Predictive Value of the Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) Index on the Oncological Outcomes of Locally Advanced Cervical Cancer Patients

Kittinun Leetanaporn, Jitti Hanprasertpong, Kittinun Leetanaporn, Jitti Hanprasertpong

Abstract

Purpose: The oncological outcomes of locally advanced cervical cancer (LACC) patients after treatment are poor and heterogeneous. This study aimed to determine the role of the hemoglobin-albumin-lymphocyte-platelet (HALP) inflammatory index in predicting oncological outcomes in LACC patients.

Patients and methods: A total of 1588 LACC patients who received radiation therapy or concurrent chemoradiation were divided into training and test sets. Characteristics, survival, and a HALP cutoff determined by X-tile software were used to build predictive survival models on the training data. Validation of the model was performed on both sets.

Results: Patients with a HALP score ≤22.2 tended to have lower age (p < 0.001), lower comorbidity rate (p = 0.016), lower body mass index (p < 0.001), higher stage (p < 0.001), larger tumor size (p < 0.001), and higher likelihood to receive radiation alone than concurrent chemoradiation (p < 0.001). Survival analysis demonstrated that HALP >22.2 was independently associated with better progression-free survival (PFS; hazard ratio; HR 0.55) and overall survival (OS; HR 0.43). Validation of survival prediction by receiver-operating characteristics demonstrated a significantly improved area under the curve of survival prediction in both sets (p < 0.001) after the addition of the HALP index to the model.

Conclusion: A lower HALP score was an independent predictive factor for poorer oncological outcomes. The addition of the HALP index can improve the accuracy of predicting the oncological outcomes of LACC patients.

Keywords: cervical cancer; hemoglobin-albumin-lymphocyte-platelet index; predictive model; radiotherapy; survival.

Conflict of interest statement

The authors report no conflicts of interest in this work.

© 2022 Leetanaporn and Hanprasertpong.

Figures

Figure 1
Figure 1
HALP index cut point determination by X-tile program: (A) HALP histogram (B) Cut-point value.
Figure 2
Figure 2
Kaplan-Meier analysis of HALP according to HALP cut-point: (A) Progression-free survival (B) Overall survival.
Figure 3
Figure 3
Predictive accuracy of HALP model on progression-free survival in both sets.
Figure 4
Figure 4
Predictive accuracy of HALP model on overall survival in both sets.
Figure 5
Figure 5
Spot predictive accuracy of HALP model on progression-free survival (PFS) in both sets: (A) 1-year PFS (B) 3-year PFS (C) 5-year PFS.
Figure 6
Figure 6
Spot predictive accuracy of HALP model on overall survival (OS) in both sets: (A) 1-year OS (B) 3-year OS (C) 5-year OS.

