Prognostic implications of thymidylate synthase gene polymorphisms in patients with advanced small bowel adenocarcinoma treated with first-line fluoropyrimidine-based chemotherapy.

Thymidylate synthase (TS) gene polymorphisms such as tandem repeat (TR) polymorphisms and single-nucleotide polymorphisms (SNPs) affect transcriptional efficiency of the TS gene and may be prognostic markers for fluoropyrimidine-based therapy in various gastrointestinal cancers. However, data for TS polymorphisms on clinical outcomes in advanced small bowel adenocarcinoma (SBA) are limited. We retrospectively enrolled 58 locally advanced/metastatic SBA patients treated with first-line fluoropyrimidine-based chemotherapy and analyzed the relationship between TS genotypes and clinical outcomes in 30 patients who were available for tumor tissue. Based on TR polymorphisms and a G>C SNP in the promoter region of the TS gene, 74% of patients had high TS expression genotypes (2R/3RG, 3RG/3RC, 3RG/3RG); the remainder had low TS expression genotypes (2R/2R, 2R/3RC, 3RC/3RC). After a median follow-up of 48.8 months, median progression-free survival (PFS) and overall survival (OS) in all patients were 6.0 and 11.3 months, respectively. However, patients with low TS expression genotypes had better median PFS (12.8 vs. 4.3 months, P=0.027) and OS (28.8 vs. 8.9 months, P=0.025) than those with high TS expression genotypes. In multivariate analysis, poor Eastern Cooperative Oncology Group performance status [hazard ratio (HR), 2.85; 95% CI, 1.02-7.93] and high TS expression genotypes (HR, 3.49; 95% CI, 1.13-10.78) were independent prognostic factors for worse OS. Therefore, TS genotypes, based on a G>C SNP in the TR sequence of the TS gene, may be a useful biomarker for predicting outcomes for fluoropyrimidine-based chemotherapy in patients with locally advanced/metastatic SBA.

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.

Noninterventional observational study using high-dose controlled-release oxycodone (CR oxycodone) for cancer pain management in outpatient clinics.

PURPOSE: Efficacy, safety, and quality of life (QoL) for patients receiving larger doses of controlled-release oxycodone (CR oxycodone) in outpatient clinics are evaluated. METHODS: The use of high-dose CR oxycodone and adjuvant drugs for pain management, pain intensity, parameters associated with quality of life, and adverse effects in cancer patients treated with high-dose CR oxycodone (≥80 mg/day) was prospectively observed for 8 weeks. Data from 486 cancer patients receiving high-dose CR oxycodone were collected from 44 hospitals during the period from February 2009 to March 2010. RESULTS: Three hundred eighteen of the total 486 patients treated with high-dose CR oxycodone were followed up for 8 weeks. Pain intensity significantly improved from a mean numeric rating scale (NRS) 5.49 to NRS 4.33 (P < 0.0001). Dosage of CR oxycodone increased from a mean of 130.0 to a mean of 174.9 (P < 0.0001). QoL including activity, walking, and sleeping significantly improved after 8 weeks. At baseline, 138 complained of adverse effects, of which constipation (30.2%) was the most common followed by dry mouth (8.8%) and dizziness (8.2%). After 8 weeks, 128 patients complained of adverse effects such as constipation (27.0%), nausea (5.7%), dry mouth (5.7%), and dizziness (5.0%). After 8 weeks of high-dose CR oxycodone, adverse effects did not increase. CONCLUSION: This study suggests that over an 8-week period, the use of high-dose CR oxycodone for cancer pain management is efficient, safe, and tolerable in outpatient clinics.

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.

Factors associated with place of death in koprean patients with terminal cancer.

AIM: To investigate factors that affect the place of death (POD) of terminal cancer patients. MATERIALS AND METHODS: We recruited 702 consecutive patients (>18 years) from 12 centers during July 2005 to October 2006, and 481 completed the questionnaire. In April 2011, we linked the data for 96.0% (n=462) of the deceased patients to the POD using the 2005-2009 death certificate data of Korea's National Statistical Office. The primary outcome variable was POD, and the predictive value of variables pertaining to patients and caregivers was evaluated using univariate and multivariate analyses. RESULTS: Most patients died in a hospital (91.5%, n=441) and age, education, preference for place of terminal care, wish to use hospice/palliative care services, terminal cancer awareness, time between diagnosis and death, and global quality-of-life subscale of the EORTC QLQ-C30 of patients, and education and preference for place of terminal care of caregivers were significant predictors in univariate analyses. On multivariate analysis, patients and caregivers who preferred hospital/palliative care as the terminal care option over home care [adjusted odds ratio (aOR), 2.68; 95% confidential interval (CI), 1.18- 7.04 and aOR: 2.65; 95%CI: 1.15-6.09 for patient and caregiver preferences, respectively] and caregivers who were highly educated (aOR, 3.19; 95%CI, 1.44-7.06) were predictors of POD. CONCLUSIONS: Most of the terminal cancer patients died in a hospital. Our findings indicate that major predictors of hospital deaths are preference of both the patient and caregiver for hospital/palliative care as the terminal care option and higher education of the caregiver.

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).

Change in cancer pain management in Korea between 2001 and 2006: results of two nationwide surveys.

