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Journal of Clinical Oncology, Vol 25, No 17 (June 10), 2007: pp. 2377-2382 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.09.2627 Phase II Study: Integrated Palliative Care in Newly Diagnosed Advanced Non–Small-Cell Lung Cancer Patients
From the Massachusetts General Hospital; and the Dana-Farber Cancer Institute, Boston, MA Address reprint requests to Jennifer S. Temel, MD, Massachusetts General Hospital, Yawkey 7B, 55 Fruit St, Boston, MA 02114; e-mail: jtemel{at}partners.org
Purpose: To assess the feasibility of early palliative care in the ambulatory setting in patients with newly diagnosed advanced non–small-cell lung cancer (NSCLC). Patients and Methods: Patients were eligible if they had a performance status of 0 to 1 and were within 8 weeks of diagnosis of advanced NSCLC. Participants received integrated care from oncology and palliative care throughout the course of their disease. Participants were scheduled to meet with the palliative care team (PCT) and complete quality-of–life (QOL) and mood questionnaires monthly for 6 months. The study was deemed feasible if 64% of patients completed at least 50% of their scheduled visits and QOL assessments. Results: Fifty-one patients were enrolled onto the trial. One died within 72 hours and was not assessable. Ninety percent (95% CI, 0.78 to 0.96) of study participants complied with at least 50% of the palliative care visits. Eight-six percent (95% CI, 0.73 to 0.94) of the participants met the full feasibility requirements by both meeting with the PCT and completing QOL assessments at least 50% of the time. QOL and mood analyses confirmed the high symptom burden in patients with newly diagnosed advanced NSCLC. At least 50% of participants experienced some degree of shortness of breath, cough, difficulty breathing, appetite loss, weight loss, or unclear thinking at their baseline assessment. More than one third of patients had a probable mood disorder at baseline. Conclusion: Integrated palliative and oncology care is feasible in ambulatory patients with advanced NSCLC.
Patients with advanced non–small-cell lung cancer (NSCLC) experience physical and emotional distress from the moment of diagnosis. Although the majority of patients have physical symptoms attributable to their cancer, even those who do not have such symptoms experience distress and anxiety related to their incurable disease.1 With more than 160,000 patients dying as a result of NSCLC each year, many patients and families suffer from the physical, emotional, and social ramifications of dealing with a terminal diagnosis.2 Few studies guide clinicians on how to best provide for the psychosocial needs of patients and families facing a life-threatening illness. Most research has focused on care at the very end of life (EOL). It has been shown that hospice care can improve the quality of EOL care and death.3,4 The care provided by hospice allows for aggressive symptom management and psychosocial and spiritual support for patients and their families.5 Despite the benefits of hospice care, the majority of cancer patients are still referred to hospice very late in the course of their disease.6 With the development of novel and less toxic cancer therapies, more and more patients are receiving multiple lines of chemotherapy. In the last several years, the number of US Food and Drug Administration–approved agents for second-line therapy of advanced NSCLC has increased from one to three.7-9 The increased availability of additional therapies has translated into more patients receiving chemotherapy near the end of their life.10 However, patients receiving chemotherapy are not eligible for hospice care, leaving many patients and families struggling without the specialized symptom management and support available through hospice and palliative care programs. Symptom management and psychosocial support for patients with advanced cancer and their families must be a part of the continuum of care, not just once life-prolonging therapies fail. Additionally, patients who have an understanding of their life expectancy and participate in advanced care planning are more likely to accept hospice care at the EOL.11,12 Thus, providing more comprehensive support for patients throughout the course of their disease may not only benefit their current health status but also allow for a more timely transition to hospice care. A new delivery model of integrating palliative and oncology care can bridge the gap between cancer-directed and comfort-oriented therapies in advanced cancer patients. Recent studies describe the development of ambulatory palliative care practices within oncology, but none include the longitudinal, continuous participation of palliative care in terminal patients beginning at the time of diagnosis.13,14 We performed a pilot study to assess the feasibility of integrating palliative care with routine oncology care in patients with advanced NSCLC, a homogeneous cohort of patients with a limited life expectancy and high symptom burden. Before beginning this study, the participating hospitals did not have an oncology ambulatory palliative care clinic. Therefore, the ease of developing and implementing such a clinic and its acceptability to patients, families, and clinicians was unknown. Although the participating hospitals did have some experience collecting QOL data as part of chemotherapy trials, neither had performed a supportive care trial that required data collection outside of chemotherapy treatment schedules. The primary goal of this study was to assess the feasibility and acceptability of this novel model of care and the ability to collect patient self-assessment questionnaires in a large, academic cancer center clinic.
