廣末 晃之

We aimed to determine the functional role of the miRNA, which affects drug sensitivity to 5-FU in oral squamous cell carcinoma (OSCC), using two types of 5-FU-resistant and parental OSCC cell lines. MiRNA microarray data showed that miR-30a was significantly upregulated in two resistant cell lines. Therefore, we investigated the effects and molecular mechanism of miR-30a on 5-FU sensitivity. Stable overexpression of miR-30a in parental OSCC cells decreased cell proliferation and attenuated drug sensitivity to 5-FU. Cell cycle analysis indicated that miR-30a overexpression increased the proportion of G1 phase cells and decreased the proportion of S phase cells. MiR-30a knockdown using siRNA reversed the effects of miR-30a overexpression. DNA microarray analysis using miR-30a-overexpressing cell lines and a TargetScan database search showed that cyclin E2 (CCNE2) is a target of miR-30a. A luciferase reporter assay confirmed that a miR-30a mimic interacted with the specific binding site in the 3' UTR of CCNE2. CCNE2 knockdown with siRNA in OSCC cells yielded decreased drug sensitivity to 5-FU, similar to miR-30a overexpressing cells. These findings suggest that miR-30a in OSCC may be a novel biomarker of 5-FU-resistant tumors, as well as a therapeutic target for combating resistance.

TP53 gene mutations can lead to mutant p53 protein accumulation in cancer cells, thereby inducing the production of serum antip53 antibodies (Ap53Ab) in patients with various types of cancer. The aim of the present study was to re-evaluate the clinicopathological and prognostic significance of Ap53Ab using the Ap53Ab ELISA kit, approved by the Japanese Health Insurance System in 2007. Ap53Ab was measured as a tumor marker in 94 patients with oral squamous cell carcinoma (OSCC), by subjecting paraffin-embedded sections obtained from biopsy specimens to immunohistochemical analysis to confirm p53 expression. The associations among Ap53Ab status, p53 expression and clinical significance in OSCC were examined. A total of 23% of the patients were Ap53Ab-positive. Ap53Ab status was found to be significantly associated with p53 expression status in primary tumors (P=0.027), clinical T-category, pathological N-category and pathological stage (P=0.04, P=0.010 and P=0.013, respectively). Kaplan-Meier curve analysis revealed that Ap53Ab status was significantly associated with poor disease-free survival (DFS; P=0.043), and Cox regression analysis revealed that Ap53Ab status was a significant prognostic factor for DFS in patients with OSCC (hazard ratio=2.807; 95% confidence interval: 1.029-7.160; P=0.044). These results suggested that Ap53Ab measurement may reflect the p53 mutation status and an aggressive malignant phenotype, and it may serve as a useful predictive marker candidate for OSCC in clinical practice.

症例は80歳男性で、左側舌縁部に腫瘤を呈して当科を紹介受診し、左側舌扁平上皮癌との診断で、術前化学放射線療法後に左側舌部分切除術、左側頸部郭清術、前腕皮弁再建術を施行した。術前にN1と診断したリンパ節には腫瘍細胞は認めず、通常のリンパ組織がみられた。以後、外来で経過観察を行っていたが、画像検査にて対側の右側頸部リンパ節に転移を疑う所見を指摘された。全身麻酔下に右側根治的頸部郭清術変法(内頸静脈、副神経温存)を施行した。術後の病理組織学的検査でリンパ節に明らかな腫瘍性病変は認めず、病理組織学的所見と免疫組織化学的所見よりRosai-Dorfman病(RDD)の診断となった。頸部リンパ節以外にRDDを疑う所見を認めず退院となった。現在、右側頸部郭清術後3年10ヵ月経過時点で再発所見なく経過良好であった。

12歳女児。右側下顎第一大臼歯の齲歯に対し近医歯科で治療を受けたが途中で中断し、2ヵ月後に右側下顎の腫脹および疼痛が出現した。抗菌薬投与、切開排膿、周囲歯肉切除術が行われたが改善に乏しかった。造影MRI、X線、造影CT各所見より、下顎骨骨髄炎と診断し、右側下顎第一臼歯の抜歯下顎骨、皮質骨除去術を行った。病理所見では創部の肉芽組織より、類上皮細胞を含む肉芽腫を認めた。また、膿培養よりMycobacterium fortuitumを検出し、多剤抗菌薬併用療法(アミカシン、イミペネム、シプロフロキサシン)を6週間行った。その後、ファロペネム、シプロフロキサシン内服に変更し、入院89日目に退院となった。退院後6ヵ月間、抗菌薬内服を継続し、下顎の腫脹および疼痛の完全な消失を認めた。

