Background. Opioid rotation is used to treat uncontrolled pain and/or opioid-related adverse effects. Our aim was to determine the frequency, indications, outcomes, and predictors of successful opioid rotation in outpatients with cancer. Methods. Medical records of consecutive outpatients with cancer who received strong opioids and returned for follow-up visit within Յ6 weeks to our supportive care center from January to December 2008 were reviewed. Data on patient characteristics, symptoms, opioid use, indications for opioid rotation, outcomes, and morphine equivalent daily dose were collected. Successful opioid rotation was defined as a two-point or 30% reduction in the symptom score or the resolution of opioid-induced neurotoxicity and continuation of the new opioid at follow-up. Results. Opioid rotation was performed in 120 of 385 patients (31%). The median patient age was 55 years. There were 6/120 patients with missing data. Of the 114 evaluable patients, 68 (60%) were men, 81 (71%) were white, 27 (24%) had gastrointestinal cancer, and 90 (80%) had advanced-stage disease. The median Eastern Cooperative Oncology Group score was 1 (interquartile range: 1-2) and the median time between opioid rotation and follow-up was 14 days (interquartile range: 7-21 days). The most common indications for opioid rotation were uncontrolled pain (95/114; 83%) and opioidinduced neurotoxicity (13/114; 12%). A total of 35 patients (31%) had partial opioid rotation. The median improvements in pain and symptom distress score were Ϫ2 (interquartile range: Ϫ4 to 0; p Ͻ .001) and Ϫ5 (interquartile range: Ϫ14 to 7; p ϭ .004), respectively. The morphine equivalent daily dose did not change significantly after opioid rotation (p ϭ .156). A total of 65% of patients (74/114) had successful opioid rotation. There were no clinically significant independent predictors for successful opioid rotation. Conclusion. Opioid rotation was conducted in 31% of outpatients with cancer, with a 65% success rate. The most frequent reason for opioid rotation was uncontrolled pain. There were no independent predictors for successful opioid rotation. The Oncologist 2013;18:212-220 Implications for Practice: Opioid rotation (OR) is the replacement of one opioid by another using an equianalgesic dose. The strategy is used to treat uncontrolled pain and intolerable opioid-related side effects like opioid-induced neurotoxicity (OIN). In this study, OR was administered in about one third of cancer outpatients receiving strong opioids. The rate of success with OR was 65%, which parallels findings of previous studies in the inpatient setting. OR was associated with improvements in pain, symptom distress score, depression, well-being, and insomnia in addition to the resolution of symptoms associated with OIN. OR can effectively manage uncontrolled pain and OIN in cancer outpatients. Further prospective studies should aim at determining the predictors of successful OR.

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Immunotherapy may improve the survival of patients with GBM.

BackgroundCryptococcal meningitis (CM) is a significant source of mortality, the pathogenesis of which has not been fully understood, especially in non-HIV infected populations. We aimed to explore the potential genetic influence of Toll-like receptor (TLR) on non-HIV CM.MethodsThis observational cohort study was done in two stages: a discovery stage and a validation stage. A case-control genetic association study was conducted between 159 non-HIV CM patients and 468 healthy controls. TLR SNPs significantly related to susceptibility went further validation in a second cohort of 583 subjects from a certain district. Associations among TLR SNPs, cerebrospinal fluid (CSF) cytokine concentrations, and clinical severity were explored in a third cohort of 99 previously untreated non-HIV CM patients. Logistic regression model was used to determine the independent predictors for disease severity.FindingsIn the discovery stage, eight TLR SNPs exhibited significant genetic susceptibility to non-HIV CM, one of which was validated in a population validation of HIV-infected cases while none survived in non-HIV cases. CSF cytokine detections showed that 18 cytokines were significantly over-expressed in severely ill patients. Two of the 8 SNPs (rs5743604 and rs3804099) were also significantly associated with disease severity. Specifically, the rs3804099 C/T genotype was further found to be correlated to 12 of the 18 up-regulated cytokines in severe patients. In addition, high levels of interleukin (IL)-10 in CSF (OR 2·97, 95% CI 1·49–5·90; p = 0·002) was suggested as an independent predictor for severity after adjusted for possible confounders.InterpretationTLR participates in both the occurrence and the pathogenesis of non-HIV CM. The in situ immune responses of CM were under genetic influence of TLR and contributed to disease severity.FundNational Natural Science Foundation of China and National Key Basic Research Program of China (973 Program).