Factors Associated with Multimodal Care Practices for Cancer Cachexia among Pharmacists.

Pharmacists' roles in cachexia care are unclear. This study aimed to clarify the knowledge and practice of cachexia care and identify factors related to the practice of cachexia care among pharmacists. Information on the knowledge and practice of cachexia care was obtained. Components of practicing multimodal care were evaluated. Participants were categorized into two groups according to practicing multimodal care levels. Comparisons were made between the groups, and multiple regression analysis was employed. Of the 451 pharmacists, 243 responded. They were categorized into the Practicing group (n = 119) and Not practicing group (n = 124). Significant differences were observed for the number of advanced cancer patients/month, frequency of caring for them, and involvement in training programs on cachexia. The Practicing group had significantly better knowledge about cachexia. The Practicing group used guidelines, items, and symptoms more frequently to detect cachexia. The Practicing group tended to detect cachexia and initiate interventions in earlier phases and in patients with a better status. Multivariate logistic regression analysis showed that the most significant factor was the regular provision of care (odds ratio, 2.07; 95% confidence interval, 1.10-3.92). The regular provision of care was associated with the practice of multimodal care.

Prognostic Impact of Malignant Wounds in Patients With Head and Neck Cancer: Secondary Analysis of a Prospective Cohort Study.

INTRODUCTION: Malignant wounds are lesions caused by metastasis from distant primary cancers or by direct invasion of the cutaneous structures of a primary cancer, and are most common in patients with breast or head and neck cancers. Malignant wounds not only cause physical symptoms, but also affect survival. Recognizing prognosis in terminal-stage cancer patients is necessary for both patients and health care providers. The prognostic impact of malignant wounds in patients with head and neck cancer has been poorly investigated. METHODS: This is a secondary analysis of the results of a prospective cohort study that investigated the dying process in patients with advanced cancer in 23 palliative care units in Japan. The primary outcome of this study was the prognostic impact of malignant wounds in patients with head and neck cancer. The difference in survival between patients with head and neck cancer who had malignant wounds and those who did not was compared using the log-rank test. RESULTS: Of 1896 patients admitted to palliative care units, 68 had head and neck cancer, and 29 of these had malignant wounds. Overall survival was significantly shorter in patients with malignant wounds than that in those without (median: 19.0 days vs 32.0 days, P = 0.046). CONCLUSION: Patients with head and neck cancer who had malignant wounds had worse overall survival than those who did not.

Myofascial pain syndrome in patients with cancer: a narrative review.

PURPOSE: Myofascial pain syndrome (MPS) is a chronic musculoskeletal pain syndrome. The purpose of this review is to describe the epidemiological and treatment evidence and to address the future research agenda in patients with cancer. METHODS: A narrative review of previous reports investigating the prevalence and treatment of MPS in the oncology field is presented. The target population is patients with cancer and cancer survivors. RESULTS: There have been three prospective and two retrospective studies investigating the prevalence of MPS. MPS is as high as 38%-45% in patients with advanced or incurable cancer and 11.9%-44.8% in cancer survivors. A total of nine reports investigated the efficacy of the following interventions: trigger point injection (TPI), myofascial techniques and ischaemic compression. TPI has been reported to be effective in four observational studies. One randomised study reported the efficacy of myofascial techniques, but two randomised studies reported no added beneficial effects of it in breast cancer survivors. Two randomised studies investigated the efficacy of ischaemic compression, but the obtained results were contradictory. CONCLUSIONS: MPS is highly prevalent. We should know that non-cancer pain is also common in both patients with cancer and survivors. In treating such pain, careful physical examination is essential. Then, non-pharmacological treatment should be considered as well as pharmacotherapy. As evidence regarding MPS in the oncology field is scarce, further research is warranted.

Factors associated with multimodal care practices for cancer cachexia among registered dietitians.

