Protocol for a confirmatory trial of the effectiveness and safety of palliative arterial embolization for painful bone metastases.

BACKGROUND: Transcatheter arterial embolization (TAE) has long been used for hemostasis of traumatic or postoperative hemorrhage and embolization of tumors. Previous retrospective studies of TAE for painful bone metastases showed 60%-80% pain reduction with a median time to response of 1-2 days. Compared with radiotherapy and bisphosphonates, time to response appeared earlier than that of radiotherapy or bone-modifying agents. However, few prospective studies have examined TAE for this indication. Here, we describe the protocol for a confirmatory study designed to clarify the efficacy and safety profile of TAE. METHODS: This study will be a multicenter, single-arm confirmatory study (phase 2-3 design). Patients with painful bone metastases from any primary tumor are eligible for enrollment. TAE will be the main intervention. Following puncture of the femoral artery under local anesthesia and insertion of an angiographic sheath, angiography will confirm that the injected region includes tumor vasculature. Catheter position will be adjusted so that the embolization range does not include non-target tissues. Spherical embolic material will then be slowly injected into the artery to embolize it. The primary endpoint (efficacy) is the proportion of subjects with pain relief at 72 h after TAE and the secondary endpoint (safety) is the incidence of all NCI Common Terminology Criteria for Adverse Events version 5.0 Grade 4 adverse events and Grade ≥ 3 necrosis of the central nervous system. DISCUSSION: If the primary and secondary endpoints are met, TAE can be a treatment choice for painful bone metastases. Trial registry number is UMIN-CTR ID: UMIN000040794. TRIAL REGISTRATION: The study is ongoing, and patients are currently being enrolled. Enrollment started in March 2021. A total of 36 patients have participated as of Aug 2022. PROTOCOL VERSION: Ver1.4, 13/07/2022.

What are the barriers to medical collaboration in community-based integrated care supporting cancer patients? A qualitative analysis of healthcare and long-term care providers' perceptions.

BACKGROUND: Patients required comprehensive cancer treatment in the community based on medical collaboration between designated cancer care hospitals and community medical and nursing care facilities to help them live life on their own terms. This study aims to describe the barriers to medical collaboration in community-based integrated care from the perspectives of healthcare providers (HCPs) and long-term care providers (LCPs) supporting cancer patients. METHODS: Semi-structured interviews were conducted with 88 HCPs and LCPs supporting cancer patients. We analyzed interview data to describe barriers to medical collaboration between designated cancer care hospitals and community medical and nursing care facilities using content analysis in MAXQDA. RESULTS: Participants were mostly HCPs, with physicians accounting for the largest proportion (27.3%). Totally, 299 codes were integrated into seven barriers to medical collaboration in community-based integrated care, including lack of information provision including life perspectives and a delay in sharing cancer patients' values with HCPs to provide end-of-life care according to the patients' wishes. Furthermore, insufficient coordination of cancer and non-cancer symptom management was identified as a barrier specific to older adults with cancer. CONCLUSIONS: Barriers related to cancer treatment that integrate lifestyle perspectives, end-of-life care emphasizing patient values, and medical collaboration between cancer and non-cancer care are distinctive. They emphasize the importance of utilizing professionals to connect treatment and lifestyle information, establishing a central coordinating organization led by the DCCH, and developing a community palliative care network. Moreover, connecting cancer and non-cancer care through government and medical collaboration is crucial.

Influence of different air CT numbers for IVDT on the dose distribution in TomoTherapy MVCT.

This study aims to evaluate the effect of different air computed tomography (CT) numbers of the image value density table (IVDT) on the retrospective dose calculation of head-and-neck (HN) radiotherapy using TomoTherapy megavoltage CT (MVCT) images. The CT numbers of the inside and outside air and each tissue-equivalent plug of the "Cheese" phantom were obtained from TomoTherapy MVCT. Two IVDTs with different air CT numbers were created and applied to MVCT images of the HN anthropomorphic phantom and recalculated by Planned Adaptive to verify dose distribution. We defined the recalculation dose with MVCT images using both inside and outside air of the IVDT as IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ , respectively. Treatment planning doses calculated on kVCT images were compared with those calculated on MVCT images using two different IVDT tables, namely, IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ . The difference between average MVCT numbers ±1 standard deviation on inside and outside air of the calibration phantom was 65 ± 36 HU. This difference in MVCT number of air exceeded the recommendation lung tolerance for dose calculation error of 2%. The dose differences between the planning target volume (PTV): D98% , D50% , D2% and the organ at risk (OAR): Dmax , Dmean recalculated by IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ using MVCT images were a maximum of 0.7% and 1.2%, respectively. Recalculated doses to the PTV and OAR with MVCT showed that IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ was 0.5%-0.7% closer to the kVCT treatment planning dose than IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ . This study showed that IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ was more accurate than IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ in recalculating the dose HN cases of MVCT using TomoTherapy.

