Palliative care is an approach to improve the quality of life for patients and their care-givers facing problems associated with life-threatening illnesses (1,2). A growing body of evidence showed that integration of palliative care into standard oncology care resulted in improvements in quality of life, symptom control, patient and caregiver satisfaction, understanding of illness, quality of end-of-life (EOL) care, survival, and cost of care (3-5).
EOL care is an essential component of palliative care. There are various ways to assess the quality of end-of-life care service. The common indicators used to define overly aggressive palliative care in end-of-life services include (6): new anti-cancer therapies or continuation of treatments very near to death; excessive/unnecessary hospital admissions of advanced cancer patients in emergency rooms or intensive care unit (ICU); low utility of hospice services/resources or late referral.
In mainland China, hospice services were in severe shortage (7). The majority of patients in cities tended to rely on case oncologists throughout their whole disease trajectory and were inclined to pass away in hospitals (8). Transferal of patients to a primary care unit or an organization with palliative care resources was often rejected by the patients and their families (9). Data of quality of end-of-life care services in various mainland cancer centers was still scarce.
Shenzhen city, a rapidly growing urban city in China with a population of approximately 11 million, shared similar problem with other major Chinese cities. In view of the huge shortage of oncology and palliative care service, the oncology center of the HKU-SZH was launched in 2013 which pledged to provide integrated oncology-palliative care service.
The HKU-SZH oncology center receives patient referrals from all other centers in China. Cancer patients might also be admitted to the center through emergency room of HKU-SZH. In the HKU-SZH oncology center, all advanced cancer patients were treated according to department’s protocol for palliative care. The palliative care protocol outlined the multidisciplinary approach to tackle various aspects of symptom control, the use of strong opioid for pain control as well as psychosocial care of patients and their caregivers in distress. When patients approached the end-of-life period, the medical and nursing team of the center would initiate structured (EOL) care program in oncology ward.
In order to evaluate the effect of the palliative care program, the current study reviewed the EOL care quality indicators of HKU-SZH cancer center, which included the use of cytotoxic chemotherapy during the last month of life, admissions to the accident and emergency department (A&E) and ICU in the last month of life, and practice of Do-Not-Resuscitate (DNR) orders. We present the following article in accordance with the PRISMA reporting checklist (available at http://dx.doi.org/10.21037/apm-19-268).
The study included all advanced solid cancer patients who expired at the HKU-SZH from March 2013 to February 2016. The clinical characteristics of patients recorded include, demographics, primary malignancy, date of recurrence or metastasis, death and last admission, last hospitalization through oncology clinics or accident & emergency department (A&E), lines of systemic anticancer therapies received, date of the last cycle of cytotoxic chemotherapy, initiation of new systemic anticancer therapies in the EOL period, the decision on DNR orders and the process leading to these, the use of cardiopulmonary resuscitation (CPR) and mechanical ventilation. The study had obtained the approval of HKU-SZH institutional review board (no: 2017-01).
Clinical descriptive data were presented as median and range. The relationships between each of the variables were assessed using the t test, chi-squared test, or Fisher’s exact test. The Kaplan-Meier method was used for survival analysis. P<0.05 denoted statistical significance. The IBM@ SPSS@ 24.0 software was used for statistical analysis.
A total of 441 patients with advanced solid cancer expired in the HKU-SZH during the study period. The most prevalent primary malignancies were lung, liver & biliary, and colorectal cancer. The median age of patients was 62 years (range: 15–93 years). The average length of last hospitalization was 22.3 days (range: 1–302 days). About half (52.7%, 232/441) of the cohort was covered by the Shenzhen city medical insurance, in which 90% of the medical expenses were reimbursed. For the rest, 30–50% of the expenses were covered by basic medical insurance provided by other provinces which had lower rate of reimbursement.
The median overall survival of the cohort, counted from the time of recurrence or metastasis to death, was 7 months (range: 0–83 months). Approximately half of the patients (47.2%; 207/441 patients) had never received any systemic anti-cancer treatment. In this group of patients, the commonest primaries were liver & biliary, lung, and stomach. The mean age of the group was older than the group who had received chemotherapy [mean age ± standard deviation (SD) 64.11±14.57; 57.16±13.94, P<0.001].
For chemotherapy use in the end-of-life period, 9.3% (41/441) underwent chemotherapy in the last month prior to death and 4.8% (21/441) in the last two weeks. Amongst those who underwent chemotherapy in the last month of their lives (41 patients), 68.3% (28/41 patients) received a new chemotherapy regimen. Patients with ovarian cancer received chemotherapy during the last month more frequently (33.3%; 7/21 patients) than patients with other types of cancer.