PURPOSE: This study aimed to determine factors associated with multimodal care practices for cancer cachexia among registered dietitians (RDs) working in cancer care. METHODS: A secondary analysis was performed using RDs' data. Data on knowledge, skills, and confidence in multimodal care were obtained. Nine items regarding multimodal care practices were evaluated. Subjects were divided into two groups based on their answers associated with the nine items. Comparisons were obtained using the Mann-Whitney U test or chi-squared test. Multiple regression analysis was performed to identify the critical factors involved in practicing multimodal care by determining the variables with significant differences between the two groups. RESULTS: Two hundred thirty-two RDs were included in this study. Significant differences were observed in their primary area of practice (p = 0.023), the number of clinical guidelines used (p < 0.001), the number of items used in cancer cachexia assessment (p = 0.002), the number of symptoms used in cancer cachexia assessment (p = 0.039), training for cancer cachexia (p < 0.001), knowledge of cancer cachexia (p < 0.001), and confidence in cancer cachexia management (p < 0.001). The number of symptoms used in cancer cachexia assessment (B = 0.42, p = 0.019), knowledge of cancer cachexia (B = 6.60, p < 0.001), and confidence in cancer cachexia management (B = 4.31, p = 0.010) were identified as critical factors according to the multiple regression analysis. CONCLUSION: The RDs' knowledge and confidence in cancer cachexia management were associated with their multimodal care practices.

Investigating the efficacy and safety of olanzapine prophylaxis for opioid-induced nausea and vomiting (JORTC-PAL20): a study protocol for an open-label, single-arm exploratory study.

INTRODUCTION: In opioid therapy for cancer pain, opioid-induced nausea and vomiting (OINV) occur in 20%-40% of patients during initial opioid treatment or increasing opioid doses. OINV result in failure to achieve pain relief due to poor opioid adherence. Therefore, antiemetics are used to prevent OINV, but their efficacy and safety in this context have not yet been fully elucidated. Olanzapine is a promising antiemetic for the prophylaxis of chemotherapy-induced nausea and vomiting. METHODS AND ANALYSIS: This single-arm, single-centre exploratory study will evaluate the prophylactic antiemetic efficacy and safety of 5 mg olanzapine in patients with cancer pain who are withholding initial regular opioid therapy. Thirty-five patients will be enrolled. The primary endpoint is the proportion of patients achieving complete control (CC) of OINV during 5 days of opioid treatment. CC was defined as the absence of emetic episodes, no need for rescue medication to treat nausea, and minimal or no nausea (3 or less on an 11-point categorical scale). Secondary endpoints include the complete response, defined as no emetic episodes and no use of rescue medication during the overall assessment period, the time from opioid initiation to first emetic episode, the time from opioid initiation to first rescue antiemetic administration, and adverse events graded by Patient-Reported Outcome (PRO) Common Terminology Criteria for Adverse Events (CTCAE) version 1.0 and CTCAE version 5.0. ETHICS AND DISSEMINATION: This study protocol was approved by National Cancer Center Hospital Certified Review Board. The results will be used as preliminary data to conduct a validation study. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCT) jRCTs031220008.

Cancer Pain Management in Patients Receiving Inpatient Specialized Palliative Care Services.

CONTEXT: Cancer pain is a common complication that is frequently undertreated in patients with cancer. OBJECTIVES: This study is aimed at assessing the time needed to achieve cancer pain management goals through specialized palliative care (SPC). METHODS: This was a multicenter, prospective, longitudinal study of inpatients with cancer pain who received SPC. Patients were continuously followed up until they considered cancer pain management successful, and we estimated this duration using the Kaplan-Meier method. We investigated the effectiveness of pain management using multiple patient-reported outcomes (PROs) and quantitative measures, including pain intensity change in the Brief Pain Inventory. A paired-sample t-test was used to compare the pain intensity at the beginning and end of the observation period. RESULTS: Cancer pain management based on the PROs was achieved in 87.9% (385/438) of all cases. In 94.5% (364/385) of these cases, cancer pain management was achieved within 1 week, and the median time to pain management was 3 days (95% confidence interval [CI], 2-3). The mean worst pain intensity in the last 24 h at the start and end of observation were 6.9 ± 2.2 and 4.0 ± 2.3, respectively, with a difference of -2.9 (95% CI, -3.2 to -2.6; p < 0.01). Overall, 81.6% of the patients reported satisfaction with cancer pain management, and 62 adverse events occurred. CONCLUSION: SPC achieved cancer pain management over a short period with a high level of patient satisfaction resulting in significant pain reduction and few documented adverse events.

Malignancy-related ascites in palliative care units: prognostic factor analysis.