Research policy in supportive care and palliative care for cancer dyspnea.

BACKGROUND: Dyspnea is a common and distressing symptom in patients with cancer. To improve its management, multicenter confirmatory studies are necessary. Research policy would be useful in conducting these studies. Here, we propose a new research policy for the management of dyspnea in patients with cancer. METHODS: The first draft was developed by a policy working group of 11 specialists in the field of supportive care or palliative care for dyspnea. Then, a provisional draft was developed after review by a research support group (the Japanese Supportive, Palliative and Psychosocial Care Study Group) and five Japanese scientific societies (Japanese Association of Supportive Care in Cancer, Japanese Society of Medical Oncology, Japanese Society of Palliative Medicine, Japanese Association of Rehabilitation Medicine and Japanese Society of Clinical Oncology), and receipt of public comments. RESULTS: The policy includes the following components of research policy on dyspnea: (i) definition of dyspnea, (ii) scale for assessment of dyspnea, (iii) reason for dyspnea or factors associated with dyspnea and (iv) treatment effectiveness outcomes/adverse events. The final policy (Ver1.0) was completed on 1 March 2021. CONCLUSIONS: This policy could help researchers plan and conduct studies on the management of cancer dyspnea.

Early specialized palliative care for patients with metastatic lung cancer receiving chemotherapy: a feasibility study of a nurse-led screening-triggered programme.

BACKGROUND: Strategies to implement early specialized palliative care have not yet been established. The present study investigated the feasibility of a nurse-led, screening-triggered early specialized palliative care intervention programme and obtained data to design a randomized controlled trial. METHODS: Patients with metastatic lung cancer undergoing first-line platinum-based chemotherapy were eligible. The intervention consisted of (1) a questionnaire-based screening programme and (2) advanced-level nurse counselling and care coordination with interdisciplinary team approach. The primary endpoint was the completion rate of the assessment questionnaire after the second course of first-line chemotherapy (T2). Secondary endpoints included changes in Functional Assessment of Cancer Therapy-Lung scores, depression and anxiety rates based on the Patient Health Questionnaire 9 and the Hospital Anxiety and Depression Scale, and the contents of specialized palliative care. RESULTS: A total of 50 patients were enrolled between August 2012 and March 2014. Median age was 66 years (range, 40-78 year) and 84% were male. A total of 38 patients had stage IV non-small cell lung carcinoma and 12 had extensive disease small-cell lung carcinoma. The completion rate was 70% (95% confidence interval 56.0-81.0). The median duration between baseline and T2 was 53 days. Improvement from baseline were observed at T2 in Functional Assessment of Cancer Therapy-Lung scores (86.0 ± 18.1 vs 94.9 ± 18.2, P = 0.057), depression (16.0 vs 5.7%; P = 0.26) and anxiety (32.0 vs 22.9%; P = 0.65); however, these results were not statistically significant. CONCLUSIONS: This early specialized palliative care intervention is feasible and could be useful in improving patients' quality of life. The present results justify the initiation of a randomized control trial.

Parenting experiences of cancer patients with minor children and their conversations about the possibility of death: a cross-sectional web-based survey for an online cancer community.

