Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: Results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04).

BACKGROUND: Cachexia, described as weight loss (mainly in lean body mass [LBM]) and anorexia, is common in patients with advanced cancer. This study examined the efficacy and safety of anamorelin (ONO-7643), a novel selective ghrelin receptor agonist, in Japanese cancer patients with cachexia. METHODS: This double-blind clinical trial (ONO-7643-04) enrolled 174 patients with unresectable stage III/IV non-small cell lung cancer (NSCLC) and cachexia in Japan. Patients were randomized to daily oral anamorelin (100 mg) or a placebo for 12 weeks. The primary endpoint was the change from the baseline LBM (measured with dual-energy x-ray absorptiometry) over 12 weeks. The secondary endpoints were changes in appetite, body weight, quality of life, handgrip strength (HGS), and 6-minute walk test (6MWT) results. RESULTS: The least squares mean change (plus or minus the standard error) in LBM from the baseline over 12 weeks was 1.38 ± 0.18 and -0.17 ± 0.17 kg in the anamorelin and placebo groups, respectively (P < .0001). Changes from the baseline in LBM, body weight, and anorexia symptoms showed significant differences between the 2 treatment groups at all time points. Anamorelin increased prealbumin at weeks 3 and 9. No changes in HGS or 6MWT were detected between the groups. Twelve weeks' treatment with anamorelin was safe and well tolerated in NSCLC patients. CONCLUSIONS: Anamorelin significantly increased LBM and improved anorexia symptoms and the nutritional state, but not motor function, in Japanese patients with advanced NSCLC. Because no effective treatment for cancer cachexia is currently available, anamorelin can be a beneficial treatment option. Cancer 2018;124:606-16. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Anamorelin (ONO-7643) in Japanese patients with non-small cell lung cancer and cachexia: results of a randomized phase 2 trial.

PURPOSE: Cancer cachexia is characterized by decreased body weight (mainly lean body mass [LBM]) and negatively impacts quality of life (QOL) and prognosis. Anamorelin (ONO-7643) is a novel selective ghrelin receptor agonist under development for treating cancer cachexia. METHODS: In this double-blind, exploratory phase 2 trial, we examined the efficacy and safety of anamorelin in Japanese patients (n = 181) with non-small cell lung cancer (NSCLC) and cancer cachexia (≥5 % weight loss within the previous 6 months). The participants were randomized into three groups and were administered 50 or 100 mg anamorelin, or placebo, orally every day for 12 weeks. The co-primary endpoints were the changes from baseline over 12 weeks in LBM and handgrip strength (HGS). Secondary endpoints included body weight, QOL, Karnofsky Performance Scale (KPS), and serum biomarkers. RESULTS: The change in LBM over 12 weeks was 0.55 and 1.15 kg in the placebo and 100-mg anamorelin groups, respectively, but the efficacy of anamorelin in HGS was not detected. The changes in body weight were -0.93, 0.54, and 1.77 kg in the placebo, 50-mg anamorelin, and 100-mg anamorelin groups, respectively. Anamorelin (100 mg) significantly improved KPS and QOL-ACD compared with placebo. Administration of anamorelin for 12 weeks was well tolerated. CONCLUSIONS: This phase 2 study showed that 100 mg anamorelin has promising results in improving lean body mass, performance status, and especially, QOL in patients with cancer cachexia.

The effects of community-wide dissemination of information on perceptions of palliative care, knowledge about opioids, and sense of security among cancer patients, their families, and the general public.

PURPOSE: Prejudices against palliative care are a potential barrier to quality end-of-life care. There have been few large-scale community-wide interventions to distribute appropriate information about palliative care, and no studies have investigated their impact on cancer patients, their families, and the general public. Thus, we conducted a 3-year community intervention and evaluated the effects of distributing such information at the community level, and explored associations among levels of exposure, perceptions, knowledge, and the sense of security achieved. METHODS: Over a period of 3 years, we provided flyers, booklets, posters, and public lectures about palliative care in four regions of Japan, and carried out pre- and post-intervention surveys with repeated cross-sectional samplings of cancer patients (pre 859, post 857), bereaved family members (1110, 1137), and the general public (3984, 1435). The levels of exposure to the provided information were measured by a multiple-choice questionnaire after intervention. Multiple logistic regression analyses were used to estimate multivariable-adjusted odds ratios (ORs) for perceptions of palliative care, knowledge about opioids, and sense of security among the exposure groups. RESULTS: Overall perceptions of palliative care, opioids, and receiving care at home improved significantly among the general public and families, but not among the patients at the community level. However, multiple regression revealed that patients of extensive exposure category had significantly more positive perceptions of palliative care to those of non-exposure category (p = 0.02). The sense of security regarding cancer care of all patients, family members, and the general public improved. Among others, the respondents who reported extensive exposure in the general public and family members scored significantly higher sense of security. CONCLUSION: Our findings indicate that providing palliative care information via small media and lectures in the community is effective in improving perceptions of palliative care and knowledge about opioids among the community dwellers, especially for caregivers of the patients. The acquisition of adequate knowledge about palliative care from various information sources may improve people's sense of security regarding cancer.

Quality of life and survival survey of cancer cachexia in advanced non-small cell lung cancer patients-Japan nutrition and QOL survey in patients with advanced non-small cell lung cancer study.

PURPOSE: Although cancer cachexia is mainly characterized by persistent loss of body weight (BW), usually in response to a malignancy, the pathophysiology of cachexia remains unresolved. To elucidate the relationship between the loss of BW and other related clinical factors, we conducted a nationwide, multi-institutional, prospective, observational study in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Treatment-naïve stage IV NSCLC patients with an Eastern Cooperative Oncology Group performance status (PS) of 0-2 were eligible. BW, handgrip strength (HGS), quality of life (QOL), Karnofsky Performance Scale (KPS), biochemical parameters, and survival were evaluated at baseline and every 4 weeks for 1 year. The relationship between BW loss and other factors was examined by linear regression analysis. Estimated survival curves were drawn by the Kaplan-Meier method and applied by the log-rank test. Clinical factors associated with cancer cachexia were identified through principal component analysis. The generalized estimating equation approach was used to analyze the deterioration of QOL resulting from the progression of cachexia. RESULTS: A total of 406 patients were analyzed. BW loss was significantly associated with worsening of QOL, HGS, KPS, and biochemical parameters. The incidence of BW loss was observed throughout the study period. Overall survival was significantly shorter in patients as BW loss progressed. BW loss, decrease in HGS, anorexia, and fatigue were identified as core factors of cachexia that contributed to the deterioration of QOL. CONCLUSION: BW loss most likely deteriorated QOL and shortened survival in patients with advanced NSCLC and should be closely monitored.

Japanese Society of Clinical Oncology clinical practice guidelines 2010 for antiemesis in oncology: executive summary.

The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT3) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT3 receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT3 receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.

Breakthrough pain management using fentanyl buccal tablet (FBT) in combination with around-the-clock (ATC) opioids based on the efficacy and safety of FBT, and its relationship with ATC opioids: results from an open-label, multi-center study in Japanese cancer patients with detailed evaluation.

OBJECTIVE: Rapid analgesic onset opioids, particularly fentanyl buccal tablet, is preferable for managing breakthrough pain. The efficacy and safety of fentanyl buccal tablet and its association with around-the-clock opioids needs to be explored with an option of dose adjustments, more closely reflecting administration in clinical practice. The aim of the study was to assess the safety and efficacy of fentanyl buccal tablet in breakthrough pain management in combination with around-the-clock opioids with the dose adjustment option, and explore the dose adjustment's influence on breakthrough pain management using detailed evaluation. METHODS: The 12-week open-label, multi-center study was conducted throughout Japan. Cancer patients aged 20 years or older, experiencing persistent pain controlled with around-the-clock opioids and breakthrough pain with supplemental medications were enrolled. Fentanyl buccal tablet and around-the-clock opioid doses could be adjusted under protocol-specified conditions. Efficacy variables were assessed at each fentanyl buccal tablet administration. Safety was assessed mainly by adverse events. RESULTS: All efficacy variables showed sustained analgesic effect. Nearly half the patients stayed on the same dose; most fentanyl buccal tablet administrations did not require additional supplemental medications. Dose increase of fentanyl buccal tablet and around-the-clock opioids seemed to improve breakthrough pain intensity and frequency, respectively. Fentanyl buccal tablet and around-the-clock opioid doses were not strongly associated. Treatment-related adverse events were all common with opioid treatment and did not increase over time. CONCLUSIONS: Fentanyl buccal tablet can stably and safely manage breakthrough pain in cancer patients with independent dose adjustment based on detailed evaluation of each patient's condition. Breakthrough pain management using fentanyl buccal tablet with around-the-clock opioids at optimal doses may be an important factor in palliative care for cancer patients with breakthrough pain.

Efficacy of corticosteroids for cancer-related fatigue: A pilot randomized placebo-controlled trial of advanced cancer patients.

OBJECTIVE: Cancer-related fatigue (CRF) is a common and one of the most important issues in palliative medicine, and it has been demonstrated to have a significant impact on patient quality of life (QoL). The present pilot randomized controlled study evaluated the efficacy and toxicity of methylprednisolone (MP) for CRF in advanced cancer patients. METHOD: Our study was planned as a randomized, double-blind, multicenter, placebo-controlled trial. Patients were randomly assigned to an MP group, who received 32 mg/day of MP orally for 7 days, and a placebo group. The primary endpoint was an improvement in visual analog scale (VAS) score for fatigue from baseline to day 7. The secondary endpoints were improvements in appetite loss and QoL as well as evaluating the safety of corticosteroids as palliative therapy. RESULTS: It was not possible to complete patient registration. In total, 35 patients were randomly assigned to an MP group (n = 18) and a placebo group (n = 17). The mean changes in VAS score for fatigue were -9.06 in the placebo group and -1.56 in the MP group, and for appetite loss -6.44 in the placebo group and -8.06 in the MP group. In addition, there was no evidence that methylprednisolone improved appetite loss or QoL compared to placebo. The incidence of adverse effects was not greater in the MP group. Significant of Result: We conclude that our sample size was too small to prove the efficacy of methylprednisolone in improving fatigue. Our results were reported as a pilot study performed to support a subsequent larger trial.

[The survey for anti-emetic guideline by using questioner].

BACKGROUND: Japan Society of Clinical Oncology published a guideline for anti-emetic therapy two years ago. This guideline was a first evidence based guideline of anti-emetic treatment for the patients who received chemotherapy in Japan. To investigate a current situation of anti-emetic treatment in Japan, we analyzed the data from nationwide questionnaire. MATERIAL: Questionnaire analysis; From June 2012 to August 2012, we gave 24 questionnaires on the Japan Society of Clinical Oncology Website and collected the response from the member of 5 major academic oncology societies. The questionnaires included degree of recognition, penetration, usefulness, problems and user type of medial stuff for the anti-emetic guideline published by (JSCO). RESULTS: Questionnaire; 1,529 medical stuff responded to our questionnaire. 1,308 (85.5%) stuffs recognized JSCO guidelines, 586 (51%) had regard for guideline and 489 (42.6%) referred to the guideline. 899 (78.3%) changed their practice in clinic to recommended practice by the guideline. But 385 (33.5%) complained high medical cost of recommended anti-emetic therapy. CONCLUSIONS: Degree of recognition and penetration of our guideline for anti-emetic therapy were very high in Japan.

Regional medical professionals' confidence in providing palliative care, associated difficulties and availability of specialized palliative care services in Japan.

BACKGROUND: Although confidence in providing palliative care services is an essential component of providing such care, factors relating to this have not been investigated in Japan. OBJECTIVE: This study aimed to explore confidence in the ability to provide palliative care and associated difficulties and to explore correlations between these variables. Design A cross-sectional mail survey of medical doctors and registered nurses in Japan was performed as part of a regional intervention trial: the Outreach Palliative Care Trial of Integrated Regional Model study. Subjects Questionnaires were sent to 7905 medical professionals, and 409 hospital doctors, 235 general practitioners, 2160 hospital nurses and 115 home visiting nurses completed them. RESULTS: Confidence in providing palliative care was low and difficulties frequent for all types of medical professionals assessed. In particular, only 8-24% of them, depending on category, agreed to 'having adequate knowledge and skills regarding cancer pain management'. In particular, 55-80% of medical professionals acknowledged difficulty with 'alleviation of cancer pain'. Multiple regression analysis revealed that confidence was positively correlated with the amount of relevant experience and, for medical doctors, with 'prescriptions of opioids (per year)'. Moreover, difficulties were negatively correlated with the amount of relevant clinical experience. CONCLUSIONS: Effective strategies for developing regional palliative care programs include basic education of medical professionals on management of cancer-related pain (especially regarding opioids) and other symptoms.

A Japanese region-wide survey of the knowledge, difficulties and self-reported palliative care practices among nurses.

OBJECTIVE: We investigated palliative care knowledge, difficulty and self-reported practice among a region-wide sample of nurses who cared for cancer patients in Japan. METHODS: A cross-sectional questionnaire survey was distributed to 9 designated cancer centers, 17 community hospitals and 73 district nurse services across 4 regions in 2008. We used the Palliative Care Knowledge Test, the Palliative Care Difficulty Scale (five-point Likert scale) and the Palliative Care Self-Reported Practices Scale (five-point Likert scale). RESULTS: In total, 2378 out of 3008 nurses (79%) responded. The knowledge, difficulty and self-reported practice scores were 51 ± 20%, 3.2 ± 0.7 and 3.7 ± 0.6, respectively. In the knowledge test, philosophy scored highest (88 ± 26%) and psychiatric problems scored lowest (37 ± 29%). In the difficulty test, alleviating symptoms scored most difficult (3.5 ± 0.8) and providing expert support scored least difficult (2.9 ± 1.3). In the self-reported practice questionnaire, pain and delirium relief were most frequently (4.0 ± 0.8) and least frequently (3.1 ± 0.9) provided, respectively. Knowledge was significantly poorer in community hospitals (P = 0.035); difficulty scores were significantly higher in community hospitals (P < 0.001) and district nurse services (P = 0.013); and self-reported practice scores were significantly poorer in community hospitals (P < 0.001) but superior in district nurse services (P < 0.001) than in designated cancer centers. CONCLUSIONS: Knowledge, difficulty and self-reported practice for symptom management, particularly psychological symptoms, were insufficient, particularly in community hospitals. Education, expert support and adequate clinical experiences would help provide quality palliative care.

Does a regional comprehensive palliative care program improve pain in outpatient cancer patients?

CONTEXT: Pain is still a major problem for cancer patients, and the effect of a population-based approach on patients' experience of pain is not fully understood. AIMS: The primary aim of this study was to clarify the changes in pain intensity in outpatients before and after a regional palliative care program. The secondary aim was to clarify the prevalence of patients who had unmet needs for pain treatment and to clarify the reasons for not wanting pain treatment. SUBJECTS AND METHODS: A regional palliative care program was implemented in four regions of Japan. A region-representative sample of metastatic/locally advanced cancer patients in outpatient settings took part in questionnaire surveys before and after the regional intervention. Responses were obtained from 859 from 1,880 and 857 from 2,123 in the preintervention and postintervention surveys, respectively. RESULTS: After a regional palliative care program, neither worst, average, nor least pain levels in outpatients changed significantly. A total of 134 patients (16 %) reported that they needed more pain treatment. There were various reasons for not wanting pain treatment, namely, minimum interference with daily life, general nonpreference for medicines, longstanding symptoms before the diagnosis of cancer, concerns about tolerance and addiction, and experienced neuropsychiatric symptoms under current medications. CONCLUSION: The regional palliative care program failed to demonstrate improvement of the pain intensity of cancer outpatients. One possible interpretation is that they are less likely to be regarded as target populations and that the study population experienced generally well-controlled pain. Future study including patients with more severe pain is needed, but to improve pain levels of cancer outpatients, intensive, patient-directed intervention seems to be more promising than region-based intervention.

Effects of a programme of interventions on regional comprehensive palliative care for patients with cancer: a mixed-methods study.

BACKGROUND: Improvement of palliative care is an important public health issue, but knowledge about how to deliver palliative care throughout a region remains inadequate. We used surveys and in-depth interviews to assess changes in the quality of palliative care after regional interventions and to gain insights for improvement of palliative care at a regional level. METHODS: In this mixed-methods study, a comprehensive programme of interventions for regional palliative care for patients with cancer was implemented from April 1, 2008, to March 31, 2011 in Tsuruoka, Kashiwa, Hamamatsu, and Nagasaki in Japan. Interventions included education, specialist support, and networking. We surveyed patients, bereaved family members, physicians, and nurses before and after the interventions were introduced. We also did qualitative interviews with health-care professionals after the interventions were introduced. Primary endpoints were numbers of home deaths, coverage of specialist services, and patient-reported and family-reported qualities of care. This trial is registered with UMIN Clinical Trial Registry, Japan (UMIN000001274). FINDINGS: 859 patients, 1110 bereaved family members, 911 physicians, and 2378 nurses provided analysable preintervention surveys; 857 patients, 1137 bereaved family members, 706 physicians, and 2236 nurses provided analysable postintervention surveys. Proportions of home deaths increased significantly, from 348 of 5147 (6.76%) before the intervention programme to 581 of 5546 (10.48%) after the intervention programme (p<0.0001). Furthermore, 194 of 221 (87.78%) family members of patients who died at home answered that these patients had wanted to die at home. The ratio of patients who received palliative care services to all patients who died of cancer increased significantly (from 0.31 to 0.50; p<0.0001). The patient-reported (effect size 0.14; adjusted p=0.0027) and family-reported (0.23; p<0.0001) qualities of care were significantly better after interventions than before interventions. Physician-reported and nurse-reported difficulties decreased significantly after the introduction of the interventions. Qualitative interviews showed improved communication and cooperation between health-care professionals because of greater opportunities for interactions at various levels. INTERPRETATION: A regional programme of interventions could improve the quality of palliative care. Improvement of communication between health-care professionals is key to improvement of services. FUNDING: Third Term Comprehensive Control Research for Cancer Health and Labor Sciences Research Grants of the Ministry of Health, Labour and Welfare of Japan.

Exploring the perceived changes and the reasons why expected outcomes were not obtained in individual levels in a successful regional palliative care intervention trial: an analysis for interpretations.

CONTEXT: The Japan Outreach Palliative Care Trial of Integrated Model (OPTIM) study, a mixed-methods study to evaluate the effects of a comprehensive regional palliative care program, revealed that the program provided broad positive outcomes at the regional level: increased home death, palliative care use, patient- and family-reported qualities of care, and health care professionals' difficulties. Not all participants however obtained positive outcomes and thus exploring the reasons why expected outcomes were observed in individual levels could be of value. AIMS: The primary aims were to explore why expected outcomes were not obtained in individual participants, and the perceived changes in daily practices of physicians and nurses were explored. SUBJECTS AND METHODS: Postintervention questionnaire survey on 857 patients, 1,137 bereaved family members, 706 physicians, and 2,236 nurses were analyzed. RESULTS: The reasons for not achieving home deaths included unexpected rapid deterioration, caregivers unavailable, concerns about adequate responses to sudden changes, and physical symptoms uncontrolled, while lack of physician availability at home and lack of information from physicians were less frequently reported. The reasons for not receiving specialized palliative care services were the lack of recommendations from physicians and no information about palliative care services. The reason for evaluating the quality of palliative care as not high was that clinicians tried to relieve symptoms, but there were limited effects and insufficient time. Many physicians and nurses reported that they became more aware of palliative care, that the availability of palliative care specialists and knowledge about palliative care improved, and that they cooperated with other regional health care providers more easily. CONCLUSION: The OPTIM study seemed to succeed in optimizing physician availability at home, improves physician information about home care, achieved maximum efforts to relieve patient distress by clinicians, and increased communication among regional health care professionals. To achieve further better outcomes, multiple interventions to the health care system to be performed on the basis of a comprehensive regional palliative care program are proposed.

Patient-perceived usefulness and practical obstacles of patient-held records for cancer patients in Japan: OPTIM study.

BACKGROUND: Although the use of a patient-held record (PHR) for cancer patients has been introduced in many settings, little is known about the role of the PHR in palliative care settings and use in Asian cultures. AIM: This study investigated the patient-perceived usefulness and practical obstacles of using the PHR specifically designed for palliative care patients. DESIGN: This study adopted a qualitative design based on semi-structured interviews and content analysis. SETTING/PARTICIPANTS: Fifty cancer patients were recruited from two regions in Japan. They used the PHR for more than three months, and then were asked to participate in a face-to-face interview. RESULTS: The content analysis revealed the following patient-perceived usefulness of the PHR: (1) increase in patient-staff communication; (2) increase in patient-family communication; (3) increase in patient-patient communication; (4) increase in understanding of medical conditions and treatments; and (5) facilitating end-of-life care discussion. The practical obstacles to using the PHR were also indicated: (1) the lack of adequate instruction about the role of the PHR; (2) undervaluing the role of the PHR and sharing information by medical professionals; (3) patients' unwillingness to participate in decision making; (4) concerns about privacy; (5) burdensome nature of self-reporting; and (6) patients' preference for their own ways of recording. CONCLUSIONS: The PHR can be helpful in facilitating communication, understanding medical conditions and treatments, and facilitating end-of-life care discussion; however, for wide-spread implementation, resolving the obstacles related to both patients and health-care professionals is required.

Quantitative classification based on CT histogram analysis of non-small cell lung cancer: correlation with histopathological characteristics and recurrence-free survival.

PURPOSE: Quantification of the CT appearance of non-small cell lung cancer (NSCLC) is of interest in a number of clinical and investigational applications. The purpose of this work is to present a quantitative five-category (α, ß, γ, δ, and ɛ) classification method based on CT histogram analysis of NSCLC and to determine the prognostic value of this quantitative classification. METHODS: Institutional review board approval and informed consent were obtained at the National Cancer Center Hospital. A total of 454 patients with NSCLC (maximum lesion size of 3 cm) were enrolled. Each lesion was measured using multidetector CT at the same tube voltage, reconstruction interval, beam collimation, and reconstructed slice thickness. Two observers segmented NSCLC nodules from the CT images by using a semi-automated three-dimensional technique. The two observers classified NSCLCs into one of five categories from the visual assessment of CT histograms obtained from each nodule segmentation result. Interobserver variability in the classification was computed with Cohen's κ statistic. Any disagreements were resolved by consensus between the two observers to define the gold standard of the classification. Using a classification and regression tree (CART), the authors obtained a decision tree for a quantitative five-category classification. To assess the impact of the nodule segmentation on the classification, the variability in classifications obtained by two decision trees for the nodule segmentation results was also calculated with the Cohen's κ statistic. The authors calculated the association of recurrence with prognostic factors including classification, sex, age, tumor diameter, smoking status, disease stage, histological type, lymphatic permeation, and vascular invasion using both univariate and multivariate Cox regression analyses. RESULTS: The κ values for interobserver agreement of the classification using two nodule segmentation results were 0.921 (P < 0.001) and 0.903 (P < 0.001), respectively. The κ values for the variability in the classification task using two decision trees were 0.981 (P < 0.001) and 0.981 (P < 0.001), respectively. All the NSCLCs were classified into one of five categories (type α, n = 8; type ß, n = 38; type γ, n = 103; type δ, n = 112; type ɛ, n = 193) by using a decision tree. Using a multivariate Cox regression analysis, the classification (hazard ratio 5.64; P = 0.008) and disease stage (hazard ratio 8.33; P < 0.001) were identified as being associated with an increased recurrence risk. CONCLUSIONS: The quantitative five-category classifier presented here has the potential to provide an objective classification of NSCLC nodules that is strongly correlated with prognostic factors.

Preferred place of care and place of death of the general public and cancer patients in Japan.

Dying at a favorite place is one of the important determinants for terminally ill cancer patients. The primary aim was to clarify (1) differences in preferred place of care and place of death among the general public across four areas across Japan and (2) preferred place of care and place of death among community-representative cancer patients. A cross-sectional mail survey was conducted on 8,000 randomly selected general population. We examined preferred place of care and place of death using two vignettes and obtained a total of 3,984 (50%) responses. For the pain scenario, approximately 50% of the general public throughout four areas chose home as their preferred place of care; and for the dependent-without-pain scenario, about 40% chose home as preferred place of care. In cancer patients, for both scenarios, approximately 40% chose home as the preferred place of care, and they were significantly less likely to choose home. The most preferred combination of place of care and place of death was home hospice for both groups. Although there were statistically significant differences in preferred place of care and place of death among the four regions, the absolute difference was less than 8%. Independent determinants of choosing home as place of care included concern about family burden and being unable to adequately respond to sudden changes out of working hours. In conclusion, establishing more accessible home and hospice service is strongly required through arranging regional resources to reduce family burden, alleviating patient-perceived burdens, and improving 24-h support at home.

Knowledge, beliefs, and concerns about opioids, palliative care, and homecare of advanced cancer patients: a nationwide survey in Japan.

PURPOSE: Patients' knowledge, beliefs, or concerns about opioids, palliative care, and homecare can be potential barriers to providing quality palliative care. The primary aim of this study was to clarify knowledge about opioids, beliefs about palliative care, and concerns about homecare in advanced cancer patients. METHODS: An anonymous questionnaire was sent to 1,619 outpatients with advanced cancer at 25 hospitals in four different regions of Japan. The respondents were asked to report their knowledge about opioids, beliefs about palliative care, and concerns about homecare, in addition to the levels of their sense of security regarding receiving cancer care in the region. RESULTS: A total of 925 responses were received. In total, 28% believed that opioids are addictive and/or shorten life; 52% believed that palliative care is only for terminally ill patients; 75% agreed that being taken care of at home puts a heavy burden on the family; and 61% agreed that home-visit services cannot respond to sudden changes in a patient's condition. Levels of patients' sense of security were significantly higher in those who agreed that "opioids can relieve most pain caused by cancer" "palliative care relieves pain and distress", "palliative care is provided along with chemotherapy and/or radiation therapy", and "pain can be alleviated as effectively through home-visit services as it can at the hospital", and those who disagreed with the statements that "home-visit services cannot respond to sudden changes in a patient's condition" and "being taken care of at home puts a burden on the family". CONCLUSIONS: Advanced cancer patients frequently had incorrect knowledge about opioids, a belief that palliative care is only for terminally ill patients, and concerns about homecare, especially the family burden and responses to sudden changes. Providing appropriate information about the safety of opioids, the availability of palliative care during the entire course of the disease, and realistic information about homecare is of marked importance to promote patients' sense of security.

A region-based palliative care intervention trial using the mixed-method approach: Japan OPTIM study.

BACKGROUND: Disseminating palliative care is a critical task throughout the world. Several outcome studies explored the effects of regional palliative care programs on a variety of end-points, and some qualitative studies investigated the process of developing community palliative care networks. These studies provide important insights into the potential benefits of regional palliative care programs, but the clinical implications are still limited, because: 1) many interventions included fundamental changes in the structure of the health care system, and, thus, the results would not be applicable for many regions where structural changes are difficult or unfeasible; 2) patient-oriented outcomes were not measured or explored only in a small number of populations, and interpretation of the results from a patient's view is difficult; and 3) no studies adopted a mixed-method approach using both quantitative and qualitative methodologies to interpret the complex phenomenon from multidimensional perspectives. METHODS/DESIGNS: This is a mixed-method regional intervention trial, consisting of a pre-post outcome study and qualitative process studies. The primary aim of the pre-post outcome study is to evaluate the change in the number of home deaths, use of specialized palliative care services, patient-reported quality of palliative care, and family-reported quality of palliative care after regional palliative care intervention. The secondary aim is to explore the changes in a variety of outcomes, including patients' quality of life, pain intensity, family care burden, and physicians' and nurses' knowledge, difficulties, and self-perceived practice. Outcome measurements used in this study include the Care Evaluation Scale, Good Death Inventory, Brief pain Inventory, Caregiving Consequence Inventory, Sense of Security Scale, Palliative Care Knowledge test, Palliative Care Difficulties Scale, and Palliative Care Self-reported Practice Scale. Study populations are a nearly representative sample of advanced cancer patients, bereaved family members, physicians, and nurses in the region.Qualitative process studies consist of 3 studies with each aim: 1) to describe the process in developing regional palliative care in each local context, 2) to understand how and why the regional palliative care program led to changes in the region and to propose a model for shaping regional palliative care, and 3) to systemically collect the barriers of palliative care at a regional level and potential resolutions. The study methodology is a case descriptive study, a grounded theory approach based on interviews, and a content analysis based on systemically collected data, respectively. DISCUSSION: This study is, to our knowledge, one of the most comprehensive evaluations of a region-based palliative care intervention program. This study has 3 unique aspects: 1) it measures a wide range of outcomes, including quality of care and quality of life measures specifically designed for palliative care populations, whether patients died where they actually preferred, the changes in physicians and nurses at a regional level; 2) adopts qualitative studies along with quantitative evaluations; and 3) the intervention is without a fundamental change in health care systems. A comprehensive understanding of the findings in this study will contribute to a deeper insight into how to develop community palliative care. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR), Japan, UMIN000001274.