OBJECTIVES: To evaluate the prognostic value of preoperative radiological findings for nodal recurrence in clinically node-negative (cN0) patients with oral tongue squamous cell carcinoma (SCC). METHODS: The study population consisted of 52 patients with cT1-2N0 oral tongue SCC classified according to the 7th edition of the Union for International Cancer Control (UICC) staging system. The subjects had undergone preoperative radiological examinations, including magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography. All patients were treated with local resection and watchful waiting for neck management. Using an unpaired t test, Pearson's chi-squared test, and the Kaplan-Meier method, the MRI-derived depth of invasion (DOI), the standardized uptake value (SUV) on FDG-PET, and the T stage according to the 7th and 8th UICC were assessed as prognostic factors. RESULTS: The MRI-derived DOI was recorded as ≤ 5 mm in 24 patients and > 5 mm in 28 patients. During the follow-up period, nine patients exhibited nodal recurrence, with the MRI-derived DOI being significantly higher in patients with positive than in those with negative (p = 0.011). The SUV was not significant. Five-year cumulative nodal recurrence probabilities were 4.5% for patients with an MRI-derived DOI ≤ 5 mm, while it was 32.1% for > 5 mm (p = 0.013). Although the T classifications were not significant, none of our patients whose T stage according to the 8th UICC was T1 suffered nodal recurrence. CONCLUSIONS: MRI-derived DOI can predict nodal recurrence, while preoperative information may assist in treatment planning for oral tongue SCC.

Pretreatment nutritional and immunological status is useful for predicting survival outcomes for various types of malignant tumors. Our objective was to determine the impact of the pretreatment Onodera's prognostic nutritional index (OPNI) on outcomes of patients who underwent definitive chemoradiotherapy for advanced oral squamous cell carcinoma (OSCC). We reviewed 47 patients treated for OSCC with definitive chemoradiotherapy (CRT) at our institution between January 2004 and December 2011. We determined the OPNI according to the following formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per μL). We determined the optimum OPNI cut-off through a receiver operating characteristic analysis. We analyzed the associations between OPNI status and various clinicopathological features and evaluated the effects of OPNI on the prognosis. We examined the relationships between OPNI and systemic inflammatory response parameters and analyzed intratumoral CD8+ T cells and their correlation with OPNI. The optimum OPNI cut-off was 42.7. A Kaplan-Meier curve analysis revealed that low OPNI was significantly associated with poor overall survival and cause-specific survival. The multivariate analysis revealed that low OPNI was independently correlated with poor 5 year overall survival and cause-specific survival. OPNI was significantly correlated with systemic inflammatory response parameters. Intratumoral CD8+ T cell counts in primary tumors were significantly lower for low OPNI than for high OPNI. The present data demonstrate that pretreatment OPNI is a valuable independent prognostic indicator of overall and cause-specific survival in advanced OSCC following definitive CRT. OPNI might reflect the tumor immune microenvironment characterization in OSCC.

OBJECTIVES: To investigate whether serum amylase can predict the recovery of salivary volume and determine the correlation of the level of cytokines, including epidermal growth factor, hepatocyte growth factor and keratinocyte growth factor, with oral mucositis during chemoradiotherapy for oral cancer. SUBJECTS AND METHODS: This study included 84 patients treated with preoperative chemoradiotherapy followed by curative surgery, following a phase II study protocol. We measured and analysed the correlation of the stimulated saliva volume, serum amylase and cytokines in resting saliva at baseline and 1 month after chemoradiotherapy with oral mucositis levels. RESULTS: We observed a negative correlation between the serum amylase level at the beginning of chemoradiotherapy and the stimulated saliva volume at 1 month after chemoradiotherapy (p = .03). Epidermal growth factor in resting saliva was significantly reduced after chemoradiotherapy (p < .01). The incidence of severe oral mucositis during chemoradiotherapy was significantly higher and negatively associated with the epidermal growth factor and keratinocyte growth factor levels (p = .04, p = .05). CONCLUSIONS: The serum amylase level at the beginning of chemoradiotherapy may be a predictor of the recovery of the saliva volume. Furthermore, cytokines such as epidermal growth factor and keratinocyte growth factor in resting saliva affect the development of oral mucositis during chemoradiotherapy.

