Early palliative care for patients with advanced cancer: a cluster ...

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Feb 19, 2014 - The study took place at Princess Margaret Cancer Centre, a comprehensive cancer centre and part of the University. Health Network in Toronto ...
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Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial Camilla Zimmermann, Nadia Swami, Monika Krzyzanowska, Breffni Hannon, Natasha Leighl, Amit Oza, Malcolm Moore, Anne Rydall, Gary Rodin, Ian Tannock, Allan Donner, Christopher Lo

Summary Background Patients with advanced cancer have reduced quality of life, which tends to worsen towards the end of life. We assessed the effect of early palliative care in patients with advanced cancer on several aspects of quality of life. Methods The study took place at the Princess Margaret Cancer Centre (Toronto, ON, Canada), between Dec 1, 2006, and Feb 28, 2011. 24 medical oncology clinics were cluster randomised (in a 1:1 ratio, using a computer-generated sequence, stratified by clinic size and tumour site [ four lung, eight gastrointestinal, four genitourinary, six breast, two gynaecological]), to consultation and follow-up (at least monthly) by a palliative care team or to standard cancer care. Complete masking of interventions was not possible; however, patients provided written informed consent to participate in their own study group, without being informed of the existence of another group. Eligible patients had advanced cancer, European Cooperative Oncology Group performance status of 0–2, and a clinical prognosis of 6–24 months. Quality of life (Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being [FACIT-Sp] scale and Quality of Life at the End of Life [QUAL-E] scale), symptom severity (Edmonton Symptom Assessment System [ESAS]), satisfaction with care (FAMCARE-P16), and problems with medical interactions (Cancer Rehabilitation Evaluation System Medical Interaction Subscale [CARES-MIS]) were measured at baseline and monthly for 4 months. The primary outcome was change score for FACIT-Sp at 3 months. Secondary endpoints included change score for FACIT-Sp at 4 months and change scores for other scales at 3 and 4 months. This trial is registered with ClinicalTrials.gov, number NCT01248624. Findings 461 patients completed baseline measures (228 intervention, 233 control); 393 completed at least one followup assessment. At 3-months, there was a non-significant difference in change score for FACIT-Sp between intervention and control groups (3·56 points [95% CI –0·27 to 7·40], p=0·07), a significant difference in QUAL-E (2·25 [0·01 to 4·49], p=0·05) and FAMCARE-P16 (3·79 [1·74 to 5·85], p=0·0003), and no difference in ESAS (–1·70 [–5·26 to 1·87], p=0·33) or CARES-MIS (–0·66 [–2·25 to 0·94], p=0·40). At 4 months, there were significant differences in change scores for all outcomes except CARES-MIS. All differences favoured the intervention group. Interpretation Although the difference in quality of life was non-significant at the primary endpoint, this trial shows promising findings that support early palliative care for patients with advanced cancer. Funding Canadian Cancer Society, Ontario Ministry of Health and Long Term Care.

Introduction The complex needs of patients with advanced cancer and their caregivers arise many months before the patient’s death.1 Correspondingly, WHO defines palliative care as “an approach that improves the quality of life of patients and their families…by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.”2 Specialised palliative care teams enact this approach, through the holistic care of patients dying from cancer or other terminal illnesses, and their presence is increasing worldwide.3 However, most of these teams provide terminal care at home or to inpatients rather than in outpatient settings,4–6 and referral to palliative care teams for most patients occurs in the last 2 months of life or not at all.7,8 We did a systematic review9 of randomised controlled trials from 1984 to 2007 assessing the effectiveness of specialised palliative care. Not all studies assessed a www.thelancet.com Vol 383 May 17, 2014

palliative care team, with interventions including a coordinating service, a nursing intervention, or counselling. Only four of 13 studies assessing quality of life had significant findings. However, most lacked statistical power and were done late in the disease process, resulting in difficulties with recruitment, attrition, and co-intervention. None specifically assessed an early palliative care intervention in patients with cancer. Since publication of this review,9 results have been reported from two randomised controlled trials assessing early palliative care interventions in patients with advanced cancer. The first was a study10 of 322 participants with advanced cancer and a prognosis of about 1 year; patients were randomised to routine care or to a palliative care problem-solving intervention through telephone contact from advanced practice nurses. In this study, and in the second, a trial11 of 151 patients with advanced nonsmall-cell lung cancer, patients randomised to the early palliative care group had better quality of life and mood.