OBJECTIVES: The prognostic factors in patients with malignancy-related ascites (MA) have been poorly investigated. This study aimed to evaluate both the prognostic impact of MA on terminally ill patients with cancer and the prognostic factors in those with MA. METHODS: This was a post hoc analysis of a multicentre, prospective cohort study. Patients with advanced cancer admitted to palliative care units at 23 institutions and aged≥18 years were enrolled between January and December 2017. Overall survival (OS) was compared according to MA. A multivariate analysis was conducted to explore prognostic factors in patients with MA. RESULTS: Of 1896 eligible patients, gastrointestinal and hepatobiliary pancreatic cancers accounted for 42.5%. 568 (30.0%) of the total had MA. Patients with MA had significantly shorter OS than those without MA (median, 14 vs 22 days, respectively; HR, 1.55; 95% CI, 1.39 to 1.72; p<0.01). A multivariate analysis showed that MA was a poor prognostic factor (HR, 1.30; 95% CI, 1.13 to 1.50; p<0.01) and that among patients with MA, significant poor prognostic factors were liver metastasis, moderately to severely reduced oral intake, delirium, oedema, gastric cancer, high serum creatinine, high serum C reactive protein, high serum total bilirubin, dyspnoea and fatigue, while significant good prognostic factors were female sex, good performance status, high serum albumin and colorectal cancer. CONCLUSIONS: MA had a negative impact on survival in terminally ill patients with cancer. A multivariate analysis revealed several prognostic factors in patients with terminal cancer and MA.

Prevalence of opioid-induced adverse events across opioids commonly used for analgesic treatment in Japan: a multicenter prospective longitudinal study.

PURPOSE: Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks of AEs by opioid type. This study was performed to compare the prevalence of AEs across opioids commonly used for analgesic treatment in Japan. METHODS: This study was conducted as a preplanned secondary analysis of a multicenter prospective longitudinal study of inpatients with cancer pain who received specialized palliative care for cancer pain relief. We assessed daily AEs until termination of follow-up. We rated the severity of AEs based on the Common Terminology Criteria for Adverse Events version 5.0. We computed adjusted odds ratios for each AE (constipation, nausea and vomiting, delirium, and drowsiness) with the following variables: opioid, age, sex, renal dysfunction, and primary cancer site. RESULTS: In total, 465 patients were analyzed. Based on the descriptive analysis, the top four most commonly used opioids were included in the analysis: oxycodone, hydromorphone, fentanyl, and tramadol. With respect to the prevalence of AEs among all analyzed patients, delirium (n = 25, 6.3%) was the most frequent, followed by drowsiness (n = 21, 5.3%), nausea and vomiting (n = 19, 4.8%), and constipation (n = 28, 4.6%). The multivariate logistic analysis showed that no single opioid was identified as a statistically significant independent predictor of any AE. CONCLUSION: There was no significant difference in the prevalence of AEs among oxycodone, fentanyl, hydromorphone, and tramadol, which are commonly used for analgesic treatment in Japan.

Factors Associated With Practice of Multimodal Care for Cancer Cachexia Among Physicians and Nurses Engaging in Cancer Care.

PURPOSE: Multimodal care for cancer cachexia is needed. This study examined factors associated with practicing multimodal cachexia care among physicians and nurses engaging in cancer care. METHODS: This was a preplanned secondary analysis of a survey investigating clinicians' perspectives on cancer cachexia. Data of physicians and nurses were used. Data on knowledge, skills, and confidence in multimodal cachexia care were obtained. Nine items on practicing multimodal cachexia care were evaluated. Participants were divided into two groups as practicing multimodal cachexia care (above median value for the nine items) or not. Comparisons were made using the Mann-Whitney U test or chi-square test. Multiple regression analysis was performed to identify the factors of practicing the multimodal care. RESULTS: Total of 233 physicians and 245 nurses were included. Significant differences were observed between the groups: female sex (P = .025), palliative care versus oncology specialization (P < .001), the number of clinical guidelines used (P < .001), the number of symptoms used (P = .005), training for cancer cachexia (P = .008), knowledge on cancer cachexia (P < .001), and confidence in cancer cachexia management (P < .001). Palliative care specialization (partial regression coefficient [B] = 0.85; P < .001), the number of clinical guidelines used (B = 0.44; P < .001), knowledge on cancer cachexia (B, 0.94; P < .001), and confidence in cancer cachexia management (B = 1.59; P < .001) were statistically significant in multiple regression analysis. CONCLUSION: Specialization in palliative care, specific knowledge, and confidence were associated with the practice of multimodal care for cancer cachexia.

Perspectives of registered dietitians and factors associated with their personal accomplishment in the management of cancer cachexia.

