RESUMEN
PURPOSE: This study aimed to analyze the treatment outcomes of single-fraction stereotactic radiosurgery (SRS) for adenoid cystic carcinoma patients. METHODS: Retrospective analysis was conducted for 55 patients with 66 lesions. SRS intentions were categorized as definitive, adjuvant, salvage, and palliative. Tumor control was defined as local (within 50% isodose line), marginal (outside 50% isodose line), and distant (metastasis outside head/neck). RESULTS: The median age was 60 years (range 21-85), with 53% males. Tumor origin was head/neck for 88% and trachea/lung for 12%. 61% were recurrent lesions. Median interval from diagnosis to SRS was 14 months. Preceding surgery was performed in 30%. SRS was administered as definitive (30 lesions), adjuvant (13), salvage (19), and palliative (4). SRS was used as a boost to external beam radiation therapy (EBRT) in 39%. Concurrent chemotherapy was administered in 26%. 5-, 10-, and 15-year local control rates were 60%, 33%, and 27%, respectively; local/marginal control rates were 29%, 13%, and 10%. For recurrent lesions treated with SRS without EBRT, 5-year local control rate was 14%, and local/marginal control rate was 5%. For recurrent lesions treated with SRS and EBRT, 5-year local control rate was 100%, and local/marginal control rate was 40%. The rate of distant failure after SRS was 40%. Older age and distant metastasis before SRS were negative factors for overall survival. CONCLUSION: SRS provided a high rate of local tumor control, but marginal failure was frequent. Integrating SRS with added EBRT exhibits potential for enhancing local and local/marginal tumor control, particularly in recurrent cases.
Asunto(s)
Neoplasias Encefálicas , Carcinoma Adenoide Quístico , Radiocirugia , Masculino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Carcinoma Adenoide Quístico/radioterapia , Carcinoma Adenoide Quístico/cirugía , Estudios Retrospectivos , Neoplasias Encefálicas/cirugía , Resultado del Tratamiento , Recurrencia Local de Neoplasia/radioterapiaRESUMEN
OBJECTIVE: There are no effective systemic therapies for adenoid cystic cancer (ACC) and lack of tumor lines and mouse models have hindered drug development.We aim to develop MYB-activated models for testing new therapeutic agents. MATERIALS AND METHODS: We studied new ACC patient-derived xenograft (PDX) models and generated a matched cell line from one patient. In addition, we generated a genetically-engineered MYB-NFIB mouse model (GEMM) that was crossed with Ink4a+/-/Arf+/- mice to study tumor spectrum and obtain tumor lines. Using human and murine ACC-like tumor lines, we analyzed MYB expression by RNA-Seq and immunoblot and tested efficacy of new MYB inhibitors. RESULTS: We detected MYB-NFIB transcripts in both UFH1 and UFH2 PDX and observed tumor inhibition by MYB depletion using shRNA in vivo. We observed rapid loss of MYB expression when we cultured UFH1 in vitro, but were able to generate a UFH2 tumor cell line that retained MYB expression for 6â¯months. RNA-Seq expression detected an ACC-like mRNA signature in PDX samples and we confirmed an identical KMT2A/MLL variant in UFH2 PDX, matched cell line, and primary biopsy. Although the predominant phenotype of the MYB-NFIB GEMM was B-cell leukemia, we also generated a MYB-activated ACC-like mammary tumor cell line. We observed tumor inhibition using a novel MYB peptidomimetic in both human and murine tumor models. CONCLUSIONS: We generated and studied new murine and human MYB-activated tumor samples and detected growth inhibition with MYB peptidomimetics. These data provide tools to define treatment strategies for patients with advanced MYB-activated ACC.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma Adenoide Quístico/genética , Proteínas Proto-Oncogénicas c-myb/genética , Activación Transcripcional , Animales , Carcinoma Adenoide Quístico/tratamiento farmacológico , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Adenoide Quístico/patología , Línea Celular Tumoral , Supervivencia Celular/genética , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Ratones , Ratones Transgénicos , Proteómica/métodos , Proteínas Proto-Oncogénicas c-myb/metabolismo , Análisis de Secuencia de ARN , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
INTRODUCTION: Primary salivary gland-type tumors of the lung (PSGTTL) are rare intrathoracic malignant neoplasms. Their description in literature is largely limited to a few case series and case reports. A systematic review and pooled analysis of the previously reported cases of PSGTTL is presented here. METHODS: Electronic database of PubMed using keywords "lung neoplasm" AND "salivary gland tumors" was used to identify the papers documenting the PSGTTL. Filters (publication date from January 1, 1900--December 31, 2015, Humans and English) were applied to refine the search. A pooled analysis of clinical, pathological, treatment, and survival data was performed. RESULTS: The present systematic review included 5 studies and a total of 233 patients. Mean age of the patients was 41 years (range 6-80 years) and there was a male preponderance (1.3:1). Common pathological types were mucoepidermoid (MEC) (56.6%), adenoid cystic (ACC) (39.5%), and epithelial-myoepithelial cancer (3.8%). Tumors were located in the central airways (trachea and major bronchi) in 43.3% of patients. Weighted median tumor size was 4.2 cm. Surgery was the primary treatment undertaken in 82.4% of the patients, while radiotherapy and chemotherapy were also used in 15.9% and 9.4% of the patients. Lymph node involvement was seen in 15.2% of the patients. Disease recurrences were observed in 21.1% of the patients (12.9% and 37.5% in MEC and ACC, respectively). Three-, 5-, and 10-year weighted overall survival was 86.4%, 81.4%, and 73.6% (93.8%, 90.0%, and 85.0%, respectively, for MEC and 76.7%, 62.8%, and 50.5%, respectively, for ACC). CONCLUSION: Surgery is the primary treatment of PSGTTL to achieve long-term survival. Role of chemotherapy and radiotherapy in the management of PSGTTL warrants further studies.
