Morphine Versus Oxycodone for Cancer Pain Using a Catechol-O-methyltransferase Genotype Biomarker: A Multicenter, Randomized, Open-Label, Phase III Clinical Trial (RELIEF Study).

BACKGROUND: We hypothesized that the high-dose opioid requirement in patients carrying the rs4680-GG variant in the COMT gene encoding catechol-O-methyltransferase would be greater for patients taking morphine than for those taking oxycodone, thus providing a much-needed biomarker to inform opioid selection for cancer pain. METHODS: A randomized, multicenter, open-label trial was conducted at a Japanese hospital's palliative care service. Patients with cancer pain treated with regular doses of nonsteroidal anti-inflammatory drugs or acetaminophen were enrolled and randomized (1:1) into morphine (group M) and oxycodone (group O) groups. The minimum standard dose of immediate-release (IR) oral opioids was repeatedly administered by palliative care physicians to achieve pain-reduction goals (Pain reduction ≥ 33% from baseline and up to ≤ 3 on a numerical rating scale). The primary endpoint was the proportion of subjects requiring high-dose opioids on day 0 with the GG genotype. RESULTS: Of 140 participants who developed cancer-related pain among 378 subjects registered and pre-screened for the genotype, 139 were evaluated in the current study. Among patients carrying a COMT rs4680-GG genotype, 48.3% required high-dose opioids in group M, compared with the 20.0% in group O (95% CI, 3.7%-50.8%; P = .029). Of those with the non-GG genotype, 41.5% treated with morphine and 23.1% with oxycodone required high-dose opioids (95% CI, 3.3%-38.3%; P = 0.098). CONCLUSION: Using the COMT rs4680 genotype alone is not recommended for selecting between morphine and oxycodone for pain relief.

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.

Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study).

BACKGROUND: Cancer patients experience pain that has physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Opioids are used in treatment of pain in patients with various types of cancer. We previously showed that the catechol-O-methyltransferase (COMT) genotype is related to the plasma level of morphine and the required dose of morphine in an exploratory prospective study. The findings showed that a group of patients with a GG single nucleotide polymorphism (SNP) rs4680 in COMT required a significantly higher dose of morphine than a non-GG group. A biomarker for selection of opioids for cancer pain relief would be particularly useful clinically, and therefore we have planned a randomized comparative study of morphine and oxycodone, using the COMT rs4680 SNP as a biomarker. This study is aimed at verifying the assumption that patients in the GG group require an increased morphine dose for pain relief. METHODS: The RELIEF study is a randomized, multi-institutional, open-label trial with a primary endpoint of the proportion of subjects requiring high-dose opioids, as calculated from the dose of a rescue preparation administered on day 0. Secondary endpoints include the Hospital Anxiety and Depression Scale, Short form McGill Pain Questionnaire-2, European Organization for Research and Treatment of Cancer QLQ-C15-PAL, Pain Catastrophizing Scale, and adverse events, Eligibility criteria are patients with advanced carcinoma with non-daily use of opioids in initial screening for registration; and cancer pain targeted for daily opioid treatment, NSAIDs or acetaminophen, NRS ≥3(average over 24 h), opioid-treatment naive within 30 h, no chemotherapy, radiotherapy, or bisphosphonate administration newly started within 2 weeks, and written informed consent at the time of second registration. Between November 2014 and June 2017, an estimated 110 patients from two sites in Japan were randomized (1:1) to morphine or oxycodone in GG and non-GG groups. DISCUSSION: A method for selection of appropriate opioids in cancer patients is a high unmet medical need. This study was designed to evaluate the efficacy of different opioids in patients with cancer based on gene polymorphism, as the first potential multi-institutional registration trial to be conducted in cancer patients with pain. TRIAL REGISTRATION: UMIN000015579 Date of registration: 4 November 2014. It is updated once every six months, the latest update is 30 June 2017. Trial status. The enrollment started in November 2014. At the time of manuscript submission (July 2017), Three-quarters of patients have participated. We thus expect to complete the recruitment by March 2018.