PURPOSE: Registered dietitians (RDs) have the potential in cancer cachexia management. We investigated RDs' knowledge on cancer cachexia and assessed the effects of factors on RDs' perception of playing an important role in cancer cachexia management. METHODS: This is a secondary analysis of a survey examining the perspectives of health care professionals on cancer cachexia management. We sent the questionnaire to 451 RDs. RDs were divided into two groups: RDs with and without the perception. Comparisons were made using the Mann-Whitney U test or chi-square test. To examine the effects of factors on the perception, estimated crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the logistic regression model were calculated. RESULTS: A total of 237 RDs were analyzed. Significant differences were observed in the number of cancer patients/month, the primary area of practice, the number of clinical guidelines used, the number of items used, the number of symptoms used, and training for cancer cachexia management (p values all < 0.05). After adjustments, the factors of cancer care experience ≥ 20 years (OR 8.32, 95% CI 1.22-56.70; p = 0.030), the number of patients/month ≥ 50 (OR 27.35, 95% CI 3.99-187.24; p = 0.001), using the clinical guidelines (OR 2.69, 95% CI 1.29-5.61; p = 0.008), the number of items ≥ 5 (OR 3.52, 95% CI 1.47-8.40; p = 0.005), and receiving training (OR 3.91, 95% CI 1.77-8.67; p = 0.001) significantly associated with the perception. CONCLUSION: Specific knowledge and training as well as abundant experience were associated with the perception.

Clinical role and safety of tapentadol in patients with cancer: A single-center experience.

OBJECTIVE: To evaluate real-world data on the use of tapentadol (TAP) in cancer patients. DESIGN: Single-center retrospective study. SETTING: Curative/palliative. PATIENTS, PARTICIPANTS: Patients who started TAP between October 2014 and December 2018 at our institution. MAIN OUTCOME MEASURE(S): The primary outcome was the reason for TAP initiation. Secondary outcomes included prescription duration, TAP cessation rate, reason for cessation, and adverse events (AEs). Since the palliative care team (PCT) tended to prescribe to cancer patients with intractable pain more often than patients in usual care, and also tended to prescribe opioids based on their characteristics, we decided to compare patients with and without PCT intervention. RESULTS: There were 175 patients who first received TAP during the study period, of whom 81 patients (46.3 percent) were male. The median age was 60 years. TAP was prescribed for opioid-naive patients in 45 (26 percent) cases and opioid switch in 130 (74 percent) cases. When comparing the PCT group (n = 121) and the non-PCT group (n = 54) using univariate analysis, the PCT group had a higher opioid switch rate (81.8 percent vs 57.4 percent, p < .001), higher proportion of patients with neuropathic pain (NP) (65.3 percent vs 16.7 percent, p < .001), and a higher proportion of patients with a history of nausea (41.3 percent vs 18.5 percent, p < .01). The cessation rate due to AEs was 8 percent overall. CONCLUSIONS: Palliative care physicians prescribed TAP for patients with NP or a history of nausea. Opioid-naive patients were preferred by oncologists. TAP has good tolerability in both groups, with a low dropout rate due to AEs.

Performance of Japanese patients in registrational studies.

INTRODUCTION: The accelerated development of lung cancer treatments has resulted in a single global study that is sufficient for a new agent and indication to be approved. Not all new treatments predominate globally, and differences in standards of care may influence the efficacy of treatments in the real world. METHODS: The results from Japanese domestic trials and global trials that included a subset population of Japanese patients were evaluated for 18 genomic targeted agents and immune therapies approved after 2000. The results were collected from drug applications that were reviewed for treatment approval in Japan. RESULTS: Japan is one of the first countries to approve and fully reimburse new agents around the world. Alectinib and nivolumab, which were first developed by Japanese pharmaceutical companies, were evaluated in an independent domestic trial, which resulted in their early approval. For most other indications, 1.1-15.8% of the patients who participated in pivotal registration studies were Japanese, and their treatment results were comparable to those of the overall population. Overall survival was less likely to be improved by four agents for which the post-protocol therapy might have been different in Japan than in other countries. CONCLUSIONS: Overall, a positive result in a global trial was emulated in Japanese patients and led to the approval of a new standard treatment in Japan. Early approvals were attained by either participating in the global registrational study or conducting a domestic phase II study. The higher efficacy of new agents may be an issue in the future, as Japanese patients had early access to the new agent and may receive better treatment after the trial.

Effects of parenteral nutrition and hydration on survival in advanced cancer patients with malignant bowel obstruction: secondary analysis of a multicenter prospective cohort study.

