Longitudinal analysis of dynamic changes of T-lymphocytes during multimodal treatment of patients with inoperable stage III NSCLC
| Autor: | Julian Taugner, Carolyn Pelikan, Elfriede Noessner, Farkhad Manapov, Saloni Mathur, Claus Belka, Thomas Philipp Hofer, Niels Reinmuth, Amanda Tufman, Chukwuka Eze, Lukas Käsmann |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 39:e20503-e20503 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | e20503 Background: Acute lymphocytopenia is associated with poor survival in solid cancers treated with multimodal therapy. A prospective analysis of peripheral blood mononuclear cells (PBMCs) during multimodal treatment in inoperable stage III NSCLC patients was performed to assess a correlation of T-lymphocytes changes with 6-months progression-free survival rates (PFS6M). Methods: Twenty patients at median age of 65.5 years (range 33-77), 85% male, 55% with adenocarcinoma and 40% with squamous cell carcinoma, were prospectively enrolled in this study. Eighteen (90%) patients received platinum-based concurrent chemo-radiotherapy (cCRT); seven (35%) patients additional concurrent and/or sequential immune check-point inhibition (four patients nivolumab and three durvalumab); patients treated with nivolumab received induction chemotherapy. Thoracic irradiation (TRT) was applied in all patients with median cumulative dose in equivalent 2Gy fractions (EQD2) of 64Gy (range: 52-65Gy). Peripheral blood was collected 5-10 days before treatment begin (A1), on the last day of TRT (RTend), and during follow-up. Samples were analyzed using polychromatic flow cytometry. Results are reported for three time-points: A1, RTend, and 6 months after TRT (C3) or the last sample available before that time-point. Results: From A1 to RTend, 16 (80%) patients experienced severe T-cell (CD3+, CD3+CD4+, CD3+CD8+) depletion, including 3 (15%) patients who received two doses of concurrent nivolumab. T-lymphocyte nadir was independent of the absolute numbers of PBMCs before treatment begin. In two patients, T-cell count remained stable, and increased in two other patients. No correlation of dynamic changes from A1 to RTend with PFS6M was observed. From RTend to C3, T-lymphocytes recovered in 11 (55%) patients; in 6 (30%) T-cell count further decreased or remained at very low levels. For total CD3 T-cells, CD3+CD4+ and CD3+CD8+ subsets, progressive disease in the first six months after TRT was associated with a decrease of median values (P = 0.03 for total CD3+ and CD3+CD4+, P = 0.08 for CD3+CD8+ T-cells). In contrast, an increase of all medians was associated with PFS6M (P = 0.007 for total CD3+, P = 0.002 for CD3+CD4+, P = 0.06 for CD3+CD8+ T-cells). Conclusions: There is a significant difference between patients with regards to T-lymphocytes recovery after the end of TRT, which is predictive for PFS6M, with poor median recovery observed in patients with early progress. |
| Databáze: | OpenAIRE |
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