Expectation of a Decrease in Pain Affects the Prognosis of Pain in Cancer Patients: a Prospective Cohort Study of Response to Morphine.

PURPOSE: Cancer pain is a multidimensional experience that includes physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Few prospective studies have examined the relationship between a patient's expectation of pain improvement and the pain prognosis. The aim of this prospective study was to investigate whether patients' expectation to pain reduction was associated with pain intensity after morphine treatment in opioid treatment-naïve patients with various types of cancer. METHODS: The subjects were patients scheduled for cancer pain treatment with morphine who were taking nonsteroidal anti-inflammatory drugs daily. Morphine treatment was performed according to the standard method, including titration (NCCN Guidelines™, Adult Cancer Pain). Simple regression analysis was performed between pain intensity numerical rating scale (NRS) (day 8) as the dependent variable, expectation of pain decrease NRS (day 1), tumor types, and the following covariates as independent variables: patients' characteristics such as age, gender, PS (day 1), genotype of catechol-O-methyltransferase, total scores of Hospital Anxiety and Depression Scale (day 1), and pain intensity NRS (day 1). Multiple regression analysis was performed using forced entry methods with pain intensity NRS (day 8) as the dependent variable, and expectation of pain decrease NRS (day 1) and the covariates as independent variables that had a p value <0.05 in the simple regression models. RESULTS: A total of 100 patients with baseline data were included, and 97 patients (51% female) met the inclusion criteria. Patients with a high expectation of pain decrease NRS had a significantly lower pain intensity NRS (day 8) (p = 0.001). CONCLUSION: Non-pharmacological factors such as expectations for pain treatment could also be important factors to treat cancer pain, which might be associated with communication skills in physicians.

Relationship between dyspnoea and related factors in patients with cancer: a cross-sectional study.

OBJECTIVES: Dyspnoea is a common and distressing symptom in patients with cancer. We aimed to analyse the association between dyspnoea and related factors and to estimate their causal relationship. METHODS: A cross-sectional study was conducted. Patients with cancer with dyspnoea and a mean Numerical Rating Scale (NRS) of ≥3 over 24 hours were enrolled at 10 institutions in Japan from December 2019 to February 2021. The outcomes included dyspnoea, cough and pain NRS over 24 hours, Eastern Cooperative Oncology Group Performance Status, Hospital Anxiety and Depression Scale, Somatosensory Amplification Scale, opioids for dyspnoea and respiratory failure. Path analyses were conducted to estimate the direct and indirect paths with reference to dyspnoea and related factors. RESULTS: A total of 209 patients were enrolled and 208 patients were included in the analysis. Cough worsened dyspnoea (ß=0.136), dyspnoea increased emotional distress (ß=1.104), emotional distress increased somatosensory amplification (ß=0.249) and somatosensory amplification worsened cough (ß=0.053) according to path analysis. CONCLUSION: There may be a vicious circle among dyspnoea and related factors: cough worsened dyspnoea, dyspnoea increased emotional distress, emotional distress increased somatosensory amplification and somatosensory amplification worsened cough. When treating dyspnoea in patients with cancer, managing these factors aimed at interrupting this vicious circle may be useful. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000038820).

Early palliative intervention for patients with advanced cancer.

BACKGROUND: Early palliative intervention in advanced cancer patients with metastatic non-small-cell-lung cancer has been shown to improve survival time. Possibly, palliative intervention at the time of outpatient care further improves patient survival time. OBJECTIVE: We performed a comparative study of late and early referrals of patients with advanced cancer to clarify the appropriate time for palliative intervention and the improvement in survival time. METHODS: Two hundred and one cancer patients, all since deceased, who were treated in our department over a period of 4 years were divided into two groups: patients who experienced outpatient services for <7 days (late referral group, 64 patients) and those who experienced outpatient services for ≥7 days (early referral group, 137 patients). Survival time, duration of chemotherapy and post-progression survival were retrospectively analyzed through examination of medical records. RESULTS: Survival time of the early referral group was longer than that of the late referral group in all the cases (19.0 vs. 6.5 months, P < 0.001). Survival time in advanced non-small-cell lung cancer was 3.5 and 14.0 months (P = 0.010) and 16.5 and 20.9 months (P = 0.039) in advanced colorectal cancer, respectively. There was no significant difference in gastric cancer (P = 0.310). Post-progression survival in each group was 0.7 and 2.7 months (P = 0.018) in non-small-cell lung cancer. CONCLUSIONS: The results of this study suggested that early outpatient referral and palliative intervention leads to improvement of the outcome in patients with advanced non-small-cell lung cancer and colorectal cancer. A prospective comparative study is warranted.

