Quality indicators for integrating oncology and home palliative care in Japan: modified Delphi study.

CONTEXT: Home palliative care service increases the chance of dying at home, particularly for patients with advanced cancer, but late referrals to home palliative care services still exist. Indicators for evaluating programs that can facilitate the integration of oncology and home palliative care have not been defined. OBJECTIVES: This study developed quality indicators for the integration of oncology and home palliative care in Japan. METHODS: We conducted a systematic literature review (Databases included CENTRAL, MEDLINE, EMBASE, and Emcare) and a modified Delphi study to develop the quality indicators. Panelists rated a potential list of indicators using a 9-point scale over three rounds according to two criteria: appropriateness and feasibility. The criterion for the adoption of candidate indicators was set at a total mean score of 7 or more. Final quality indicators with no disagreement were included. RESULTS: Of the 973 publications in our initial search, 12 studies were included. The preliminary list of quality indicators by systematic literature review comprised 50 items. In total, 37 panelists participated in the modified Delphi study. Ultimately, 18 indicators were identified from the following domains: structure in cancer hospitals, structure in home palliative care services, the process of home palliative care service delivery, less aggressive end-of-life care, patient's psychological comfort, caregiver's psychological comfort, and patient's satisfaction with home palliative care service. CONCLUSION: Comprehensive quality indicators for the integration of oncology and home palliative care were identified. These indicators may facilitate interdisciplinary collaboration between professional healthcare providers in both cancer hospitals and home palliative care services.

Integrating home palliative care in oncology: a qualitative study to identify barriers and facilitators.

PURPOSE: Access to and close links with home palliative care services are essential to ensure seamless transitions between care settings in anticancer treatment. However, the timing of referrals to home palliative care services is often delayed. We explored barriers to and facilitators of improving the integration of home palliative care and medical oncology experienced by healthcare professionals in Japan. METHODS: This qualitative study involved semi-structured focus groups and individual interviews conducted via a web conferencing system. Participants were 27 healthcare professionals, including oncologists, palliative care physicians, home palliative care physicians, nurses from both cancer hospitals and home visit nursing agencies, and social workers from cancer hospitals. RESULTS: Barriers and facilitators were grouped into three themes: (1) perspectives and ideas on integrating oncology and home palliative care; (2) barriers; and (3) facilitators. Barriers included seven sub-themes: lack of referral criteria for home palliative care services; financial elements related to home palliative care services; patients' lack of understanding of the illness trajectory; collusion in doctor-patient communication about imminent death; frequent visits to cancer hospitals; variations in home palliative care services; and problems in providing treatment and care at home. Facilitators included two sub-themes: relationships between oncologists and home palliative care physicians, and cancer hospital staff experience/knowledge of home palliative care. CONCLUSION: This study identified barriers and facilitators to integrating home palliative care and oncology. Some barriers experienced by professionals were comparable with barriers to early integration of palliative care into oncology.

[Current Status and Improvement Strategies for Integrating Home Palliative Care in Oncology-A Qualitative Study].

This study aimed to investigate healthcare providers' experiences and examine potential strategies for integrating oncologic home palliative care(HPC). This qualitative study was conducted using semi-structured interviews via a web-conferencing system. The data underwent thematic analysis. The participants were 27 healthcare professionals, including oncologists, palliative care physicians, home palliative care physicians, nurses, and medical social workers. Two themes were identified; current status and improvement strategies. Current status encompassed 3 sub-themes: late HPC services involvement, few opportunities for early HPC services introduction, and early referral to HPC establishes rapport with patients. Improvement strategies included 6 sub-themes: interdisciplinary teams meeting to consider patients' hope, identification of outpatients that would benefit from HPC services, HPC service introduction via home visit nursing agencies and outpatient clinics, HPC services introduction via outpatient palliative care clinics, and booklet for patients and families. Numerous participants regarded the timing of HPC services referral as late and had experienced few cases of integrated oncologic HPC. Potential strategies existed in both hospital and home settings. The interdisciplinary collaboration between healthcare providers in both hospital and home settings may facilitate the integration of HPC in oncology.

Low Transthyretin Levels Predict Poor Prognosis in Cancer Patients in Palliative Care Settings.

