Efficacy of a Decision Aid Consisting of a Video and Booklet on Advance Care Planning for Advanced Cancer Patients: Randomized Controlled Trial.

CONTEXT: Few randomized controlled trials of advance care planning (ACP) with a decision aid (DA) show an effect on patient preferences for end-of-life (EOL) care over time, especially in racial/ethnic settings outside the U.S. OBJECTIVES: The objective of this study was to examine the effect of a decision aid consisting of a video and an ACP booklet for EOL care preferences among patients with advanced cancer. METHODS: Using a computer-generated sequence, we randomly assigned (1:1) patients with advanced cancer to a group that received a video and workbook that both discussed either ACP (intervention group) or cancer pain control (control group). At baseline, immediately after intervention, and at 7 weeks, we evaluated the subjects' preferences. The primary outcome was preference for EOL care (active treatment, life-prolonging treatment, or hospice care) on the assumption of a fatal disease diagnosis and the expectation of death 1) within 1 year, 2) within several months, and 3) within a few weeks. We used Bonferroni correction methods for multiple comparisons with an adjusted P level of 0.005. RESULTS: From August 2017 to February 2018, we screened 287 eligible patients, of whom 204 were enrolled to the intervention (104 patients) or the control (100 patients). At postintervention, the intervention group showed a significant increase in preference for active treatment, life-prolonging treatment, and hospice care on the assumption of a fatal disease diagnosis and the expectation of death within 1 year (P < 0.005). Assuming a life expectancy of several months, the change in preferences was significant for active treatment and hospice care (P < 0.005) but not for life-prolonging treatment. The intervention group showed a significant increase in preference for active treatment, life-prolonging treatment, and hospice care on the assumption of a fatal disease diagnosis and the expectation of death within a few weeks (P < 0.005). From baseline to 7 weeks, the decrease in preference in the intervention group was not significant for active treatment, life-prolonging treatment, and hospice care in the intervention group in the subset expecting to die within 1 year, compared with the control group. Assuming a life expectancy of several months and a few weeks, the change in preferences was not significant for active treatment and for life-prolonging treatment but was significantly greater for hospice care in the intervention group (P < 0.005). CONCLUSION: ACP interventions that included a video and an accompanying book improved preferences for EOL care.

Correction to: The impact of caregiver's role preference on decisional conflicts and psychiatric distresses in decision making to help caregiver's disclosure of terminal disease status.

In the original publication of the article, the incorrect grant number HC13C1391 was published in the acknowledgement section. The correct grant number is HC15C1391.

The impact of caregiver's role preference on decisional conflicts and psychiatric distresses in decision making to help caregiver's disclosure of terminal disease status.

PURPOSE: The objective of this study was to investigate the impact of caregivers' role preference in decision making on conflicts and psychiatric distresses. METHODS: The responses of 406 caregivers of terminal cancer patients enrolled in a trial determining the efficacy of a decision aid focused on the disclosure of terminal disease status were included in this secondary analysis. The outcomes include the change scores of the Decision Conflict Scale (DCS) and depression and anxiety subscales of the Hospital Anxiety and Depression Scale (HADS) at the 1 and 3 months from baseline. The linear mixed model was employed to discover the impact of caregivers' decisional role preference on the outcomes. FINDINGS: Of the 406, 137 (33.7%) showed an active role preference and 269 (66.3%) showed a passive role preference. In the post hoc analysis of the adjusted differences of change scores between passive caregivers who received decision aid (passive-decision aid) and active caregivers with decision aid (active-decision aid), non-significant differences were observed in the DCS. However, at the 3-month, the change scores of the HADS depression subscale increased by 4.43 (effect size, 0.71) and those of the HADS anxiety subscale increased by 4.14 (effect size, 0.61) in the passive-decision aid group than in active-decision aid group, showing moderate to large difference. CONCLUSIONS: These findings suggest that information might be ethically recommended in a format that is interactive and tailored to how much an individual wishes to be involved in the decision-making process.

