ABSTRACT
BACKGROUND: T2N0 glottic squamous cell carcinoma (SCC) typically responds well to radiotherapy (RT); however, achieving local control remains challenging. In cases of RT failure, total laryngectomy may be necessary. Improved local control and preservation of the larynx directly enhances patients' quality of life. Our retrospective analysis using the Japan Head and Neck Cancer Registry (JHNCR) aimed to compare the clinical benefits of RT and chemoradiotherapy (CRT) in patients with T2N0 glottic SCC. METHODS: Using data from the JHNCR (2011-2015), we included 1,231 patients with T2N0 glottic SCC. Among them, 346 received curative RT and 425 underwent curative CRT. The CRT group was further divided into the oral CRT (Oral CRT, N=120) and intravenous CRT (DIV CRT, N=305) groups. This study assessed local control rate (LCR), progression-free survival (PFS), and overall survival (OS). A 1:1 propensity score-matching analysis was used to adjust for patient characteristics. RESULTS: After matching, 105 pairs compared RT with Oral CRT, and 224 pairs compared RT with DIV CRT. The variables were well-balanced in the matched populations. In the matched populations, the Oral CRT group had significantly better 5-year LCR and PFS than the RT group (LCR, 89.4 % vs. 80.6 %, P=0.043; and PFS, 85.5 % vs. 72.3 %, P=0.025, respectively), while the DIV RT group had significantly better 5-year PFS than the RT group (80.1 % vs. 68.6 %, P=0.026). CONCLUSIONS: The clinical benefits of better local and disease controls were observed when oral chemotherapy was added to RT in patients with T2N0 glottic SCC. Thus, the significance of adding oral chemotherapeutic agents to RT in the treatment of T2N0 glottic SCC requires further prospective investigation.
Subject(s)
Chemoradiotherapy , Glottis , Laryngeal Neoplasms , Registries , Humans , Male , Female , Japan , Aged , Middle Aged , Chemoradiotherapy/methods , Laryngeal Neoplasms/therapy , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/mortality , Glottis/pathology , Retrospective Studies , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/drug therapy , Administration, Oral , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/mortality , Adult , Aged, 80 and overABSTRACT
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.