Lancet 2014; 383: 1721–30 Published Online February 19, 2014 http://dx.doi.org/10.1016/ S0140-6736(13)62416-2 See Comment page 1699 See Online for video Division of Medical Oncology and Haematology, Department of Medicine (C Zimmermann MD, M Krzyzanowska MD, B Hannon MBChB, N Leighl MD, Prof A Oza MD [Lon], Prof M Moore MD, Prof I Tannock MD), and Department of Psychiatry (C Zimmermann, Prof G Rodin MD, C Lo PhD), University of Toronto, Toronto, ON, Canada; Department of Psychosocial Oncology and Palliative Care (C Zimmermann, N Swami BSc, B Hannon, A Rydall MSc, Prof G Rodin, C Lo), Department of Medical Oncology (M Krzyzanowska, N Leighl, Prof A Oza, Prof M Moore, Prof I Tannock), and Campbell Family Cancer Research Institute (C Zimmermann, Prof G Rodin, Prof I Tannock), Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; and Western University, London, ON, Canada (Prof A Donner PhD) Correspondence to: Dr Camilla Zimmermann, Department of Psychosocial Oncology and Palliative Care, Princess Margaret Cancer Centre, Toronto, ON, Canada [email protected]

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However, the former study10 did not assess intervention by a palliative care team and the latter11 included only patients with non-small-cell lung cancer. We report a cluster-randomised controlled trial of early palliative care in patients with advanced cancer. We opted for cluster rather than individual randomisation (randomising clinics, rather than individual patients) on the basis of evidence from the health-services literature9,12,13 and advice from oncologists that it is difficult to recruit patients to be individually randomised (or not) to an intervention such as palliative care, in view of strong preconceived preferences among patients and their oncologists. The design implications of cluster-randomised trials were thoroughly taken into account in our trial.14 We postulated that, compared with standard cancer care, early intervention (clinical prognosis of 6–24 months) by a palliative care team would be associated with improved patient quality of life, symptom control, and

satisfaction with care, and less difficulty with clinician– patient interactions.

Methods Study design and participants The study took place at Princess Margaret Cancer Centre, a comprehensive cancer centre and part of the University Health Network in Toronto, ON, Canada, between Dec 1, 2006, and Feb 28, 2011. Recruitment involved daily screening of participating oncology clinics by research personnel to establish eligibility. Eligible patients were aged 18 years or older, had stage IV cancer (for breast or prostate cancer, refractory to hormonal therapy was an additional criterion; patients with stage III cancer and poor clinical prognosis were included at the discretion of the oncologist); an estimated survival of 6–24 months (assessed by their main oncologist);15 and Eastern Cooperative Oncology Group (ECOG) performance

Early palliative care intervention

Standard care

Outpatient clinics Staff

Palliative care physician and nurse

Oncologist and oncology nurses

Visits

Routine once monthly; more often if necessary

Ad hoc; mainly based on chemotherapy or radiation schedule

Symptom assessment in clinic

Routine, structured assessment during every visit by palliative care nurse and physician

No structured assessment

Psychosocial assessment in clinic

Routine assessment and discussion of goals of care, of patient and family support needs, and of patient and family coping and psychological distress; discussion of advance care planning according to patient and family readiness

No routine assessment

Telephone follow-up

Routine by palliative care nurse after each visit; more often as As needed by oncology nurse; rare access to oncologist needed by palliative care nurse and physician

On-call service

24-h on-call service explained during first visit; provided by specialised palliative care physicians

Access to 24-h on-call service (oncology resident or clinical associate)

Inpatient care

Direct access to palliative care unit for symptom management

No access to palliative care unit; admission to oncology ward or medical ward (via emergency department for urgent care)

Inpatient staff

Primary care by trained palliative care nurses and physicians

Primary care by oncology nurses and clinical associates

Palliative care training for nurses

Formal 10-day training at opening of palliative care unit, and continued education by palliative care unit advance practice nurse

No formal palliative care training

Palliative care inpatient follow-up

Follow-up by palliative care team when admitted to No follow-up by palliative care team non-palliative-care-unit service at University Health Network

Hospital service

Home care Community care access centre services* Explained and offered during first visit; reassessed at each visit

Ad hoc; generally no home care referral until referral to palliative care team

Communication with family physician and community care access centre

Routine

Rarely; ad hoc

Home palliative care physician†

Explained during first visit; offered when ECOG performance status ≥3 or when patient requests

None

Multidisciplinary, addressing physical, psychological, social and spiritual needs

Ad hoc, mainly addressing physical needs

Approach to care All care providers

ECOG=Eastern Cooperative Oncology Group. *Community care access centre services include personnel such as nursing, personal support, physical therapy, occupational therapy, and equipment such as hospital bed, walker, wheelchair. †Home palliative care physicians provide either back-up support to family physicians doing house calls or direct care if (as is the case for most patients) the family physician does not provide house calls.

