Prognostic Factors and Clinical Outcome in Parotid Gland Tumors: a Single Institution Experience from the Eastern Black Sea Region of Turkey

Purpose: To review clinical characteristics, treatment outcomes and prognostic factors in patients with parotid gland tumors treated with surgery and postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 69 patients with parotid gland tumors, with a median follow-up of 52 months (range, 2-228 months). and a median radiotherapy dose of 60Gy (range, 30-69 Gy). Results: There were 24 (35%) females and 45 (65%) males, at a ratio of 1/1.9. Median age at presentation was 58.9±17.2 (range 13-88) years. The most common histology was adenoid cystic carcinoma (33%) and mucoepidermoid carcinoma (28%). The mean overall survival (OS) was 65.3±8 (95% confidence interval [CI], 49.6-81.1) months and the median overall survival was 40.0 ± 7 (95% CI, 26.2-53.7) months. The -1, -3, -5 and -10 year OS rates were 78%, 52.4%, 35.3% and 19.6% respectively. The mean disease free survival (DFS) was 79.2±10 (95% CI, 59.3-97.1) months and the median disease free survival was 38±13 (95% CI, 7.05-88.7) months. The -1,-3,-5 and -10 year DFS rates were 71.9%, 50.1%, 43.7% and 30.1% respectively. On univariate analysis, the OS was significantly better with female sex (p<0.005), < 50 age (p<0.021), T stage (p<0.0001), absence of lymph node involvement (p<0.0001), lower tumor grade (p<0.0001), absence of lymphovascular invasion (p<0.002), absence of perineural invasion (p<0.0001), absence of extracapsuler extension (p<0.0001), surgical margin negativity (p<0.006), ≤60 Gy radiotherapy dose (p<0.0001) and absence of distant metastasis (p<0.027). Conclusions: Employing existing standards of postoperative radiotherapy is a possible treatment that was found to be mainly effective in patients with parotid gland carcinomas.


Prognostic Factors and Clinical Outcome in Parotid Gland Tumors: a Single Institution Experience from the Eastern Black Sea Region of Turkey
Mustafa Kandaz*, Gulsen Soydemir, Zumrut Bahat, Emine Canyılmaz, Adnan Yoney PORT is indicated for patients with tumor size >4cm, tumor with deep lobe settlement, high grade tumor, lymph node involvement, advanced stage, positive surgery margins, perivascular and perineural invasion, nerve infiltration, recurrent tumor and sof tissue extension (Alterio et al., 2011).
In this study was evaluate clinical outcomes and prognostic factors in patietns with parotid carcinomas treated with surgery and RT at our institution.

Patients selection
We retrospectivly analyzed the data of 69 patiens treated with surgery and RT for parotid carcinomas from January 1997 and December 2014. Locoregional clinical staging was performed using clinical examinations and computed tomography (CT) and/or magnetic resonance (MR) and/or PET-CT. Distant metastases were detected using total-body CT, abdominal ultrasonography (USG) and/or MR. Surgical procedure (superficial or total parotidectomy, lymph node dissection) were recorded. Different surgical approaches depended on tumor location, histological characteristic and stage. Ipsilateral neck disection was performed in patients of high-grade tumors, radiological or clinical evidence of lymph node metastasis or with the risk of lymph node involvement.

Treatment
PORT was given to patients in advanced stage, positive surgical margins, recurrent tumor, high grade histology and presence of lymph node metastasis. Ipsilateral neck lymph nodes were irradiated in patients of pathological lymph nodes or, as elective treatment, in high-risk patients. Total PORT dose was planned ranged from 60 Gy to 66 Gy for negative and positive microscopic surgical bed margins, respectively, and from 50 Gy to 60 Gy for negative and positive nodes with or without extracapsular extension, respectively. RT was performed with linear accelerator of 6 MV-energy and/or cobalt-60. RT was performed with some patients IMRT and some cases with 2-D and/or 3-D confomal technique. One daily fraction of 1.8 to 2 Gy for 5 days/week was used for all patients. When the tumor infiltrated the skin or was located in the superficial lobe, a waterequivalent bolus was added for all of the treatment duration and/or a mixed photon-electron beam technique was used according to personalized treatment plans. The spinal cord doses was limited between 45 Gy to 50 Gy. Head and neck mask was used for immobilization, simulation of all therapy phases. When computed tomography-based treatment was planned, organ at risk contouring and dose prescription and target volume were performing according to the International Commission on Radiation Units (ICRU) 62 guidelines. Radiotherapy-related acute and late mucosa, soft tissue, skin and temporomandibular joint toxicity was commentate according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scoring system.

