Identification of core symptoms and symptom clusters in primary hepatocellular carcinoma during the intermittent period between transcatheter arterial chemoembolization treatments

Abstract

Introduction: Patients with liver cancer frequently receive multiple transcatheter arterial chemoembolization (TACE) treatments. While some studies have investigated the symptoms and symptom clusters that occur following TACE, there is limited understanding of the core symptoms and symptom clusters experienced during the intervals between TACE treatments.

Objective: This study aims to identify core symptoms and symptom clusters in patients with primary hepatocellular carcinoma (HCC) during the intermittent period of TACE, providing a reference for precise symptom management.

Methods: A convenience sample of 344 patients undergoing intermittent TACE was recruited. Symptom prevalence and severity were evaluated using the Chinese version of the MD Anderson symptom inventory and the HCC-specific symptom module. Principal component analysis was used to extract symptom clusters. A symptom network was constructed to illustrate inter-symptom relationships and to calculate centrality indices.

Results: Four symptom clusters were identified: upper gastrointestinal, feeling of illness, emotional-psychological, and liver function impairment. Lack of appetite demonstrated the highest strength ( rs = 1.10) and closeness (rc = 0.0076) centrality in the symptom network. The strongest marginal association was found between distress and sadness (r = 0.545).

Conclusion: Lack of appetite emerged as the core symptom, while the emotional–psychological cluster was the core symptom cluster. Nursing interventions should prioritize addressing appetite loss and managing emotional symptoms such as distress and sadness to enhance the effectiveness of symptom management during the intermittent period of TACE in patients with primary HCC.

Keywords

Core symptom / Network analysis / Primary liver cancer / Symptom clusters / Transcatheter arterial chemoembolization

Acknowledgements

We would like to thank all patients who participated in this study.

Funding

None.

Conflict of interest

The authors declare that they have no conflict of interest.

Author contributions

Conceptualization: Jianfeng Zhang

Formal analysis: Xia Shen

Investigation: Jianfeng Zhang, Hongyan Duan, Jie Zhang

Methodology: Mengchen Ji

Writing–original draft: Jianfeng Zhang

Writing–review & editing: Yueqin Ni

Ethics approval and consent to participate

This study was reviewed and approved by the Ethics Committee of Jiangnan University (Approval number: JNU20221201IRB39). Written informed consent was obtained from all participants prior to their enrollment.

Consent for publication

Written informed consent for publication was obtained from all participants before their enrollment.

Availability of data

The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request.

References

[1] Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Center. 2024; 4(1): 47-53. doi: 10.1016/j.jncc.2024.01.006

[2] Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022; 77(6): 1598-1606. doi: 10.1016/j.jhep.2022.08.021

[3] Wu J, Liu W, Qiu X, et al. A noninvasive approach to evaluate tumor immune microenvironment and predict outcomes in hepatocellular carcinoma. Phenomics. 2023; 3(6): 549-564. doi: 10.1007/s43657-023-00136-8

[4] Firkins JL, Tarter R, Driessnack M, Hansen L. A closer look at quality of life in the hepatocellular carcinoma literature. Qual Life Res. 2021; 30(6): 1525-1535. doi: 10.1007/s11136-021-02789-2

[5] Deng ZT, Liang SF, Huang GK, et al. Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer. J Integr Med. 2024; 22(3): 295-302. doi: 10.1016/j.joim.2024.03.011

[6] Wang H, Yu H, Qian YW, Cao ZY, Wu MC, Cong WM. Postoperative adjuvant transcatheter arterial chemoembolization improves the prognosis of patients with huge hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2021; 20(3): 232-239. doi: 10.1016/j.hbpd.2020.12.018

[7] Kim HJ, Mcguire DB, Tulman L, Barsevick AM. Symptom clusters: Concept analysis and clinical implications for cancer nursing. Cancer Nurs. 2005; 28(4): 270-282; quiz 283-4. doi: 10.1097/00002820-200507000-00005

[8] Miaskowski C. Future directions in symptom cluster research. Semin Oncol Nurs. 2016; 32(4): 405-415. doi: 10.1016/j.soncn.2016.08.006