Changes in health-related quality of life and quality of care among terminally ill cancer patients and survival prediction: Multicenter prospective cohort study.

OBJECTIVE: This study examined changes in health-related quality of life (HRQoL) and quality of care (QoC) as perceived by terminally ill cancer patients and a stratified set of HRQoL or QoC factors that are most likely to influence survival at the end of life (EoL). METHOD: We administered questionnaires to 619 consecutive patients immediately after they were diagnosed with terminal cancer by physicians at 11 university hospitals and at the National Cancer Center in Korea. Subjects were followed up over 161.2 person-years until their deaths. We measured HRQoL using the core 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, and QoC using the Quality Care Questionnaire-End of Life (QCQ-EoL). We evaluated changes in HRQoL and QoC issues during the first three months after enrollment, performing sensitivity analysis by using data generated via four methods (complete case analysis, available case analysis, the last observation carried forward, and multiple imputation). RESULTS: Emotional and cognitive functioning decreased significantly over time, while dyspnea, constipation, and pain increased significantly. Dignity-conserving care, care by healthcare professionals, family relationships, and QCQ-EoL total score decreased significantly. Global QoL, appetite loss, and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scores were significantly associated with survival. SIGNIFICANCE OF RESULTS: Future standardization of palliative care should be focused on assessment of these deteriorated types of quality. Accurate estimates of the length of life remaining for terminally ill cancer patients by such EoL-enhancing factors as global QoL, appetite loss, and ECOG-PS are needed to help patients experience a dignified and comfortable death.

The Understanding of Terminal Cancer and Its Relationship with Attitudes toward End-of-Life Care Issues.

BACKGROUND: Although terminal cancer is a widely used term, its meaning varies, which may lead to different attitudes toward end-of-life issues. The study was conducted to investigate differences in the understanding of terminal cancer and determine the relationship between this understanding and attitudes toward end-of-life issues. METHODS: A questionnaire survey was performed between 2008 and 2009. A total of 1242 cancer patients, 1289 family caregivers, 303 oncologists from 17 hospitals, and 1006 participants from the general population responded. RESULTS: A "6-month life expectancy" was the most common understanding of terminal cancer (45.6%), followed by "treatment refractoriness" (21.1%), "metastatic/recurrent disease" (19.4%), "survival of a few days/weeks" (11.4%), and "locally advanced disease" (2.5%). The combined proportion of "treatment refractoriness" and "6-month life expectancy" differed significantly between oncologists and the other groups combined (76.0% v. 65.9%, P = 0.0003). Multivariate analyses showed that patients and caregivers who understood terminal cancer as "survival of a few days/weeks" showed more negative attitudes toward disclosure of terminal status compared with participants who chose "treatment refractoriness" (adjusted odds ratio [aOR] 0.42, 95% confidence interval [CI] 0.22-0.79 for patients; aOR 0.34, 95% CI 0.18-0.63 for caregivers). Caregivers who understood terminal cancer as "locally advanced" or "metastatic/recurrent disease" showed a significantly lower percentage of agreement with withdrawal of futile life-sustaining treatment compared with those who chose "treatment refractoriness" (aOR 0.19, 95% CI 0.07-0.54 for locally advanced; aOR 0.39, 95% CI 0.21-0.72 for metastatic/recurrent). CONCLUSIONS: The understanding of terminal cancer varied among the 4 participant groups. It was associated with different preferences regarding end-of-life issues. Standardization of these terms is needed to better understand end-of-life care.

Employment status and work-related difficulties among family members of terminally ill patients compared with the general population.

