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Background: We previously established a patient‐derived xenograft (PDX) model, patient‐derived organoids (PDOs), and PDX‐derived organoids (PDXOs) for salivary duct carcinoma (SDC). Using these models, this study examined the therapeutic effect of human epidermal growth factor receptor 2 (HER2) blockade on HER2‐positive SDC. Methods: The therapeutic effect of lapatinib was assessed in SDC PDXOs with regards to cell growth, receptor/downstream signaling molecule expression, phosphorylation levels, and apoptosis. Effect of lapatinib treatment was evaluated in vivo in SDC PDX mice. Results: The siRNA knockdown of HER2 and lapatinib suppressed cell proliferation in SDC PDXOs. Lapatinib inhibited the phosphorylation of HER2 and its downstream targets, and induced apoptosis in SDC PDXOs. Lapatinib also significantly reduced tumor volumes compared with that of the control in SDC PDX mice. Conclusion: For the first time, we demonstrated the efficacy of anti‐HER2 therapy in HER2‐positive SDC using preclinical models of SDC PDX and PDXO. [ABSTRACT FROM AUTHOR]

To generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) whose biology is still unclear due to the paucity of stable cell cultures. To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient‐derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. Tumor specimens from surgically resected salivary ACC were proceeded for the preparation of PDX and organoid culture. The orthotopic transplantation of patient‐derived or PDX‐derived organoids was demonstrated into submandibular glands of NSG mice and those histology was evaluated. PDX‐derived organoid cells were evaluated for the presence of MYB‐mediated fusion genes and proceeded for in vitro drug sensitivity assay. Human ACC‐derived organoids were successfully generated in three‐dimensional culture and confirmed the ability of these cells to form tumors by orthotopic injection. Short‐term organoid cell cultures from two individual ACC PDX tumors were also established that maintain the characteristic MYBL1 translocation and histological features of the original parent and PDX tumors. Finally, the establishment of drug sensitivity tests on these short‐term cultured cells was confirmed using three different agents. This is the first to report an approach for the generation of human ACC‐derived organoids as in vitro and in vivo cancer models, providing insights into understanding of the ACC biology and creating personalized therapy design for patients with ACC. What's new? The biological underpinnings of salivary adenoid cystic carcinoma (ACC) remain largely unknown, owing to a lack of preclinical model systems. In this study, the authors describe the successful generation of human salivary ACC cell lines from organoid culture and the subsequent development of an in vivo salivary ACC mouse model. The orthotopic xenograft mouse model was established efficiently from ACC organoid cells from patient‐derived xenografts (PDX). Short‐term cultures of PDX‐derived ACC organoid cells further were amenable for in vitro drug‐sensitive studies with several agents. This novel approach could be useful for investigating personalized therapies for patients with salivary ACC. [ABSTRACT FROM AUTHOR]

Background: Transoral surgery (TOS) has been widely applied for early T‐stage head and neck cancer (HNC). The resection is performed with a minimum safety margin for function preservation under a limited surgical field; therefore, it is difficult to have a strong conviction about the complete resection. This study aims to evaluate the completeness of the initial TOS procedure; possibility of primary control by TOS alone; and predictive factors in patients with early T‐stage laryngeal, oropharyngeal, and hypopharyngeal cancer. Methods: Patients were treated by TOS at the primary site with or without neck dissection. The patients were divided into two groups based on the pathological evaluation of their surgical specimens: the control (observation) group, in that the resection was considered complete and the intervention (second‐look procedure) group, in that incomplete tumor resection was suspected. The predictive factors for the possibility and/or limitations of complete resection by TOS were then analyzed. Results: The study enrolled 26 and 25 patients in the control and intervention group, respectively. The success rate for single resection was 66% and the predictive factor was tumor depth obtained by enhanced computed tomography (CT) examination (odds ratio, 7.870, P = .0243). The success rate for definitive therapy by TOS alone was 83% and the predictive factor was poor differentiation observed on pathological examination (odds ratio, 6.800, P = .0248). Conclusions: TOS has the potential for both definitive resection and function preservation with minimal invasiveness. Identification of the risk factors for TOS is advantageous for accurate treatment selection in patients with early T‐stage HNC. [ABSTRACT FROM AUTHOR]

