Abstract
Purpose
Few large-scale studies have focused on the prevalence of symptoms and signs during the last days of patients diagnosed with advanced cancer. Identifying the patterns of specific symptoms according to cancer type is helpful to provide end-of-life care for patients with advanced cancer. We investigated the prevalence and severity of symptoms and signs associated with impending death in patients with advanced cancer.
Methods
In this secondary analysis of an international multicenter cohort study conducted in three East Asian countries, we compared the severity of symptoms and signs among dying patients in the last 3 days of life according to the type of primary cancer using one-way analysis of variance (ANOVA). Post hoc analysis was conducted for multiple comparisons of each symptom according to the type of primary cancer.
Results
We analyzed 2131 patients from Japan, Korea, and Taiwan. The prevalence of most symptoms and signs were relatively stable from 1 week after admission to the last 3 days of life. According to cancer type, edema of the lower extremities was the most common symptom and fatigue/ ascites were the most severe symptoms in digestive tract cancer. For lung cancer, respiratory secretion was the most prevalent and dyspnea/respiratory secretion were the most severe symptoms.
Conclusion
We demonstrated the prevalence and severity of symptoms and signs associated with the impending death of patients with advanced cancer in East Asia. Our study can enable clinicians to recognize the specific symptoms and signs at the very end of life.
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Data availability
The data that support the findings of this study are available from the corresponding author, Sang-Yeon Suh, upon reasonable request. All authors agree to provide data to the journal for review if needed.
Code availability
Not applicable.
References
Plonk WM Jr, Arnold RM (2005) Terminal care: the last weeks of life. J Palliat Med 8:1042–1054
Kehl KA, Kowalkowski JA (2013) A systematic review of the prevalence of signs of impending death and symptoms in the last 2 weeks of life. Am J Hosp Palliat Care 30:601–616
Lee IC, Kim CK, Suh SY et al (2007) Validation of scoring system for survival prediction in terminal cancer patients in Korea. J Korean Acad Fam Med 28:682–689
Chuang RB, Hu WY, Chiu TY et al (2004) Prediction of survival in terminal cancer patients in Taiwan: constructing a prognostic scale. J Pain Symptom Manage 28:115–122
Domeisen Benedetti F, Ostgathe C et al (2013) International palliative care experts’ view on phenomena indicating the last hours and days of life. Support Care Cancer 21:1509–1517
Hwang IC, Ahn HY, Park SM et al (2012) Clinical changes in terminally cancer patients and death within 48 h: when should we refer patients to a separate room? Support Care Cancer 21:835–840
Hui D, Hess K, dos Santos R et al (2015) A diagnostic model for impending death in cancer patients: preliminary report. Cancer 121:3914–3921
Hui D, dos Santos R, Chishoim G et al (2014) Clinical signs of impending death in cancer patients. Oncologist 19:681–687
Shin J, Kim SH, Suh SY et al (2021) Physical and psychological symptoms and signs in dying digestive tract cancer patients: the East Asian collaborative cross-cultural study to elucidate the dying process (EASED). Support Care Cancer 29:3603–3612
Shinjo T, Morita T, Hirai K et al (2010) Care for imminently dying cancer patients: family members’ experiences and recommendations. J Clin Oncol 28:142–148
National Clinical Guideline Centre (UK) (2015) Care of dying adults in the last days of life. National Institute for Health and Care Excellene (NICE), London
Mori M, Morita T, Igarashi N et al (2018) Communication about the impending death of patients with cancer to the family: a nationwide survey. BMJ Support Palliat Care 8:221–228
Shimizu Y, Miyashita M, Morita T et al (2014) Care strategy for death rattle in terminally ill cancer patients and their family members: recommendations from a cross-sectional nationwide survey of bereaved family members’ perceptions. J Pain Symptom Manage 48:2–12
Hui D, Dos Santos R, Chisholm G et al (2015) Bedside clinical signs associated with impending death in patients with advanced cancer: preliminary findings of a prospective, longitudinal cohort study. Cancer 121:960–967
Sakurai H, Miyashita M, Imai K et al (2019) Validation of the integrated palliative care outcome scale (IPOS)—Japanese version. Jpn J Clin Oncol 49:257–262
Breitbart W, Rosenfeld B, Roth A et al (1997) The Memorial Delirium Assessment Scale. J Pain Symptom Manag 13:128–137
Oken MM, Creech RH, Tormey DC et al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655
Downing GM, Wainwright W (2006) Medical care of the dying, 4th edn. Victoria Hospice Society, Victoria, BC
Morita T, Hyodo I, Yoshimi T et al (2005) Association between hydration volume and symptoms in terminally ill cancer patients with abdominal malignancies. Ann Oncol 16:640–647
Morita T, Hyodo I, Yoshimi T et al (2006) Artificial hydration therapy, laboratory findings, and fluid balance in terminally ill patients with abdominal malignancies. J Pain Symptom Manag 31:130–139
Suh SY, Won SH, Hiratsuka Y et al (2022) Assessment of changes in symptoms Is feasible and prognostic in the last weeks of life: an international multicenter cohort study. J Palliat Med 25:388–395
Merchant SJ, Brogly SB, Booth CM et al (2019) Palliative care and symptom burden in the last year of life: a population-based study of patients with gastrointestinal cancer. Ann Surg Oncol 26:2336–2345
