy. Statistical analysis was conducted using SPSS 13.0. A p < 0.05 was considered to be significant. 3. Results A total of 38 patients (36 male and two female) were included in the study (Table 1) and the mean age was 59.9 years (range: 43e79). Using the UICC 2002 staging system, patient's tumors were classified as follows: two tumors were stage T1, four tumors were stage T2, six tumors were stage T3 and 26 tumors were stage T4. Of the 30 patients who received selective neck dissection, 14 cases had positive neck node metastasis. Pathological examinations revealed nerve invasion in 26 patients. Analysis of the preoperative HouseeBrackmann grade indicated that 19 patients had a grade of Ⅰ, 10 patients had a grade of Ⅱ, six patients had a grade of Ⅲ and the remaining patients had a grade of Ⅳ. The mean follow-up time was 39.1 months (range: 15e84). After discharge from the hospital, 14 patients received postoperative radiotherapy. Our follow-up revealed that 18 patients had developed a recurrence: 13 cases recurred locally, three cases recurred regionally and two cases had lung metastasis. Sixteen patients had died due to the disease. The 5-year DSS and RFS rates were 45% and 30%, respectively. We performed a correlation analysis which showed that tumor stage was significantly associated with the HouseeBrackmann grade (Spearman r ¼ 0.521, p ¼ 0.001). The univariate analysis revealed that node metastasis and preoperative HouseeBrackmann grade were associated with RFS (all p < 0.05). Node metastasis, facial nerve invasion and preoperative HouseeBrackmann grade were significantly associated with DSS (all p < 0.05). The Cox model revealed that node metastasis and preoperative HouseeBrackmann grade were independent prognosis factors for RFS, while node metastasis, nerve invasion and preoperative HouseeBrackmann grade were independent prognosis factors for DSS (Table 2).
Table 1 Patient information. Case Age Sex T stage Nerve HouseeBrackmann Postoperative Results invasion grade radiotherapy 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38
47 45 67 79 60 79 78 53 53 56 43 73 60 76 50 54 55 59 52 48 72 59 70 54 78 70 57 54 55 73 72 56 57 50 58 45 48 61
M M M M M M M M M M M M M M F M M M M M M M M M M M M M M M M M M M M M M F
T2 T4 T4 T3 T4 T4 T4 T4 T3 T1 T4 T4 T2 T4 T4 T4 T4 T4 T3 T4 T3 T4 T4 T1 T4 T4 T4 T4 T2 T4 T4 T3 T4 T4 T3 T4 T4 T2
No Yes Yes No Yes Yes Yes Yes No No Yes Yes No Yes Yes Yes Yes Yes No Yes No Yes Yes No Yes Yes Yes Yes No Yes Yes No Yes Yes No Yes Yes No
Ⅰ Ⅰ Ⅱ Ⅰ Ⅰ Ⅰ Ⅳ Ⅱ Ⅰ Ⅰ Ⅲ Ⅳ Ⅰ Ⅱ Ⅲ Ⅲ Ⅲ Ⅱ Ⅰ Ⅱ Ⅲ Ⅰ Ⅰ Ⅰ Ⅰ Ⅱ Ⅳ Ⅱ Ⅰ Ⅰ Ⅱ Ⅰ Ⅰ Ⅲ Ⅰ Ⅱ Ⅱ Ⅰ
Yes No No No No Yes No Yes No No Yes No No Yes Yes No No Yes No No No Yes Yes No Yes No No Yes Yes No No No No No No Yes Yes No
Alive Alive Alive Dead Alive Alive Dead Alive Alive Alive Dead Dead Alive Alive Dead Dead Dead Dead Alive Alive Dead Alive Alive Alive Alive Dead Dead Dead Alive Alive Dead Alive Alive Dead Alive Dead Dead Alive
M: male, F: female.
4. Discussion In this study we investigated the survival rates of patients diagnosed with parotid duct carcinoma (PDC) and analyzed the associated risk factors. Our study was based on results from 38 patients who were diagnosed between 2005 and 2012. One of the first factors that we examined from this cohort was age and we were surprised to discover that elderly patients had a similar prognosis to younger patients. This is in contrast to the results reported by Jayaprakash et al. (2014), who found that SDC
Table 2 Survival analysis of the patients with parotid duct carcinoma. Variables
Sex Age (