BACKGROUND: Although caregiving to patients with terminal illness is known to be a stressful burden to family members, little attention has been focused on work-related problems. We aimed to investigate employment status and work-related difficulties of family caregivers of terminal cancer patients, comparing with the general population. METHODS: Using structured questionnaires, we assessed family caregivers of 481 cancer patients determined by physicians to be terminally ill, from 11 university hospitals and the National Cancer Center in Korea. RESULTS: Among 381 family caregivers of terminal cancer patients (response rate, 87.6%), 169 (43.9%) were not working before cancer diagnosis, but currently 233 (63.7%) were not working. Compared with the general population (36.5%), the percentage of not working among the family caregivers was higher (OR = 2.39; 95% CI= 1.73-3.29). A major reason for not working was to provide assistance to the patients (71.6%). 40.6% of those who continued working and 32.3% of those who not working family members reported extreme fatigue. Caregivers of old age, those who were female, those with a lower household income, and those caring for patients with a low performance status were not working at a more significant rate. CONCLUSION: Family caregivers of terminal cancer patients suffer job loss and severe work-related difficulties, probably due to caregiving itself and to fatigue. We need to develop supportive programs to overcome the burden of caregivers of the terminally ill.

The attitudes of Korean cancer patients, family caregivers, oncologists, and members of the general public toward advance directives.

PURPOSE: The purpose of this study was to investigate Korean attitudes toward advance directives (ADs) among cancer patients, family caregivers, oncologists, and the general public. METHODS: A multicenter survey study explored the attitudes of participants to ADs, and hospice-palliative care (HPC) was conducted. A total of 1,242 cancer patients, 1,289 family caregivers, 303 oncologists, and 1,006 members of the general public participated in the survey. RESULTS: The majority of patients, family caregivers, oncologists, and general public agreed with the necessity of ADs. However, oncologists regard "when became terminal status" as an optimal timing for completion of ADs (52.2 %), while other groups regard earlier periods as it. More than 95 % oncologist answered that cardiopulmonary resuscitation and mechanical ventilator are necessity items for ADs form, while around 70 % of other groups answered so. Multivariate analysis revealed that several factors including agreement with terminal disclosures and a positive attitude toward HPC were independently associated with necessity of ADs. CONCLUSIONS: We found that attitudes toward ADs among cancer patients, family caregivers, oncologists, and the general public were significantly different. Our study also suggests that favorable attitudes toward comfort end-of-life care and HPC are keys that influence the perceived need for ADs.

Complementary and alternative medicine use among cancer patients at the end of life: Korean national study.

OBJECTIVES: To investigate in depth the use of complementary and alternative medicines (CAMs) by cancer patients at the end-of-life (EOL) and how they communicate with physicians about them. DESIGN AND LOCATION: In 17 hospitals in Korea between January and December 2004 we identified 4,042 families of cancer patients. RESULTS: The prevalence of CAM use among cancer patients at the EOL was 37.0%, and 93.1% had used pharmacologic types of agents. The most frequent motive for CAM use was the recommendation of friends or a close relative (53.4%) or a physician (1.6%). Only 42.5% discussed CAM use with their physicians. Satisfaction with CAMS was recalled for 37.1% . The most common reason given for that satisfaction was improvement of emotional or physical well-being, while ineffectiveness was the most common reason given for dissatisfaction. The average cost of CAM during the last month of life was $US 900. CAM use was associated with longer disease periods, primary cancers other than liver, biliary, and pancreatic, and need of support from physicians or religion. CONCLUSIONS: CAM use among cancer patients at the EOL was common, not discussed with physicians, and associated with expectation of cure. Expectations were generally unmet while the treatments were a financial burden. Further studies evaluating the effects of CAM at the EOL and factors that enhance communication with the physician are needed.

Use of a decision aid to help caregivers discuss terminal disease status with a family member with cancer: a randomized controlled trial.