Morita T, Hyodo I, Yoshimi T et al (2004) Incidence and underlying etiologies of bronchial secretion in terminally ill cancer patients: a multicenter, prospective, observational study. J Pain Symptom Manag 27:533–539
Valvani A, Martin A, Devarajan A et al (2019) Post-obstructive pneumonia in lung cancer. Ann Transl Med 7:357
Morita T, Tsunoda J, Inoue S et al (2002) Risk factors for death rattle in terminally ill cancer patients A prospective exploratory study. Palliat Med 14:19–23
Bennett MI (1996) Death rattle: an audit of hyoscine (scopolamine) use and review of management. J Pain Symptom Manage 12:229–233
Katz MHG, Wang H, Fleming JB et al (2009) Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol 16:836–847
Muers MF, Round CE (1993) Palliation of symptoms in non-small cell lung cancer: a study by the Yorkshire regional cancer organisation thoracic group. Thorax 8:339–343
Bruera E, Schmitz B, Pither J et al (2000) The frequency and correlates of dyspnea in patients with advanced cancer. J Pain Symptom Manage 19:357–362
Walsh D, Donnelly S, Rybicki L (2000) The symptoms of advanced cancer: relationship to age, gender, and performance status in 1,000 patients. Support Care Cancer 8:175–179
Reuben DB, Mor V (1986) Dyspnea in terminally ill cancer patients. Chest 9:234–236
Heyse-Moore LH, Ross V, Mullee MA (1991) How much of a problem is dyspnoea in advanced cancer? Palliat Med 5:20–26
van Esch HJ, van Zuylen L, Geijteman ECT et al (2021) Effect of prophylactic subcutaneous scopolamine butylbromide on death rattle in patients at the end of life: the SILENCE randomized clinical trial. JAMA 326:1268–1276
Yamashita R, Arao H, Takao A et al (2017) Unfinished business in families of terminally ill with cancer patients. J Pain Symptom Manage 4:861–869
Yao CA, Hu WY, Lai YF et al (2007) Does dying at home influence the good death of5 terminal cancer patients? J Pain Symptom Manage 4:497–504
Sakurai H, Miyashita M, Morita T et al (2021) Comparison between patient-reported and clinician-reported outcomes: validation of the Japanese version of the Integrated Palliative care Outcome Scale for staff. Palliat Support Care 5:1–7
Mori M, Yamaguchi T, Matsuda Y et al (2020) Unanswered questions and future direction in the management of terminal breathlessness in patients with cancer. ESMO Open 5:e000603
Acknowledgements
We appreciate all EASED investigators in Japan, Korea, and Taiwan for collecting data.
We are grateful to Harrisco Encorrection (Seoul, Korea) for proofreading this manuscript for grammar and clarity.
Funding
This work was supported in part by a grant-in-aid from the Japanese Hospice Palliative Care Foundation: Grant Numbers 16H05212 and 16KT0007.
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Authors and Affiliations
Contributions
Yusuke Hiratsuka: conceptualization, data curation, formal analysis, investigation, methodology, project administration, writing – original draft, writing – review and editing.
Sang-Yeon Suh: conceptualization, investigation, methodology, project implementation, supervision, writing – review and editing.
Seon-Hye Won: investigation, writing – review and editing.
Sun-Hyun Kim: investigation, writing – review and editing.
Seok-Joon Yoon: investigation, writing – review and editing.
Su-** Koh: investigation, writing – review and editing.
Jung Hye Kwon: investigation, writing – review and editing.
Jeanno Park: investigation, writing – review and editing.
Hong-Yup Ahn: Formal analysis, writing – review and editing.
Shao-Yi Cheng: investigation, writing – review and editing.
**-Jen Chen: investigation, writing – review and editing.
Takashi Yamaguchi: investigation, writing – review and editing.
Tatsuya Morita: funding acquisition, investigation, writing – review and editing.
Satoru Tsuneto: supervision, writing – review and editing.
Masanori Mori: conceptualization, investigation, methodology, project administration, resources, supervision, writing – review and editing.
Akira Inoue: investigation, supervision, writing – review and editing.
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Ethics approval
This study was approved by the local Institutional Review Boards of all participating institutions. The independent ethics committee of Tohoku University School of Medicine (approval no. 2016–1-689) approved this study.
Consent to participate
In accordance with the ethical guidelines for human research issued by the Ministry of Health, Labor, and Welfare in Japan, patients’ informed consent was waived because of the completely observational nature of the study. Patients were provided with the opportunity to opt out. In Korea and Taiwan, informed consent was obtained from the patients or their families (in case the patient lacked the capacity to decide).
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The authors affirm that human research participants provided informed consent for the publication of the article.
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The authors declare no competing interests.
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Hiratsuka, Y., Suh, SY., Won, SH. et al. Prevalence and severity of symptoms and signs in patients with advanced cancer in the last days of life: the East Asian collaborative cross-cultural study to elucidate the dying process (EASED). Support Care Cancer 30, 5499–5508 (2022). https://doi.org/10.1007/s00520-022-06969-9
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DOI: https://doi.org/10.1007/s00520-022-06969-9