BACKGROUND: Oral squamous cell carcinoma (OSCC) has increased morbidity, and its high metastatic potential affects patient survival. Bromodomain containing 4 (BRD4) is a chromatin protein that associates with acetylated histone lysines and facilitates transcription. BRD4 has been implicated in cell proliferation, metastasis, and prognosis in several types of cancer. However, the role of BRD4 in OSCC remains to be elucidated. METHODS: We investigated the role of BRD4 and its potential utility as a therapeutic target in OSCC. RESULTS: JQ1, the BRD4 inhibitor, suppressed the cell proliferation, migration, and invasion in the OSCC cell lines and in vivo. JQ1 reduced the expression levels of 15 metastasis genes in OSCC, including matrix metallopeptidase 2 (MMP2). Our chromatin immunoprecipitation assay showed that JQ1 reduced the BRD4 binding to the histone H3 lysine 27 acetylation-enriched sites in the MMP2 locus. Analyses of biopsy specimens from OSCC patients revealed that the BRD4 and MMP2 expression levels were correlated in the cancerous regions, and both were highly expressed in lymph node metastasis cases, including delayed metastasis. CONCLUSIONS: BRD4 contributes to metastasis in OSCC, through the epigenetic regulation of the MMP2 gene, and thus BRD4 may represent a therapeutic target and a novel prediction indicator for metastasis.

BACKGROUND: To review a single institutional experience of the Radiation Therapy Oncology Group (RTOG) 8502 "QUAD shot" regimen using volumetric modulated arc radiotherapy (VMAT) for incurable head and neck cancer (HNC). METHODS: Thirty-four consecutive patients with HNC were treated with at least one cycle of the RTOG 8502 regimen. Treatment plans included the use of VMAT with 6 MV photons generated by a linear accelerator. Two daily fractions of 3.7 Gy were delivered with an interval of at least 6 h for 2 consecutive days, totaling 14.8 Gy over 4 fractions. This was repeated every 3-4 weeks for a total of three cycles. No concurrent systemic therapy was performed. RESULTS: The number of completed cycles was 1 in 6 (18%) patients, 2 in 5 (15%), and 3 in 23 (68%). Tumor response was achieved in 29 (85%) patients and symptom relief in 20 (77%) of 26 patients. Overall response (tumor response or symptom relief) was achieved in 32 (94%) patients. All patients who received 2 or more treatment cycles achieved overall response. Median overall survival (OS) was 5.7 months. Multivariate analysis revealed that completion of all three treatment cycles was significantly associated with better OS (P = 0.002). Grade 2 toxicity was observed in four (12%) patients, but no acute Grade ≥ 3 or late toxicity was observed. CONCLUSIONS: The RTOG 8502 "QUAD shot" regimen using VMAT is effective for incurable HNC with highly reduced toxicity. Treatment with multiple cycles is recommended for better treatment response and/or survival.

症例は30歳女性で、14歳時、近在歯科医院にて顎下腺管内唾石症のため、口腔内より唾石摘出術を受けた。その後、左側口底部の腫脹をきたし舌下型ラヌーラと診断され、複数回の開窓術を受けたが再発を繰り返していた。今回、セカンドオピニオン目的に紹介元歯科医院を受診したところラヌーラ再発が疑われたため、精査加療目的に当科紹介受診となった。液体貯留が左側頸部から鎖骨上窩と上縦隔まで広範囲に進展しており、同部のドレナージの必要性について当院耳鼻咽喉科・頭頸部外科へ対診を行った。その結果、明らかな感染兆候を認めないため、口腔外からのドレナージは必要ないとの判断に至った。よって、全身麻酔下での舌下腺摘出術を施行し、経過観察を行う方針とした。術後3ヵ月、術後9ヵ月時点でのMRI所見では、左側頸部から鎖骨上窩と上縦隔にみられた唾液貯留は消失しており、再発は認められなかった。

Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) modulates various cell functions through IGF-dependent or independent mechanisms. However, its biological roles in the radiosensitivity of oral squamous cell carcinoma (OSCC) remain largely unknown. The purpose of this study was to determine the clinical significance and molecular mechanisms of the association between IGFBP-3 and OSCC radiosensitivity. We performed an immunohistochemical analysis of IGFBP-3 in 52 OSCC specimens from patients treated with preoperative chemoradiotherapy and surgery (phase II study). Associations between IGFBP-3 expression and clinicopathological features were also evaluated. In addition, we examined the effects of IGFBP-3 on post-X-ray irradiation radiosensitivity and DNA damage in vitro. High IGFBP-3 expression was significantly correlated with poor chemoradiotherapy responses and prognosis. With IGFBP-3 knockdown, irradiated OSCC cells exhibited significantly higher radiosensitivity compared with that of control cells. Moreover, IGFBP-3 depletion in OSCC cells reduced phosphorylation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which is required for DNA double-strand break repair during non-homologous end joining. These findings indicate that IGFBP-3 may have a significant role in regulating DNA repair and is be a potential biomarker for predicting clinical response to radiotherapy and prognosis in OSCC.

Salivary microbiota is considered a source of microorganisms for the respiratory and digestive tracts, and a trigger for diseases in these distant organs. Meanwhile, the microbiota on the tongue surface is thought to be a major source of salivary microbiota. Therefore, surgical resection of the tongue for definitive treatment of oral cancer could drastically change the salivary bacterial balance and virulence. Here, we investigated the shift of the salivary microbiota following surgical resection in patients with tongue cancer. The stimulated saliva samples were collected from 25 tongue cancer patients pre- and post-resection of the tongue, and bacterial density and composition was determined using quantitative PCR analysis and 16S ribosomal RNA (rRNA) gene sequencing, respectively. Although no significant difference in the total bacterial density in saliva pre- and post-surgery was observed, the bacterial composition significantly differed according to the analysis of similarity. Among predominant operational taxonomic units (OTUs) with ≥1% of relative abundance, the proportions of OTUs corresponding to Streptococcus salivarius, Prevotellamelaninogenica, and Prevotellahisticola were significantly decreased following the tongue resection. On the other hand, the proportions of OTUs corresponding to Lautropiamirabilis, Neisseriaflava, Streptococcussanguinis, and Fusobacterium nucleatum, known to be inhabitants of dental plaque, were significantly increased. These results suggest that surgical resection of the tongue causes a compositional shift of the salivary microbiota, characterized by an increase in bacterial species derived from dental plaque, including periodontal pathogens. These results suggest the necessity of more careful and frequent postoperative oral care after surgical resection of tongue cancer.

It has been reported that 20% of early-stage oral squamous cell carcinoma (OSCC) patients treated with surgery alone (SA) may exhibit postoperative relapse within 2-3 years and have poor prognoses. We aimed to determine the safety of S-1 adjuvant chemotherapy and the potential differences in the disease-free survival (DFS) between patients with T2N0 (stage II) OSCC treated with S-1 adjuvant therapy (S-1) and those treated with SA. This single-center retrospective cohort study was conducted at Kumamoto University, between April 2004 and March 2012, and included 95 patients with stage II OSCC. The overall cohort (OC), and propensity score-matched cohort (PSMC) were analyzed. In the OC, 71 and 24 patients received SA and S-1, respectively. The time to relapse (TTR), DFS, and overall survival were better in the S-1 group, but the difference was not significant. In the PSMC, 20 patients each received SA and S-1. The TTR was significantly lower in the S-1 group than in the SA group, while the DFS was significantly improved in the former. S-1 adjuvant chemotherapy may be more effective than SA in early-stage OSCC.

RATIONALE AND OBJECTIVE: To evaluate the inter-rater reliability of the magnetic resonance imaging (MRI)-derived depth of invasion (DOI) and the agreement between MRI and pathological measurements of oral tongue cancer. MATERIALS AND METHODS: The institutional review board approved this retrospective study. The study population consisted of 29 patients with clinical T2N0 oral tongue cancer treated by surgery. Routine pretreatment MRI was performed on a 3T superconducting imager. Two raters with 23 and 18 years of head-and-neck MRI experience, respectively, independently chosen MRI sequences for each patient, then delineate the tumor, and then used three protocols to measure the MRI-derived DOI: the axial reconstructed thickness (method 1), the axial invasive portion (method 2), and the coronal invasive portion (method 3). Then they consensually selected the optimal among the three methods for each patient; it was designated method 4. The Bland-Altman plots, intraclass correlation coefficients (ICCs), and the paired samples test were used. According to the median follow-up of 41 months, the relationship between the MRI-derived DOI and nodal recurrence was also investigated. RESULTS: The inter-rater reliability of methods 2 and 4 was excellent (ICC of 0.829 and 0.807, respectively). The correlation between MRI and pathological measurements was good for method 4 (ICC of 0.611), however, all measurements recorded on MRI were 2-3 mm larger than on pathology. No patients whose MRI-derived DOI was less than 5 mm suffered nodal recurrence. CONCLUSION: The MRI-derived DOI was valuable for the preoperative staging. The optimal measurement method should be selected on a case-by-case basis.

