Fluorine‐18‐fluorodeoxyglucose‐positron emission tomography evaluation in metastatic bone lesions in lung cancer: Possible prediction of pain and skeletal‐related events

Background Fluorine‐18‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) uptake in primary lesions has been well studied, but little information is available about metastatic bone lesions in patients with lung cancer. The present study was performed to evaluate the relationships between metastatic bone FDG uptake and clinical parameters in patients with lung cancer. Methods FDG uptake was evaluated as the maximum standardized uptake (SUVmax) value of each targeted bone lesion, and the bone to primary lesion ratio of SUVmax (B/P ratio) was calculated. Forty‐nine patients (27 men and 22 women) with a diagnosis of lung cancer (small cell lung cancer [SCLC], n = 7; non‐small cell lung cancer [NSCLC], n = 42) with bone metastasis, and a total of 185 bone metastatic lesions were evaluated. Results The SUVmax in bone and the B/P ratio were significantly higher in patients with pain and subsequent development of skeletal‐related events than in those without pain or skeletal‐related events, respectively. In addition, the SUVmax in metastatic bone lesions and the B/P ratio in SCLC were significantly lower than those in NSCLC, despite similar FDG uptake in the primary tumor. Conclusion Our findings suggest that FDG‐PET evaluation in metastatic bone lesions could be useful to predict initial pain and subsequent clinical outcomes of local bone status in initially diagnosed lung cancer patients with bone metastasis. In addition, our results suggest that there could be histological differences in the biological activity of bone metastatic lesions in lung cancer, especially between SCLC and NSCLC

Long-term outcomes of delayed clozapine initiation in treatment-resistant schizophrenia: a multicenter retrospective cohort study

Abstract Background Clozapine is the only antipsychotic medication with proven efficacy against treatment-resistant schizophrenia. This multicenter retrospective cohort study aimed to evaluate the impact of a delay in clozapine initiation on long-term outcomes. Methods Patients who initiated clozapine treatment between July 2009 and December 2018 were included in this study. According to the length of time from the diagnosis of schizophrenia to clozapine initiation, the patients were categorized into one of three groups: early (≤ 9 years), intermediate (10–19 years), and late (≥ 20 years) initiation. The endpoints were psychiatric rehospitalization and all-cause clozapine discontinuation within 3 years. Hazard ratios (HR) and 95% confidence interval (CI) were estimated using the Fine and Gray method or the Cox proportional hazards model. Results The incidence rates of rehospitalization within three years, according to the cumulative incidence function, were 32.3% for early, 29.7% for intermediate, and 62.2% for late initiation, respectively. Late initiation had a significantly higher risk of psychiatric rehospitalization than early initiation (HR, 2.94; 95% CI, 1.01– 8.55; P = 0.016 by the Gray's test). The risk of psychiatric rehospitalization was not significantly different between the early and intermediate initiation groups. The incidence rate of all-cause clozapine discontinuation within three years using the Kaplan–Meier method was 13.0% for early, 10.6% for intermediate, and 20.1% for late initiation. The risk of all-cause clozapine discontinuation was not significantly among the groups. The late initiation group had more patients discontinuing because of death due to physical diseases than the other groups. Conclusions The study suggests that clozapine should be initiated promptly in patients with treatment-resistant schizophrenia to prevent psychiatric rehospitalization during long-term treatment. Further prospective studies with appropriate consideration of confounding factors and large sample sizes are needed to strengthen the evidence