Patient Selection Patients within 8 weeks of diagnosis of advanced NSCLC (stage IIIB with pleural or pericardial effusions or stage IV) confirmed by histology or cytology were eligible for this study. Other eligibility requirements included age more than 18 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, and ability to read and respond to questions in English. Participants were also required to receive their cancer care at a participating Dana-Farber/Partners Cancer Center (DF/PCC) institution. All patients provided written informed consent before participation.
Integrated Palliative Care The study protocol contained guidelines to provide consistency to the palliative care intervention. All visits with the PCT included a focused physical exam, psychosocial and spiritual history, symptom and functional status assessment, and the establishment of a palliative care plan (Table 1). The palliative care plan was recorded in the patient's electronic medical record and included a problem list, medication changes, and referrals to other care providers.
QOL and Symptom Assessments Several questionnaires that have been validated in patients with advanced NSCLC were used to assess QOL and symptom status. Questionnaires were self-administered in the clinic. If patients were unable to come into the clinic but were still willing to complete the questionnaires, they were completed over the telephone with a study nurse. Questionnaires completed within 20 days of the 3- and 6-month time points were considered acceptable for analysis. The results of the self-assessment questionnaires were not provided to the oncologist or PCT and thus did not impact patient care during the study. We used the Functional Assessment of Cancer Therapy-Lung (FACT-L) to measure health-related QOL. The FACT Measurement System questionnaires evaluate health-related QOL in cancer patients.15 The response format consists of a five-point Likert scale that assesses QOL of the previous week. A 26-item version of the questionnaire, the FACT-General (FACT-G), addresses multiple QOL dimensions, including physical, functional, emotional, and social well-being. The FACT-L consists of the FACT-G plus a Lung Cancer Subscale (LCS), addressing seven symptoms specific to lung cancer, including cough, shortness or breath, and chest discomfort.16 The FACT-L was scored using published guidelines.17 The optional question regarding satisfaction with sex life was eliminated to allow for ease of scoring. A higher score on the total FACT-L or any of its components indicates better QOL. A score of less than 24 on the LCS is considered symptomatic.8,18 We also administered the Hospital Anxiety and Depression Scale (HADS), a 14-item self-report instrument designed to limit the contribution of somatic symptoms in assessing mood and anxiety in medically-ill patients.19 It is the most widely used instrument to measure depressive symptoms in cancer patients.20 Two seven-item subscales assess depression and anxiety in the preceding week. The score on each subscale ranges from 0 to 21 and a score of 8 or above is suggestive of a possible case of depression or anxiety.
Feasibility Criteria for Integrated Palliative Care
Statistical Analysis We also prospectively evaluated QOL (FACT-L), symptom burden (LCS), mood (HADS), and overall survival. Specifically, we first calculated symptom frequencies, means and standard deviations to estimate patient QOL, degree of symptom burden, and mood at baseline and 3 and 6 months. We used repeated-measures analysis of variance to examine changes in QOL and LCS scores across the three time points and conducted linear regression analyses to explore the relationship between symptom burden scores on the LCS and number of palliative care visits. Survival time was calculated from the date of consent to the date of death using the Kaplan-Meier method. Patients who were alive on the date of last follow-up were censored on that date.
From October 2003 and June 2005, 51 patients were accrued to the study. One patient who died within 72 hours of signing informed consent was not assessable. Four other patients withdrew from the study, but their data are included in this analysis. Of these, two patients cited refusal to meet with the PCT as the reason for withdrawal; one patient withdrew at the request of his primary care physician; and one transferred her care to another facility. At the time of data analysis, eight patients were alive and one was lost to follow-up and censored at the last known time point. Baseline characteristics are shown in Table 2. The median survival of the entire cohort was 9.0 months with a range of 1.2 to 32.4 months and a 1-year survival of 36%.
Study Feasibility Ninety percent of the participants (45 of 50) completed at least 50% of their scheduled appointments with the PCT in the 6-month study period (Table 3). Ninety-two percent of the participants (46 of 50) completed at least 50% of their monthly QOL assessments and thus met criteria for compliance with the FACT-L. The overall study compliance with both the palliative care visits and the QOL assessment was 86% (43 of 50).
Palliative Care Involvement Although the primary goal of the study was feasibility, the PCT became active participants in the care of the study patients. Therefore, study participants and/or the PCT could choose to meet more than once per month depending on patient care needs. The number of visits with the PCT ranged from zero to 17, with a median of six. 20% of the participants met with the PCT eight or more times (Fig 1). All participants surviving greater than 6 months choose to continue to meet with the PCT regularly after the measurement period was over.
