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  • br Table br Characteristics of


    Table 1
    Characteristics of patients with parotid gland cancer and pretreatment facial weakness (n = 45).
    Mucoepidermoid carcinoma 6 (13.3)
    Carcinoma ex pleomorphic adenoma 4 (8.9)
    (Carcinoma components)
    Salivary duct carcinoma 2 (4.4)
    Intermediate-grade 1 (2.2)
    Mild dysfunction 11 (24.4) Treatment
    Adenocarcinoma, NOS: Not otherwise specified.
    FN: facial nerve, RT: radiation treatment, CCRT: concurrent chemo-radiation.
    1 Other pathologies: Myoepithelial carcinoma, oncocytic carcinoma, carci-nosarcoma, neuroendocrine carcinoma.
    2 High-grade tumors included adenoid cystic carcinomas because of locally infiltrative characteristics of adenoid cystic carcinomas.
    3 T and N classification: pT and pN in cases with surgery, cT and cN in cases with non-surgical management. 4 House-Brackmann grades 5–6.
    5 House-Brackmann grade ≤4.
    6 Radiation, concurrent chemo-radiation, or chemotherapy alone.
    To confirm the major prognostic factors in these patients, survival analyses were conducted based on known clinico-pathological factors (Table 3). Interestingly, tumor size and tumor grade were not sig-nificant prognosticators for survival. Metastasis (lymph node or distant sites) was a significant risk factor for worse survival, in consistent with a previous report [18].
    There may be interaction between variables in multivariable ana-lysis; the potential association and independency was evaluated in two ways. First, variance inflation factors of each variable showed values ranging from 1 to 2, suggesting that the multicollinearity among vari-ables was not significant (Supplementary Table S1). Second, correlation analysis between some variables was conducted to show that initial systemic disease status was significantly associated with non-surgical treatment. As a result, treatment modality variable was omitted from multivariable analysis. We did not identify any potential interaction
    Fig. 2. Overall and progression-free survival in all patients with pre-treatment facial weakness (n = 45).
    between tumor grade and BODIPY 505/515 node metastasis, which might be due to the limited number of patients. Thus, this point should be re-eval-uated in a larger cohort.
    Functional outcomes of facial weakness
    Next, the functional outcomes of facial expression were assessed according to treatment modality. Post-treatment facial function was evaluated at 6–12 months after completing treatment (Supplementary Fig. S2). Facial function in nerve-resected patients was stationary or decreased, compared to the initial facial paralysis grades. In some pa-tients, nerve graft was conducted by skilled surgeons, who had more than 5 years of experience in microsurgery. Even with a facial nerve graft, improved facial nerve function was not observed in our series.
    As for the cases with facial nerve preservation (n = 5), the patho-logical diagnoses were 3 salivary duct carcinoma, one carcinoma ex pleomorphic adenoma (carcinoma component = high-grade adeno-carcinoma NOS) and one low-grade mucoepidermoid carcinomas. Even with high-grade pathology, it was possible to safely separate the facial nerve from the tumors during surgery without disruption of tumor. As 
    expected, cases with facial nerve preservation during surgery had the best functional outcomes in terms of the facial expression (Supplementary Fig. S3). The functional improvements (House-Brack-mann grades 3–1 and grade 5–3) were observe in most of patients, except one (House-Brackmann grades 3–4), at post-treatment 6–12 months.
    Pathological analysis of local tumor invasion into the facial nerve
    We also investigated whether pretreatment facial weakness suggests local tumor invasion of the facial nerve. To explore this, the pathology specimens of resected facial nerves were assessed (n = 26). To trace the whole resected facial nerve, multiple slide sections were reviewed for each tumor (15–16 sections), and the area between the facial nerve and tumor was scrutinized. Approximately ⅔ of tumors showed peri-neural or intra-neural tumor invasion of the facial nerve, and ⅓ of tumors did not have local tumor invasion of the facial nerve (Fig. 3). These findings suggest that the facial nerve can be preserved safely in ⅓ of patients even with pretreatment facial weakness.