PURPOSE: Many cancer patients with minor children experience difficulty talking about their illness with their children. This study aimed to investigate the parenting experiences of cancer patients with minor children and their conversations about the possibility of death. METHODS: A cross-sectional web-based survey was conducted between April and May 2019. Cancer patients with at least one child aged < 18 years were recruited from an online peer support group called "Cancer Parents." The participants were asked to complete a questionnaire about their experiences of talking about their illnesses with their children. The participants were classified into those who disclosed their cancer to their children ("disclosing group"), and those who did not disclose ("non-disclosing group"). The association between whether they talked with their children about their cancer, and whether it included conversations about the possibility of death, was examined. RESULTS: A total of 370 parents participated (with 80.8% female parents, with a median age of 43.0 years). The disclosing group (n = 274, 74.1%) wanted to know what their child felt, more than the non-disclosing group did (p < 0.001). Members of the non-disclosing group had a greater tendency than those in the disclosing group to report that they did not want their children to see their suffering (p = 0.002) and did not know how to explain their disease status (p < 0.002). Some members of both the disclosing (42.1%) and non-disclosing (6.5%) groups told their children about the possibility of death. CONCLUSION: This study showed that 74.1% of the patients with minor children disclosed their cancer to their children. The parents' feelings when thinking about interacting with their children differed significantly between the disclosing and non-disclosing groups. It is important for healthcare professionals treating patients with cancer to provide appropriate multidisciplinary support for discussing their diagnosis and prognosis with their children.

Palliative care physicians' recognition of patients after immune checkpoint inhibitors and immune-related adverse events.

PURPOSE: This study investigated the experience of palliative care physicians (PCPs) and their knowledge and recognition of immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs) in clinical practice as well as the need to provide palliative care services for patients after ICI treatments. METHODS: A cross-sectional survey with self-administered questionnaires was conducted between February and April 2020. A total of 759 questionnaires were sent to PCPs in Japan. The changes in the PCPs' knowledge and recognition of ICIs and irAEs due to the increased experiences of treating patients after ICI treatments were analyzed. RESULTS: Four hundred ninety-two responses (64.8%) were analyzed. Only 15.0% of respondents had no experience of patients after ICI treatments, while 53.9% had experience of more than six patients. On the other hand, 40% of respondents had no experience of patients with suspected irAEs, while only 13.4% had experience of more than six patients. Respondents with more experience of patients after ICI treatments or those with suspected irAEs had extensive knowledge of ICIs and irAEs, were more confident in treating these patients, and tended to consider irAEs as therapeutic indications. The majority of respondents required guidelines and efficient consultation systems with oncologists. CONCLUSION: This study demonstrated that PCPs with experience had extensive knowledge and confidence of ICIs and irAEs and tended to recognize irAEs as therapeutic indications. The establishment of a more intimate relationship between PCPs and oncologists is important for providing better treatment for these patients.

Gliosarcoma with unusual glial components: Two case reports.

Gliosarcoma is characterized by the presence of alternating lesions of glial and mesenchymal components. Although many mesenchymal components have been reported, there are few reports on glial components. We here report two cases of gliosarcoma. Case 1 was a 42-year-old woman with right hemiparesis and motor aphasia. Magnetic resonance imaging (MRI) identified a tumor in the left frontal lobe. Pathological analysis of the tumor removal specimen revealed gliosarcoma, with a glial component resembling pleomorphic xanthoastrocytoma. Postoperatively, radiotherapy and chemotherapy were conducted, and the patient was symptom-free over 12 months after surgery. Case 2 was a 67-year-old woman with a consciousness disorder and left hemiparesis. MRI revealed a tumor in the right frontal lobe. Pathological analysis of the first tumor removal specimen identified gliosarcoma, with a glial component characterized by large tumor cells. Additionally, the Ki-67 labeling index of the glial component was greater than that of the mesenchymal component, and molecular genetic analysis disclosed a mutation in the telomerase reverse transcriptase (TERT) gene (TERT). Chemotherapy and radiotherapy were performed. Four months later, MRI revealed recurrence, and the second surgery was performed. Pathological analysis revealed giant cell glioblastoma without TERT mutation. The patient died due to tumor progression 12 months after the first surgery. It is essential to continue histopathological evaluation of glial components, and further genetic evaluation on gliosarcoma is required.

Availability of and factors related to interventional procedures for refractory pain in patients with cancer: a nationwide survey.

