Document Type : Original Article(s)
Authors
- Yaser Arafat 1
- Amrallah Mohammed 1
- Ahmad Barakat Waley 1
- Basma Soliman K 2
- Mohamed S. Bayomi 3
- Amira Hanna 4
- Basant EL-Shafaay 4
- Marwa M. EL- Mosely 5
- Doaa Mandour 4
1 Medical Oncology Department, Faculty of Medicine, Zagazig University, Egypt
2 RadiodiagnosisDepartment, Faculty of Medicine, Zagazig University, Egyptt
3 General Surgery Department, Faculty of Medicine, Zagazig University, Egypt
4 Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Zagazig University, Egypt
5 Pathology Department, Faculty of Medicine, Zagazig University, Egypt
Abstract
Background: The preoperative identification of tumor-infiltrating lymphocyte (TIL) status in hepatocellular carcinoma (HCC) is clinically important, but the ability of magnetic resonance imaging (MRI) features combined with clinical parameters to predict TIL levels remains unclear. The present study aimed to investigate whether MRI features and clinical parameters can predict TIL levels in patients with HCC undergoing surgical resection.
Method: A retrospective study of 156 HCC patients categorized TILs into; group 0 (low TIL, 0%–10%), group 1 (intermediate TIL, 11%–59%), and group 2 (high TIL, ≥60%). Continuous and categorical variables were compared using appropriate tests. Logistic regression identified predictors of TILs.
Results: Of 131 included patients, 37.9% were included in group 0, 12.2% in group 1, and 50.4% in group 2. Group 0 was significantly associated with ≥60 years of age, grade III, microvascular invasion, alpha-fetoprotein (AFP) >400 ng/ml, satellite nodules, unclear tumor boundaries, irregular shapes, non-smooth margins, absence of tumor capsule, and larger size (P < 0.05 for all). AFP level (odds ratio (OR) 0.19; 95% confidence interval (CI) 0.08-0.75, P = 0.03), tumor shape (OR 6.31; 95% CI 2.44-40.31, P = 0.01), margin (OR 0.13; 95% CI 0.05-0.6, P = 0.03), and tumor size on MRI (OR 0.99; 95% CI 1.06-1.49, P = 0.04) were independent predictors of TIL levels.
Conclusion: Preoperative MRI features, including tumor morphology, margin characteristics, and tumor size, together with serum AFP levels, showed a significant value in predicting TIL density in HCC patients undergoing surgical resection. These findings highlight MRI as a non-invasive tool for preoperative assessment and risk stratification.
Keywords
Main Subjects
Please cite this article as: Arafat Y, Mohammed A, BarakatWaley A, K Soliman B, S. Bayomi M, Hanna A, et al. Impact of MRI Findings and Clinical Parameters on Predicting Tumor-Infiltrating Lymphocytes in Hepatocellular Carcinoma Patients. Middle East J Cancer. 2026: in press. doi: 10.30476/mejc.2026.110435.2398.
- Singh SP, Madke T, Chand P. Global epidemiology of hepatocellular carcinoma. J ClinExpHepatol. 2025;15(2):102446. doi: 10.1016/j.jceh.2024.102446. PMID: 39659901; PMCID: PMC11626783.
- Parra NS, Ross HM, Khan A, Wu M, Goldberg R, Shah L, et al. Advancements in the diagnosis of hepatocellular carcinoma. Int J Transl Med. 2023;3:51-65. doi:10.3390/ijtm3010005.
- Cucchetti A, Elshaarawy O, Han G, Chong CCN, Serra C, O'Rourke JM, et al. 'Potentially curative therapies' for hepatocellular carcinoma: how many patients can actually be cured? Br J Cancer. 2023;128(9):1665-71. doi: 10.1038/s41416-023-02188-z. PMID: 36807338; PMCID: PMC10133312.
- Cucchetti A, Zhong J, Berhane S, Toyoda H, Shi K, Tada T, et al. The chances of hepatic resection curing hepatocellular carcinoma. J Hepatol. 2020;72(4):711-7. doi: 10.1016/j.jhep.2019.11.016. PMID: 31790765.
- Du M, Cai YM, Yin YL, Xiao L, Ji Y. Evaluating tumor-infiltrating lymphocytes in hepatocellular carcinoma using hematoxylin and eosin-stained tumor sections. World J Clin Cases. 2022;10(3):856-69. doi: 10.12998/wjcc.v10.i3.856. PMID: 35127901; PMCID: PMC8790462.
- Chen YD, Zhang L, Zhou ZP, Lin B, Jiang ZJ, Tang C, et al. Radiomics and nomogram of magnetic resonance imaging for preoperative prediction of microvascular invasion in small hepatocellular carcinoma. World J Gastroenterol. 2022;28(31):4399-416. doi: 10.3748/wjg.v28.i31.4399. PMID: 36159011; PMCID: PMC9453772.
- Dakal TC, George N, Xu C, Suravajhala P, Kumar A. Predictive and prognostic relevance of tumor-infiltrating immune cells: Tailoring personalized treatments against different cancer types. Cancers (Basel). 2024;16(9):1626. doi: 10.3390/cancers16091626. PMID: 38730579; PMCID: PMC11082991.