OBJECTIVES: Although transthyretin (TTR) is a nutritional indicator and is influenced by systemic inflammation, it may be a good prognostic indicator for cancer patients in palliative care settings. This study investigates the correlation between low TTR levels and survival among cancer patients in palliative care settings. METHODS: This was a sub-analysis of a prospective, multicenter cohort study. Patients who had advanced-stage cancer and who were newly referred to palliative care services were eligible to participate; however, those receiving anti-tumor therapy were excluded. Survival analyses were performed to clarify predictors of poor prognosis. RESULTS: A total of 144 patients were enrolled (45.1% female; median age, 72 years). Cox regression analysis revealed that low TTR levels (<10.9 mg/l) (hazard ratio 1.74, P = 0.025), poor muscle power (1.71, P = 0.045), and fatigue (1.89, P = 0.024) were predictors of poor prognosis. Median survival in patients with low TTR levels (<10.9 mg/l) was 26 days, which was significantly shorter than those with high TTR levels (≥10.9 mg/l) (50 days; P < 0.001). CONCLUSION: Low TTR levels may be indicators for poor prognosis among cancer patients in palliative care settings.

Predictors of responses to corticosteroids for anorexia in advanced cancer patients: a multicenter prospective observational study.

PURPOSE: Although corticosteroids are widely used to relieve anorexia, information regarding the factors predicting responses to corticosteroids remains limited. The purpose of the study is to identify potential factors predicting responses to corticosteroids for anorexia in advanced cancer patients. METHODS: Inclusion criteria for this multicenter prospective observational study were patients who had metastatic or locally advanced cancer and had an anorexia intensity score of 4 or more on a 0-10 Numerical Rating Scale (NRS). Univariate and multivariate analyses were conducted to identify the factors predicting ≥2-point reduction in NRS on day 3. RESULTS: Among 180 patients who received corticosteroids, 99 (55 %; 95 % confidence interval [CI], 47-62 %) had a response with ≥2-point reduction. Factors that significantly predicted responses were Palliative Performance Scale (PPS) > 40 and absence of drowsiness. In addition, factors that tended to be associated with ≥2-point reduction in NRS included PS 0-3, absence of diabetes mellitus, absence of peripheral edema, presence of lung metastasis, absence of peritoneal metastasis, baseline anorexia NRS of >6, presence of pain, and presence of constipation. A multivariate analysis showed that the independent factors predicting responses were PPS of >40 (odds ratio = 2.7 [95 % CI = 1.4-5.2]), absence of drowsiness (2.6 [1.3-5.0]), and baseline NRS of >6 (2.4 [1.1-4.8]). CONCLUSIONS: Treatment responses to corticosteroids for anorexia may be predicted by PPS, drowsiness, and baseline symptom intensity. Larger prospective studies are needed to confirm these results.

Multicenter cohort study on the survival time of cancer patients dying at home or in a hospital: Does place matter?

BACKGROUND: Although the place of death has a great influence on the quality of death and dying for cancer patients, whether the survival time differs according to the place of death is unclear. The primary aim of this study was to explore potential differences in the survival time of cancer patients dying at home or in a hospital. METHODS: This multicenter, prospective cohort study was conducted in Japan from September 2012 through April 2014 and involved 58 specialist palliative care services. RESULTS: Among the 2426 patients recruited, 2069 patients were analyzed for this study: 1582 receiving hospital-based palliative care and 487 receiving home-based palliative care. A total of 1607 patients actually died in a hospital, and 462 patients died at home. The survival of patients who died at home was significantly longer than the survival of patients who died in a hospital in the days' prognosis group (estimated median survival time, 13 days [95% confidence interval (CI), 10.3-15.7 days] vs 9 days [95% CI, 8.0-10.0 days]; P = .006) and in the weeks' prognosis group (36 days [95% CI, 29.9-42.1 days] vs 29 days [95% CI, 26.5-31.5 days]; P = .007) as defined by Prognosis in Palliative Care Study predictor model A. No significant difference was identified in the months' prognosis group. Cox proportional hazards analysis revealed that the place of death had a significant influence on the survival time in both unadjusted (hazard ratio [HR], 0.86; 95% CI, 0.78-0.96; P < .01) and adjusted models (HR, 0.87; 95% CI, 0.77-0.97; P = .01). CONCLUSIONS: In comparison with cancer patients who died in a hospital, cancer patients who died at home had similar or longer survival. Cancer 2016;122:1453-1460. © 2016 American Cancer Society.

A Multicenter Cohort Study to Explore Differentiating Factors between Tumor Fever and Infection among Advanced Cancer Patients.