BACKGROUND: Cancer pain may be refractory to standard pharmacological treatment. Interventional procedures are important for quality of analgesia. The aim of the present study was to clarify the availability of four interventional procedures (celiac plexus neurolysis/splanchnic nerve neurolysis, phenol saddle block, epidural analgesia, and intrathecal analgesia), the number of procedures performed by specialists, and their associated factors. In addition, we aimed to establish how familiar home hospice physicians and oncologists are with the different interventional procedures available to manage cancer pain. METHODS: A cross-sectional survey using a self-administered questionnaire was conducted. Subjects were certified pain specialists, interventional radiologists, home hospice physicians, and clinical oncologists. RESULTS: The numbers of valid responses/mails were 545/1,112 for pain specialists, 554/1,087 for interventional radiology specialists, 144/308 for home hospice physicians, and 412/800 for oncologists. Among pain specialists, depending on intervention, 40.9-75.2% indicated that they perform each procedure by themselves, and 47.5-79.8% had not performed any of the procedures in the past 3 years. Pain specialists had performed the four procedures 4,591 times in the past 3 years. Among interventional radiology specialists, 18.1% indicated that they conduct celiac plexus neurolysis/splanchnic nerve neurolysis by themselves. Interventional radiology specialists had performed celiac plexus neurolysis/splanchnic nerve neurolysis 202 times in the past 3 years. Multivariate analysis revealed that the number of patients seen for cancer pain and the perceived difficulty in gaining experience correlated with the implementation of procedures among pain specialists. Among home hospice physicians and oncologists, depending on intervention, 3.5-27.1% responded that they were unfamiliar with each procedure. CONCLUSIONS: Although pain specialists responded that the implementation of each intervention was possible, the actual number of the interventions used was limited. As interventional procedures are well known, it is important to take measures to ensure that pain specialists and interventional radiology physicians are sufficiently utilized to manage refractory cancer pain.

Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy.

DNA double-strand break (DSB) is considered the most deleterious type of DNA damage, which is generated by ionizing radiation (IR) and a subset of anticancer drugs. DNA-dependent protein kinase (DNA-PK), which is composed of a DNA-PK catalytic subunit (DNA-PKcs) and Ku80-Ku70 heterodimer, acts as the molecular sensor for DSB and plays a pivotal role in DSB repair through non-homologous end joining (NHEJ). Cells deficient for DNA-PKcs show hypersensitivity to IR and several DNA-damaging agents. Cellular sensitivity to IR and DNA-damaging agents can be augmented by the inhibition of DNA-PK. A number of small molecules that inhibit DNA-PK have been developed. Here, the development and evolution of inhibitors targeting DNA-PK for cancer therapy is reviewed. Significant parts of the inhibitors were developed based on the structural similarity of DNA-PK to phosphatidylinositol 3-kinases (PI3Ks) and PI3K-related kinases (PIKKs), including Ataxia-telangiectasia mutated (ATM). Some of DNA-PK inhibitors, e.g., NU7026 and NU7441, have been used extensively in the studies for cellular function of DNA-PK. Recently developed inhibitors, e.g., M3814 and AZD7648, are in clinical trials and on the way to be utilized in cancer therapy in combination with radiotherapy and chemotherapy.

Expression and Role of CFTR in Human Esophageal Squamous Cell Carcinoma.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent chloride (Cl-) anion conducting channel, and its role in esophageal squamous cell carcinoma (ESCC) was examined in the present study. METHODS: Overexpression experiments were conducted on human ESCC cell lines following the transfection of a CFTR plasmid, and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. A microarray analysis was performed to examine gene expression profiles. Fifty-three primary tumor samples collected from ESCC patients during esophagectomy were subjected to an immunohistochemical analysis. RESULTS: Transfection of the CFTR plasmid into the ESCC KYSE 170 and KYSE 70 cell lines suppressed cell proliferation, migration, and invasion and induced apoptosis. The microarray analysis showed the up-regulated expression of genes involved in the p38 signaling pathway in CFTR plasmid-transfected KYSE 170 cells. Immunohistochemical staining revealed a relationship between the CFTR expression pattern at the invasive front and the pN category. A relationship was also observed between the weak expression of CFTR at the invasive front and a shorter postoperative survival in a prognostic analysis. CONCLUSIONS: The overexpression of CFTR in ESCC activated the p38 signaling pathway and was associated with a good patient prognosis. These results indicate the potential of CFTR as a mediator of and/or a biomarker for ESCC.

