End-of-Life Characteristics Associated With Short Hospice Length of Stay for Patients With Solid Tumors Enrolled in Phase I Clinical Trials

View More View Less
  • 1 Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and
  • | 2 Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University, Baltimore, Maryland.
Restricted access

Background: Patients participating in phase I trials represent a population with advanced cancer and symptoms, with quality-of-life implications arising from both disease and treatment. Transitions to end-of-life care for these patients have received little attention. Good empirical data are needed to better understand the role of advance care planning and palliative care during phase I trial transitions. We investigated how physician–patient communication at the time of disease progression, patient characteristics, and patterns of care were associated with end-of-life care. Methods: We conducted a retrospective chart review of all patients with solid tumors enrolled in phase I trials at a comprehensive cancer center from January 2015 to December 2017. We captured physician–patient communication during disease progression. Among patients who died, we assessed palliative care referral, advance care planning, place of death, healthcare use in the final month of life, hospice enrollment, and hospice length of stay (LOS). Factors independently associated with a short hospice LOS (defined as ≤3 days) were estimated from a multivariable model building approach. Results: Among 207 participants enrolled in phase I intervention studies at Johns Hopkins Hospital, the median age was 61 years (range, 31–91 years), 48% were women, 21% were members of racial minority groups, and 41.5% were referred from an outside institution. At the time of disease progression, 53% had goals of care documented, 47% were previously referred to palliative care, and 41% discussed hospice with their oncologist. A total of 82% of decedents died within 1 year of study enrollment, and 85% enrolled in hospice. Among the 147 participants who enrolled in hospice, 22 (15%) had a short LOS (≤3 days). Factors independently associated with an increased risk of short hospice LOS in the multivariable model included age >65 years (odds ratio [OR], 1.12; 95% CI, 1.01–1.24; P=.04), whereas remaining at the same institution (OR, 0.72; 95% CI, 0.65–0.80; P<.001) and referral to palliative care before progression (OR, 0.83; 95% CI, 0.75–0.92; P<.001) were associated with a decreased risk of short hospice LOS. Conclusions: Reported data support the benefit of palliative care for patients in phase I trials and the risks associated with healthcare transitions for all patients, particularly older adults, regardless of care received. Leaving a clinical trial is a time when clear communication is paramount. Phase I studies will continue to be vital in advancing cancer treatment. It is equally important to advance the support provided to patients who transition off these trials.

Submitted May 5, 2020; final revision received August 26, 2020; accepted for publication August 27, 2020.

Published online January 21, 2021.

Author contributions: Study concept and design: Sedhom, Blackford, Carducci. Provision of study materials or patients: Griffiths, Heussner, Carducci. Data collection and assembly: Sedhom, Blackford, Gupta, Griffiths. Data analysis and interpretation: All authors. Administrative support: Carducci. Manuscript preparation: All authors.

Disclosures: Dr. Carducci has disclosed that he has a consulting or advisory role with Astellas Pharma, AbbVie, Roche/Genentech, Pfizer, and Foundation Medicine, and has received grant/research support from Bristol-Myers Squibb, Pfizer, AstraZeneca, Gilead Sciences, EMD Serono, and eFFECTOR Therapeutics. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Ramy Sedhom, MD, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 North Broadway, Baltimore, MD 21231. Email: rsedhom1@jhmi.edu
  • 1.

    Agrawal M , Grady C , Fairclough DL, et al. . Patients’ decision-making process regarding participation in phase I oncology research. J Clin Oncol 2006;24:44794484.

    • Search Google Scholar
    • Export Citation
  • 2.

    Agrawal M , Emanuel EJ. Ethics of phase 1 oncology studies: reexamining the arguments and data. JAMA 2003;290:10751082.

  • 3.

    Godskesen T , Nygren P , Nordin K, et al. . Phase 1 clinical trials in end-stage cancer: patient understanding of trial premises and motives for participation. Support Care Cancer 2013;21:31373142.