Novel single nucleotide polymorphism biomarkers to predict opioid effects for cancer pain.

There have been few studies on predictive biomarkers that may be useful to select the most suitable opioids to optimize therapeutic efficacy in individual patients with cancer pain. We recently investigated the efficacy of morphine and oxycodone using single nucleotide polymorphisms (SNPs) of the catechol-O-methyltransferase (COMT) rs4680 gene as a biomarker (RELIEF study). To explore additional biomarkers that may enable the selection of an appropriate opioid for individual patients with cancer pain, three SNPs were examined: C-C motif chemokine ligand 11 (CCL11; rs17809012), histamine N-methyltransferase (HNMT; rs1050891) and transient receptor potential V1 (TRPV1; rs222749), which were screened from 74 pain-related SNPs. These SNPs, which were identified as being significantly associated with the analgesic effect of morphine, were then used to genotype the 135 patients in the RELIEF study who had been randomized into a morphine group (n=69) or an oxycodone group (n=66). The present study then assessed whether the SNPs could also be used as selective biomarkers to predict which opioid(s) might be the most suitable to provide pain relief for patients with cancer. Oxycodone tended to provide superior analgesic effects over morphine in patients carrying the genotype AA for the CCL11 rs17809012 SNP (P=0.012 for interaction), suggesting that it could serve as a potential biomarker for personalized analgesic therapy for patients suffering with cancer pain.

Clinical Characteristics of Noncancer-Related Upper Back Pain on Initiation of Palliative Care in Patients with Incurable Cancer.

Background: Cancer patients experience various types of pain unrelated to their malignancy. However, no previous study has reported the prevalence of noncancer-related pain among patients with incurable cancer. Objective: We aimed to investigate the frequency of noncancer-related upper back pain, the type of noncancer disease, and pain intensity among patients. Design: This is a multicenter cross-sectional survey. Setting/Subjects: Subjects were patients with incurable cancer who underwent initiation of palliative care at two university hospitals in Japan. Measurements: Data for patient characteristics were recorded, and the upper back pain intensity, duration, analgesic use, and opioid drug use with dose were determined. Appropriate statistical tests were also performed. Results: Among the 103 patients with upper back pain, 20 (19.4%) had cancer-related pain, 28 (27.2%) had both cancer- and noncancer-related pain, and 53 (51.5%) had only noncancer-related pain. Myofascial pain was suspected in the 72 (88.9%) participants with noncancer-related pain. The median pain numerical rating scale score was four in the cancer-related pain group and seven in the other two groups (p = 0.005). Conclusions: A high proportion of outpatients with incurable cancer undergoing palliative care initiation had noncancer-related upper back pain. Severe pain at the initiation of palliative care in patients with incurable cancer may include noncancer-related pain. Trial Registration: UMIN000038371. Registered December 1, 2019.

Clinical characteristics of alexisomia in patients with incurable cancer.