References

    1. Zhang X, Zeng Q, Cai W, Ruan W. Trends of cervical cancer at global, regional, and national level: data from the Global Burden of Disease Study 2019. BMC Public Health. 2021;21:894. doi:10.1186/s12889-021-10907-5
    1. Network NCC. Cervical cancer (Version 1.2021); 2020. Available from: . Accessed June 9, 2022.
    1. Kim TE, Park BJ, Kwack HS, Kwon JY, Kim JH, Yoon SC. Outcomes and prognostic factors of cervical cancer after concurrent chemoradiation. J Obstet Gynaecol Res. 2012;38:1315–1320. doi:10.1111/j.1447-0756.2012.01871.x
    1. Endo D, Todo Y, Okamoto K, Minobe S, Kato H, Nishiyama N. Prognostic factors for patients with cervical cancer treated with concurrent chemoradiotherapy: a retrospective analysis in a Japanese cohort. J Gynecol Oncol. 2015;26:12–18. doi:10.3802/jgo.2015.26.1.12
    1. Kumar L, Gupta S. Integrating chemotherapy in the management of cervical cancer: a critical appraisal. OCL. 2016;91:8–17.
    1. Liu Z, Shi H. Prognostic role of squamous cell carcinoma antigen in cervical cancer: a meta-analysis. Dis Markers. 2019;2019:1–10.
    1. Sabeena S, Kuriakose S, Damodaran B, Ravishankar N, Arunkumar G. Human Papillomavirus (HPV) DNA detection in uterine cervix cancer after radiation indicating recurrence: a systematic review and meta-analysis. J Gynecol Oncol. 2019;31:e20. doi:10.3802/jgo.2020.31.e20
    1. Ibeanu OA. Molecular pathogenesis of cervical cancer. Cancer Biol Ther. 2011;11:295–306. doi:10.4161/cbt.11.3.14686
    1. Mueller C. Inflammation and malnutrition. Top Clin Nutr. 2011;26:3–9. doi:10.1097/TIN.0b013e318209e38b
    1. Medina-Jiménez AK, Monroy-Torres R. Repurposing individualized nutritional intervention as a therapeutic component to prevent the adverse effects of radiotherapy in patients with cervical cancer. Front Oncol. 2020;10:595351. doi:10.3389/fonc.2020.595351
    1. Wilde L, Roche M, Domingo-Vidal M, et al. Metabolic coupling and the reverse Warburg effect in cancer: implications for novel biomarker and anticancer agent development. Semin Oncol. 2017;44:198–203. doi:10.1053/j.seminoncol.2017.10.004
    1. Polterauer S, Grimm C, Tempfer C, et al. C-reactive protein is a prognostic parameter in patients with cervical cancer. Gynecol Oncol. 2007;107:114–117. doi:10.1016/j.ygyno.2007.06.001
    1. Wang H, Wang MS, Zhou YH, Shi JP, Wang WJ. Prognostic values of LDH and CRP in cervical cancer. Onco Targets Ther. 2020;13:1255–1263. doi:10.2147/OTT.S235027
    1. Nuchpramool P, Hanprasertpong J. Preoperative neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are not clinically useful in predicting prognosis in early stage cervical cancer. Surg Res Pract. 2018;2018:9162921. doi:10.1155/2018/9162921
    1. Lee J, Meyerhardt JA, Giovannucci E, Jeon JY. Association between body mass index and prognosis of colorectal cancer: a meta-analysis of prospective cohort studies. PLoS One. 2015;10:e0120706. doi:10.1371/journal.pone.0120706
    1. Hua X, Long ZQ, Huang X, et al. The value of Prognostic Nutritional Index (PNI) in predicting survival and guiding radiotherapy of patients with T1-2N1 breast cancer. Front Oncol. 2020;9:1562. doi:10.3389/fonc.2019.01562
    1. Peng D, Zhang CJ, Gong YQ, et al. Prognostic significance of HALP (Hemoglobin, Albumin, Lymphocyte and Platelet) in patients with bladder cancer after radical cystectomy. Sci Rep. 2018;8:794. doi:10.1038/s41598-018-19146-y
    1. Jiang H, Li H, Li A, et al. Preoperative combined hemoglobin, albumin, lymphocyte and platelet levels predict survival in patients with locally advanced colorectal cancer. Oncotarget. 2016;7:72076–72083. doi:10.18632/oncotarget.12271
    1. Chen XL, Xue L, Wang W, et al. Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study. Oncotarget. 2015;6:41370–41382. doi:10.18632/oncotarget.5629
    1. Jiamset I, Hanprasertpong J. Impact of diabetes mellitus on oncological outcomes after radical hysterectomy for early stage cervical cancer. J Gynecol Oncol. 2016;27:e28. doi:10.3802/jgo.2016.27.e28