    • Search Google Scholar
    • Export Citation
  • 4.

    Horng S , Grady C. Misunderstanding in clinical research: distinguishing therapeutic misconception, therapeutic misestimation, and therapeutic optimism. IRB 2003;25:1116.

    • Search Google Scholar
    • Export Citation
  • 5.

    Jenkins V , Solis-Trapala I , Langridge C, et al. . What oncologists believe they said and what patients believe they heard: an analysis of phase I trial discussions. J Clin Oncol 2011;29:6168.

    • Search Google Scholar
    • Export Citation
  • 6.

    Kass N , Taylor H , Fogarty L, et al. . Purpose and benefits of early phase cancer trials: what do oncologists say? What do patients hear? J Empir Res Hum Res Ethics 2008;3:5768.

    • Search Google Scholar
    • Export Citation
  • 7.

    Pentz RD , White M , Harvey RD, et al. . Therapeutic misconception, misestimation, and optimism in participants enrolled in phase 1 trials. Cancer 2012;118:45714578.

    • Search Google Scholar
    • Export Citation
  • 8.

    Joffe S , Miller FG. Rethinking risk-benefit assessment for phase I cancer trials. J Clin Oncol 2006;24:29872990.

  • 9.

    Halpern J , Paolo D , Huang A. Informed consent for early-phase clinical trials: therapeutic misestimation, unrealistic optimism and appreciation. J Med Ethics 2019;45:384387.

    • Search Google Scholar
    • Export Citation
  • 10.

    Arkenau HT , Olmos D , Ang JE, et al. . Clinical outcome and prognostic factors for patients treated within the context of a phase I study: the Royal Marsden Hospital experience. Br J Cancer 2008;98:10291033.

    • Search Google Scholar
    • Export Citation
  • 11.

    Decoster G , Stein G , Holdener EE. Responses and toxic deaths in phase I clinical trials. Ann Oncol 1990;1:175181.

  • 12.

    Hui D , Parsons H , Nguyen L, et al. . Timing of palliative care referral and symptom burden in phase 1 cancer patients: a retrospective cohort study. Cancer 2010;116:44024409.

    • Search Google Scholar
    • Export Citation
  • 13.

    Institute of Medicine. Dying in America: Improving Quality and Honoring Individual Preferences Near the End of Life. Washington, DC: The National Academies Press; 2015.

  • 14.

    Markman M. The ethical dilemma of phase I clinical trials. CA Cancer J Clin 1986;36:367369.

  • 15.

    World Health Organization. Transitions of Care: Technical Series on Safer Primary Care. Geneva, Switzerland: World Health Organization; 2016.

    • Search Google Scholar
    • Export Citation
  • 16.

    Bradley EH , Prigerson H , Carlson MDA, et al. . Depression among surviving caregivers: does length of hospice enrollment matter? Am J Psychiatry 2004;161:22572262.

    • Search Google Scholar
    • Export Citation
  • 17.

    Kris AE , Cherlin EJ , Prigerson H, et al. . Length of hospice enrollment and subsequent depression in family caregivers: 13-month follow-up study. Am J Geriatr Psychiatry 2006;14:264269.

    • Search Google Scholar
    • Export Citation
  • 18.

    Miller SC , Mor V , Teno J. Hospice enrollment and pain assessment and management in nursing homes. J Pain Symptom Manage 2003;26:791799.

    • Search Google Scholar
    • Export Citation
  • 19.

    Schilsky RL , Wehrwein P. Gains against cancer, but enter ‘financial toxicity’. Manag Care 2015;24:46–47, 52–54.

  • 20.

    Rickerson E , Harrold J , Kapo J, et al. . Timing of hospice referral and families’ perceptions of services: are earlier hospice referrals better? J Am Geriatr Soc 2005;53:819823.

    • Search Google Scholar
    • Export Citation
  • 21.

    Teno JM , Casarett D , Spence C, et al. . It is “too late” or is it? Bereaved family member perceptions of hospice referral when their family member was on hospice for seven days or less. J Pain Symptom Manage 2012;43:732738.

    • Search Google Scholar
    • Export Citation
  • 22.

    Ahluwalia SC , Tisnado DM , Walling AM, et al. . Association of early patient-physician care planning discussions and end-of-life care intensity in advanced cancer. J Palliat Med 2015;18:834841.

    • Search Google Scholar
    • Export Citation
  • 23.

    Sedhom R , Barile D. Discussing goals of care with families using the four steps [published online August 21, 2016]. Gerontol Geriatr Med, doi: 10.1177/2333721416664446

    • Search Google Scholar
    • Export Citation
  • 24.

    Sudore RL , Lum HD , You JJ, et al. . Defining advance care planning for adults: a consensus definition from a multidisciplinary Delphi panel. J Pain Symptom Manage 2017;53:821–832.e1.

    • Search Google Scholar
    • Export Citation
  • 25.

    Silveira MJ , Kim SYH , Langa KM. Advance directives and outcomes of surrogate decision making before death. N Engl J Med 2010;362:12111218.

    • Search Google Scholar
    • Export Citation
  • 26.

    Bischoff KE , Sudore R , Miao Y, et al. . Advance care planning and the quality of end-of-life care in older adults. J Am Geriatr Soc 2013;61:209214.

    • Search Google Scholar
    • Export Citation
  • 27.

    Khandelwal N , Hough CL , Downey L, et al. . Prevalence, risk factors, and outcomes of financial stress in survivors of critical illness. Crit Care Med 2018;46:e530539.

    • Search Google Scholar
    • Export Citation
  • 28.

    Sedhom R , Sedhom D. To grow as a physician, try responding to suffering. J Palliat Care 2019;34:34.

  • 29.

    Bakitas MA , Tosteson TD , Li Z, et al. . Early versus delayed initiation of concurrent palliative oncology care: patient outcomes in the ENABLE III randomized controlled trial. J Clin Oncol 2015;33:14381445.

    • Search Google Scholar
    • Export Citation
  • 30.

    El-Jawahri A , Greer JA , Pirl WF, et al. . Effects of early integrated palliative care on caregivers of patients with lung and gastrointestinal cancer: a randomized clinical trial. Oncologist 2017;22:15281534.

    • Search Google Scholar
    • Export Citation
  • 31.

    Ferrell BR , Temel JS , Temin S, et al. . Integration of palliative care into standard oncology care: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2017;35:96112.

    • Search Google Scholar
    • Export Citation
  • 32.

    Greer JA , Jackson VA , Meier DE, et al. . Early integration of palliative care services with standard oncology care for patients with advanced cancer. CA Cancer J Clin 2013;63:349363.

    • Search Google Scholar
    • Export Citation
  • 33.

    Greer JA , Pirl WF , Jackson VA, et al. . Effect of early palliative care on chemotherapy use and end-of-life care in patients with metastatic non-small-cell lung cancer. J Clin Oncol 2012;30:394400.

    • Search Google Scholar
    • Export Citation
  • 34.

    Hui D , Kim SH , Roquemore J, et al. . Impact of timing and setting of palliative care referral on quality of end-of-life care in cancer patients. Cancer 2014;120:17431749.

    • Search Google Scholar
    • Export Citation
  • 35.

    Smith TJ , Temin S , Alesi ER, et al. . American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care. J Clin Oncol 2012;30:880887.

    • Search Google Scholar
    • Export Citation
  • 36.

    Temel JS , Greer JA , Muzikansky A, et al. . Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010;363:733742.

    • Search Google Scholar
    • Export Citation
  • 37.

    Zimmermann C , Swami N , Krzyzanowska M, et al. . Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial. Lancet 2014;383:17211730.

    • Search Google Scholar
    • Export Citation
  • 38.

    Sedhom R , Gupta A , MacNabb L, et al. . The impact of palliative care dose intensity on outcomes for patients with cancer. Oncologist 2020;25:913915.

    • Search Google Scholar
    • Export Citation
  • 39.

    Ferrell BR , Chung V , Koczywas M, et al. . Palliative care and phase 1 trials: intervention to improve quality of life and provide education. Clin J Oncol Nurs 2017;21:473479.

    • Search Google Scholar
    • Export Citation
  • 40.

    Ferrell BR , Chung VM , Koczywas M, et al. . Integration of palliative care for patients with solid tumors on phase I clinical trials [abstract]. J Clin Oncol 2016;34(Suppl):Abstract 138.

    • Search Google Scholar
    • Export Citation
  • 41.

    Zafar SF , Heilbrun LK , Vishnu P, et al. . Participation and survival of geriatric patients in phase I clinical trials: the Karmanos Cancer Institute (KCI) experience. J Geriatr Oncol 2011;2:1824.

    • Search Google Scholar
    • Export Citation
  • 42.

    Wheler J , Tsimberidou AM , Hong D, et al. . Survival of 1,181 patients in a phase I clinic: the MD Anderson Clinical Center for targeted therapy experience. Clin Cancer Res 2012;18:29222929.

    • Search Google Scholar
    • Export Citation
  • 43.

    Stephen B , Wheler JJ , Tsimberidou AM, et al. . Survival of 1,181 patients in a phase I clinic: the University of Texas M. D. Anderson Cancer Center experience [abstract]. J Clin Oncol 2011;29(Suppl):Abstract 2528.

    • Search Google Scholar
    • Export Citation
  • 44.

    Sun V , Cooke L , Chung V, et al. . Feasibility of a palliative care intervention for cancer patients in phase I clinical trials. J Palliat Med 2014;17:13651368.

    • Search Google Scholar
    • Export Citation
  • 45.

    Ferrell BR , Paterson CL , Hughes MT, et al. . Characteristics of participants enrolled onto a randomized controlled trial of palliative care for patients on phase I studies. J Palliat Med 2017;20:13381344.

    • Search Google Scholar
    • Export Citation
  • 46.

    Smith TJ , Schnipper LJ. The American Society of Clinical Oncology program to improve end-of-life care. J Palliat Med 1998;1:221230.

    • Search Google Scholar
    • Export Citation
  • 47.

    Byock I. Completing the continuum of cancer care: integrating life-prolongation and palliation. CA Cancer J Clin 2000;50:123132.

  • 48.

    Cancer care during the last phase of life. J Clin Oncol 1998;16:19861996.

  • 49.

    Sedhom R , Gupta A , Von Roenn J, et al. . The case for focused palliative care education in oncology training. J Clin Oncol 2020;38:23662368.

    • Search Google Scholar
    • Export Citation
  • 50.

    Esper P , Hampton JN , Finn J, et al. . A new concept in cancer care: the supportive care program. Am J Hosp Palliat Care 1999;16:713722.

  • 51.

    Meyers FJ , Carducci M , Loscalzo MJ, et al. . Effects of a problem-solving intervention (COPE) on quality of life for patients with advanced cancer on clinical trials and their caregivers: simultaneous care educational intervention (SCEI): linking palliation and clinical trials. J Palliat Med 2011;14:465473.

    • Search Google Scholar
    • Export Citation
  • 52.

    Byock I , Miles SH. Hospice benefits and phase I cancer trials. Ann Intern Med 2003;138:335337.

  • 53.

    Levine DR , Johnson LM , Mandrell BN, et al. . Does phase 1 trial enrollment preclude quality end-of-life care? Phase 1 trial enrollment and end-of-life care characteristics in children with cancer. Cancer 2015;121:15081512.

    • Search Google Scholar
    • Export Citation
  • 54.

    Cho HL , Danis M , Grady C. Post-trial responsibilities beyond post-trial access. Lancet 2018;391:14781479.

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 479 479 470
PDF Downloads 270 270 263
EPUB Downloads 0 0 0