Table 1: Comparison of early palliative care intervention and standard care

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status of 0, 1, or 2 (assessed by their main oncologist).16 Consenting patients completed baseline measures to be eligible. Exclusion criteria were insufficient English literacy to complete questionnaires and inability to pass the cognitive screening test (Short Orientation-MemoryConcentration Test score 10 errors).17 Patients provided written, informed consent to participate and the study was approved by the Research Ethics Board of the University Health Network.

Randomisation and masking In this cluster-randomised controlled trial, oncology clinics were the units of randomisation and patients the units of inference.14 A clinic was defined as a unique, consistent time and location for outpatient oncology care by a medical oncologist. Written consent was obtained from all 16 medical oncologists in the five largest site groups (lung, gastrointestinal, genitourinary, breast, and gynaecology) to randomise their 24 clinics either to immediate consultation and follow-up by a palliative care team, or to standard care. Randomisation was done by the statistical team at Western University (London, ON, Canada) using a computer-generated sequence, was in a 1:1 ratio, and was stratified by clinic size and tumour site: lung (four clinics), gastrointestinal (eight clinics), genitourinary (four clinics), breast (six clinics), and gynaecological (two clinics). Eight oncologists had clinics in two tumour sites, and were therefore randomised to two clusters; five oncologists had their two clinics randomised within the same trial group and three to different groups. Although complete masking of interventions was not possible, patients provided written informed consent to participate in their own study group, without being informed of the existence of another group. This form of masking is common in cluster randomised trials,18 and avoids potential bias from patients in the control group requesting the intervention or otherwise altering their behaviour. Oncologists and investigators were aware of assignment.

depending on the status of the patient, included: arrangement of home nursing care services; transfer of care to a home palliative care physician (when the patient’s ECOG performance status was 3 or worse, or when requested); and admission to the Princess Margaret Cancer Centre palliative care unit for urgent symptom control or terminal care. This model was assessed in our pilot study,20 which showed improvement in symptom control and satisfaction of patients. The study duration was 4 months; on completion of the study, patients in the intervention group were offered continued follow-up in the oncology palliative care clinic. The control group received no formal intervention, but palliative care referral was not denied, if requested. Participants in the control group referred to the palliative care service received the same care as patients in the intervention group, but did not have the same standardised monthly follow-up. On completion of the 4-month measures, which represented the end of the trial, patients in the control group continued with standard care and were referred (or not) to the palliative care team when this referral would normally occur. Study measures consisted of several scales. The Functional Assessment of Chronic Illness Therapy—

24 clusters (clinics) randomised

12 clinics allocated to control 1367 patients screened for eligibility

1134 excluded 944 ineligible to participate 99 declined participation 57 not interested 23 time required 9 too ill 10 other reason 91 did not complete baseline assessment

12 clinics allocated to intervention 1926 patients screened for eligibility

1698 excluded 1357 ineligible to participate 251 declined participation 87 not interested 75 time required 54 no symptoms 14 too ill 7 palliative wording 14 other reason 90 did not complete baseline assessment

Procedures Table 1 shows how the intervention differs from standard care. The Princess Margaret Cancer Centre palliative care service consists of an outpatient oncology palliative care clinic, a 12-bed palliative care unit, and an inpatient consultant team.19 The core intervention was consultation and follow-up in the oncology palliative care clinic by a palliative care physician and nurse, consisting of: (1) comprehensive, multidisciplinary assessment of symptoms, psychological distress, social support, and home services, within 1 month of recruitment (60–90 min duration); (2) routine telephone contact from a palliative care nurse 1 week after the first consultation, and thereafter as needed; (3) monthly outpatient palliative care follow-up (20–50 min); and (4) a 24-h on-call service for telephone management of urgent issues. Ancillary interventions, www.thelancet.com Vol 383 May 17, 2014

233 assigned to control

17 died 24 withdrew

192 completed at least one follow-up assessment

9 died 28 withdrew

155 completed study

228 assigned to intervention

15 died 12 withdrew

201 completed at least one follow-up assessment

29 died 41 withdrew

131 completed study

Figure 1: Trial profile

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Intervention (n=228) Age (years)

