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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)

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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

  1. Plonk WM Jr, Arnold RM (2005) Terminal care: the last weeks of life. J Palliat Med 8:1042–1054

    Article  Google Scholar 

  2. 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

    Article  Google Scholar 

  3. 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

    Google Scholar 

  4. 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

    Article  Google Scholar 

  5. 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

    Article  Google Scholar 

  6. 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

    Article  Google Scholar 

  7. 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

    Article  Google Scholar 

  8. Hui D, dos Santos R, Chishoim G et al (2014) Clinical signs of impending death in cancer patients. Oncologist 19:681–687

    Article  Google Scholar 

  9. 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

    Article  Google Scholar 

  10. 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

    Article  Google Scholar 

  11. 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

  12. 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

    Article  Google Scholar 

  13. 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

    Article  Google Scholar 

  14. 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

    Article  CAS  Google Scholar 

  15. 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

    Article  Google Scholar 

  16. Breitbart W, Rosenfeld B, Roth A et al (1997) The Memorial Delirium Assessment Scale. J Pain Symptom Manag 13:128–137

    Article  CAS  Google Scholar 

  17. 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

    Article  CAS  Google Scholar 

  18. Downing GM, Wainwright W (2006) Medical care of the dying, 4th edn. Victoria Hospice Society, Victoria, BC

    Google Scholar 

  19. 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

    Article  CAS  Google Scholar 

  20. 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

    Article  Google Scholar 

  21. 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

    Article  Google Scholar 

  22. 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

    Article  Google Scholar 

  23. 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

    Article  Google Scholar 

  24. Valvani A, Martin A, Devarajan A et al (2019) Post-obstructive pneumonia in lung cancer. Ann Transl Med 7:357

    Article  Google Scholar 

  25. 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

    Article  Google Scholar 

  26. Bennett MI (1996) Death rattle: an audit of hyoscine (scopolamine) use and review of management. J Pain Symptom Manage 12:229–233

    Article  CAS  Google Scholar 

  27. 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

    Article  Google Scholar 

  28. 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

    Article  Google Scholar 

  29. 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

    Article  CAS  Google Scholar 

  30. 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

    Article  CAS  Google Scholar 

  31. Reuben DB, Mor V (1986) Dyspnea in terminally ill cancer patients. Chest 9:234–236

    Article  Google Scholar 

  32. Heyse-Moore LH, Ross V, Mullee MA (1991) How much of a problem is dyspnoea in advanced cancer? Palliat Med 5:20–26

    Article  Google Scholar 

  33. 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

    Article  Google Scholar 

  34. 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

    Article  Google Scholar 

  35. 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

    Article  Google Scholar 

  36. 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

    Google Scholar 

  37. 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

    Article  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Palliative Medicine, Takeda General Hospital, Aizuwakamatsu, Japan

    Yusuke Hiratsuka

  2. Department of Palliative Medicine, Tohoku University School of Medicine, Sendai, Japan

    Yusuke Hiratsuka & Akira Inoue

  3. Department of Family Medicine, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi-do, South Korea

    Sang-Yeon Suh & Seon-Hye Won

  4. Department of Medicine, Dongguk University Medical School, Pildong 1-30, Jung-gu, Seoul, South Korea

    Sang-Yeon Suh

  5. Department of Family Medicine, School of Medicine, Catholic Kwandong University International St. Mary’s Hospital, Incheon, South Korea

    Sun-Hyun Kim

  6. Department of Family Medicine, Chungnam National University Hospital, Daejeon, South Korea

    Seok-Joon Yoon

  7. Department Hematology and Oncology, Ulsan University Hospital Ulsan University College of Medicine, Ulsan, South Korea

    Su-Jin Koh

  8. Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, South Korea

    Jung Hye Kwon

  9. Department of Internal Medicine, Bobath Hospital, Seongnam, South Korea

    Jeanno Park

  10. Department of Statistics, Dongguk University, Seoul, South Korea

    Hong-Yup Ahn

  11. Department of Family Medicine, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan

    Shao-Yi Cheng

  12. Department of Family Medicine, Kaohsiung Medical University Hospital, and School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ping-Jen Chen

  13. Division of Psychiatry, Marie Curie Palliative Care Research Department, University College London, London, UK

    Ping-Jen Chen

  14. Division of Palliative Care Konan Medical Center, Kobe, Japan

    Takashi Yamaguchi

  15. Division of Palliative and Supportive Care, Seirei Mikatahara General Hospital, Hamamatsu, Japan

    Tatsuya Morita & Masanori Mori

  16. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Satoru Tsuneto

Authors
  1. Yusuke Hiratsuka
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  2. Sang-Yeon Suh
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  3. Seon-Hye Won
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  4. Sun-Hyun Kim
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  13. Tatsuya Morita
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  14. Satoru Tsuneto
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  15. Masanori Mori
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  16. Akira Inoue
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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-Jin 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.

Ping-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.

Corresponding author

Correspondence to Sang-Yeon Suh.

Ethics declarations

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).

Consent for publication

The authors affirm that human research participants provided informed consent for the publication of the article.

Conflict of interest

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

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