Follow-up
Follow-up was performed every 3 months for the first 2 years, every 6 months for the subsequent 3 years, and once a year thereafter. Clinical and radiological examinations were performed for each visit.

Statistical methods
In this study, clinical outcome was evaluated of diease-free and overall survival. Disease-free survival was evaluated between the end of PORT and the occurrence of local and/or distant recurrence. The association between clinical outcome (distant metastasis and local recurrence) and tumor characteristics (stage, grade, lynph node metastasis, positive surgical margins, extracapsular extension and perineural invasion) were analyzed. The association between total dose applied, surgical technique and toxicity (mucosa, soft tissue and skin) was also appraised.
Survival rates were calculated using Kaplan-Meier technique. All significant tests and statistical significance were accepted for a calculated p value of <0.005.

Toxicity
Acute toxicity was noted by seeing skin lesions and oral mucositis. 12 (17.4%) patients had grade I skin lesions, 38 (55.1%) patients had grade II, 13 (18.8%) patients had grade III and 6 (8.7%) patients hade grade IV. 16 (23.2%) patients had grade I oral mucositis, 39 (56.5%) patients had grade II, 10 (14.5%) patients had grade III and 4 (5.8%) patients had grade IV. Acute toxicity was shown in table 1. None of the patients developed grade 3 and 4 late toxicity of soft tissues, skin or oral mucosa.

Discussion
Parotid tumors represent 1-5% of all head and neck tumors and 0.1-0.5 of all human tumors (Lima et al., 2005;Kaur et al., 2014). Malignant parotid neoplasms have low incidence and heterogeneity of histological types (Mercante et al., 2014). Our retrospective study included 69 patients who had surgery and PORT. We evaluated in this study clinical outcome and the incidence of acute toxicity.
Various studies have shown mucoepidermoid carcinoma, adenoid cystic carcinoma and adenocarcinoma are the most common histology affecting parotid glands (Nascimento et al., 1986;Feinstein et al., 2011;Al-Mamgani et al., 2012;Mercante et al., 2014). The most frequently recorded histological types in our series were adenoid cystic carcinoma followed by mucoepidermoid carcinoma and malign mixt tumor.
Some studies have shown that the lymphndode is involved at the time of diagnosis (Koivunen et al., 2002), but some studies have shown often there is lymph node involvement at the time of diagnosis (Al-Mamgani et al., 2012;Mercante et al., 2014). In our series, was 57% had lymph node involvement. Parotid glands cancers oftenly dont have extracapsuler extansion at the time of diagnosis (Mercante et al., 2014). In our study, there was 6% extracapsuler extansion. Parotid glands cancers is mostly diagnosed at intermediate and high grade (Al-Mamgani et al., 2012). In our series, 61% occured in intermediate grade and 32% high grade.
Surgery and/or neck disection remains the primary treatment option for parotid malignancies (Al-Mamgani et al., 2012;Mercante et al., 2014). In our study there was 51% neck disection in patients.
Radiotherapy doses, of at least 60 Gy, >65 Gy and 70 Gy were thus recommended for microscopically negative and positive margins and gross residual disease, respectively (Terhaard et al., 2005). In our study applied the same protocol.
Different acute and late treatment toxicities have been described when RT was delivered to the patients (Garden et al., 1997) soft tissue fibrosis, bone and temporal lobe necrosis, hearing loss, frozen temporomandibular joint, brachial plexopathy. These toxicities could be related to different factors: dose, fraction, radiotherapy technique and size of treatment field. In our study, the acute toxicity was observed in all patients, but late toxicity was not observed.
Large studies in literature have shown age, sex, T stage, N stage, grade and perineural invasion as the most common important prognostic variables for parotid gland malignancy (North et al., 1990;Hocwald et al., 2001;Iqbal et al., 2014). In line with the literature data, in our univariate analysis, the OS was prognostic factors with gender, age, T stage, N stage, tumor grade, lymphovasculer invasion, perineural invasion, extracapsuler extansion, surgical margin, radiotherapy dose and distant metastasis. The DFS was prognostic factors with gender, T stage, N stage, tumor grade, lymphovasculer invasion, perineural invasion, extracapsuler extansion, surgical margin and radiotherapy dose.
In conclusion, We believe that our findings contribute significantly to the awareness of the demographic and pathologic features of parotid gland tumors in the Turkish population and that they are similar to what has been reported elsewhere in the world.