PURPOSE: We tested whether a decision aid explaining how to discuss the approach of death with a family member with cancer would help family caregivers decide to discuss a terminal prognosis. PATIENTS AND METHODS: We randomly assigned caregivers of terminally ill patients with cancer to a group that received a video and a companion workbook that showed either how they can discuss the prognosis with their patient (experimental arm) or how cancer pain can be controlled (control arm). At baseline and 1 month, we evaluated the decision to discuss terminal prognosis as the primary outcome. At 0, 1, 3, and 6 months, we assessed the caregivers' decisional conflict and satisfaction as secondary outcomes using a Decision Conflict Scale (DCS). RESULTS: We found no difference in changes in the decision to discuss terminal prognosis between the two groups. Conflict (P = .003), uncertainty (P = .019), and value clarity (P = .007) subscale scores and total DCS score (P = .008) improved from baseline to 1 month significantly more in the experimental arm than in the control arm. Over 6 months, the significant between-group differences continued for the conflict (P = .031), uncertainty (P = .014), and value clarity (P = .039) subscale scores and total DCS score (P = .040). CONCLUSION: Decision aids can help caregivers, with the aid of trained professionals, to communicate with patients about their terminal illness.

Attitudes of cancer patients, family caregivers, oncologists and members of the general public toward critical interventions at the end of life of terminally ill patients.

BACKGROUND: Whereas most studies have focused on euthanasia and physician-assisted suicide, few have dealt comprehensively with other critical interventions administered at the end of life. We surveyed cancer patients, family caregivers, oncologists and members of the general public to determine their attitudes toward such interventions. METHODS: We administered a questionnaire to four groups about their attitudes toward five end-of-life interventions--withdrawal of futile life-sustaining treatment, active pain control, withholding of life-sustaining measures, active euthanasia and physician-assisted suicide. We performed multivariable analyses to compare attitudes and to identify sociodemographic characteristics associated with the attitudes. RESULTS: A total of 3840 individuals--1242 cancer patients, 1289 family caregivers and 303 oncologists from 17 hospitals, as well as 1006 members of the general Korean population--participated in the survey. A large majority in each of the groups supported withdrawal of futile life-sustaining treatment (87.1%-94.0%) and use of active pain control (89.0%-98.4%). A smaller majority (60.8%-76.0%) supported withholding of life-sustaining treatment. About 50% of those in the patient and general population groups supported active euthanasia or physician-assisted suicide, as compared with less than 40% of the family caregivers and less than 10% of the oncologists. Higher income was significantly associated with approval of the withdrawal of futile life-sustaining treatment and the practice of active pain control. Older age, male sex and having no religion were significantly associated with approval of withholding of life-sustaining measures. Older age, male sex, having no religion and lower education level were significantly associated with approval of active euthanasia and physician-assisted suicide. INTERPRETATION: Although the various participant groups shared the same attitude toward futile and ameliorative end-of-life care (the withdrawal of futile life-sustaining treatment and the use of active pain control), oncologists had a more negative attitude than those in the other groups toward the active ending of life (euthanasia and physician-assisted suicide).

Impact of awareness of terminal illness and use of palliative care or intensive care unit on the survival of terminally ill patients with cancer: prospective cohort study.

PURPOSE: We conducted this study to evaluate the validity of the perception that awareness of their terminal prognosis and use of palliative care or nonuse of an intensive care unit (ICU) causes patients to die sooner than they would otherwise. PATIENTS AND METHODS: In this prospective cohort study at 11 university hospitals and the National Cancer Center in Korea, we administered questionnaires to 619 consecutive patients immediately after they were determined by physicians to be terminally ill. We followed patients during 6 months after enrollment and assessed how their survival was affected by the disclosure of terminal illness and administration of palliative care or nonuse of the ICU. RESULTS: In a follow-up of 481 patients and 163.8 person-years, we identified 466 deceased patients. Nineteen percent of the patients died within 1 month, while 41.3% lived for 3 months, and 17.7% lived for 6 months. Once the cancer was judged terminal, the median survival time was 69 days. On multivariate analysis, neither patient awareness of terminal status at baseline (adjusted hazard ratio [aHR], 1.20; 95% CI, 0.96 to 1.51), use of a palliative care facility (aHR, 0.96; 95% CI, 0.76 to 1.21), nor general prostration (aHR, 1.23; 95% CI, 0.96 to 1.57) was associated with reduced survival. Use of the ICU (aHR, 1.47; 95% CI, 1.06 to 2.05) and poor Eastern Cooperative Oncology Group performance status (aHR, 1.37; 95% CI, 1.10 to 1.71) were significantly associated with poor survival. CONCLUSION: Patients' being aware that they are dying and entering a palliative care facility or ICU does not seem to influence patients' survival.