For the hospitalization data, more than half of the patients (51.5%; 217/441 patients) were admitted through the outpatient department, while 48.5% (214/441 patients) through the A&E. In the latter group, 46.7% (100/214 patients) visited the HKU-SZH for the first time and subsequently expired during this last hospitalization. Notably, 5.2% patients (23/441) expired in the ICU; 1.4% (6/441) were transferred to the ICU during the last month but afterwards expired in the general ward. CPR had been performed in 8.4% of patients (37/441), most frequently in the ICU (34.8%; 8/23 patients) compared with the wards of clinical oncology department (5.0%, 18/359) or other departments (18.6%, 11/59). These differences were statistically significant (P=0.000).
Vast majority of patients (92.3%; 407/441) had DNR order in place before death. Within the group, 99.3% of the DNR order (404/407) were placed after discussion with family members but not with the patients themselves. The rate of DNR acceptance was higher in the clinical oncology center than other departments (OR 5.1, P<0.001). Despite the DNR order, 1.7% (7/407) patients still received CPR due to absence of family members when the patient was going to die.
The median time between the date of last admission to the placement of DNR was 9 days (range 0–131 days). The median time of the placement of DNR order before death was 2 days (0–89 days). The interval between DNR placement and death was not significant different for oncology center, ICU and other departments (P=0.13).
The tendency for the administration of chemotherapy in the last month, consent to the DNR order, and admission to the ICU in the last month are shown in Figure 1. Clinical characteristics in relation to the administration of chemotherapy in the last month and consent to the DNR order are presented in Table 1. There was no correlation between the two factors (OR 1.3, P=0.23).
The current cohort of consecutive 441 deceased patients with advanced cancer showed that satisfactory EOL care can be achieved with multidisciplinary, integrative palliative care services in an urban oncology center of mainland China. The overuse of chemotherapy and over-aggressive EOL care (mechanical ventilation / ICU admission) in the last month of life were low at 9.3% and 9.2% respectively, and the placement of DNR order was achieved in 92.3% of all patients.
The use of chemotherapy in the end-of-life period
The overuse of chemotherapy in the end-of-life period is a common problem world-wide. It had been shown in a prospective study that the administration of chemotherapy in patients with end-stage cancer and a physician-estimated life expectancy of ≤6 months did not improve quality of life. Overuse of chemotherapy may be harmful even in patients with a good performance status (10).
The American Society for Clinical Oncology (ASCO) stated that discontinuation of EOL chemotherapy may improve patient care and reduce cost (11). The ASCO recommended not to use cancer-directed therapy in patients with solid tumors who have the following characteristics: poor performance status (3 or 4), no beneﬁt from prior evidence-based interventions, ineligibility for a clinical trial, and weak evidence supporting the clinical value of further anticancer treatment.
However, according to a survey from African cancer center (12), among all adult patients with reported cancer deaths between 2014 and 2015, 65.9% received chemotherapy and more than 45% of patients received chemotherapy in the last 30 days of life. In France (13), among a total of 279,846 hospitalized patients who died from metastatic cancer between January 2010 and December 2013, there were 19.5% of patients received chemotherapy during the last month before death, and 11.3% during the last 2 weeks. Compared with university hospitals, patients who died in profit-making clinics/hospital or comprehensive cancer centers were more likely to receive chemotherapy. High-volume centers and hospitals without palliative care units reported greater-than-average rates of chemotherapy near the end of life. A retrospective study investigating 3,350 decedents from six representative hospitals across China from 2010 through 2014 reported that 16.9% of patients received chemotherapy during the last month of their lives (14).
The phenomenon of over-using chemotherapy might be attributed to a number of reasons. Firstly, oncologists often fail to accurately estimate the survival of individual patients (15). Over-optimistic estimation may lead to continual use of late-line chemotherapy. Secondly, a number of patients did not recognize that chemotherapy was not going to cure their cancer (16). Patients with an understanding of the incurable nature of cancer were less likely to receive chemotherapy in EOL period and associated with increased enrollment to hospice services prior to death (17).
In the present study at the HKU-SZH, 9.3% of patients received cytotoxic chemotherapy during the last month. This percentage was relatively low compared with other reports in the literature as listed above. For example, one major hospital in Central China reported more than 40% chemotherapy use in the last 1-3 months of life (18). This favorable outcome may be attributed to several reasons.
Firstly, in the HKU-SZH, we emphasized open and thorough communication of the treatment plan with families (19). In the communication process, we discussed the prognosis and defined the goal of care. We actively offered the option of best supportive care alone among the patients who had very poor prognosis and no evidence-based anti-cancer treatment options. Besides, if the patients and families decided to try a new chemotherapy regimen with limited evidence or efficacy, such decisions would be reviewed by senior oncologists. Once late-line chemotherapy was initiated, patient would be closely monitored for the treatment response and toxicity. The team would promptly stop the treatment if the early results of the regimen was unfavorable.
Another notable finding was that 47.2% of patients in the current cohort had never received cytotoxic chemotherapy or other systemic anti-cancer therapies. This group of patients were older, and more likely to have primaries of lung, hepatobiliary tract and stomach. Possible reasons for this phenomenon were manifold. It might be related to the lack of effective systemic treatment options for these cancers. This was especially the case before the approval of immunotherapies in China. Many novel targeted agents, which might be less toxic than conventional chemotherapy, were either not available or too expensive in mainland China at the time of the cohort. Besides, integrated palliative care was readily provided by the HKU-SZH team which was a reasonable alternative to the ineffective and toxic systemic treatments.
