ABSTRACT
Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy based on a monoclonal antibody (mAb) conjugated to a photosensitizer (IR700Dye). The conjugate can be activated by near-infrared light irradiation, causing necrotic cell death with high selectivity. In this study, we investigated NIR-PIT using a small protein mimetic (6-7 kDa, Affibody) which has more rapid clearance and better tissue penetration than mAbs for epidermal growth factor receptor (EGFR)-positive salivary gland cancer (SGC). The level of EGFR expression was examined in vitro using immunocytochemistry and Western blotting. Cell viability was analyzed using the alamarBlue assay. In vivo, the volume of EGFR-positive tumors treated with NIR-PIT using the EGFR Affibody-IR700Dye conjugate was followed for 43 days. It was found that NIR-PIT using the EGFR Affibody-IR700Dye conjugate induced the selective destruction of EGFR-positive SGC cells and restricted the progression of EGFR-positive tumors. We expect that NIR-PIT using the EGFR Affibody-IR700Dye conjugate can efficiently treat EGFR-positive SGC and preserve normal salivary function.
Subject(s)
Phototherapy , Salivary Gland Neoplasms , Humans , Cell Line, Tumor , Immunotherapy , Photosensitizing Agents/pharmacology , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , ErbB Receptors , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: Major salivary gland cancers (MSGCs) are often treated with primary surgery followed by adjuvant therapy for high-risk pathology. Patients with these cancers may opt out of recommended postoperative radiation therapy (PORT) for many reasons and consequently may suffer worse outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database. METHODS: Patients diagnosed with MSGC from 2004 to 2016 were identified, and overall survival and risk factors for refusal of recommended PORT were analyzed based on demographic, socioeconomic, and clinical factors. Multivariable logistic regression and a Cox model were used to conduct the analysis. RESULTS: 211 out of 4704 qualifying patients (4.5%) refused recommended PORT. Multivariable analysis demonstrated increased PORT refusal for age >74 years (odds ratio OR 4.34, confidence interval [CI] [2.43-7.85]), Asian race (OR 2.25, CI [1.10-4.23]), and certain facility types (comprehensive cancer center, OR 2.39, CI [1.08-6.34]; academic research program, OR 3.29, CI [1.49-8.74]; and integrated network cancer program, OR 2.75, CI [1.14-7.7]). N2 stage was associated with decreased PORT refusal (OR 0.67, CI [0.45-0.98]). The 5-year overall survival for patients who received and refused PORT were significantly different at 65.8% and 53.8%, respectively (p < .001). When controlling for several factors, PORT refusal was independently associated with significantly lower overall survival (HR 1.54, CI [1.21-1.98]). CONCLUSION: Patient refusal of recommended PORT in MSGC is rare, associated with various disease and socioeconomic factors, and may decrease overall survival. Our findings can assist clinicians in counseling patients and identifying those who may be more likely to opt out of recommended PORT.
Subject(s)
Salivary Gland Neoplasms , Humans , Aged , Retrospective Studies , Socioeconomic Factors , Proportional Hazards Models , Salivary Gland Neoplasms/radiotherapy , Salivary Gland Neoplasms/surgery , Combined Modality TherapyABSTRACT
BACKGROUND: In recent years the number of studies on special tumor entities in the head and neck region has increased. During the 2021 meetings of the American Society of Clinical Oncology (ASMO) and the European Society for Medical Oncology (ESMO), several studies were presented which predict changes in clinical treatment algorithms for nasopharyngeal carcinoma, salivary gland, and thyroid cancer. OBJECTIVE: Future treatment alterations in specific head and neck tumor entities were evaluated after screening clinical studies presented at the 2021 ASCO and ESMO meetings. MATERIALS AND METHODS: A systematic analysis of the phase II and III clinical trials for nasopharyngeal carcinoma, salivary gland, and thyroid cancer treatment presented at ASCO and ESMO 2021 was performed. Taking into account current treatment standards, the results are structured in terms of their potential clinical significance. RESULTS AND CONCLUSION: In curative treatment of advanced nasopharyngeal carcinoma, adjuvant therapy with capecitabine after primary chemoradiation should be discussed as a new standard. In the palliative treatment of nasopharyngeal carcinoma, an increasing role of immunotherapy can be predicted. Recurrent or metastatic salivary gland cancer can often be treated very effectively with targeted substances if molecular target lesions are present. Immunotherapies currently play a subordinate role; they only seem to be effective in a few patients with salivary gland cancer, who cannot currently be reliably identified using predictive markers. Patients with radioiodine-refractory differentiated thyroid cancer benefit from treatment with the multi-tyrosine kinase inhibitor cabozantinib after failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) therapy.
Subject(s)
Nasopharyngeal Neoplasms , Thyroid Neoplasms , Humans , Iodine Radioisotopes/therapeutic use , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/therapy , Salivary Glands/pathology , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/therapy , Vascular Endothelial Growth Factor A/therapeutic useABSTRACT
BACKGROUND: Various chemotherapeutic agents have been used largely for the treatment of salivary gland cancer. However, results are disappointing, and these agents can cause some serious side effects. Therefore, recent studies have focused on the possible roles of natural products to overcome these limitations. METHODS: Salivary gland cancer cells treated with or without Convallaria keiskei (MECK) for 24 hours. Apoptotic changes were evaluated by live/dead assay, immunoblotting, and expression levels of caspase-3 and B-cell lymphoma-2 family member. RESULTS: MECK significantly inhibited salivary gland cancer growth. At the molecular level, MECK dramatically reduced myeloid cell leukemia-1 (Mcl-1) in a translation-dependent manner and thereby induced apoptosis through Bax/Bid. Furthermore, we found that Mcl-1 could be a potential therapeutic target of MECK-induced apoptosis and its stability is regulated by extracellular signal-regulated kinases 1/2 (ERK1/2) signaling CONCLUSION: MECK can be used as a safe and efficient therapeutic alternative for the treatment of salivary gland cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E761-E770, 2016.