Background: Tumor fever and infection are common febrile etiologies among advanced cancer patients. To date, only few studies have been conducted to differentiate between tumor fever and infections. Objective: This study aimed to identify discriminating factors that provide rapid results and are feasible and minimally invasive for discriminating between tumor fever and infection in advanced cancer patients. Methods: This is a retrospective cohort study. Advanced cancer patients with clinically diagnosed tumor fever or infection, who received medical treatment from palliative care specialists in 10 nationwide Japanese hospitals, were consecutively identified during August 2012 and November 2014. The symptoms, physical findings, blood test results at baseline and during fever, imaging findings, and sociodemographic factors of these patients were retrospectively extracted. Results: Thirty-three patients with tumor fever and 72 patients with infection were identified. Their mean age was 68.8 years, 68 (64.8%) were men, and the median palliative performance status (PPS) was 50. Statistically significant factors predicting tumor fever by logistic regression analysis were as follows: deterioration of PPS (odds ratio, 0.078), shaking chills during fever (0.067), and change from baseline data of neutrophil/lymphocyte ratio of ≥5 (0.14). Conclusions: Shaking chills during fever, and changes from baseline of performance status and white blood cell differentiation can be useful to differentiate between tumor fever and infection among advanced cancer patients. Further confirmatory studies are needed.

C-reactive protein, symptoms and activity of daily living in patients with advanced cancer receiving palliative care.

BACKGROUND: The association between C-reactive protein (CRP) level, symptoms, and activities of daily living (ADL) in advanced cancer patients is unclear. METHODS: Secondary data analysis of a multicenter prospective cohort study consisted of 2426 advanced cancer patients referred to palliative care settings was conducted to examine the cross-sectional relationships between CRP level, symptoms, and ADL disabilities. Laboratory data, symptoms, ADL, and manual muscle testing (MMT) results were obtained at baseline. Participants were divided into four groups: low (CRP < 1 mg/dl), moderate (1 = < CRP <5 mg/dl), high (5 = < CRP < 10 mg/dl), and very high CRP (10 mg/dl = < CRP). The proportions of eight symptoms, five ADL disabilities, and three categories of MMT according to the CRP groups were tested by chi-square tests. Multiple-adjusted odd ratios (ORs) were calculated by using ordinal logistic regression after adjustment for age, gender, site of primary cancer, metastatic disease, performance status, chemotherapy, and setting of care. RESULTS: A total of 1702 patients were analysed. Positive rates of symptoms and ADL disabilities increased with increasing CRP level. In the very high-CRP group, rates of positivity for anorexia, fatigue, and weight loss were 89.8%, 81.0%, and 79.2%, respectively, and over 70% of patients received assistance for bathing, dressing, going to the toilet, and transfer. The grade of MMT also deteriorated with increasing CRP level. Adjusted ORs for the accumulated symptoms significantly increased with increasing CRP level in the moderate-CRP, high-CRP, and very high-CRP groups [1.6 (95% confidence interval 1.2-2.0), P < 0.001; 2.5 (1.9-3.2), P < 0.001; 3.5 (2.7-4.6), P < 0.001, respectively]. Adjusted ORs for the accumulated ADL disabilities significantly increased in the very high-CRP groups [2.1 (1.5-2.9), P < 0.001]. CONCLUSIONS: Associations between CRP level, symptoms, and ADL were observed in advanced cancer patients receiving palliative care.

Predictors of Delirium in Corticosteroid-Treated Patients with Advanced Cancer: An Exploratory, Multicenter, Prospective, Observational Study.

BACKGROUND: Corticosteroids are often used to treat fatigue and anorexia, but occasionally produce delirium. Information on the predictors of delirium in corticosteroid-treated cancer patients remains limited. OBJECTIVE: To identify potential factors predicting the development of delirium in corticosteroid-treated cancer patients. DESIGN: An exploratory, multicenter, prospective, observational study. SETTING/SUBJECTS: Inclusion criteria for this study were patients who had metastatic or locally advanced cancer and a fatigue or anorexia intensity score of 4 or more on a 0-10 Numerical Rating Scale. MEASUREMENT: Univariate and multivariable analyses were performed to identify the predictors of delirium diagnosed by the Confusion Assessment Method (CAM) within three days of initiation of corticosteroids. RESULTS: Among 207 patients administered corticosteroids, 35 (17%; 95% confidence interval [CI] 12%-23%) developed at least one episode of delirium diagnosed by the CAM. Factors predictive of the development of delirium were as follows: Palliative Performance Scale ≤20, Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 4, the Support Team Assessment Schedule (STAS) score of drowsiness >1, concurrent opioid use, parenteral hydration volume ≤500 mL, and the absence of lung metastasis. A multivariable analysis identified the independent factors predicting responses as ECOG PS = 4 (odds ratio [OR] 4.0; 95% CI 1.7-9.3), STAS score of drowsiness >1 (OR 3.4; 95% CI 1.4-8.2), and concurrent opioid use (OR 3.7; 95% CI 1.0-13). CONCLUSION: Delirium in corticosteroid-treated advanced cancer patients may be predicted by PS, drowsiness, and concurrent opioid use. Larger prospective studies are needed to confirm these results.

