ABSTRACT
BACKGROUND: Genome analysis could provide tools to assess predictive molecular biomarkers of radioresistance. METHODS: Head and neck squamous cell carcinoma patients included in ProfiLER study and who underwent a curative radiotherapy were screened. Univariate and Cox multivariate analyses were performed to explore the relationships between molecular abnormalities, infield relapse and complete tumor response after radiation. RESULTS: One hundred and forty-three patients were analyzed. PIK3CA mutation and genomic instability of MAP kinases pathway were found to be prognostic factors of loco-regional relapse in multivariate analysis with respectively HR 0.33, 95% CI 0.13-0.83, p = 0.005 and HR 0.61, 95% CI 0.38-0.96, p = 0.025. Instability of apoptosis pathway was found to be a prognostic factor of complete response after radiotherapy with HR 0.24, 95% CI 0.07-0.88, p = 0.04. CONCLUSION: This sub analysis suggests that PIK3CA mutation, variation of copy number of MAP kinases and apoptosis pathways play a significant role in the radioresistance phenomenon.
Subject(s)
Carcinoma, Squamous Cell , Class I Phosphatidylinositol 3-Kinases/genetics , Head and Neck Neoplasms , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/radiotherapy , Genomics , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/radiotherapy , Humans , Neoplasm Recurrence, Local/genetics , Prognosis , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/radiotherapySubject(s)
Adenocarcinoma of Lung/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/therapy , Lung Neoplasms/therapy , Mutation , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Acrylamides/administration & dosage , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adult , Aged , Aniline Compounds/administration & dosage , Brain Neoplasms/genetics , Brain Neoplasms/secondary , Crizotinib/administration & dosage , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , PrognosisABSTRACT
Primary malignant melanoma of the esophagus is rare, accounting for less than 0.1-0.2% of all esophageal malignancies. It is associated with a poor outcome due to late detection and high metastatic potential. Here, we report a case of esophageal cancer, which was initially diagnosed as an adenocarcinoma and finally was confirmed as a primary malignant melanoma. This 75-year-old Caucasian male had a history of dysphagia and recent lingering abdominal pain. First biopsy showed a poorly-differentiated adenocarcinoma. He was then treated with neoadjuvant radiochemotherapy. Biopsies were repeated because of an incomplete tumor response, evaluated by endoscopic and imaging studies. The final diagnosis was a malignant melanoma. The patient has been treated with immune-checkpoint inhibitor, nivolumab, an anti-PD1 antibody.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Esophageal Neoplasms/drug therapy , Melanoma/drug therapy , Nivolumab/therapeutic use , Aged , Esophageal Neoplasms/pathology , Humans , Immunotherapy/methods , Male , Melanoma/pathologyABSTRACT
Disseminated melanoma is an incurable disease whose prognosis has remained unchanged over the past 20 years. To date, no consensus treatment has emerged. No treatment strategy has proved superior to dacarbazine (Deticene) monochemotherapy that remains considered as the reference treatment for this disease. Both multidrug chemotherapy and biochemotherapy have provided disappointing results, with poorer quality of life and no survival benefit for the patients. Other treatment approaches, particularly immunotherapy, remain to be investigated in clinical trials.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Dacarbazine/therapeutic use , Lymph Nodes/pathology , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Humans , Lymphatic Metastasis , Melanoma/pathology , Prognosis , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Early clinical trials, mostly in the setting of melanoma, have shown that dendritic cells (DCs) expressing tumor antigens induce some immune responses and some clinical responses. A major difficulty is the extension to other tumors, such as breast carcinoma, for which few defined tumor-associated antigens are available. We have demonstrated, using both prostate carcinoma and melanoma as model systems, that DCs loaded with killed allogeneic tumor cell lines can induce CD8+ T cells to differentiate into cytotoxic T lymphocytes (CTLs) specific for shared tumor antigens. METHODS: The present study was designed to determine whether DCs would capture killed breast cancer cells and present their antigens to autologous CD4+ and CD8+ T cells. RESULTS: We show that killed breast cancer cells are captured by immature DCs that, after induced maturation, can efficiently present MHC class I and class II peptides to CD8+ and CD4+ T lymphocytes. The elicited CTLs are able to kill the target cells without a need for pretreatment with interferon gamma. CTLs can be obtained by culturing the DCs loaded with killed breast cancer cells with unseparated peripheral blood lymphocytes, indicating that the DCs can overcome any potential inhibitory effects of breast cancer cells. CONCLUSION: Loading DCs with killed breast cancer cells may be considered a novel approach to breast cancer immunotherapy and to identification of shared breast cancer antigens.