RESUMEN
OBJECTIVE: To observe the influence of RNA interference targeting against survivin gene on the biological behaviors of human adenoid cystic cancer (ACC) cells and propose the action mechanism. METHOD: Specific siRNA (small interfering RNA) was constructed and transfected into ACC-2 cells using liposomes. The expressions of survivin and Caspase-3 in the transfected ACC-2 cells were detected by Western Blot and RT-PCR. Cell apoptosis was detected by transmission electron microscopy, TUNEL method and flow cytometry; ultrastructural changes and cell cycles were observed. RESULTS: Recombinant siRNA interference plasmid specifically targeting against survivin gene was constructed successfully. Survivin protein expression in the transfected ACC-2 cells was downregulated significantly, while Caspase-3 protein and mRNA expressions were upregulated and cell proliferation was inhibited considerably. CONCLUSION: Recombinant siRNA interference plasmid inhibited survivin mRNA and protein expressions at high efficiency, thereby inhibiting the proliferation of ACC cells.
RESUMEN
BACKGROUND: Due to the rarity of adenoid cystic carcinoma (ACC), information on outcome is based upon small retrospective case series. The aim of our study was to create a large multiinstitutional international dataset of patients with ACC in order to design predictive nomograms for outcome. METHODS: ACC patients managed at 10 international centers were identified. Patient, tumor, and treatment characteristics were recorded and an international collaborative dataset created. Multivariable competing risk models were then built to predict the 10 year recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and cancer specific mortality (CSM). All predictors of interest were added in the starting full models before selection, including age, gender, tumor site, clinical T stage, perineural invasion, margin status, pathologic N-status, and M-status. Stepdown method was used in model selection to choose predictive variables. An external dataset of 99 patients from 2 other institutions was used to validate the nomograms. FINDINGS: Of 438 ACC patients, 27.2% (119/438) died from ACC and 38.8% (170/438) died of other causes. Median follow-up was 56 months (range 1-306). The nomogram for OS had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N-status and M-status) with a concordance index (CI) of 0.71. The nomogram for CSM had the same variables, except margin status, with a concordance index (CI) of 0.70. The nomogram for RFP had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N status and perineural invasion) (CI 0.66). The nomogram for DRFP had 6 variables (gender, clinical T stage, tumor site, pathologic N-status, perineural invasion and margin status) (CI 0.64). Concordance index for the external validation set were 0.76, 0.72, 0.67 and 0.70 respectively. INTERPRETATION: Using an international collaborative database we have created the first nomograms which estimate outcome in individual patients with ACC. These predictive nomograms will facilitate patient counseling in terms of prognosis and subsequent clinical follow-up. They will also identify high risk patients who may benefit from clinical trials on new targeted therapies for patients with ACC. FUNDING: None.
Asunto(s)
Carcinoma Adenoide Quístico/terapia , Técnicas de Apoyo para la Decisión , Recurrencia Local de Neoplasia , Nomogramas , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma Adenoide Quístico/mortalidad , Carcinoma Adenoide Quístico/patología , Conducta Cooperativa , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Estadificación de Neoplasias , Selección de Paciente , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Objective:To explore the effects of cysteine-rich 6 1 (Cyr6 1 )on biological behavior of human adenoid cystic carcinoma ACC-LM and ACC2 cells.Methods:The chemically synthesized Cyr6 1-siRNA was transfected into ACC-LM and ACC2 cells.Cell proliferation was measured by the MTT method,the invasive ability was evaluated by Transwell chamber assay,and cell apoptosis was analyzed using flow cytometry by double staining with Annexin V and propidium iodide.Results:Cyr61-siRNA significantly down-regu-lated Cyr61 protein expression in ACC-LMand ACC2 cells.Cyr61-siRNA markedly inhibited the proliferation and invasion of the cells, however,there was no significant difference in cell apoptosis between Cyr6 1-siRNA and control groups.Conclusion:Cyr6 1 promote the proliferation and invasion of adenoid cystic cancer cells.