Misericordia Hospital, Grosseto, Italy
Edoardo Francini , Fang-Shu Ou , Stefano Lazzi , Roberto Petrioli , Andrea Giovanni Multari , Guido Pesola , Luciana Messuti , Elena Colombo , Virginia Livellara , Serena Bazzurri , Sara Cherri , Miano Salvatora , Eric Wolfe , Steven R Alberts , Joleen Marie Hubbard , Harry H. Yoon , Guido Francini
Background: Previous studies have reported high TILs are a favorable prognostic factor in stage II CC. However, whether the impact of TILs on overall survival (OS) differs among pts who did or did not receive ADJ is still to be determined. We assessed the prognostic value of CD3+ TILs in pts with stage II CC according to whether they received ADJ or not (no-ADJ). Methods: Pts treated with curative surgery for stage II CC (2002-2013) were identified through the Santa Maria alle Scotte Hospital database. CD3+ TILs at the invasive front, center of tumor, and stroma, were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as > 20%. Pts were classified as high or low TILs (L-TILs) and ADJ or no-ADJ. Cox models were used to assess OS with hazard ratio estimates (95% CI). Results: Of the 678 pts included (356 deaths), 137 (20%) received ADJ while 541 (80%) did not. ADJ comprised fluoropyrimidine +/- oxaliplatin. Median follow-up was 8.5 years. The distributions of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ pts had a significantly longer OS (P < .0001) regardless of the TILS rate while L-TILs/no ADJ had significantly shorter OS and higher risk of death (HR = 1.41; 95% CI, 1.06-1.88; P < .0001) [See table]. On multivariable analysis, adjusting for perforation, obstruction, T-stage, grade, < 12 lymph nodes resected, lymphovascular and perineural invasion, the adverse prognostic impact of L-TILs (vs H-TILs) in no-ADJ pts was confirmed (HR = 1.36; 95% CI 1.02, 1.82; P = .0373). Conclusions: Low CD3+ TILs rate was independently associated with shorter OS in stage II CC pts who did not receive ADJ, but was not prognostic among pts who had ADJ. These data suggest a potentially different impact of TILs in chemo-treated vs -untreated stage II CC which could affect clinical decision making.
Pts (Events) | 7 year OS rate (95% CI) | Hazard Ratio (95% CI) |
P-value | |
---|---|---|---|---|
L-TILs/ADJ | 106 (24) | 82 (75-90) | 0.33 (0.21-0.54) | < .0001 |
H-TILs/ADJ | 31 (8) | 90 (79-100) | 0.35 (0.17-0.73) | |
L-TILs/no-ADJ | 437 (267) | 44 (39-49) | 1.41 (1.06-1.88) | |
H-TILs/no-ADJ | 104 (57) | 53 (44-63) | 1 |
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