    1. Leetanaporn K, Hanprasertpong J. Impact of obesity on clinical outcomes in patients with early-stage cervical cancer after radical hysterectomy with pelvic node dissection. Oncol Res Treat. 2019;42:553–563. doi:10.1159/000502752
    1. Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10:7252–7259. doi:10.1158/1078-0432.CCR-04-0713
    1. Cong L, Hu L. The value of the combination of hemoglobin, albumin, lymphocyte and platelet in predicting platinum-based chemoradiotherapy response in male patients with esophageal squamous cell carcinoma. Int Immunopharmacol. 2017;46:75–79. doi:10.1016/j.intimp.2017.02.027
    1. Guo Y, Shi D, Zhang J, et al. The Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score is a novel significant prognostic factor for patients with metastatic prostate cancer undergoing cytoreductive radical prostatectomy. J Cancer. 2019;10:81–91. doi:10.7150/jca.27210
    1. Peng D, Zhang C, Tang Q, et al. Prognostic significance of the combination of preoperative Hemoglobin and Albumin Levels and Lymphocyte and Platelet Counts (HALP) in patients with renal cell carcinoma after nephrectomy. BMC Urol. 2018;18:20. doi:10.1186/s12894-018-0333-8
    1. Xu SS, Li S, Xu HX, et al. Haemoglobin, albumin, lymphocyte and platelet predicts postoperative survival in pancreatic cancer. World J Gastroenterol. 2020;26:828–838. doi:10.3748/wjg.v26.i8.828
    1. Zhai B, Chen J, Wu J, et al. Predictive value of the Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score and Lymphocyte-to-Monocyte Ratio (LMR) in patients with non-small cell lung cancer after radical lung cancer surgery. Ann Transl Med. 2021;9:976. doi:10.21037/atm-21-2120
    1. Feng JF, Wang L, Yang X. The preoperative Hemoglobin, Albumin, Lymphocyte and Platelet (HALP) score is a useful predictor in patients with resectable esophageal squamous cell carcinoma. Bosn J Basic Med Sci. 2021;21:773–781. doi:10.17305/bjbms.2021.5666
    1. Yang N, Han X, Yu J, Shu W, Qiu F, Han J. Hemoglobin, albumin, lymphocyte, and platelet score and neutrophil-to-lymphocyte ratio are novel significant prognostic factors for patients with small-cell lung cancer undergoing chemotherapy. J Can Res Ther. 2020;16:1134. doi:10.4103/jcrt.JCRT_1066_19
    1. Shen XB, Zhang YX, Wang W, Pan YY. The Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score in patients with small cell lung cancer before first-line treatment with etoposide and progression-free survival. Med Sci Monit. 2019;25:5630–5639. doi:10.12659/MSM.917968
    1. Nemeth E, Ganz T. Anemia of inflammation. Hematol Oncol Clin North Am. 2014;28:671–681. doi:10.1016/j.hoc.2014.04.005
    1. Dunst J, Kuhnt T, Strauss HG, et al. Anemia in cervical cancers: impact on survival, patterns of relapse, and association with hypoxia and angiogenesis. Int J Radiat Oncol Biol Phys. 2003;56:778–787. doi:10.1016/S0360-3016(03)00123-8
    1. Rockwell S, Dobrucki IT, Kim EY, Marrison ST, Vu VT. Hypoxia and radiation therapy: past history, ongoing research, and future promise. Curr Mol Med. 2009;9:442–458. doi:10.2174/156652409788167087
    1. Rokkam VR, Kotagiri R. Secondary thrombocytosis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2021.
    1. Cao W, Yao X, Cen D, Zhi Y, Zhu N, Xu L. Prognostic role of pretreatment thrombocytosis on survival in patients with cervical cancer: a systematic review and meta-analysis. World J Surg Oncol. 2019;17:132. doi:10.1186/s12957-019-1676-7
    1. Rocha NP, Fortres RC. Total lymphocyte count and serum albumin as predictors of nutritional risk in surgical patients. Arq Bras Cir Dig. 2015;28:193–196. doi:10.1590/S0102-67202015000300012
    1. Kobayashi Y, Banno K, Kunitomi H, et al. Warburg effect in gynecologic cancers. J Obstet Gynaecol Res. 2019;45:542–548. doi:10.1111/jog.13867
    1. Sun L, Guan A, Jin Y, et al. Comparison of prognostic value of red cell-related parameters of biliary tract cancer after surgical resection and integration of a prognostic nomogram: a retrospective study. Adv Ther. 2021;38:1227–1244. doi:10.1007/s12325-020-01595-5

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться