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ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 2  |  Page : 274-279
 

Prognostic factors in postoperative radiotherapy in salivary gland carcinoma: A single institution experience from Turkey


Department of Radiation Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

Date of Web Publication6-Jan-2017

Correspondence Address:
M Kandaz
Department of Radiation Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.197721

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 » Abstract 

Background: We reviewed clinical characteristics, treatment outcomes, local and distant failure and prognostic factors in patients with salivary gland carcinoma treated with surgery and postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 75 patients with salivary gland cancer. 69 (%92) patients had cancer of the parotid gland, 3 (%4) patients had cancer of the submandibular gland and 3 (%4) patients had cancer of the minor salivary gland. 4 patients underwent postoperative chemoradiotherapy and 71 patients underwent postoperative radiotherapy. Median radiotherapy dose was 60Gy (range, 30Gy to 69Gy). Results: Median age was 59.6±17.9 (13-88) and the female/male ratio was 1/1.7. Median follow-up 52 months (2-228 months). The mean overall survival 69.2±8 (95%confidence interval[CI], 53.4-85.1) months. The 1-,3-,5- and 10- year overall survival rates were 79.8%, 53.2%, 37.4% and 22.8% respectively. The mean disease free survival 79.7±10 (95%CI, 60.1-99.3) months. The 1-,3-,5- and 10- year disaese free survival rates were 72.8%, 51.9%, 44.1% and 30.4% respectively. On multivariate analysis, the OS was significantly better for the female sex (hazard ratio[HR]:3,0;95%CI:1.5-5.6;P=0.001), absence of lymph node involvement ([HR]:3,0;95%CI:1.7-5.3;P=0.0001), lower tumor grade ([HR]:25,7;95%CI:3.3-199.3;P=0.002), negativity of the surgical margin ([HR]:2,3;95%CI:1.3-4.2;P=0.005), absence of lymphovasculer invasion ([HR]:2,6;95%CI:1.5-4.6;P=0.001), absence of extracapsuler extension ([HR]:6,5;95%CI:2.2-19.1;P=0.001), absence of perineural invasion ([HR]:4,8;95%CI:2.6-8.7;P=0.0001) and ≤60Gy radiotherapy dose ([HR]:3,1;95%CI:1.7-5.5;P=0.0001). They observed local recurrens in17 (23%) patients and distant metastasis in 33 (44%) patients. Conclusions: Employing existing standards of postoperative radiotherapy is a possible treatment that was found to be effective mainly in patients with salivary gland carcinomas.


Keywords: Clinical outcome, patients characteristics, prognostic factors, salivary gland cancers


How to cite this article:
Kandaz M, Soydemir G, Bahat Z, Canyılmaz E, Yöney A. Prognostic factors in postoperative radiotherapy in salivary gland carcinoma: A single institution experience from Turkey. Indian J Cancer 2016;53:274-9

How to cite this URL:
Kandaz M, Soydemir G, Bahat Z, Canyılmaz E, Yöney A. Prognostic factors in postoperative radiotherapy in salivary gland carcinoma: A single institution experience from Turkey. Indian J Cancer [serial online] 2016 [cited 2019 Dec 7];53:274-9. Available from: http://www.indianjcancer.com/text.asp?2016/53/2/274/197721



 » Introduction Top


Salivary gland cancers represent 0.05% of all cancers and 3–7% of all head and neck cancers in adults.[1] The site of origin of salivary gland cancers can be major (parotid, submandibular, and sublingual) or minor salivary gland (nasal cavity, paranasal sinuses, palate, lacrimal gland, and trachea).[2] Of all the salivary gland tumors, 3 out of 4 are benign and 1 out of 4 are malignant.[3] About 20–30% of the parotid gland tumors are malignant.[4] About 20–25% of the parotid gland, 40% of submandibular gland, and 90% of sublingual gland tumors are malignant. Mucoepidermoid carcinoma (MEC) is the most common malign carcinoma of parotid gland, whereas adenoid cystic carcinoma (ACC) represents the most frequent histological type of submandibular and minor salivary gland cancer.[5] The peak age is the sixth and seventh decade.[6]

Radical surgery remains the primary treatment option in management of malign cancer of salivary glands. Indications of combined modality treatment of surgery followed by postoperative radiotherapy (PORT) include tumor size (≥4 cm), deep lobe settlement, high grade, positive surgery margin, local advanced stage, lymph node metastases, soft tissue or bone infiltration, perivascular and perineural invasion, lymphovascular invasion, nerve infiltration, and recurrent carcinoma.[7] Chemotherapy is usually used in the metastatic disease. The objective of this study was to report patients' characteristics, treatment modalities, and disease-free survival (DFS) and overall survival (OS) in patients with malign cancers of salivary glands in Eastern Black Sea Region of Turkey.