A Japanese translation, cultural adaptation, and linguistic and content validity confirmation of the Scored Patient-Generated Subjective Global Assessment.

PURPOSE: The Scored Patient-Generated Subjective Global Assessment (PG-SGA©) is a globally recognized and used nutritional screening, assessment, monitoring, and triaging tool. The aim of this study was to translate and culturally adapt the original English PG-SGA for the Japanese speaking populations and to assess its linguistic validity (i.e., comprehensibility, difficulty) and content validity, as perceived by Japanese patients and healthcare professionals. METHODS: In accordance with methodology used in previous Dutch, Thai, German, and Norwegian PG-SGA studies, we followed the ten steps of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles of Good Practice for Translation and Cultural Adaptation for Patient-Reported Outcome Measures. The study enrolled 50 patients and 50 healthcare professionals (HCPs) to evaluate the comprehensibility and difficulty of the translated and culturally adapted PG-SGA. The HCPs also evaluated the content validity of the translation. We evaluated each item and quantified scale indices for content validity (item content validity index (I-CVI), scale content validity index (S-CVI)), comprehensibility (item comprehensibility index (I-CI), scale comprehensibility index (S-CI)), and difficulty (item difficulty index (I-DI), scale difficulty index (S-DI)). RESULTS: Patients evaluated the comprehensibility and difficulty of the patient component as excellent (S-CI = 0.97, S-DI = 0.96). The professionals rated the Japanese version of both components of the PG-SGA as very relevant (S-CVI = 0.94). The professionals evaluated the comprehensibility of the professional component as being acceptable (S-CI = 0.88) but difficult (S-DI = 0.69), based predominantly on items related to physical examination (I-DI = 0.33-0.67). CONCLUSION: The PG-SGA was systematically translated and culturally adapted for the Japanese setting according to the ISPOR process. The Japanese version of the PG-SGA was perceived as comprehensive, easy to use, and relevant. Perceived difficulty in professional components, specifically in the context of metabolic demand and physical examination, will require appropriate training for professionals in order to optimize implementation.

Patient-perceived symptomatic benefits of olanzapine treatment for nausea and vomiting in patients with advanced cancer who received palliative care through consultation teams: a multicenter prospective observational study.

PURPOSE: To examine the safety, effectiveness, and patient-perceived benefit of treatment with olanzapine for nausea and vomiting (N/V) in patients with advanced cancer. METHODS: We conducted a multicenter prospective observational study in a tertiary care setting (Trial registration number: UMIN000020493, date of registration: 2016/1/12). We measured the following: average nausea in the last 24 h using a Numeric Rating Scale (NRS: range 0-10) at baseline and day 2, patient-perceived treatment benefit (based on a 5-point verbal scale), and adverse events (AEs; using the Common Terminology Criteria for Adverse Events version 4). RESULTS: The 85 participants (45% men) had a mean age of 58.7±15.8 years. Major causes of N/V were opioids (44%) and chemotherapy (34%). All patients received a daily dose of olanzapine of 5 mg or less as first-line treatment (N=35) or second- or later-line treatment (N=50). Nausea NRS decreased from 6.1±2.2 to 1.8±2.0 (differences: -4.3, 95% CI -3.7 to -4.9, p<0.001). The proportion of patients who did not experience vomiting episodes in the last 24 h increased from 40-89%. Mean decrease in nausea NRS by patient-perceived treatment benefit were as follows: -0.8 for "none" (n=4, 5%); -2.8 for "slight" (n=17, 20%); -3.3 for "moderate" (n=14, 16%); -4.7 for "lots" (n=25, 29%); and -6.1 for "complete" (n=25, 29%; p-for-trend<0.001). The most prevalent AE was somnolence (n=15, 18%). CONCLUSION: Short-term and relatively low-dose olanzapine treatment was effective for multifactorial N/V. Confirmatory studies with longer observation periods are needed to clarify the duration of the effect and adverse events.

Iatrogenic Middle Meningeal Arteriovenous Fistula During Embolization: Two Case Reports and Literature Review.