Objective/hypothesis: We previously reported that the metabolic tumor volume (MTV) of a primary tumor was an independent prognostic factor for survival in laryngeal carcinoma treated by radiotherapy (RT)-based protocol. The purpose of this study was to evaluate the difference in survival outcomes between surgery-based and RT-based treatment in patients with a MTV laryngeal cancer.Study Design: An individual retrospective cohort study.Methods: We reviewed the records of 63 patients with laryngeal cancer showing a primary tumor with a high MTV value (≥ 4.9 mL). The patients were separated into two groups by primary treatment strategy: 22 patients were included in the surgery group, and 41 patients were included in the RT group. Clinical factors and treatment modalities were analyzed for their association with survival.Results: Multivariate analysis, including age, sex, subsite, T classification, nodal metastasis, and treatment modality, showed that the subsite (hazard ratio [HR] 2.55, P = 0.043) and treatment modality (HR 3.98, P = 0.019) were independent predictors for survival. The Kaplan-Meier curves for 2-year relapse-free survival rates and overall survival rates for patients in the surgery and RT groups were 74.2% versus 38.8% (P = 0.025) and 80.1% versus 66.7% (P = 0.078).Conclusions: Patients with a high metabolic volume laryngeal cancer treated by a surgery-based protocol showed better relapse-free survival and overall survival than did those undergoing RT-based treatment. Pretreatment MTV assessment could be useful in planning the treatment strategy for patients with a laryngeal cancer.Level Of Evidence: 2b. Laryngoscope, 127:862-867, 2017. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to elucidate the prognostic significance of the pretreatment metabolic tumor volume (MTV) in patients with piriform sinus carcinoma treated by radiation-based therapy. Methods This retrospective study included 100 patients with piriform sinus carcinomas who had received treatment by radiation-based therapy. The MTV values were obtained from pretreatment positron emission tomography (PET). The association between clinical factors, including the MTV, and survival was analyzed. Results Kaplan-Meier estimates revealed the 5-year disease-free survival (DFS) rates were significantly poorer for patients with a high MTV compared to those with a low MTV. In the multivariate analysis, MTV ( p < .001), nodal metastasis ( p = .011), and applied chemotherapy regimen ( p = .004) were found to be independent prognostic factors for DFS. Conclusion The locoregional MTV is a prognostic factor for DFS in patients with piriform sinus carcinoma treated by radiation-based therapy. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016 [ABSTRACT FROM AUTHOR]

Background Radioresistance remains a critical issue in the use of radiotherapy for the treatment of head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy of combination treatment with OBP-301, a telomerase-specific replication-selective adenovirus, and radiotherapy in overcoming radioresistance by examining its effect on radiation-resistant HNSCC cells. Methods Radiation-resistant HNSCC cells were treated with OBP-301 and radiation in vitro and in an orthotopic nude mouse model in vivo and synergism was assessed. Apoptosis and expression of MRN complex, which plays a key role in DNA repair machinery, were also analyzed. Results Infection with OBP-301 was found to enhance the antitumor efficacy of radiation both in vitro and in vivo by inhibiting MRN complex expression and increasing apoptosis induction. Conclusion Combined OBP-301 and radiation therapy seems to overcome radioresistance in HNSCC cells by inhibiting DNA repair machinery, and may thus be a novel therapeutic strategy for treating HNSCC. © 2013 Wiley Periodicals, Inc. Head Neck 36: 411-418, 2014 [ABSTRACT FROM AUTHOR]

Cetuximab is a chimeric IgG1 monoclonal antibody that targets epidermal growth factor receptor (EGFR). Cetuximab binds to EGFR and prevents phosphorylation of EGFR. Moreover, preclinical results have shown the ability of cetuximab to induce either complement-mediated tumor cell killing (CDC) or antibody-dependent cell-mediated-cytotoxicity (ADCC). We previously reported mutation in EGFR regarding head and neck squamous cell carcinoma (HNSCC) cell lines. In the present study, we analyzed the same 16 HNSCC cell lines for mutations in KRAS, PIK3CA, BRAF and PTEN. Furthermore, we evaluated cetuximab-mediated biological activities (antiproliferative effect by the MTT assay and ADCC) regarding these cell lines. Mutations in PIK3CA and PTEN were observed in two cell lines (2/16, 12.5%), but no mutation was observed in KRAS and BRAF. The antiproliferative effect of cetuximab by the MTT assay was not strong, and no correlation was observed between the antiproliferative effect of cetuximab and mutations in EGFR, KRAS, PIK3CA, BRAF and PTEN in these cell lines. Therefore, the mutation status of EGFR and downstream molecules were not useful for predicting the antitumor effects of cetuximab on HNSCC. Cetuximab-mediated ADCC was observed in these cell lines and might have been influenced by the expression of EGFR. Therefore, cetuximab-mediated ADCC seems to be an important part of the antitumor mechanisms of cetuximab and the expression levels of EGFR might influence the antitumor activity of cetuximab. Therefore, besides the antiproliferative effect of cetuximab by the MTT assay, it appeared important to evaluate cetuximab-mediated ADCC as well as EGFR expression in HNSCC cells. ( Cancer Sci 2011; 102: 1717-1723) [ABSTRACT FROM AUTHOR]