[9] Wang Y, O’connor M, Xu Y, Liu X. Symptom clusters in Chinese patients with primary liver cancer. Oncol Nurs Forum. 2012; 39(6): E468-E479. doi: 10.1188/12.ONF.E468-E479

[10] Cao W, Li J, Hu C, et al. Symptom clusters and symptom interference of HCC patients undergoing TACE: A cross-sectional study in China. Support Care Cancer. 2013; 21(2): 475-483. doi: 10.1007/s00520-012-1541-5

[11] Ryu E, Kim K, Cho MS, Kwon IG, Kim HS, Fu MR. Symptom clusters and quality of life in Korean patients with hepatocellular carcinoma. Cancer Nurs. 2010; 33(1): 3-10. doi: 10.1097/NCC.0b013e3181b4367e

[12] Chung MH, Wang SY, Lin CC. Symptom clusters and impact of fatigue and sleep disturbance on symptom experiences of hepatoma patients in taiwan. Cancer Nurs. 2017; 40(5): 403-411. doi: 10.1097/NCC.0000000000000417

[13] Lu K, Yang K, Niyongabo E, et al. Integrated network analysis of symptom clusters across disease conditions. J Biomed Inform. 2020; 107: 103482. doi: 10.1016/j.jbi.2020.103482

[14] Henneghan A, Wright ML, Bourne G, Sales AC. A cross-sectional exploration of cytokine-symptom networks in breast cancer survivors using network analysis. Can J Nurs Res. 2021; 53(3): 303-315. doi: 10.1177/0844562120927535

[15] National Health Commission, PRC, General Office of the National Health Commission, Guidelines for the Diagnosis and Treatment of Primary Liver Cancer; 2022. Available from: https://www.nhc.gov.cn/yzygj/s7659/202201/a01ceb75c62b486fa459e36ba0fdfdbc.shtml [Last accessed on 2022 Dec 30].

[16] Epskamp S, Borsboom D, Fried EI. Estimating psychological networks and their accuracy: A tutorial paper. Behav Res Methods. 2018; 50(1): 195-212. doi: 10.3758/s13428-017-0862-1

[17] Cleeland CS, Mendoza TR, Wang XS, et al. Assessing symptom distress in cancer patients: The M. D. Anderson symptom inventory. Cancer. 2000; 89(7): 1634-1646. doi: 10.1002/1097-0142(20001001)89:7<1634:aid-cncr29>3.0.co;2-v

[18] Wang XS, Wang Y, Guo H, Mendoza TR, Hao XS, Cleeland CS. Chinese version of the M. D. Anderson symptom inventory: Validation and application of symptom measurement in cancer patients. Cancer. 2004; 101(8): 1890-1901. doi: 10.1002/cncr.20448

[19] Jing F, Zhu Z, Qiu J, et al. Contemporaneous symptom networks and correlates during endocrine therapy among breast cancer patients: A network analysis. Front Oncol. 2023; 13: 1081786. doi: 10.3389/fonc.2023.1081786

[20] Zhu Z, Sun Y, Kuang Y, et al. Contemporaneous symptom networks of multidimensional symptom experiences in cancer survivors: A network analysis. Cancer Med. 2023; 12(1): 663-673. doi: 10.1002/cam4.4904

[21] Papachristou N, Barnaghi P, Cooper B, et al. Network analysis of the multidimensional symptom experience of oncology. Sci Rep. 2019; 9(1): 2258. doi: 10.1038/s41598-018-36973-1

[22] Yang WF, Chan YH, Griva K, Kuparasundram S, Mahendran R. Lifestyle and symptom management needs: A network analysis of family caregiver needs of cancer patients. Front Psychiatry. 2021; 12(9): 739776. doi: 10.3389/fpsyt.2021.739776

[23] Che GH, Lu HJ, Li XR, et al. Comparative analysis of symptom cluster in patients after transcatheterhepatic chemoembolization for primary hepatic carcinoma. J Nurs Sci. 2014; 29(4): 15-18. doi: 10.3870/hlxzz.2014.04.015