BACKGROUND: Alexisomia is a clinical concept that describes difficulties in the awareness and expression of bodily feelings regarding physical diseases and symptoms. The study aim was to investigate whether incurable cancer patients with alexisomia had a higher incidence of latent trigger points, higher pain intensity, and higher pain-improvement goals. METHODS: A multicenter cross-sectional survey was conducted among patients with incurable cancer referred to a palliative care service at two university hospitals in Japan. Alexisomia was evaluated using the Shitsu-Taikan-Sho Scale (STSS). All patients were manually examined on their upper trapezius to identify latent trigger points. Patients who experienced pain reported their pain numerical rating scale (PNRS) and personalized pain goal (PPG) scores. RESULTS: A total of 262 patients were selected as participants. Incurable cancer patients with alexisomia were observed in 30.2% of all participants [95% confidence interval (CI): 24.7-35.7]. The latent trigger points risk ratio in the alexisomic group versus the non-alexisomic group was 4.06 (95% CI: 2.24-7.37). Incurable cancer patients with alexisomia tended to have higher PNRS and PPG scores (P<0.001), but there was no significant difference in PPG achievement (P=0.641). CONCLUSIONS: In examining incurable cancer patients with alexisomia, we must recognize that their latent trigger points risk ratio and PPGs are higher (lower symptom improvement goals) than cancer patients without alexisomia, and their rate of seeking help for pain may be low.

Additive Duloxetine for Cancer-Related Neuropathic Pain Nonresponsive or Intolerant to Opioid-Pregabalin Therapy: A Randomized Controlled Trial (JORTC-PAL08).

CONTEXT: Although opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails. OBJECTIVES: We investigated the efficacy of duloxetine for CNP nonresponsive or intolerant to opioid-pregabalin combination therapy. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was performed at 12 specialized palliative care services in Japan. Patients with CNP average pain scores (Brief Pain Inventory [BPI]-Item 5) ≥ 4 in the previous 24 hours and nonresponsive or intolerant to opioid-pregabalin combination therapy were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine 20 mg/day titrated to 40 mg/day or placebo for 10 days. The primary endpoint was BPI-Item 5 on Day 10. Responder analysis measured proportions of patients with 30% and 50% pain decreases. RESULTS: Seventy patients were enrolled. Complete case analysis revealed mean BPI-Item 5 on Day 10 of 4.03 for Group D vs. 4.88 for Group P (P = 0.053). Baseline observation carried forward analysis revealed mean BPI-Item 5 on Day 10 of 4.06 and 4.91 for Groups D and P, respectively (P = 0.048). Clinically meaningful pain improvement (≥30%) was reported by 44.1% (n = 15) of patients in Group D vs. 18.2% (n = 6) in Group P (P = 0.02); 32.4% (n = 11) vs. 3.0% (n = 1) of patients in Groups D and P, respectively, reported pain reduction ≥ 50% (P = 0.002). CONCLUSION: Adding duloxetine to opioid-pregabalin therapy might have clinical benefit in alleviating refractory CNP. Further studies are needed to conclude the efficacy of adding duloxetine.

Avoiding diagnostic errors in psychosomatic medicine: a case series study.

BACKGROUND: Non-organic lesions or diseases of unknown origin are sometimes misdiagnosed as "psychogenic" disorders or "psychosomatic" diseases. For the quality of life and safety of patients, recent attention has focused on diagnostic error. The aim of this study was to clarify the factors that affected misdiagnoses in psychosomatic medicine by examining typical cases and to explore strategies that reduce diagnostic errors. CASE PRESENTATION: The study period was from January 2001 to August 2017. The data of patients who had visited the Department of Psychosomatic Medicine, Kindai University Hospital and its branches, Sakai Hospital and Nihonbashi Clinic, were collected. All patients were aged 16 years or over. Multiple factors, such as age, sex, presenting symptoms, initial diagnosis, final diagnosis, sources of re-diagnosis and types of diagnostic errors were retrospectively analyzed from the medical charts of 20 patients. Among them, four typical cases can be described as follows. Case 1; a 79-year-old woman, initially diagnosed with psychogenic vomiting due to depression that was changed to gastric torsion as the final diagnosis. Case 2; a 24-year-old man, diagnosed with an eating disorder that was later changed to esophageal achalasia. Case 10; a 60-year-old woman's diagnosis changed from conversion disorder to localized muscle atrophy. Case 19; a 68-year-old man, appetite loss from depression due to cancer changed to secondary adrenal insufficiency, isolated ACTH deficiency (IAD). CONCLUSION: This study showed that multiple factors related to misdiagnoses were combined and had a mutual influence. However, they can be summarized into two important clinical observations, diagnostic system-related problems and provider issues. Provider issues contain mainly cognitive biases such as Anchoring, Availability, Confirmation bias, Delayed diagnosis, and Representativeness. In order to avoid diagnostic errors, both a diagnostic system approach and the reduction of cognitive biases are needed. Psychosomatic medicine doctors should pay more attention to physical symptoms and systemic examination and can play an important role in accepting a perception of patients based on a good, non prejudicial patient/physician relationship.