The life-sustaining treatments among cancer patients at end of life and the caregiver's experience and perspectives.

GOALS OF WORK: The goal of this study was to investigate the utilization of and attitudes toward life-sustaining treatments (LSTs) at the end of life. MATERIALS AND METHODS: We identified 4,042 families of cancer patients who had died at any of 17 hospitals in Korea during 2004. Among those, we analyzed the interviews provided by 1,592 (39.4%) primary caregivers. Only women who provided information in baseline and follow-up point could be included for internal comparison. MAIN RESULTS: Most caregivers did not discuss with their patient the option of utilizing the intensive care unit (ICU; 92.7%) or cardiopulmonary resuscitation (CPR; 93.7%) to prolong an ending life. Logistic regressions indicated that the ICU was more likely to be utilized when patients experienced an unexpected medical problem before dying, discussed the ICU with the family caregiver, or were low-educated. CPR was more likely to be used if the patient died within 6 months of diagnosis or the family caregiver was <65 years old. Family caregivers more likely to use the ICU if placed in the same situation again were those whose patients had a higher monthly income or died within 6 months of diagnosis, low-educated, or had utilized the ICU. CONCLUSIONS: Our findings underscore the importance of discussing LST with terminally ill patients based on adequate information.

Impact of caregivers' unmet needs for supportive care on quality of terminal cancer care delivered and caregiver's workforce performance.

GOALS OF WORK: Family caregivers play an important role in caring for cancer patients, but the impact of caregivers' unmet needs on the quality of end-of-life (EOL) care they deliver and on their workplace performance are less understood. PATIENTS AND METHODS: We identified 1,662 family caregivers of cancer patients who had died at any of 17 hospitals in Korea during 2004. The caregivers answered a telephone questionnaire about needs that were not met when they delivered terminal cancer care and how those unmet their needs affected their workplace performance; they also answered the Quality Care Questionnaire-End of Life (QCQ-EOL). RESULTS: Compared with caregivers who did not have unmet needs, caregivers who had unmet needs for symptom management, financial support, or community support showed poorer QCQ-EOL scores (P < 0.01). Caregivers who had unmet needs for financial support (adjusted odds ratio (aOR) = 7.55; 95% confidential interval (CI) 3.80-15.00), psychosocial support (aOR = 6.24; 95% CI 2.95-13.05), symptom management (aOR = 3.21; 95% CI 2.26-4.54), community support (aOR = 3.82; 95% CI 2.38-6.11), or religious support (aOR = 4.55; 95% CI 1.84-11.26) were more likely to experience work limitations. Caregivers of patients receiving conventional hospital care were more likely to have unmet needs for symptom management (aOR = 1.21; 95% CI 1.00-1.47), psychosocial support (aOR = 1.99; 95% CI 1.37-2.88), and religious support (aOR = 1.73; 95% CI 1.08-2.78) than those of patients receiving palliative hospice care. CONCLUSIONS: Caregivers' unmet needs negatively affected both the quality of EOL care they delivered and their workplace performance. More investment in caregiver support and public policies that meet caregiver needs are needed, and hospice use should be encouraged.

Multicenter study of pain and its management in patients with advanced cancer in Korea.