Questionnaire Completion Baseline, 3-month, and 6-month QOL and mood data are shown in Table 4. Ninety-eight percent of patients (49 of 50) completed the baseline FACT-L. At 3 months, 70% of the participants (28 of 40) alive and not receiving hospice care completed the FACT-L within the required time frame. At the 6-month time point, 64% of patients (21 of 33) alive and not receiving hospice care completed the FACT-L on time. Completion of the HADS at baseline, 3 months, and 6 months was slightly lower at 96%, 65%, and 61% respectively.
Symptom Assessment Study participants were symptomatic at their baseline QOL assessment, with a median LCS score of 19.9 (standard deviation, 4.3; Table 4). Despite the ability of patients to meet with the PCT more frequently than once per month, there was no association between the baseline QOL score and the number of visits with the PCT. FACT-L and LCS scores remained fairly stable throughout the study period. Thirty-seven and a half percent of study participants (18 of 48) had a probable mood disorder at baseline. The rates of depressive and anxiety symptoms were high, 21% and 31% respectively, and confirm previous work in this area.1 The rate of depressive symptoms remained high throughout the course of the study, with at least 15% of patients reporting symptoms at each time point. The breakdown of the baseline LCS is shown in Table 5. The only symptom in which the majority of patients were asymptomatic at baseline was [tightness in chest.] At least 50% of participants reported some degree of symptoms for shortness of breath, cough, difficulty breathing, appetite loss, weight loss, and unclear thinking. At least 20% of patients reported severe symptoms of shortness or breath and appetite loss. There were no significant differences in the rates of symptom severity on the LCS over time.
In a 1998 Special Article, ASCO stated, [The role of the oncologist and the care team is not simply to treat cancer, but to provide comprehensive palliative and anticancer therapy throughout the course of an illness.]25 Although other organizations such as the Institute of Medicine and the WHO have published similar recommendations, few strides have been made in providing this form of care to our patients.26,27 The traditional dichotomy between cancer-directed therapy and palliative care hinders the provision of comprehensive care for patients and their families. It is essential that we identify how to provide these services to our patients in a more timely fashion throughout the course of their illness, rather than solely at the EOL. One of the main barriers to accomplishing the aim stated by ASCO is the lack of evidence that palliative and oncology care can be coordinated from the outset of a cancer diagnosis. Our pilot study shows that integrating palliative and oncology care is feasible in patients with newly diagnosed advanced NSCLC. Participants in this study were expected to meet with the PCT at least every other month during the study period. The actual results far exceeded our expectations, as the majority of patients met with the team at least monthly. Only two patients withdrew from the study, citing that they did not want to meet with the PCT. No oncologists asked that their patient be removed from the study, although a primary care physician did request that one patient withdraw. This suggests that the integrated care model was acceptable to the majority of patients and involved clinicians. The study also demonstrates the feasibility of collecting longitudinal QOL data at specified time points outside of a treatment-related clinical trial. The precise timing of assessments is an important element in QOL analysis and treatment studies that include QOL time the collection of data to chemotherapy cycles or radiation schedules.28 Although collection of QOL data outside of these treatment schedules has proven to be a challenge in previous investigations, compliance with the QOL assessments in our study was quite high.23,24 The QOL and mood data from our study are consistent with prior reports and confirm the high symptom burden and emotional distress in patients with newly diagnosed metastatic disease.1,18,29,30 This study adds a new perspective to other studies that have sought to provide an integrated care model. Several of these studies, including Project Safe Conduct and Project Enable, were mainly demonstration projects for the development of palliative care teams.31,32 Other studies have sought to provide integrated or simultaneous care for cancer patients, but have been limited in the scope or timing of the palliative care involvement. For example, in one study, participants interacted exclusively with a social worker, and visits occurred only three times during the 1-year program.33,34 Other studies have focused only on patients participating in phase I or II clinical trials, which often includes patients who are already at the end stages of life.35,36 Our study entailed longitudinal and frequent palliative care visits beginning at the time of diagnosis, and therefore truly represents an innovative, novel integrated care model. A few limitations of this study deserve comment. First, we did not collect data on the number of patients who were offered study participation and then declined, and it is possible that our study population is not generalizable. However, the median age, median survival, and treatments received by the study participants are all consistent with patient characteristics of those enrolled in clinical trials nationally.37 Our baseline QOL data is also consistent with published chemotherapy trials that include QOL assessments.29,30,38 Second, we did not collect data on the reasons for missing or incomplete QOL and mood assessments. Lastly, although we provided palliative care guidelines in the protocol, we did not prospectively collect data on the PCT's involvement in specific domains or their associated interventions. Although the involvement of palliative care needs to be somewhat flexible to meet the varying needs of patients and families, it would be useful to gain insight into which components of their care were most frequently provided in this patient population. Our current study demonstrates that palliative care can play a role in the care of patients who are living with incurable NSCLC. However, key questions remain about whether and how patients benefited from the care they received from the palliative care team. In addition to cancer-related symptoms and health-related QOL, important outcomes that need to be measured include family caregiver satisfaction with care, prognostic understanding, hospice referrals and length of stay in hospice, timing of orders to forgo cardiopulmonary resuscitation and life-sustaining interventions, and the use of other aggressive measures at the EOL.10 To assess the impact of integrated care on these significant outcomes, we are currently performing a randomized study of integrated versus standard palliative care in patients with advanced NSCLC.
Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment: N/A Leadership: N/A Consultant: N/A Stock: N/A Honoraria: N/A Research Funds: Jennifer S. Temel, Amgen Testimony: N/A Other: N/A
Conception and design: Jennifer S. Temel, Vicki A. Jackson, J. Andrew Billings, Constance Dahlin, Susan D. Block, Mary K. Buss, Thomas J. Lynch Provision of study materials or patients: Jennifer S. Temel, Panos Fidias, Thomas J. Lynch Collection and assembly of data: Jennifer S. Temel, Patricia Ostler, William F. Pirl Data analysis and interpretation: Jennifer S. Temel, J. Andrew Billings, Alona Muzikansky, Joseph A. Greer, William F. Pirl Manuscript writing: Jennifer S. Temel, J. Andrew Billings, Joseph A. Greer, William F. Pirl, Thomas J. Lynch Final approval of manuscript: Jennifer S. Temel, Vicki A. Jackson, J. Andrew Billings, Constance Dahlin, Susan D. Block, Mary K. Buss, Patricia Ostler, Panos Fidias, Alona Muzikansky, Joseph A. Greer, William F. Pirl, Thomas J. Lynch
Supported by an investigator-initiated research grant from Amgen (J.S.T.). Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005, and the 11th World Lung Cancer Conference, Barcelona, Spain, July 3-6, 2005. Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. Hopwood P, Stephens RJ: Depression in patients with lung cancer: Prevalence and risk factors derived from quality-of-life data. J Clin Oncol 18:893-903, 2000 2. Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2006. CA Cancer J Clin 56:106-130, 2006 3. Higginson IJ, Finlay IG, Goodwin DM, et al: Is there evidence that palliative care teams alter end-of-life experiences of patients and their caregivers? J Pain Symptom Manage 25:150-168, 2003[CrossRef][Medline] 4. Cohen SR, Boston P, Mount BM, et al: Changes in quality of life following admission to palliative care units. Palliat Med 15:363-371, 2001 5. Herbst L: Hospice care at the end of life. Clin Geriatr Med 20:753-765, 2004[CrossRef][Medline] 6. Christakis NA, Escarce JJ: Survival of Medicare patients after enrollment in hospice programs. N Engl J Med 335:172-178, 1996 7. Hanna N, Shepherd FA, Fossella FV, et al: Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 22:1589-1597, 2004 8. Kris MG, Natale RB, Herbst RS, et al: Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: A randomized trial. JAMA 290:2149-2158, 2003 9. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al: Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353:123-132, 2005 10. Earle CC, Neville BA, Landrum MB, et al: Trends in the aggressiveness of cancer care near the end of life. J Clin Oncol 22:315-321, 2004 11. Steinhauser KE, Christakis NA, Clipp EC, et al: Factors considered important at the end of life by patients, family, physicians, and other care providers. JAMA 284:2476-2482, 2000 12. Aabom B, Kragstrup J, Vondeling H, et al: Defining cancer patients as being in the terminal phase: Who receives a formal diagnosis, and what are the effects? J Clin Oncol 23:7411-7416, 2005 13. Jordhoy MS, Fayers P, Loge JH, et al: Quality of life in palliative cancer care: Results from a cluster randomized trial. J Clin Oncol 19:3884-3894, 2001 14. Strasser F, Sweeney C, Willey J, et al: Impact of a half-day multidisciplinary symptom control and palliative care outpatient clinic in a comprehensive cancer center on recommendations, symptom intensity, and patient satisfaction: A retrospective descriptive study. J Pain Symptom Manage 27:481-491, 2004[CrossRef][Medline] 15. Yellen SB, Cella DF, Webster K, et al: Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain Symptom Manage 13:63-74, 1997[CrossRef][Medline] 16. Cella DF, Bonomi AE, Lloyd SR, et al: Reliability and validity of the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. Lung Cancer 12:199-220, 1995[CrossRef][Medline] 17. FACIT Web site. www.facit.org 18. Cella D, Herbst RS, Lynch TJ, et al: Clinically meaningful improvement in symptoms and quality of life for patients with non-small-cell lung cancer receiving gefitinib in a randomized controlled trial. J Clin Oncol 23:2946-2954, 2005 19. Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361-370, 1983[Medline] 20. Pirl WF: Evidence report on the occurrence, assessment, and treatment of depression in cancer patients. J Natl Cancer Inst Monogr 32-39, 2004 21. Grande GE, Todd CJ: Why are trials in palliative care so difficult? Palliat Med 14:69-74, 2000 22. Rinck GC, van den Bos GA, Kleijnen J, et al: Methodologic issues in effectiveness research on palliative cancer care: A systematic review. J Clin Oncol 15:1697-1707, 1997[Abstract] 23. Sherman DW, McSherry CB, Parkas V, et al: Recruitment and retention in a longitudinal palliative care study. Appl Nurs Res 18:167-177, 2005[CrossRef][Medline] 24. Stromgren AS, Sjogren P, Goldschmidt D, et al: A longitudinal study of palliative care: Patient-evaluated outcome and impact of attrition. Cancer 103:1747-1755, 2005[CrossRef][Medline] 25. American Society of Clinical Oncology: Cancer care during the last phase of life. J Clin Oncol 16:1986-1996, 1998[Abstract] 26. Cancer pain relief and palliative care: Report of a WHO expert committee. World Health Organ Tech Rep Ser 804:1-75, 1990[Medline] 27. Foley KM, Gelband H: Improving Palliative Care for Cancer. Washington, DC, National Academies Press, 2001 28. Moinpour CM, Lyons B, Grevstad PK, et al: Quality of life in advanced non-small-cell lung cancer: Results of a Southwest Oncology Group randomized trial. Qual Life Res 11:115-126, 2002[CrossRef][Medline] 29. Cella D, Eton DT, Fairclough DL, et al: What is a clinically meaningful change on the Functional Assessment of Cancer Therapy-Lung (FACT-L) Questionnaire? Results from Eastern Cooperative Oncology Group (ECOG) study 5592. J Clin Epidemiol 55:285-295, 2002[CrossRef][Medline] 30. Langer CJ, Manola J, Bernardo P, et al: Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: Implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst 94:173-181, 2002 31. Ford Pitorak E, Beckham Armour M, Sivec HD: Project safe conduct integrates palliative goals into comprehensive cancer care. J Palliat Med 6:645-655, 2003[CrossRef][Medline] 32. Bakitas M, Stevens M, Ahles T, et al: Project ENABLE: A palliative care demonstration project for advanced cancer patients in three settings. Journal of Palliative Medicine 7:363-372, 2004[CrossRef][Medline] 33. Rabow MW, Petersen J, Schanche K, et al: The comprehensive care team: A description of a controlled trial of care at the beginning of the end of life. J Palliat Med 6:489-499, 2003[CrossRef][Medline] 34. Rabow MW, Dibble SL, Pantilat SZ, et al: The comprehensive care team: A controlled trial of outpatient palliative medicine consultation. Arch Intern Med 164:83-91, 2004 35. Meyers FJ, Linder J, Beckett L, et al: Simultaneous care: A model to resolve conflict between investigational therapy and palliative care. Presented at the 38th Annual Meeting of the American Society of Clincial Oncology, Orlando, FL, May 18-21, 2002 36. Meyers FJ, Linder J, Beckett L, et al: Simultaneous care: A model approach to the perceived conflict between investigational therapy and palliative care. J Pain Symptom Manage 28:548-556, 2004[CrossRef][Medline] 37. Schiller JH, Harrington D, Belani CP, et al: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92-98, 2002 38. Marsland TA, Garfield DH, Khan MM, et al: Sequential versus concurrent paclitaxel and carboplatin for the treatment of advanced non-small cell lung cancer in elderly patients and patients with poor performance status: Results of two Phase II, multicenter trials. Lung Cancer 47:111-120, 2005[CrossRef][Medline] Submitted September 28, 2006; accepted March 16, 2007. This article has been cited by other articles:
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