[Oncolytic viral therapy for cancer therapy].

Recently, tumor-selective replicating viruses offer appealing advantages over conventional cancer therapy and are a promising new approach for the human cancer therapy. The development of oncolytic viral therapeutics is based on various strategies that each provides a different foundation for tumor-selective targeting and replication. Results from clinical trials of oncolytic viral therapy demonstrate the safety and feasibility of a new approach for cancer. Strategies to overcome various obstacles and challenges to this therapy are currently being searched. In the future, the development of oncolytic viral therapies will extend the range of tumors that can be treated using this novel treatment modality. In this paper, I would like to summarize the advances in the field including the findings from the viral treatment that we are currently utilizing.

A resected case of symptomatic acinar cell cystadenoma of the pancreas displacing the main pancreatic duct.

Acinar cell cystadenoma (ACA) of the pancreas has been newly recognized as an entity by the World Health Organization (WHO) definition (2010), and its pathogenesis has not been known adequately because of the rarity. Here, we report a case of a 22-year-old female who had been followed up for a cystic lesion at the tail of the pancreas pointed out by a screening computed tomography (CT) scan 7 years ago. The tumor grew in size from 3.3 to 5.1 cm in diameter for 6 years (0.3 cm per year). Particularly, it rapidly grew up to 6.3 cm in the latest 3 months in concurrence with the emergence of epigastralgia. A contrasted CT scan revealed the irregularly formed, multilocular cystic tumor having thin septum and calcification. The intratumoral magnetic resonance imaging intensity in the T1 and T2 weighted images were low and high, respectively. No communications between the tumor and the main pancreatic duct (MPD) were found, but the tumor displaced the MPD. She underwent surgical resection because the tumor was growing, turned symptomatic, and it seemed difficult to be diagnosed correctly until totally biopsied. Spleen-preserved distal pancreatectomy was performed. It was pathologically diagnosed as ACA; the cyst was lined by cells with normal acinar differentiation; cuboidal cells with round, basally oriented nuclei and eosinophilic granules in its apical cytoplasm. The abdominal pain has disappeared, and no recurrences have been found during a 5-year follow-up. Clinicians are recommended to consider an ACA as one of differential diagnoses of cystic tumors of the pancreas to provide appropriate diagnostics and therapeutics.

Predictors of Responses to Corticosteroids for Cancer-Related Fatigue in Advanced Cancer Patients: A Multicenter, Prospective, Observational Study.

CONTEXT: Although corticosteroids are widely used to relieve cancer-related fatigue (CRF), information regarding the factors predicting responses to corticosteroids remains limited. OBJECTIVES: The aim of this study was to identify potential factors predicting responses to corticosteroids for CRF in advanced cancer patients. METHODS: Inclusion criteria for this multicenter, prospective, observational study were patients who had metastatic or locally advanced cancer and had a fatigue intensity score of 4 or more on a 0-10 Numerical Rating Scale (NRS). Univariate and multivariate analyses were conducted to identify the factors predicting two-point reduction or more in NRS on day 3. RESULTS: Among 179 patients who received corticosteroids, 86 (48%; 95% CI 41%-56%) had a response with two-point reduction or more. Factors that significantly predicted responses were performance status score of 3 or more, Palliative Performance Scale score more than 40, absence of ascites, absence of drowsiness, absence of depression, serum albumin level greater than 3 mg/dL, serum sodium level greater than 135 mEq/L, and baseline NRS score greater than 5. A multivariate analysis showed that the independent factors predicting responses were baseline NRS score greater than 5 (odds ratio [OR] 6.6, 95% CI 2.8-15.4), Palliative Performance Scale score more than 40 (OR 4.4, 95% CI 2.1-9.3), absence of drowsiness (OR 3.4, 95% CI 1.7-6.9), absence of ascites (OR 2.3, 95% CI 1.1-4.7), and absence of pleural effusion (OR 2.2, 95% CI 1.0-5.0). CONCLUSION: Treatment responses to corticosteroids for CRF may be predicted by baseline symptom intensity, performance status, drowsiness, and severity of fluid retention symptoms. Larger prospective studies are needed to confirm these results.