- Hectors SJ, Wagner M, Bane O, Besa C, Lewis S, Remark R, et al. Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging. Sci Rep. 2017;7(1):2452. doi: 10.1038/s41598-017-02706-z. PMID: 28550313; PMCID: PMC5446396.
- Kovac JD, Milovanovic T, Dugalic V, Dumic I. Pearls and pitfalls in magnetic resonance imaging of hepatocellular carcinoma. World J Gastroenterol. 2020;26(17):2012-29. doi: 10.3748/wjg.v26.i17.2012. PMID: 32536771; PMCID: PMC7267693.
- Mohammed AA, MostafaElsayed F, Algazar M, Rashed HE. Predictive and prognostic value of tumor- infiltrating lymphocytes for pathological response to neoadjuvant chemotherapy in triple negative breast cancer. Gulf J Oncolog. 2022;1(38):53-60. PMID: 35156645.
- Fu Y, Liu S, Zeng S, Shen H. From bench to bed: the tumor immune microenvironment and current immunotherapeutic strategies for hepatocellular carcinoma. J ExpClin Cancer Res. 2019;38(1):396. doi: 10.1186/s13046-019-1396-4. PMID: 31500650; PMCID: PMC6734524.
- Oura K, Morishita A, Tani J, Masaki T. Tumor immune microenvironment and immunosuppressive therapy in hepatocellular carcinoma: A review. Int J Mol Sci.2021;22(11):5801. doi: 10.3390/ijms22115801. PMID: 34071550; PMCID: PMC8198390.
- Zheng X, Jin W, Wang S, Ding H. Progression on the roles and mechanisms of tumor-infiltrating t lymphocytes in patients with hepatocellular carcinoma. Front Immunol. 2021;12:729705. doi: 10.3389/fimmu.2021.729705. PMID: 34566989; PMCID: PMC8462294.
- Zhao Y, Deng J, Rao S, Guo S, Shen J, Du F, et al. Tumor infiltrating lymphocyte (TIL) therapy for solid tumor treatment: Progressions and challenges. Cancers (Basel). 2022;14(17):4160. doi: 10.3390/cancers14174160. PMID: 36077696; PMCID: PMC9455018.
- Dushyanthen S, Beavis PA, Savas P, Teo ZL, Zhou C, Mansour M, et al. Relevance of tumor-infiltrating lymphocytes in breast cancer. BMC Med. 2015;13:202. doi: 10.1186/s12916-015-0431-3. PMID: 26300242; PMCID: PMC4547422.
- Kang BW, Seo AN, Yoon S, Bae HI, Jeon SW, Kwon OK, et al. Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer. Ann Oncol. 2016;27(3):494-501. doi: 10.1093/annonc/mdv610. PMID: 26673353.
- Schalper KA, Brown J, Carvajal-Hausdorf D, McLaughlin J, Velcheti V, Syrigos KN, et al. Objective measurement and clinical significance of TILs in non-small cell lung cancer. J Natl Cancer Inst. 2015;107(3):dju435. doi: 10.1093/jnci/dju435. PMID: 25650315; PMCID: PMC4565530.
- Brummel K, Eerkens AL, de Bruyn M, Nijman HW. Tumour-infiltrating lymphocytes: from prognosis to treatment selection. Br J Cancer. 2023;128(3):451-8. doi: 10.1038/s41416-022-02119-4. PMID: 36564565; PMCID: PMC9938191.
- Gao F, Xie K, Xiang Q, Qin Y, Chen P, Wan H, et al. The density of tumor-infiltrating lymphocytes and prognosis in resectable hepatocellular carcinoma: a two-phase study. Aging (Albany NY). 2021;13(7):9665-78. doi: 10.18632/aging.202710. PMID: 33744864; PMCID: PMC8064144.
- Yao W, He JC, Yang Y, Wang JM, Qian YW, Yang T, et al. The prognostic value of tumor-infiltrating lymphocytes in hepatocellular carcinoma: a systematic review and meta-analysis. Sci Rep. 2017;7(1):7525. doi: 10.1038/s41598-017-08128-1. PMID: 28790445; PMCID: PMC5548736.
- Torbenson MS, Ng IOL, Park, YN,Roncalli M, Sakamoto M. WHO Classification of Tumours: Digestive System Tumours. 5thed. International Agency for Research on Cancer: Lyon, France, 2019.p.229-239.
- Liao H, Zhang Z, Chen J, Liao M, Xu L, Wu Z, et al. Preoperative radiomic approach to evaluate tumor-infiltrating CD8+ T cells in hepatocellular carcinoma patients using contrast-enhanced computed tomography. Ann SurgOncol. 2019;26(13):4537-47. doi: 10.1245/s10434-019-07815-9. PMID: 31520208.
- Chen S, Feng S, Wei J, Liu F, Li B, Li X, et al. Pretreatment prediction of immunoscore in hepatocellular cancer: a radiomics-based clinical model based on Gd-EOB-DTPA-enhanced MRI imaging. EurRadiol. 2019;29(8):4177-87. doi: 10.1007/s00330-018-5986-x. PMID: 30666445.
- Ronot M, Chernyak V, Burgoyne A, Chang J, Jiang H, Bashir M, et al. Imaging to predict prognosis in hepatocellular carcinoma: Current and future perspectives. Radiology. 2023;307(3):e221429. doi: 10.1148/radiol.221429. PMID: 37014244.
)