Tumor-Infiltrating T Cell Receptor-Beta Repertoires are Linked to the Risk of Late Chemoradiation-Induced Temporal Lobe Necrosis in Locally Advanced Nasopharyngeal Carcinoma
| Autor: | Yih-Lin Chung, LiFu Wu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Neutrophils T-Lymphocytes medicine.medical_treatment T cell Lymphocyte Receptors Antigen B-Cell Antineoplastic Agents Systemic inflammation 030218 nuclear medicine & medical imaging Leukocyte Count Necrosis 03 medical and health sciences Temporal lobe necrosis Lymphocytes Tumor-Infiltrating 0302 clinical medicine Immune system Risk Factors Internal medicine Tumor Microenvironment medicine Humans Radiology Nuclear Medicine and imaging Radiation Injuries Analysis of Variance Chemotherapy Nasopharyngeal Carcinoma Radiation business.industry Nasopharyngeal Neoplasms Chemoradiotherapy medicine.disease Temporal Lobe Radiation therapy medicine.anatomical_structure Nasopharyngeal carcinoma 030220 oncology & carcinogenesis Fluorouracil Radiotherapy Intensity-Modulated Cisplatin medicine.symptom business |
| Zdroj: | International Journal of Radiation Oncology*Biology*Physics. 104:165-176 |
| ISSN: | 0360-3016 |
| DOI: | 10.1016/j.ijrobp.2019.01.002 |
| Popis: | Purpose Temporal lobe necrosis (TLN), a late complication of nasopharyngeal carcinoma (NPC) after concurrent chemoradiotherapy (CCRT), causes permanent neurologic deficits. We aimed to investigate the risk factors for the development of CCRT-induced TLN in locally advanced NPC patients. Methods and Materials The incidence of CCRT-induced TLN was assessed in consecutive patients with NPC initially staged with T3-4N0-3M0 receiving curative intensity modulated radiation therapy (IMRT) and cisplatin-based chemotherapy with long-term follow-up. The TLN risk was evaluated with radiation dose-volume histograms (a dosimetric risk indicator of organ injury) and the dynamics of blood circulating neutrophil-to-lymphocyte ratios (a clinical indicator of systemic inflammation) by linear and logistic regression models. High-throughput unbiased T cell receptor-beta (TCRbeta) sequencing was performed to correlate the different TCRbeta repertoires of NPC-infiltrating lymphocytes (a biological factor of the immune microenvironment) with TLN incidence. Results In the era of modern IMRT-based CCRT, radiation doses of up to 74 Gy achieved local control rates of more than 90% in both T3 and T4 diseases but still induced a remarkably higher incidence of TLN in the T4 patients (30.14%) compared with the rare incidence of TLN observed in the T3 patients (2.78%) (P Conclusions The associations of tumor-infiltrating lymphocyte repertoires and blood circulating neutrophil-to-lymphocyte ratios with TLN occurrence in T4 NPC patients suggest that the immune and inflammatory milieus play roles in the late brain damage caused by CCRT. Modulated or provoked by CCRT locally and systemically, the reciprocal interactions of neutrophils and lymphocytes in the intracranial NPC-associated immune microenvironment could be a key driver of chronic TLN pathogenesis. |
| Databáze: | OpenAIRE |
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