[Promising new injection method to prevent angialgia/phlebitis from epirubicin hydrochloride therapy for breast cancer].

Epirubicin hydrochloride(EPI)is well known to cause phlebitis as a typical adverse drug reaction. By preventing the development of severe phlebitis, patients are expected to continue effective chemotherapy with EPI without a decrease in QOL. We have previously reported promising results of a new injection method to prevent phlebitis from occurring during EPI therapy thorough a prospective clinical trial in our hospital(Jpn J Cancer Chemother 36: 969-974, 2009). In the present study, we have compared the conventional injection method(EPI main -route method, n=15)with our new method, which has been consistently practiced at present(EPI sub -route method, n=77). We found that in the EPI main -route method, angialgia/phlebitis developed in 14 of 15 cases(Grade 3, 53. 3%), leading to alteration of the regimen in 3 cases. On the other hand, with the EPI sub -route method, incidence of angialgia/phlebitis was markedly decreased, and only 6 of 77 cases developed these adverse reactions(Grade 3, 0%). One possible explanation for these results is that the reduction of intimal stimulation by the EPI sub -route method might be caused by the dilution and washout of EPI with pre-medication, as well as the shortened infusion times of EPI. Therefore, on the basis of the above hypothesis, we conclude that the EPI sub-route method might be a more effective treatment for the expected prevention of angialgia/phlebitis.

Introduction of endobronchial ultrasonography (EBUS) in bronchoscopy clearly reduces fluoroscopy time: comparison of 147 cases in groups before and after EBUS introduction.

BACKGROUND: Endobronchial ultrasonography (EBUS) has been used in diagnosing peripheral lung cancer and has allowed for higher rates of peripheral lung cancer diagnosis. However, no studies have reported that fluoroscopy time is shortened by the use of endobronchial ultrasonography. We aimed to investigate whether fluoroscopy time is shortened using endobronchial ultrasonography. METHODS: We retrospectively researched fluoroscopy time in terms of the rate of diagnosis, lesion size, age, gender, histologic type and lesion site in 147 cases of malignant lesions from January 2006 to September 2007 at the Tokai University Hospital. The location of the bronchial brush or biopsy forceps was confirmed by fluoroscopy without endobronchial ultrasonography with guide-sheath group in 96 of the 147 cases, while fluoroscopy with endobronchial ultrasonography guide sheath group was confirmed in 51 cases. RESULTS: The result was that fluoroscopy time was significantly shortened in the endobronchial ultrasonography guide-sheath group (4.08 ± 3.27 min) compared with the non-endobronchial ultrasonography guide-sheath group (7.06 ± 3.99 min), but there was no significant difference between either groups in terms of bronchoscopic diagnosis, lesion size, age, gender, histologic type and lesion site. CONCLUSION: The use of endobronchial ultrasonography guide sheath allows a reduction in fluoroscopy time and may reduce the adverse effects of radiation exposure on patients and staff.