CONTEXT: In Korea, many health care professionals have shown increased concern about the management of cancer pain. Five years after a pain management guideline was distributed to Korean physicians, the Korean Society of Hospice and Palliative Care evaluated the change in cancer pain management. The period evaluated was between 2001 and 2006. METHODS: We did a prospective, cross-sectional cancer pain survey on the change of the pain prevalence and pain intensity, its impact on daily activities and the adequacy of pain management between 2001 and 2006. RESULTS: Overall, 7565 patients were enrolled from 72 cancer hospitals in the 2001 cancer pain survey and 7245 patients were enrolled from 63 cancer hospitals in the 2006 cancer pain survey. The overall prevalence of cancer pain and the percentage of patients reporting a negative pain management index were significantly decreased in the 2006 cancer pain survey compared with the 2001 cancer pain survey (44.9% vs. 52.1%, P<0.0001 and 41.6% vs. 45.0%, respectively, P=0.0005). However, in 2006, physicians did not prescribe analgesics to 25.8% of the patients with severe pain and they did not adjust the prescribed analgesics properly in 47.4% of the patients with severe pain. CONCLUSION: Some improvement in cancer pain management was noted during the five years between 2001 and 2006. However, all of the physicians who care for cancer patients should pay more attention to cancer pain management, and an educational program for cancer pain management should be distributed to all of the physicians who care for cancer patients.

Gemcitabine and oxaliplatin in patients with unresectable biliary cancer including gall bladder cancer: a Korean Cancer Study Group phase II trial.

PURPOSE: Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months in patients with biliary tract cancers (BTCs). The aim of this study was to evaluate the efficacy and safety of the combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) in patients with BTCs including gall bladder cancer. METHODS: We carried out a nationwide multicenter phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTCs received gemcitabine 1,000 mg/m(2) (day 1 and 8) and oxaliplatin 100 mg/m(2) (day 1), every 3 weeks. RESULTS: Fifty-three patients were evaluated, 60% had cholangiocarcinoma and the remaining 40% gall bladder cancer; the objective response rate was 18.9% (10/53 patients including 1 Complete response) [14.9%; 95% confidence interval (CI), 7.4-25.7%] in the treated population. Stable disease were observed in 27/53 (50.9%) patients, disease control rate was achieved in 69.8% of all patients. Median progression-free survival was 4.8 months (3.1-6.5, 95% CI) and median overall survival was 8.3 months (5.8-10.8, 95% CI). Grade 3/4 toxicities included neutropenia (33.9% of patients) and thrombocytopenia (7.6%). CONCLUSIONS: The GEMOX regimen demonstrated a modest antitumor activity and is well tolerated in patients with advanced BTCs.

Change in patients' satisfaction with pain control after using the Korean cancer pain assessment tool in Korea.

Appropriate pain assessment is very important for managing cancer pain. This study was designed to evaluate the utility of the Korean Cancer Pain Assessment Tool (KCPAT) by assessing changes in the management of cancer pain. The changes in pain intensity, the pattern of drug prescriptions, and the patients' satisfaction with pain control were analyzed after using the KCPAT. The results indicated that pain medicine prescriptions were changed in 194 (51.5%) cases after using the KCPAT, and 69.5% of these changes were affected by the KCPAT. After using the KCPAT, pain intensity as assessed by the Visual Analogue Scale (VAS, 0-10cm) decreased (4.31+/-2.35 vs. 3.60+/-2.45, P<0.0001), and the presence of associated symptoms and psychosocial items was significantly reduced. The patients' satisfaction with pain control was improved. Forty-four physicians (89.8%) thought that the KCPAT was useful. The KCPAT improved patients' satisfaction with pain control and was a useful tool for evaluating and managing cancer pain.

Hyperfractionated radiotherapy with concurrent chemotherapy for para-aortic lymph node recurrence in carcinoma of the cervix.

PURPOSE: To evaluate efficacy, toxicity, and patterns of relapse in patients treated with hyperfractionated radiotherapy (HFRT) with concurrent chemotherapy for para-aortic lymph node (PALN) recurrence of cervical carcinoma. METHODS AND MATERIALS: Between September 1997 and October 2000, 12 cervical carcinoma patients with isolated PALN recurrence who had previously received radical or postoperative radiotherapy were treated with HFRT and concurrent chemotherapy. The initial FIGO stage was Stage IB in 4 (33%) patients, Stage IIA in 2 (17%), and Stage IIB in 6 (50%). The radiation field encompassed the gross recurrent PALN with the superior margin at the upper end of the T12 body and the inferior margin between L5 and S1. The fractionated dose was 1.2 Gy in 2 daily fractions, and the median total dose was 60 Gy. The weekly concurrent chemotherapy consisted of paclitaxel in 11 patients and cisplatin in 1. The median number of cycles of chemotherapy was 5. RESULTS: The latent period to PALN recurrence from the time of initial treatment for all patients ranged from 2 to 92 months (median: 12 months). One month after treatment, the clinical tumor response evaluated was complete in 33% (4/12) and partial in 67% (8/12). The 3-year overall survival rate and median survival were 19% and 21 months, respectively. The latent period to PALN recurrence was the only significant prognostic factor; the median survival of patients who relapsed in < or =24 months from the initial treatment of cervical carcinoma was 13 months vs. 45 months for those relapsed at >24 months (p = 0.026). Grade 3-4 hematologic toxicity developed in 2 patients. Six (50%) patients experienced Grade 2 nausea. There were no late gastrointestinal or neurologic complications during the follow-up period. Subsequent distant metastases after PALN treatment developed in 58% (7/12). CONCLUSION: HFRT of 60 Gy to PALN with concurrent chemotherapy could be regarded as an effective treatment modality without significant acute or late toxicity. Patients with a latent period >24 months until PALN recurrence had a more favorable survival rate than those with a latent period