C Mirjolet1, C Charon-Barra2, S Ladoire3,4, F Arbez-Gindre5, A Bertaut6, F Ghiringhelli3,4, A Leroux7, D Peiffert8, C Borg9,10, J F Bosset11, G Créhange1,12. 1. Department of Radiation-Oncology, Centre Georges François Leclerc, Dijon, FRANCE. 2. Department of Pathology, Centre Georges François Leclerc, Dijon, FRANCE. 3. Department of Medical Oncology, Centre Georges François Leclerc, Dijon, FRANCE. 4. INSERM U866, University of Burgundy, Dijon, France. 5. Department of Pathology, University Hospital Jean Minjoz, Besançon, FRANCE. 6. Biostatistics Unit, Centre Georges François Leclerc, Dijon, FRANCE. 7. Department of Pathology, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy Cedex France. 8. Department of Radiation-Oncology, Institut de Cancérologie de Lorraine Vandoeuvre-les-Nancy CedexFrance. 9. Department of Medical Oncology, University Hospital Jean Minjoz, Besançon, FRANCE. 10. UMR1098 INSERM/Université de Franche Comté/Etablissement Français du Sang, Besançon, France. 11. Department of Radiation-Oncology, University Hospital Jean Minjoz, Besançon, FRANCE. 12. Medical Imaging Group, Laboratory of Electronics, Computer Science and Imaging, (Le2I), University of Burgundy, Dijon, France.
Abstract
Introduction: Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC). Materials & Methods: We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impact of infiltration of the tumor or tumor site after preopRT on progression-free survival (PFS) and overall survival (OS). Secondary endpoints were the impact of dose fractionation scheme on TILs. Results: In univariate analysis, several factors significantly correlated (p<0.05) with PFS and/or OS (T-stage, M-stage, the delay between RT and surgery). A high level of post-treatment FoxP3+ TIL density correlated significantly with a better PFS (p = 0.007). In multivariate analysis, a decrease in the CD8+/FoxP3+ iTILs ratio after preopRT correlated with better PFS and OS (p = 0.049 and p = 0.024, respectively). More particularly, patients with a delta CD8+/FoxP3+ <-3.8 had better PFS and OS. Interestingly, the dose fractionation scheme significantly influenced the CD8+/FoxP3+ ratio after treatment (p = 0.027) with a lower ratio with hypofractionated RT (≥2 Gy). Conclusion: Patients with LARC who had a significant decrease in the CD8+/FoxP3+ ratio after preopRT were more likely to live longer. This ratio needs to be validated prospectively to guide physicians in adjuvant treatment decision-making.
Introduction: Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC). Materials & Methods: We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impact of infiltration of the tumor or tumor site after preopRT on progression-free survival (PFS) and overall survival (OS). Secondary endpoints were the impact of dose fractionation scheme on TILs. Results: In univariate analysis, several factors significantly correlated (p<0.05) with PFS and/or OS (T-stage, M-stage, the delay between RT and surgery). A high level of post-treatment FoxP3+ TIL density correlated significantly with a better PFS (p = 0.007). In multivariate analysis, a decrease in the CD8+/FoxP3+ iTILs ratio after preopRT correlated with better PFS and OS (p = 0.049 and p = 0.024, respectively). More particularly, patients with a delta CD8+/FoxP3+ <-3.8 had better PFS and OS. Interestingly, the dose fractionation scheme significantly influenced the CD8+/FoxP3+ ratio after treatment (p = 0.027) with a lower ratio with hypofractionated RT (≥2 Gy). Conclusion:Patients with LARC who had a significant decrease in the CD8+/FoxP3+ ratio after preopRT were more likely to live longer. This ratio needs to be validated prospectively to guide physicians in adjuvant treatment decision-making.
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