 » Materials and Methods Top


This was a retrospective review of patients with malign salivary gland cancer registered with our center database from January 1997 to December 2015. All patients were staged according to the tumor node metastasis staging system of the American Joint Committee on Cancer 6th edition for salivary gland cancers. Histopathology types were classified using the World Health Organization classification.

PORT selection criteria included T3–T4 tumor, lymph node positivity, close or positive margin, high grade, perivascular and perineural invasion, lymphovascular invasion, and recurrence disease. PORT was administered as either linear accelerator or intensity-modulated radiotherapy. Gross tumor volume included tumor bed or residual tumor and nodal positivity. Clinical target volume (CTV); CTV tumor: Tumor bed or residual tumor plus 2 cm margin. CTV nodal positivity: Metastatic lymph nodes plus 1 cm margin. CTV elective node (Level I–III): Lymph nodes plus 0.5–1 cm margin (if deep lobe of the retropharyngeal nodes). Postoperative 60 Gy (2 Gy/daily) was the standard radiotherapy protocol. If there is close or positive margin, high-grade tumor, and positive lymph node, they were given 66 Gy as their radiotherapy dose. Patients with a negative lymph node were given 50 Gy, whereas patients with positive lymph node were given 60 Gy as their radiotherapy dose.

All statistical analysis was performed on SPSS 13.0 software (SPSS Inc., Chicago, Illinois). DFS and OS were calculated using Kaplan–Meier method. Univariate and multivariate Cox regression analysis was performed. A P < 0.05 was considered statistically significant.


 » Results Top


Patients characteristics

A total of 75 patients with salivary gland cancers were registered from January 1997 to December 2015. There were 28 (37%) female and 47 (63%) male, at a ratio of 1/1.7. Median age at presentation was 59.6 ± 17.9 (range 13–88) years. Out of the 75 patients, 19 (25%) were <50 years old and 56 (75%) were ≥50 years. Among the 75 patients, 69 (92%) had the tumor at the parotid gland (a patient had bilateral parotid gland tumor), 3 had at the submandibular gland (4%), and 3 at the minor salivary gland (4%). The most common histology was ACC (33%), MEC (28%), malign mixt tumor (17%), and squamous cell carcinoma (9%). The rarer histology was ductal carcinoma (4%), undifferentiated carcinoma (3%), pleomorphic carcinoma (1.5%), acinic cell carcinoma (1.5%), adenosquamous carcinoma (1.5%), and papillary adenocarcinoma (1.5%). Pathological T stage: 3 (4%) patients were in Stage I, 37 (49%) patients were in Stage II, 29 (39%) patients were in Stage III, and 6 (8%) patients were in Stage IV. Forty-five (60%) patients had lymph node involvement. Pathological grade was low grade in 7 (9%) patients, intermediate grade in 46 (62%) patients, and high-grade in 22 (29%) patients. Lymphovascular invasion was seen in 30 (40%) patients. Perineural invasion was seen in 35 (47%) patients. Four (5%) patients had extracapsular spread.

Treatment

Excision of the salivary gland was performed to all patients. Nine (12%) patients underwent unilateral functional neck dissection, 27 (36%) patients underwent unilateral radical neck dissection, and 1 (1.5%) patient underwent bilateral neck dissection. Pathological margins were negative in 33 (44%), positive in 34 (45%), and close (<5 mm) in 8 (11%) patients.

All patients (one patient with benign parotid tumors, radiotherapy was indicated only in case of recurrent disease) had surgical treatment followed by PORT. Median radiotherapy dose was 60 Gy (range, 30–69 Gy) and fractional dose 1.8/2 Gy daily. Eight (11%) patients received tumor bed irradiation. Fifty-seven (76%) patients were treated with tumor bed, and unilateral neck nodal irradiation and 10 (13%) patients were treated with tumor bed and bilateral neck nodal irradiation. Four (5%) patients underwent concurrent chemotherapy.

Locoregional recurrence and distant metastasis

Median follow-up 52 months (range, 2–228 months). Seventeen (23%) patients developed locoregional recurrence (5–126 months). Twelve of the relapse cases were seen at the treatment area, and 5 of the relapse cases was noted to be around the neighborhood. The locoregional recurrence cases included 12 (71%) male. Six (35%) ACC, 5 (29%) MEC, 8 (47%) lymph node involvement, 7 (41%) positive surgical margin, 6 (35%) lymphovascular invasion, and 7 (41%) perineural invasion, and Grade 2–3 was seen in all patients. Six (35%) patients had prognostic factors ≥2. After locoregional recurrence, the average survival is 30.5 (range, 2–96) months.