Prospective replication study implicates the catechol-O-methyltransferase Val158Met polymorphism as a biomarker for the response to morphine in patients with cancer.

Genetic differences in humans cause clinical difficulties in opioid treatment. Previous studies indicate that a single nucleotide polymorphism in the catechol-O-methyltransferase (COMT) gene (rs4680; p.Val158Met) may present as a predictive biomarker for the response to morphine treatment. In our previous pilot exploratory study, patients with a G/G genotype were demonstrated to require a higher dose of morphine, compared with patients with A/A and A/G genotypes. In the present study, the aim was to replicate the findings in an independent cohort of opioid-treatment-naïve patients exhibiting various types of cancer. This prospective study was conducted from 2011 to 2012 at the Kindai University Faculty of Medicine. A total of 50 patients with opioid-treatment naïve and histologically confirmed malignant neoplasms who were scheduled to undergo opioid treatment were evaluated in the present study. Assessments were conducted pre-treatment (day 1), post-treatment (day 1), and one week after treatment (day 8). The required dose of morphine on day 1 was significantly higher for patients with the G/G genotype of COMT, compared with those with the A/A and A/G genotypes (P=0.013). The results of the present study provide additional evidence that the COMT genotype may be a predictive biomarker for the response to morphine treatment.

Incidence of carnitine deficiency in patients with cancer pain: A pilot study.

Carnitine deficiency is reportedly associated with increased pain sensation in diabetes mellitus and fibromyalgia, but the association between serum carnitine concentration and cancer pain has not been fully elucidated. We investigated the incidence of carnitine deficiency in patients with cancer pain, and examined the effect of the patients' demographic and clinical characteristics on pain intensity and carnitine deficiency. The serum carnitine concentration was measured in 50 patients with cancer pain receiving non-steroidal anti-inflammatory drugs, but not opioids. Multivariate regression analysis was used to determine the association of carnitine concentration, pain intensity, age and gender with hemoglobin and C-reactive protein (CRP) concentrations. Carnitine deficiency was detected in 9 of the patients (18.0%) and found to be significantly correlated with an elevated CRP concentration (P=0.039). In conclusion, although there does not appear to be an association between carnitine deficiency and cancer pain, it may be affected by inflammation or infection.

The physical and psychological problems of immigrants to Japan who require psychosomatic care: a retrospective observation study.

BACKGROUND: As the number of immigrants to Japan increases, the health problems of foreign nationals also have an increasing impact on Japanese medical institutions. The aim of this study was to clarify the Japan-specific health problems related to both the physical and psychological symptoms of foreign nationals from the viewpoint of psychosomatic medicine. The second aim was to clarify the measures that should be taken in Japan and similar countries where immigration may still be considered less than common. CASE PRESENTATION: The study period was from June 2004 to May 2015. The data of non-Japanese patients who had visited the Department of Psychosomatic Medicine, Kinki University Hospital and its branches, Sakai Hospital and Nihonbashi Clinic, were collected. All patients were aged 16 years or over. Multiple factors, such as age, sex, nationality, length of stay, marital status, employment status, level of Japanese proficiency, clinical symptoms, physical and psychiatric diagnosis, psycho-social factors and therapy were retrospectively analyzed from the medical charts of 20 non-Japanese patients. Cases were divided into two groups; early onset and late onset cases. This study showed that multiple factors related to the health problems of non-Japanese patients were combined and had a mutual influence, however, they can be summarized into two important clinical observations. These are 1) cultural differences, and 2) language barriers related to both the physical and psychological symptoms of non-Japanese patients from the viewpoint of psychosomatic medicine. CONCLUSIONS: Future efforts should focus on sensitizing health care professionals in Japan to the psychosomatic problems of non-Japanese patients as well as on facilitating medical systems with services such as medical professional interpreters and liaison-consultation models. It is essential to take measures against language barriers and to promote the field of transcultural psychiatry and psychosomatic medicine in Japan. In addition, the Japanese government should introduce a more comprehensive social support system for non-Japanese people.