Control (n=233)

61·2 (12·0)

60·2 (11·3)

Women

136 (59·6%)

125 (53·6%)

Married or common law partner

156 (68·4%)

167 (71·7%)

43 (18·9%)

42 (18·0%)

Living alone Employment status Retired

104 (45·6%)

101 (43·3%)

Employed

45 (19·7%)

59 (25·3%)

Unemployed

29 (12·7%)

24 (10·3%)

Disability

50 (21·9%)

49 (21·0%)

Below high school

18 (8·0%)

24 (10·3%)

High school

56 (24·8%)

57 (24·6%)

152 (67·3%)

151 (65·1%)

Lung

55 (24·1%)

46 (19·7%)

Gastrointestinal

74 (32·5%)

65 (27·9%)

Genitourinary

27 (11·8%)

51 (21·9%)

Breast

41 (18·0%)

31 (13·3%)

Gynaecological

31 (13·6%)

40 (17·2%)

Education*

College, university, or other Tumour site

Active chemotherapy No

29 (12·7%)

25 (10·7%)

Awaiting chemotherapy

25 (11·0%)

26 (11·2%)

174 (76·3%)

182 (78·1%)

Radiation treatment

Yes

16 (7·0%)

13 (5·6%)

CCI total score >0†

75 (32·9%)

71 (30·5%)

ECOG performance status‡ 0

61 (26·8%)

76 (32·6%)

1

149 (65·4%)

143 (61·4%)

2

18 (7·9%)

14 (6·0%)

FACIT-Sp§ (n=443)

101 (20·3)

105 (18·8)

QUAL-E¶ (n=436)

73 (11·1)

74 (11·5)

ESAS|| (n=461)

28 (15·5)

23 (15·7)

FAMCARE-P16** (n=449)

64 (9·7)

68 (9·7)

Score

CARES-MIS†† (n=448)

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4·7 (5·6)

Spiritual Well-Being (FACIT-Sp) scale measures quality of life, including physical, social and family, emotional, functional, and spiritual domains (score range 0–156, higher scores are better).21,22 The Quality of Life at the End of Life (QUAL-E) scale measures quality of life in domains of life completion, effect of symptoms, relationship with health provider, and preparation for end of life (range 21–105, higher scores are better).23 The Edmonton Symptom Assessment System (ESAS) consists of nine numerical scales with anchors of 0 (best) and 10 (worst) for pain, fatigue, drowsiness, nausea, anxiety, depression, appetite, dyspnoea, and wellbeing; individual symptom scores are summed for the ESAS Distress Score, ranging from 0–90.24 The FAMCARE-P16 scale measures satisfaction with information-giving, availability of care, psychological care, and physical care in patients with advanced cancer (range 16–80, higher scores are better).25 The Cancer Rehabilitation Evaluation System Medical Interaction Subscale (CARES-MIS) assesses specific problems of patients in their interactions with nurses and doctors, including those related to information seeking, communication, and control of the medical team (range 0–44, higher scores are worse).26 Follow-up measures were distributed in person or by mail. Patients who did not respond within 2 weeks received a reminder telephone call and an offer for research staff to help with completion of forms. Patients who could not be reached or declined help were deemed lost to follow-up. Medical records for each patient were reviewed at recruitment and at each follow-up visit. All measures were completed by the patient monthly for 4 months after enrolment. The 4-month study interval was chosen on the basis of two considerations: that there should be sufficient time for improvement in quality of life (or deterioration in patients in the control group, which tends to occur in all patients with advancing

3·9 (5·4)

Intervention group (n=228)

Control group (n=233)

Data are mean (SD) or n (%). CCI=Charlson Comorbidity Index; ECOG=Eastern Cooperative Oncology Group. FACIT-Sp=Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being scale. QUAL-E=Quality of Life at the End of Life scale. ESAS=Edmonton Symptom Assessment System. FAMCARE-P16=FAMCARE patient satisfaction with care measure. CARES-MIS=Cancer Rehabilitation Evaluation System Medical Interaction Subscale. *Data missing for two patients in intervention group and one patient in control group. †The CCI is a measure of comorbidity for patients with cancer; it generates a weighted score on the basis of the presence of various medical disorders, each disorder is assigned a score of 1, 2, 3, or 6 based on the CCI scoring index, scores are summed to provide a total score for each patient.28 ‡An ECOG score of 0 indicates fully active at predisease performance; 1 ambulatory but restricted in physically strenuous activity; 2 not fully ambulatory but lying or sitting