The present study identified that younger patients and patients who had undergone previous anticancer therapies are more likely to continue chemotherapy in the last month of their life. Furthermore, our data suggest that patients with ovarian cancer are most likely to receive chemotherapy in the last month. These results were consistent with other reports (20). Further studies are needed to evaluate the decision-making process as well as the impact of such an aggressive approach on EOL care and bereavement process of care-givers.
Emergency admission and ICU utilization in the EOL period
The present study found that 48.5% of patients with advanced cancer were admitted via the A&E department. In this group of patients, about half of them were visiting HKU-SZH for the first time and subsequently expired during the admission.
The cause of such high rate of A&E utilization was multifold. The home-care service or family physician system were in infancy in mainland China. The social support of patients at Shenzhen City was also weaker than traditional community as Shenzhen is a city of immigrants. Many patients were thousand miles away from their ancestral home and hence was inaccessible to their social supportive network.
Besides, many hospitals in the city were reluctant to admit critically ill late-stage cancer patients while HKU-SZH A&E had performance pledge to accept all patients. The high rate of A&E utilization was consistent with other reports, including the study conducted at the Seoul National University Hospital that (21) visits to the emergency room by cancer patients during the last month of their life had increased from 22.8% in 2002 to 74.8% in 2012.
For ICU utilization in EOL period, the rate improved from 18% in the first year of HKU-SZH service to 4–5% in 2nd to 3rd year. The rate was comparative low compared with other major center in mainland China which reported the rate of around 25% (18). The improvement was likely contributed to maturation of the clinical teams and improved collaboration amongst different departments. In the current cohort, the use of chemotherapy in the last month was strongly associated with ICU admission in the EOL period. This was consistent with other reports which suggested chemo in EOL period was associated with an increased risk of undergoing CPR, mechanical ventilation, and dying in the ICU (22,23).
Placement of DNR orders
In the present study at the HKU-SZH, the overall rate of consent to the DNR order was >90%. In a similar report at Guangdong Lung Cancer Institute, Wang et al. reported that consent to the DNR order among patients with lung cancer was 74.7% (24). This disparity may be due to different practices between these two medical institutions. The Guangdong Lung Cancer Institute is a specialized lung cancer center focusing on the anticancer treatment. In contrast, the HKU-SZH Cancer Center is a general comprehensive hospital aiming at provision of integrated palliative care service.
The current cohort at Shenzhen and another palliative care unit from Shanghai report (25) were different from Western reports that most of the DNR order was placed after discussion of health care team with the families, rather than patients themselves. The median interval between the placement of DNR order and death was 2 days, that means most of the DNR decision occurred very close to patients’ death. Such a “last minutes” DNR order was common in mainland China. This was probably related to the cultural meaning of “seeing the patient for the last time”. Doctors usually would not consider DNR until the impending death was certain and would wait until all the significant family members had “seen” the patients.
The rate of DNR placement differed between departments with HKU-SZH, being higher in the clinical oncology center (96.1%) than other departments (83.1%). The team approach of clinical oncology center may contribute to this higher success rate of DNR placement. This highlighted the importance of integrative palliative care team in acute hospital setting and the need of more training on EOL care in other clinical departments.
The major limitation to our study was that the data were retrospectively collected in design. Besides we could not review the minority of patients (n<10) who were discharged near death, which might have affected the accuracy of the rate of chemotherapy in the last 30 days. We are conducting a prospective longitudinal observational study in a cohort of patients with advanced cancer admitted in the palliative unit in HKU-SZH. We are also in the process of standardizing an integrative palliative care model reimbursement system of Shenzhen.
The integrative oncology service of the new public hospital HKU-SZH had yielded a satisfactory level of palliative care in advanced cancer patients. Further studies are warranted to investigate the impact of the system on quality of life of patients and their caregivers, as well as the best model to promote early integration of palliative care in mainland China.
The authors are extremely grateful for the generous contributions of the nurses, social workers, medical record administrators and other staff in this project.
Funding: This study was supported by Health and Family Planning Commission of Shenzhen Municipality, which had changed to Shenzhen Municipal Health Commission (Project ID: SZFZ201706).
Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Palliative Medicine for the series “Integrating Palliative Medicine in Oncology Care: The Hong Kong Experience”. The article has undergone external peer review.
Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at http://dx.doi.org/10.21037/apm-19-268
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/apm-19-268). The series “Integrating Palliative Medicine in Oncology Care: The Hong Kong Experience” was commissioned by the editorial office without any funding or sponsorship. TCL served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study had obtained the approval of HKU-SZH institutional review board (no: 2017-01). As it is a retrospective descriptive study, there was no informed consent.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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