The highly malignant phenotype of oral squamous cell carcinoma (OSCC), including the presence of nodal and distant metastasis, reduces patient survival. High-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor that is involved in advanced malignant phenotypes and poor prognosis in several human cancers. However, its biological role in OSCC remains to be elucidated. The purpose of this study was to determine the clinical significance and role of HMGA2 in the malignant potential of OSCC. We first investigated the expression pattern of HMGA2 and its clinical relevance in 110 OSCC specimens using immunohistochemical staining. In addition, we examined the effects HMGA2 on the regulation of vascular endothelial growth factor (VEGF)-A, VEGF-C, and fibroblast growth factor (FGF)-2, which are related to angiogenesis, in vitro. High expression of HMGA2 was significantly correlated with distant metastasis and poor prognosis. Further, HMGA2 depletion in OSCC cells reduced the expression of angiogenesis genes. In OSCC tissues with high HMGA2 expression, angiogenesis genes were increased and a high proportion of blood vessels was observed. These findings suggest that HMGA2 plays a significant role in the regulation of angiogenesis and might be a potential biomarker to predict distant metastasis and prognosis in OSCC.

MicroRNAs are a class of small, endogenous, noncoding 18- to 24-nucleotide-long RNAs that can regulate multiple processes related to cancer progression. However, their clinical value in patients with oral squamous cell carcinoma has not yet been fully explored. Therefore, the aim of this study was to investigate the clinical significance of circulating microRNAs in oral squamous cell carcinoma patients. The expression levels of circulating miR-1246 and miR-1290 in healthy volunteers and oral squamous cell carcinoma patients were examined by quantitative real-time polymerase chain reaction. The expression levels of both microRNAs in the radioresistant oral squamous cell carcinoma cell line (SAS-R) and the parent cell line (SAS) and in the conditioned medium obtained from these cell lines were also examined by quantitative real-time polymerase chain reaction. In addition, the correlations between circulating microRNA status and various clinicopathological features in 55 oral squamous cell carcinoma patients with locally advanced oral squamous cell carcinoma who underwent surgery following 5-fluorouracil-based chemoradiotherapy were examined. The expression level of miR-1290 was significantly lower in the plasma of oral squamous cell carcinoma patients than in that of healthy volunteers (p < 0.01). The expression levels of microRNAs in the conditioned medium and in the cells varied from cell to cell. In the clinicopathological analyses, the frequency of patients with low miR-1290 levels was significantly higher among cases with lower pathological differentiation and among those with a poor pathological response for preoperative chemoradiotherapy (p = 0.030 each). Furthermore, Cox regression analysis based on the 5-year overall survival and disease-free survival revealed that miR-1290 status was a significant prognostic factor for patients with oral squamous cell carcinoma (hazard ratio = 0.169, p = 0.008, and hazard ratio = 0.186, p = 0.008, respectively). Circulating miR-1290 status could be a valuable biomarker for predicting the clinical response to chemoradiotherapy as well as overall survival in patients with oral squamous cell carcinoma.

Occult neck metastasis is an important prognostic factor in patients with tongue squamous cell carcinoma (TSCC) who are deemed clinically negative for neck metastasis. The purpose of this study was to identify predictive factors for occult neck metastasis arising from TSCC and to determine patient prognosis. Ninety-seven patients with cT2N0 TSCC who underwent surgical resection of their primary lesion as initial therapy were enrolled in this retrospective study. Cutoff values for depth of invasion (≥3.3 mm) and the tumor budding score (≥4) were determined using receiver operator characteristic analyses. Univariate and multivariate analyses revealed that a tumor budding score ≥4 is a significant independent predictive factor for the occurrence of occult neck metastasis, which in turn is a significant independent prognostic factor. When evaluating tumor budding, we demonstrated greater interobserver and intraobserver agreement when using immunohistochemical staining for cytokeratin AE1/AE3 than with hematoxylin and eosin staining (HE). We conclude that the evaluation of tumor budding is effective for identifying populations at high risk of occult neck metastasis, which will enable the planning of appropriate therapeutic strategies for patients with cT2N0 TSCC. Furthermore, cytokeratin staining is recommended over HE staining for simpler and more accurate evaluation of tumor budding.