PURPOSE: The benefits of parenteral nutrition and hydration (PNH) in patients with advanced cancer remain unknown. Therefore, we conducted a prospective multicenter cohort study to assess the effects of PNH on survival in patients with malignant bowel obstruction (MBO). METHODS: The present study was a secondary analysis. Data on primary nutritional administration routes during the first week of admission to palliative care units, i.e., parenteral nutrition and parenteral hydration, were obtained. Data on the averaged calorie sufficiency rate/total calorie intake (75% ≤ or 750 kcal/day ≤ , 50-75% or 500-750 kcal/day, 25-50% or 250-500 kcal/day, and < 25% or < 250 kcal/day) were also obtained. Participants with MBO were included and divided into two groups: PNH-high (25% ≤ or 250 kcal/day ≤) and PNH-low (< 25% or < 250 kcal/day). We performed time-to-event analyses using the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression analyses. RESULTS: Patients were divided into the PNH-high (n = 68) and PNH-low (n = 76) groups. A significant difference was observed in survival rates between the two groups (log-rank P < 0.001). Median survival times were 35.5 (95% CI 27-44) and 17.5 (95% CI 13-21) days, respectively. In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the PNH-high group (HR 0.55 (95% CI 0.36-0.83), P = 0.005) than in the PNH-low group. CONCLUSION: The present results indicated the beneficial effects of PNH for prolonging survival in advanced cancer patients with MBO in palliative care units.

Prognostic impact of peripheral blood neutrophil to lymphocyte ratio in advanced-stage pulmonary large cell neuroendocrine carcinoma and its association with the immune-related tumour microenvironment.

BACKGROUND: The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) with large cell neuroendocrine carcinoma (LCNEC) patients remains unclear. Thus, we performed a retrospective study to examine the relationship between the pretreatment NLR and clinical outcome in advanced LCNEC patients and the impact of the immune-related tumour microenvironment (TME). METHODS: This retrospective study included 63 advanced LCNEC patients who had received chemotherapy. We collected clinical data and investigated the TME status (CD4, CD8, CD20 and FOXP3). RESULTS: The overall survival of the patients with a low NLR (<5) was significantly longer than those with a high NLR (≥5) (14.9 vs. 5.2 months; p < 0.001). A multivariate analysis identified a high NLR as a predictor of a poor prognosis (HR, 3.43; 95% CI, 1.73-6.79; p < 0.001). The NLR was inversely correlated with tumoural and stromal CD8-positive tumour-infiltrating lymphocytes (tumoural: r = -0.648, p = 0.005, stromal: r = -0.490, p = 0.046). CONCLUSIONS: A high NLR was associated with a poor prognosis in advanced LCNEC patients. Our study revealed that the NLR can reflect the TME, at least in part, suggesting that the NLR plays an important role not only as a clinical outcome predictor but also as a tumour immune status indicator.

Leptin enhances cytokine/chemokine production by normal lung fibroblasts by binding to leptin receptor.

BACKGROUND: Obesity is a known risk and exacerbation factor for bronchial asthma. Leptin is an adipokine secreted by adipocytes and enhances energy consumption. Earlier studies have shown that leptin also activates inflammatory cells and structural cells, including airway epithelial cells, thereby exacerbating inflammation. However, little is known about leptin's effect on normal human lung fibroblasts (NHLFs), which are deeply involved in airway remodeling in asthma. This study aimed to elucidate the direct effect of leptin on NHLFs. METHODS: NHLFs were co-cultured with leptin, and production of cytokines/chemokines was analyzed with real-time PCR and cytometric bead arrays (CBA). Expression of alpha smooth muscle actin (α-SMA) in the lysate of NHLFs stimulated with leptin was assessed by western blotting. Expression of leptin receptor (Ob-R) was analyzed by real-time PCR and flow cytometry. NHLFs were transfected with Ob-R small interference ribonucleic acid (siRNA) by electroporation and used for experiments. RESULTS: Leptin enhanced production of CCL11/Eotaxin, monocyte chemoattractant protein-1 (CCL2/MCP-1), CXCL8/IL-8, interferon gamma-induced protein 10 (CXCL10/IP-10) and IL-6 by NHLFs at both the protein and messenger ribonucleic acid (mRNA) levels. Leptin also slightly, but significantly, elevated expression of α-SMA. We found robust Ob-R expression on cell surfaces, and transfection with Ob-R siRNA suppressed the enhanced production of CCL11/Eotaxin, CXCL10/IP-10 and IL-6 by leptin, although not completely. CONCLUSIONS: These findings indicate that leptin may contribute to worsening of asthma in obese patients by enhancing production of inflammatory mediators by binding to Ob-R and accelerating myofibroblast differentiation.