The aim of this study was to evaluate the prevalence, severity, and management of pain in Korean patients with advanced cancer, and to identify the predictors of inadequate management of cancer pain in Korea. From 8 university hospitals, 655 patients with advanced cancer were surveyed. Information concerning analgesics prescribed was acquired from the medical records by the investigator. Physicians, nurses and caregivers were asked to estimate patients' pain. The Korean Brief Pain Inventory and the Barrier Questionnaire were completed by the patients. The Pain Management Index was estimated. Among all patients, 70.8% (464 of 655) reported pain. Among those who had pain, 63.6% (295 of 464) reported pain rated 5 or higher on a 0-10 scale. Thirty-nine percent of the patients had not received any analgesics and 53.2% were not receiving optimal pain management. Although there was a correlation between patients' pain ratings and those of doctors, nurses, and caregivers, there was no significant correlation between patients' ratings and health care providers' ratings at pain levels above moderate intensity. Cancer pain was more poorly managed in advanced cancer than terminal cancer patients (OR:3.20, 95%C.I, 1.83-5.60), in patients with better performance(OR:3.17, 95%C.I, 1.64-6.11), and in those patients whose pain was underestimated by the doctor (OR:2.58, 95%C.I. 1.42-4.69). Despite the high prevalence and severity of pain in cancer patients, the assessment and management of cancer pain were found to be inadequate in Korea.

Involvement of Ras in survival responsiveness to nitric oxide toxicity in pheochromocytoma cells.

Nitric oxide (NO) plays a key role in attenuation of tumor growth by activated macrophages that generate large amount of cytotoxic/cytostatic free radicals. However, some tumor cells may survive from NO cytotoxicity and continue to proliferate to malignant tumors. Since a protooncogene product Ras was shown to be activated by NO, this study investigated the involvement of Ras in the cell survival in response to NO cytotoxicity in pheochromocytoma (PC12) cells. Treatment with Ras inhibitor or constitutive expression of dominant negative Ras markedly increased NO-induced cell death. NO-resistant PC12 cells (PC12-NO-R) exhibited higher steady state Ras activity than the parental PC12 cells. Inducible expression using tetracycline-on (Tet-on) system of Ras mutants (dominant negative Ras or dominant active Ras) demonstrated that blockade of Ras activity increased NO-induced cell death whereas enhancement of Ras activity attenuated NO-induced cell death. Furthermore, inducible expression of NO-insensitive mutant Ras selectively increased cellular vulnerability to NO but not to ROS. NO, Ras inhibitor and extracellular signal-regulated kinase (Erk) blocker synergistically increased cell death. These observations suggest that Ras activity may be a critical factor for survival response of tumor cells to NO toxicity and pharmacological agents affecting Ras activity may enhance efficacy of NO-mediated tumor therapies.

Efficacy of Combination Chemotherapy with Paclitaxel and Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer.

PURPOSE: To evaluate the efficacy and toxicity of the combination therapy of paclitaxel and cisplatin in advanced, non-small cell, lung cancer patients. MATERIALS AND METHODS: Between December 1997 and September 2001, 37 patients with advanced, non-small cell, lung cancer were enrolled in this study. Patients were treated with paclitaxel (135 mg/m2, 24 hr infusion) and cisplatin (75 mg/m2). The treatments were repeated every 4 weeks. RESULTS: Among the 37 patients enrolled, 21 were treated with paclitaxel and cisplatin as a first-line and 16 patients as a second-line. The median age of the patients was 59. In the first-line group, 10 had stage IIIB and 11 had stage IV, non small cell lung cancer. Of 21 patients in first-line treatment group that could be evaluated, objective responses were observed in 6 patients (response rate: 28.6%, CR: 4.8%, PR: 23.8%). The mediansurvival duration for patients was 48 weeks. With the second-line group, 3 patients showed a partial response (response rate: 18.7%) to treatment, with median survival duration of 44 weeks. Grade 3-4 leukopenia was observed in 27.1% of the first-line, and 23.6% in second- line, treatment groups. CONCLUSION: Combination chemotherapy, with paclitaxel and cisplatin, in non-small cell lung cancer has acceptable toxicities in both first and second-line treatment groups. In terms of efficacy, no superior response was shown for either group. More randomized studies, with a larger group of patients, are required to prove the true efficacy.