A 70-year-old Japanese man with recurrent squamous cell carcinoma of the head and neck presented with severe interstitial pneumonia associated with nivolumab, after talc slurry pleurodesis. Following the development of malignant pleural effusion, he underwent chest drainage and was administered intrathoracic talc as a pleurodesis. Two weeks later, we administered nivolumab (3mg/kg) to be repeated every 2 weeks. However, on day 12, chest computed tomography scan demonstrated diffuse non-segmental ground-glass opacity and mild bronchiectasis. We diagnosed interstitial pneumonia associated with nivolumab. Although corticosteroid pulse therapy was initiated, the patient died of respiratory failure on day 14.

FBXW7 (F-box and WD repeat domain containing-7) is a tumor suppressor protein that regulates the degradation of various oncoproteins in several malignancies. However, limited information is available regarding FBXW7 expression in oral squamous cell carcinoma. Therefore, this study aimed to determine the clinical significance of FBXW7 expression in oral squamous cell carcinoma. The FBXW7 expression patterns in oral squamous cell carcinoma and adjacent normal tissues from 15 patients who underwent radical resection were evaluated using quantitative real-time polymerase chain reaction and immunohistochemical staining. In addition, immunohistochemistry was performed using paraffin-embedded sections from biopsy specimens obtained from 110 patients with oral squamous cell carcinoma who underwent surgery after 5 fluorouracil-based chemoradiotherapy. The associations of FBXW7 expression with various clinicopathological features and prognosis were evaluated in these patients. As a results, in the 15 matched samples, the FBXW7 expression was significantly decreased in the oral squamous cell carcinoma tissues compared to that in the adjacent normal tissues. In the clinicopathological analysis, compared to high protein expression, low FBXW7 expression was found to significantly associate with a poor histological response to preoperative chemoradiotherapy. Kaplan-Meier curve analysis revealed that low FBXW7 expression was significantly associated with a poor prognosis, and FBXW7 expression was found to be an independent predictor of overall survival in the multivariate analysis. Our results suggest that FBXW7 may function as a tumor suppressor protein in oral squamous cell carcinoma. In addition, FBXW7 could be a potential biomarker for predicting not only the clinical response to chemoradiotherapy but also overall survival in patients with oral squamous cell carcinoma.

Salivary duct carcinoma is a highly aggressive disease with a poor prognosis. Surgical resection is currently the only curative treatment, as there is no effective systemic therapy for this malignancy. Recently, trastuzumab has been shown to exhibit therapeutic efficacy in the treatment of salivary duct carcinoma; similarly, molecularly targeted agents, such as cetuximab, are expected to be useful for salivary duct carcinoma treatment. We herein describe the case of a 56-year-old man diagnosed with salivary duct carcinoma in the left submandibular region, with ipsilateral multiple metastases to the neck lymph nodes. Radical resection of the tumor and submandibular gland with neck dissection were performed. One month after radical surgery, computed tomography (CT) scans indicated metastasis in the lower lobe of the left lung. CT-guided transthoracic fine-needle aspiration biopsy revealed a single metastasis and lung metastasectomy was immediately performed. The tumor cells of the primary lesion and those of the lung metastasis were immunohistochemically positive for epidermal growth factor receptor. One month later, multiple right lung metastases appeared, and the patient was treated with cisplatin/5-fluorouracil (5-FU) chemotherapy plus cetuximab, achieving a complete radiographic response. However, multiple lung metastases developed during adjuvant weekly cetuximab monotherapy. Subsequently, treatment with S-1 and weekly cetuximab was initiated, and the multiple lung metastases have been maintained as stable disease for 5 months. To the best of our knowledge, this is the first report of cetuximab use for the treatment of salivary duct carcinoma. Although cisplatin/5-FU chemotherapy plus cetuximab was efficacious in treating the lung metastasis, cetuximab monotherapy was insufficient for controlling tumor growth.