[A phase I study of TS-1 and weekly cisplatin in patients with advanced gastric cancer].

This is a phase I study to determine the maximum tolerated dose (MTD) and toxicity of a combination of TS-1 and weekly cisplatin (CDDP) in advanced gastric cancer patients. TS-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2. One course consisted of 21 days' consecutive administration followed by 14 days' rest. Cisplatin (CDDP) was injected intravenously on days 8, 15 and 22 using the following dose levels: dose level 1 20 mg/m2, dose level 2 25 mg/m2, and dose level 3 30 mg/m2. Twelve patients were entered in this trial. One of the 6 patients at dose level 3 had neutropenia NCI-CTC grade 3, while another patient at dose level 3 suffered from DLT (liver function grade 3. The maximal tolerable dose (MTD) was not reached using dose level 3. Partial responses were seen in 5 (62.5%) of 8 patients with evaluable lesions. At level 2 (25 mg/m2), the response rate was 100%. We recommended dose level 2 for phase II trials from the standpoint of toxicity and response rate.

The Accuracy of Physicians' Clinical Predictions of Survival in Patients With Advanced Cancer.

CONTEXT: Accurate prognoses are needed for patients with advanced cancer. OBJECTIVES: To evaluate the accuracy of physicians' clinical predictions of survival (CPS) and assess the relationship between CPS and actual survival (AS) in patients with advanced cancer in palliative care units, hospital palliative care teams, and home palliative care services, as well as those receiving chemotherapy. METHODS: This was a multicenter prospective cohort study conducted in 58 palliative care service centers in Japan. The palliative care physicians evaluated patients on the first day of admission and followed up all patients to their death or six months after enrollment. We evaluated the accuracy of CPS and assessed the relationship between CPS and AS in the four groups. RESULTS: We obtained a total of 2036 patients: 470, 764, 404, and 398 in hospital palliative care teams, palliative care units, home palliative care services, and chemotherapy, respectively. The proportion of accurate CPS (0.67-1.33 times AS) was 35% (95% CI 33-37%) in the total sample and ranged from 32% to 39% in each setting. While the proportion of patients living longer than CPS (pessimistic CPS) was 20% (95% CI 18-22%) in the total sample, ranging from 15% to 23% in each setting, the proportion of patients living shorter than CPS (optimistic CPS) was 45% (95% CI 43-47%) in the total sample, ranging from 43% to 49% in each setting. CONCLUSION: Physicians tend to overestimate when predicting survival in all palliative care patients, including those receiving chemotherapy.

Independent validation of the modified prognosis palliative care study predictor models in three palliative care settings.

CONTEXT: Accurate prognostic information in palliative care settings is needed for patients to make decisions and set goals and priorities. The Prognosis Palliative Care Study (PiPS) predictor models were presented in 2011, but have not yet been fully validated by other research teams. OBJECTIVES: The primary aim of this study is to examine the accuracy and to validate the modified PiPS (using physician-proxy ratings of mental status instead of patient interviews) in three palliative care settings, namely palliative care units, hospital-based palliative care teams, and home-based palliative care services. METHODS: This multicenter prospective cohort study was conducted in 58 palliative care services including 16 palliative care units, 19 hospital-based palliative care teams, and 23 home-based palliative care services in Japan from September 2012 through April 2014. RESULTS: A total of 2426 subjects were recruited. For reasons including lack of followup and missing variables (primarily blood examination data), we obtained analyzable data from 2212 and 1257 patients for the modified PiPS-A and PiPS-B, respectively. In all palliative care settings, both the modified PiPS-A and PiPS-B identified three risk groups with different survival rates (P<0.001). The absolute agreement ranged from 56% to 60% in the PiPS-A model and 60% to 62% in the PiPS-B model. CONCLUSION: The modified PiPS was successfully validated and can be useful in palliative care units, hospital-based palliative care teams, and home-based palliative care services.

[A case of recurrent advanced gastric cancer with lung metastasis effectively treated by combined chemotherapy of TS-1 and weekly CDDP].

We report a case of a patient with recurrent gastric cancer and lung metastasis, who responded remarkably to combination chemotherapy using TS-1 and weekly CDDP. The patient was administered 2 courses of TS-1 (80 mg/m2/day, on day 1-21) and CDDP (25 mg/m2/day, on day 8, 15, 22) every 5 weeks. The regimen was done on an outpatient basis. The treatment resulted in the metastatic tumors in the lung disappearing after 1 course. No severe side effects were observed. This combination therapy proved useful for treating lung metastasis from gastric cancer in this patient.