[24] Hongqi M, Xiangmin X, Yabo G, et al. Study on perioperative symptom cluster and related factors in patients with primary carcinoma of liver. J Nurs Sci. 2018; 33(4): 19-23. doi: 10.3870/j.issn.1001-4152.2018.04.019

[25] Gong Y, Shang B, Tan J, et al. Core and bridge symptoms of demoralization in Chinese female cancer patients: A network analysis. Front Psychiatry. 2024; 15: 1273411. doi: 10.3389/fpsyt.2024.1273411

[26] Lu H, Zheng C, Liang B, Xiong B. Mechanism and risk factors of nausea and vomiting after TACE: A retrospective analysis. BMC Cancer. 2021; 21(1): 513. doi: 10.1186/s12885-021-08253-1

[27] Puri P, Dhiman RK, Taneja S, et al. Nutrition in chronic liver disease: Consensus statement of the indian national association for study of the liver. J Clin Exp Hepatol. 2021; 11(1): 97-143. doi: 10.1016/j.jceh.2020.09.003

[28] Wang K, Diao M, Yang Z, Salvador JT, Zhang Y. Identification of core symptom cluster in patients with digestive cancer: A network analysis. Cancer Nurs. 2023; 48: E55-E63. doi: 10.1097/NCC.0000000000001280

[29] Borsboom D. A network theory of mental disorders. World Psychiatry. 2017; 16(1): 5-13. doi: 10.1002/wps.20375

[30] Murri MB, Caruso R, Christensen AP, Folesani F, Nanni MG, Grassi L. The facets of psychopathology in patients with cancer: Cross-sectional and longitudinal network analyses. J Psychosom Res. 2023; 165: 111139. doi: 10.1016/j.jpsychores.2022.111139

[31] Chen NY, Chen KH, Wang YW, Tsai HH, Lee WC, Weng LC. The impact of symptom distress on health-related quality of life in liver cancer patients receiving arterial chemoembolization: The mediating role of hope. BMC Gastroenterol. 2022; 22(1): 456. doi: 10.1186/s12876-022-02529-x

[32] Guo JG, Zhao LP, Rao YF, et al. Novel multimodal analgesia regimen improves post-TACE pain in patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2018; 17(6): 510-516. doi: 10.1016/j.hbpd.2018.08.001

[33] Ostovar S, Chahardehi AM, Mohd Hashim IH, Othman A, Kruk J, Griffiths MD. Prevalence of psychological distress among cancer patients in Southeast Asian countries: A systematic review. Eur J Cancer Care (Engl). 2022; 31(6): e13669. doi: 10.1111/ecc.13669

[34] Shim EJ, Ha H, Suh YS, et al. Network analyses of associations between cancer-related physical and psychological symptoms and quality of life in gastric cancer patients. Psychooncology. 2021; 30(6): 946-953. doi: 10.1002/pon.5681

[35] Teo I, Krishnan A, Lee GL. Psychosocial interventions for advanced cancer patients: A systematic review. Psychooncology. 2019; 28(7): 1394-1407. doi: 10.1002/pon.5103

[36] Ma Y, He B, Jiang M, et al. Prevalence and risk factors of cancer-related fatigue: A systematic review and meta-analysis. Int J Nurs Stud. 2020; 111: 103707. doi: 10.1016/j.ijnurstu.2020.103707

[37] Shun SC, Chen CH, Sheu JC, Liang JD, Yang JC, Lai YH. Quality of life and its associated factors in patients with hepatocellular carcinoma receiving one course of transarterial chemoembolization treatment: A longitudinal study. Oncologist. 2012; 17(5): 732-739. doi: 10.1634/theoncologist.2011-0368

[38] Hilfiker R, Meichtry A, Eicher M, et al. Exercise and other non-pharmaceutical interventions for cancer-related fatigue in patients during or after cancer treatment: A systematic review incorporating an indirect-comparisons meta-analysis. Br J Sports Med. 2018; 52(10): 651-658. doi: 10.1136/bjsports-2016-096422