Thirty-three (44%) patients developed distant metastasis. Twenty (60%) patients had lung metastases (lungs and bone metastases in 2 patients, lungs and brain metastases in 1 patient, and lungs and liver metastases in 3 patients), brain metastases in 4 (12%) patients, liver metastases in 1 (3%) patient, bone metastases in 6 (18%) patients, and mediastinal lymph node metastases in 2 (6%) patients. Nine (12%) patients had both locoregional and distant metastasis. The distant metastasis cases included 24 (73%) male, 14 (42%) ACC, 8 (24%) malign mixt tumor, 18 (55%) lymph node involvement, 19 (58%) positive surgical margin, 16 (49%) lymphovascular invasion, and 18 (55%) perineural invasion. Fourteen (42%) patients had prognostic factors ≥2. After distant metastasis, the average survival is 18.1 (range, 0–86) months. In contrast to the high rate of distant failure, local or regional failure is less common.

Survival analysis

The mean OS 69.2 ± 8 (95% confidence interval [CI], 53.4–85.1) months and the median OS 42.0 ± 8 (95% CI, 25.7–58.2) months. The 1-, 3-, 5-, and 10-year OS rates were 79.8%, 53.2%, 37.4%, and 22.8%, respectively [Figure 1].
Figure 1: Overall survival

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The mean DFS 79.7 ± 10 (95% CI, 60.1–99.3) months and the median DFS 39 ± 14 (95% CI, 9.95–98.04) months. The 1-, 3-, 5- and 10-year DFS rates were 72.8%, 51.9%, 44.1%, and 30.4%, respectively [Figure 2]. [Table 1] demonstrates patient characteristics and results of log-rank univariate analysis for OS and DFS.
Figure 2: Disease-free survival

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Table 1: Patient characteristics of log-rank univariate analysis for overall survival

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On univariate analysis, the OS was significantly better with the female sex (P < 0.0001), age of <50 years (P < 0.018), T-stage (P < 0.0001), absence of lymph node involvement (P < 0.0001), lower tumor grade (P < 0.0001), absence of lymphovascular invasion (P < 0.001), absence of perineural invasion (P < 0.0001), absence of extracapsular extension (P < 0.001), surgical margin negativity (P < 0.004), ≤60 Gy radiotherapy dose (P < 0.0001), and absence of distant metastasis (P < 0.037). The DFS was significantly better with the female sex (P < 0.001), T-stage (P < 0.0001), absence of lymph node involvement (P < 0.0001), lower tumor grade (P < 0.0001), absence of lymphovascular invasion (P < 0.001), absence of perineural invasion (P < 0.0001), absence of extracapsular extension (P < 0.002), surgical margin negativity (P < 0.01), and ≤60 Gy radiotherapy dose (P < 0.0001). [Table 2] and [Table 3] demonstrate tumor characteristics and treatment characteristics results of log-rank univariate analysis for OS.
Table 2: Tumor characteristics of log-rank univariate analysis for overall survival

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Table 3: Treatment characteristics and results of log-rank univariate analysis for overall survival

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We used Cox proportional hazards regression multivariate analyses to evaluate OS and disease-specific survival. On multivariate analysis, the OS was significantly better with the female sex (hazard ratio [HR]: 3.0; 95% CI: 1.5–5.6; P = 0.001), absence of lymph node involvement (HR: 3.0; 95% CI: 1.7–5.3; P = 0.0001), lower tumor grade (HR: 25.7; 95% CI: 3.3–199.3; P = 0.002), surgical margin negativity (HR: 2.3; 95% CI: 1.3–4.2; P = 0.005), absence of lymphovascular invasion (HR: 2.6; 95% CI: 1.5–4.6; P = 0.001), absence of extracapsular extension (HR: 6.5; 95% CI: 2.2–19.1; P = 0.001), absence of perineural invasion (HR: 4.8; 95% CI: 2.6–8.7; P = 0.0001), and ≤60 Gy radiotherapy dose (HR: 3.1; 95% CI: 1.7–5.5; P = 0.0001). The DFS was significantly better with the female sex (HR: 3.1; 95% CI: 1.5–6.5; P = 0.002), absence of lymph node involvement (HR: 3.1; 95% CI: 1.6–5.9; P = 0.0001), lower tumor grade (HR: Not reached; 95% CI: Not reached; P = 0.01), surgical margin negativity (HR: 2.1; 95% CI: 1.1–4.1; P = 0.02), absence of lymphovascular invasion (HR: 2.4; 95% CI: 1.3–4.6; P = 0.004), absence of extracapsular extension (HR: 5.7; 95% CI: 1.6–19.4; P = 0.005), absence of perineural invasion (HR: 3.4; 95% CI: 1.8–6.6; P = 0.0001), and ≤ 60 Gy radiotherapy dose (HR: 3.1; 95% CI: 1.7–5.9; P = 0.0001). Univariate and multivariate analysis results are shown in [Table 4].
Table 4: Results of univariate and multivariate analysis for overall survival and disease-free survival by Cox proportional hazard model

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 » Discussion Top


This retrospective study provides insight to the clinical presentation, management, and survival of patients with salivary gland cancer. Clinical characteristics, pathological variables, treatment options, local and distant failure, and survival outcome were comparable to published reports from other parts of the world.

Salivary gland cancers occur more commonly in men and in patients between the ages of 60 and 80 years. The mean age at presentation in our study (59 years) is similar to that reported in previously published series.[8],[9] In addition to that, the female/male ratio in our study was 1/1.7, which is also consistent with other reports that there is a male preponderance.

Various studies of salivary gland tumors found that between 60% and 90% of all salivary gland tumors occurred in the parotid gland, 5–20% in the submandibular gland, and ≤10% in the sublingual gland and minor salivary glands.[10],[11] In our series, 69 (92%) occurred in the parotid gland, 3 (4%) in the submandibular glands, and 3 (4%) in the minor salivary gland.

Large studies in the literature have shown MEC, ACC, and Acinic cell carcinoma (AC) as the most common histology affecting salivary glands.[12],[13],[14] A number of studies have shown that ACC is more common in the minor salivary glands than in the major glands,[15],[16] our study found the opposite. ACC was the most common histology in this study (33%) followed by MEC (28%), malignant mixed tumors (17%), and squamous cell carcinoma (9%).

Salivary gland tumors are mostly diagnosed at a later stage.[17] In our series, 49% were diagnosed at stage T2, 39% at stage T3, and 8% at stage T4.

Salivary gland tumors oftenly have lymph node involvement at the time of diagnosis.[18] In our study, 40% of the patients had lymph node involvement.

Age, T stage, N stage, grade, and perineural invasion are the most important prognostic variables for salivary gland malignancy.[19],[20] In our univariate analysis, the OSs prognostic factors were gender, age, T stage, N stage, tumor grade, lymphovascular invasion, perineural invasion, extracapsular extension, surgical margin, radiotherapy dose, and distant metastasis. The DFSs prognostic factors were gender, T stage, N stage, tumor grade, lymphovascular invasion, perineural invasion, extracapsular extension, surgical margin, and radiotherapy dose. In our multivariate analysis, the OSs prognostic factors were gender, N stage, tumor grade, lymphovascular invasion, perineural invasion, extracapsular extension, surgical margin, and radiotherapy dose. The DFSs prognostic factors were gender, T stage, N stage, tumor grade, lymphovascular invasion, perineural invasion, extracapsular extension, surgical margin, and radiotherapy dose.


 » Conclusion Top


We believe that our findings contribute significantly to the awareness of the demographic and pathologic features of salivary gland tumors in the Turkish population and that they are similar to what has been reported elsewhere in the world.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

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Matsuba HM, Thawley SE, Devineni VR, Levine LA, Smith PG. High-grade malignancies of the parotid gland: Effective use of planned combined surgery and irradiation. Laryngoscope 1985;95(9 Pt 1):1059-63.  Back to cited text no. 4
    
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Bell RB, Dierks EJ, Homer L, Potter BE. Management and outcome of patients with malignant salivary gland tumors. J Oral Maxillofac Surg 2005;63:917-28.  Back to cited text no. 14
    
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Caselitz J, Schulze I, Seifert G. Adenoid cystic carcinoma of the salivary glands: An immunohistochemical study. J Oral Pathol 1986;15:308-18.  Back to cited text no. 15
    
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Feinstein TM, Lai SY, Lenzner D, Gooding W, Ferris RL, Grandis JR, et al. Prognostic factors in patients with high-risk locally advanced salivary gland cancers treated with surgery and postoperative radiotherapy. Head Neck 2011;33:318-23.  Back to cited text no. 16
    
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Ito FA, Ito K, Vargas PA, de Almeida OP, Lopes MA. Salivary gland tumors in a Brazilian population: A retrospective study of 496 cases. Int J Oral Maxillofac Surg 2005;34:533-6.  Back to cited text no. 17
    
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Koivunen P, Suutala L, Schorsch I, Jokinen K, Alho OP. Malignant epithelial salivary gland tumors in northern Finland: Incidence and clinical characteristics. Eur Arch Otorhinolaryngol 2002;259:146-9.  Back to cited text no. 18
    
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North CA, Lee DJ, Piantadosi S, Zahurak M, Johns ME. Carcinoma of the major salivary glands treated by surgery or surgery plus postoperative radiotherapy. Int J Radiat Oncol Biol Phys 1990;18:1319-26.  Back to cited text no. 19
    
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Hocwald E, Korkmaz H, Yoo GH, Adsay V, Shibuya TY, Abrams J, et al. Prognostic factors in major salivary gland cancer. Laryngoscope 2001;111:1434-9.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

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