Gender differences in cancer-related distress in Japan: a retrospective observation study.

BACKGROUND: Cancer care is currently the most important medical issue in Japan. Total pain of cancer patients consists of a combination of four factors: physical, psychological, social distress, and spiritual pain. Previous studies showed female cancer patients ask for more psychological support and seem to suffer different types of distress compared with male patients, for example, appearance-related symptoms. However, other factors of cancer distress related to gender have not been defined comprehensively. The aim of this study is to clarify the gender differences in cancer distress types in order to elucidate the measures that should be taken in Japan to improve the quality of whole cancer care based on gender-based medicine. METHODS: The data of new patients who had visited the psycho-oncology outpatient service of Kinki University Hospital during the period of May 2013 to October 2015 were collected. Demographic factors and all assessed items were extracted from the patients' medical charts retrospectively. Based on an inquiry of cancer patients in 2010, each item representing the four factors of "total pain" of cancer patients was chosen, i.e., physical distress (pain, changes in appearance), psychological distress (anxiety, depression), social distress (family problems, job-related problems), and spiritual pain; together with sexuality issues, and answers were analyzed. Hospital Anxiety Depression Scale (HADS) was used for the assessment of psychological distress. Chi-square test and Fisher's exact test were performed for gender differences in the cancer distress types. Pearson's analysis and multiple logistic regression analysis were performed for the association of gender with each item. RESULTS: The data of 101 cancer patients were analyzed and there were more female patients than male patients (female: male ratio = 71:30). Female cancer patients were more likely to suffer from psycho-social issues such as changes in appearance, family problems and sexuality issues than male patients, and male patients were more likely to have spiritual pain. CONCLUSIONS: There were gender differences in the distress types of cancer patients. In order to improve the quality of whole cancer care, more intensive intervention by medical professionals and social support is needed from the viewpoint of gender-based medicine and psycho-oncology.

Clinical outcome of node-negative oligometastatic non-small cell lung cancer.

INTRODUCTION: The concept of "oligometastasis" has emerged as a basis on which to identify patients with stage IV non-small cell lung cancer (NSCLC) who might be most amenable to curative treatment. Limited data have been available regarding the survival of patients with node-negative oligometastatic NSCLC. PATIENTS AND METHODS: Consecutive patients with advanced NSCLC who attended Kindai University Hospital between January 2007 and January 2016 were recruited to this retrospective study. Patients with regional lymph node-negative disease and a limited number of metastatic lesions (≤5) per organ site and a limited number of affected organ sites (1 or 2) were eligible. RESULTS: Eighteen patients were identified for analysis during the study period. The most frequent metastatic site was the central nervous system (CNS, 72%). Most patients (83%) received systemic chemotherapy, with only three (17%) undergoing surgery, for the primary lung tumor. The CNS failure sites for patients with CNS metastases were located outside of the surgery or radiosurgery field. The median overall survival for all patients was 15.9 months, with that for EGFR mutation-positive patients tending to be longer than that for EGFR mutation-negative patients. CONCLUSION: Cure is difficult to achieve with current treatment strategies for NSCLC patients with synchronous oligometastases, although a few long-term survivors and a smaller number of patients alive at last follow-up were present among the study cohort. There is an urgent clinical need for prospective evaluation of surgical resection as a treatment for oligometastatic NSCLC, especially negative for driver mutations.

Psychological problems for non-Japanese speaking patients in Japan.

The psychological problems of non-Japanese people are becoming more outstanding, in accordance with the increase of foreign nationals in Japan. Five illustrative cases of English-speaking patients were analyzed, from the viewpoint of psychosomatic medicine. The most common psychiatric disorders were adjustment disorders, because of the cultural differences and language barriers.