Objective Dural arteriovenous fistulae of the middle meningeal artery are rare. There are few reports of complications associated with endovascular therapy. This report describes two cases of iatrogenic middle meningeal arteriovenous fistula due to vascular injury sustained during endovascular treatment. Case description Case 1 was that of a 46-year-old woman. She was treated for an incidentally discovered dural arteriovenous fistula of the cerebellar tentorium by transarterial embolization. During the procedure, a middle meningeal arteriovenous fistula occurred because of vessel laceration by the forced advancement of the distal access catheter (DAC). After the intervention, she developed tinnitus. Follow-up angiography revealed a middle meningeal arteriovenous fistula. The fistula was treated by coil embolization of the affected middle meningeal artery. The second case was that of a 56-year-old woman who developed a middle meningeal arteriovenous fistula from the perforation caused by the microguidewire during tumor embolization. The fistula was treated by occluding the proximal segment of the affected artery with coils. Both patients were discharged without neurological complications after the endovascular procedures. Conclusion Endovascular surgeons should be aware of the possibility of middle meningeal arteriovenous fistula as a potential complication of endovascular procedures.

Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.

Usefulness of painDETECT and S-LANSS in identifying the neuropathic component of mixed pain among patients with tumor-related cancer pain.

PURPOSE: Tumor-related cancer pain often comprises mixed pain with both nociceptive and neuropathic components. Whether tumor-related cancer pain includes a neuropathic component impacts the therapeutic strategy. The aim of this cross-sectional study was to investigate the usefulness of two screening tools for neuropathic pain, painDETECT and Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), in identifying the neuropathic component of mixed pain among patients with tumor-related cancer pain. METHOD: This cross-sectional study recruited consecutive inpatients and outpatients at a single site. The diagnostic accuracy of painDETECT and S-LANSS was evaluated using receiver operating characteristic curve analysis and classification probability. RESULTS: Of the study group, 106 patients had tumor-related cancer pain. Analyses of the nociceptive and mixed pain groups (n = 104) showed that neither painDETECT nor S-LANSS had satisfactory areas under the curve (AUCs) for identifying the neuropathic component of mixed pain (0.59 for painDETECT and 0.56 for S-LANSS). By pain intensity, the AUC for painDETECT was significantly higher in the mild pain group than in the moderate or severe pain group (0.77 vs. 0.43, P = 0.002). All parameters of classification probability for both tools were higher in the mild pain group than in the moderate or severe pain group. CONCLUSIONS: painDETECT and S-LANSS could not identify the neuropathic component of mixed pain among patients with tumor-related cancer pain, especially when pain was moderate or severe. Contrarily, these screening tools might be useful for identifying the neuropathic component of mixed pain for mild pain.

The association between health-related quality of life and achievement of personalized symptom goal.

PURPOSE: The aim of study was to explore the potential association between patient's self-reported physical symptom management goals as personalized symptom goal (PSGs) and health-related quality of life (HRQOL) in cancer patients. The secondary outcome was to investigate the relationship between number of physical symptoms not achieving the PSGs and HRQOL in cancer patients. METHODS: This single-center prospective observational study comprised 140 consecutive outpatients. We evaluated the PSGs and HRQOL using the Functional Assessment of Cancer Therapy-General (FACT-G). Patients were administered a self-report questionnaire, including reports on their physical symptom intensity and PSGs using Edmonton Symptom Assessment System-revised (ESAS-r) scores. We investigated the correlation between PSGs achievement (ESAS-r score ≤ PSG score) and FACT-G total scores, and relationship between and number of physical symptoms not achieving the PSGs (ESAS-r score > PSG score) and FACT-G total scores. RESULTS: The patients who did not achieve PSGs of pain, tiredness, lack of appetite, and shortness of breath had a lower FACT-G total score (p < 0.05). Multivariate linear regression showed that higher number of physical symptoms not achieving the PSGs correlated with lower FACT-G scores (decreasing by 1.826 points for each such symptom, p < 0.01). Predictors of increased number of physical symptoms not achieving the PSGs were younger age and a higher symptom intensity of anxiety. CONCLUSION: PSGs achievement was associated with HRQOL in cancer patients. Additionally, the number of unachieved PSGs were independent determinant of poor HRQOL, particularly in younger cancer patients and those with higher symptom intensity of anxiety.

How successful are we in relieving terminal dyspnea in cancer patients? A real-world multicenter prospective observational study.

