Morrison Steven L, Han Gang, Elenwa Faith, Vetto John T, Fowler Graham, Leong Stanley P, Kashani-Sabet Mohammed, Pockaj Barbara A, Kosiorek Heidi E, Zager Jonathan S, Sondak Vernon K, Messina Jane L, Mozzillo Nicola, Schneebaum Schlomo, Han Dale
Division of Surgical Oncology, Oregon Health and Science University, Portland, Oregon.
Department of Epidemiology and Biostatistics, Texas A&M University, College Station, Texas.
Cancer. 2022 Apr 1;128(7):1418-1428. doi: 10.1002/cncr.34013. Epub 2022 Feb 1.
The significance of tumor-infiltrating lymphocytes (TILs) in melanoma is debated. This article presents a multicenter, retrospective study assessing the predictive and prognostic value of TILs.
The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with known TIL data. TILs were categorized as absent or present, which included nonbrisk (NB), brisk (B), and present but unspecified TIL levels. Clinicopathologic factors were correlated with TILs, sentinel lymph node (SLN) status, and melanoma-specific survival (MSS).
Overall, 3203 patients were included. The median thickness was 1.5 mm, and 469 cases had SLN metastases. TILs were present in 2458 cases (76.7%), with NB, B, and unspecified TILs seen in 1691 (68.8%), 691 (28.1%), and 76 (3.1%), respectively. Multivariable analysis showed that the presence of TILs significantly predicted a negative SLN biopsy (P < .05). The median follow-up was 25.2 months. MSS was significantly better for cases with TILs than cases without TILs (P < .001). According to multivariable analysis, age, gender, thickness, mitotic rate, ulceration, lymphovascular invasion, and SLN status were significantly prognostic of MSS (all P values < .05). Although TILs were not prognostic of MSS, when multiple imputation was used and the SLN status was excluded, the presence of TILs was significantly prognostic of improved MSS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.95; P = .0154).
TILs are a favorable marker because their presence significantly predicts a negative SLN, and the absence of TILs may be a prognostic marker of worse survival in patients with a positive SLN but not a negative SLN. TILs may also serve as a prognostic marker of survival when the SLN status is not considered.
肿瘤浸润淋巴细胞(TILs)在黑色素瘤中的意义存在争议。本文介绍了一项多中心回顾性研究,评估TILs的预测和预后价值。
查询1993年至2018年哨兵淋巴结工作组数据库中已知TIL数据的病例。TILs分为无或有,其中有包括不活跃(NB)、活跃(B)和有但未明确TIL水平。临床病理因素与TILs、哨兵淋巴结(SLN)状态和黑色素瘤特异性生存(MSS)相关。
总体纳入3203例患者。中位厚度为1.5mm,469例有SLN转移。2458例(76.7%)有TILs,其中NB、B和未明确的TILs分别见于1691例(68.8%)、691例(28.1%)和76例(3.1%)。多变量分析显示,TILs的存在显著预测SLN活检结果为阴性(P <.05)。中位随访时间为25.2个月。有TILs的病例的MSS明显优于无TILs的病例(P <.001)。根据多变量分析,年龄、性别、厚度、有丝分裂率、溃疡、淋巴管侵犯和SLN状态对MSS有显著预后意义(所有P值<.05)。虽然TILs对MSS无预后意义,但当采用多重填补法并排除SLN状态时,TILs的存在对改善MSS有显著预后意义(风险比,0.78;95%置信区间,0.64 - 0.95;P =.0154)。
TILs是一个有利的标志物,因为它们 的存在显著预测SLN为阴性,而TILs缺失可能是SLN阳性但非阴性患者生存较差的预后标志物。当不考虑SLN状态时,TILs也可作为生存的预后标志物。