PURPOSE: Parenteral morphine is widely used for dyspnea of imminently dying cancer patients, but the outcomes to expect over time remain largely unknown. We examined outcomes after the administration of parenteral morphine infusion over 48 h in cancer patients with a poor performance status. METHODS: This was a multicenter prospective observational study. Inclusion criteria were metastatic/locally advanced cancer, ECOG performance status = 3-4, a dyspnea intensity ≥ 2 on a Support Team Assessment Schedule, Japanese version (STAS-J), and receiving specialized palliative care. After initiating parenteral morphine infusion, we measured dyspnea STAS-J as well as Memorial Delirium Assessment Scale (MDAS), item 9, and Communication Capacity Scale (CCS), item 4, every 6 h over 48 h. RESULTS: We enrolled 167 patients (median survival = 4 days). The mean age was 70 years, 80 patients (48%) had lung cancer, and 109 (65%) had lung metastases. The mean STAS-J scores decreased from 3.1 (95% confidence interval (CI) = 3.0-3.2) at the baseline to 2.1 (95%CI = 1.9-2.2) at 6 h, and remained 1.6-1.8 over 12-48 h. The proportion of patients with dyspnea relief (STAS-J ≤ 1) increased to 39% at 6 h, and ranged between 49 and 61% over 12-48 h. In contrast, up to 6.6 and 20% of patients showed hyperactive delirium (MDAS item 9 ≥ 2) and an inability to communicate (CCS item 4 = 3), respectively, over 48 h. CONCLUSIONS: Overall, terminal dyspnea was relatively well controlled with parenteral morphine, though a significant number of patients continued to suffer from dyspnea. Future efforts are needed to improve outcomes following standardized dyspnea treatment using patient-reported outcomes for imminently dying patients.

Predictors of duloxetine response in patients with neuropathic cancer pain: a secondary analysis of a randomized controlled trial-JORTC-PAL08 (DIRECT) study.

PURPOSE: Duloxetine has some effect against cancer neuropathic pain (CNP); however, predictors of duloxetine response are unclear. This study sought to identify predictors of duloxetine response in patients with CNP. METHODS: Patients (N = 70) with CNP unresponsive to or intolerant of opioid-pregabalin combination therapy, with a brief pain inventory-short form (BPI-SF) Item 5 score (average pain) ≥ 4, and with a total hospital anxiety and depression scale score < 20, were randomized to a duloxetine or a placebo group. Multiple linear regression analysis was conducted to identify predictors of duloxetine response as a secondary analysis with the change in the average pain score on day 10 from day 0 as the dependent variable, and the following five covariates; baseline (day 0) average pain score, baseline opioid dose, continuation/discontinuation of pregabalin, and items 20 and 21 score of the short-form McGill pain questionnaire 2 (SF-MPQ-2) as independent variables. RESULTS: Of the four domains (continuous pain, intermittent pain, neuropathic pain, and affective descriptors) score of SF-MPQ-2 on day 0, significant differences were observed in the neuropathic pain domain (p = 0.040) in change on the average pain between day 10 and day 0 in the duloxetine group. Multiple linear regression analysis revealed that patients with a high score for SF-MPQ-2 Item 21 (tingling pain) on day 0 had a significantly greater change in average pain between day 10 and day 0 (p = 0.046). CONCLUSION: Patients with a high score for SF-MPQ-2 Item 21 might benefit more from duloxetine.

Differential expression of DNA-dependent protein kinase catalytic subunit in the brain of neonatal mice and young adult mice.

It is generally thought that younger people are more susceptible to cancer development after exposure to ionizing radiation in reference to epidemiological studies and animal experiments. However, little is known about the age-dependent alteration in DNA repair ability. In the present study, we examined the expression levels of proteins involved in the repair of DNA double-strand breaks through non-homologous end joining (NHEJ), i.e., DNA-dependent protein kinase catalytic subunit (DNA-PKcs), X-ray repair cross-complementing 4 (XRCC4) and XRCC4-like factor (XLF). We found that the expression of DNA-PKcs in brain tissues was higher in neonatal mice (1 week after birth) than in young adult mice (7 weeks after birth). In association with this, DNA double-strand breaks were repaired more rapidly in the brain tissues of neonatal mice than in those of young adult mice. The current results suggested a possible role for DNA-PKcs protecting developing brain tissues from DNA double-strand breaks.