Validation of a novel risk score to predict early and late recurrence in solitary fibrous tumour.

BACKGROUND: Current risk models in solitary fibrous tumour (SFT) were developed using cohorts with short follow-up and cannot reliably identify low-risk patients. We recently developed a novel risk model (G-score) to account for both early and late recurrences. Here, we aimed to validate the G-score in a large international cohort with long-term follow-up. METHODS: Data were collected from nine sarcoma referral centres worldwide. Recurrence-free interval (RFi) was the primary endpoint. RESULTS: The cohort comprised 318 patients with localised extrameningeal SFTs. Disease recurrence occurred in 96 patients (33%). The estimated 5-year RFi rate was 72%, and the 10-year RFi rate was 52%. G-score precisely predicted recurrence risk with estimated 10-year RFi rate of 84% in low risk, 54% in intermediate risk and 36% in high risk (p < 0.001; C-index 0.691). The mDemicco (p < 0.001; C-index 0.749) and SalasOS (p < 0.001; C-index 0.674) models also predicted RFi but identified low-risk patients less accurate with 10-year RFi rates of 72% and 70%, respectively. CONCLUSIONS: G-score is a highly significant predictor of early and late recurrence in SFT and is superior to other models to predict patients at low risk of relapse. A less intensive follow-up schedule could be considered for patients at low recurrence risk according to G-score.

Prevalence and prognostic impact of comorbidities and peripheral blood indices in sarcomas.

BACKGROUND: The prognostic impact of comorbidities in patients with sarcomas is not well defined. The aims of this study were to examine the implications of comorbidities and abnormal peripheral blood indices in patients with sarcomas. METHODS: A population-based database was assembled to extract patients with sarcoma in Hong Kong between January 2004 and March 2018. Charlson's Comorbidity Index (CCI) score and prevalence of comorbidities, neutrophil, lymphocyte and platelet counts at diagnosis were assessed. The prognostic values of CCI, neutrophil-lymphocyte (NLR) and platelet-lymphocyte ratios (PLR) were estimated using Cox proportional hazard models. Restricted cubic spline plots were used to explore the association of baseline NLR and PLR with all-cause and cancer-specific mortality. RESULTS: Among 3358 eligible patients with sarcomas, 52.2% died after a median 26 months of follow-up. The most common comorbidities were diabetes mellitus (9.8%) and cerebrovascular disease (4.8%). Patients with higher CCI had higher mortality (CCI=3 vs CCI=2; HR 1.49; 95% CI 1.19 to 1.87; p<0.01; CCI ≥7 vs CCI =2; HR 3.20; 95% CI 2.62 to 3.92; p<0.001). Abnormal NLR and PLR levels were associated with higher all-cause mortality (NLR: HR 1.698, p<0.001, 95% CI 1.424 to 2.025; PLR: HR 1.346, p<0.001, 95% CI 1.164 to 1.555) and cancer-related mortality (NLR: HR 1.648, p<0.001, 95% CI 1.341 to 2.024; PLR: HR 1.430, p<0.001, 95% CI 1.205 to 1.697). CONCLUSIONS: This is the largest population-based soft-tissue or bone sarcoma cohort worldwide. Comorbidities have significant negative prognostic impact on the survival of patients with sarcomas. Moreover, NLR and PLR are robust prognostic factors, and abnormal NLR and PLR have negative effects yet non-linear effects on survival.

A novel near-infrared nanomaterial with high quantum efficiency and its applications in real time in vivo imaging.

Fluorescence imaging signal is severely limited by the quantum efficiency and emission wavelength. To overcome these challenges, novel NIR-emitting K5NdLi2F10 nanoparticles under NIR excitation was introduced as fluorescence imaging probe for the first time. The photostability of K5NdLi2F10 nanoparticles in the water, phosphate buffer saline, fetal bovine serum and living mice was investigated. The fluorescence signal was detected with depths of 3.5 and 2.0 cm in phantom and pork tissue, respectively. Fluorescence spectrum with a significant signal-to-background ratio of 10:1 was captured in living mice. Moreover, clear NIR images were virtualized for the living mice after intravenous injection. The imaging ability of nanoparticles in tumor-beard mice were evaluated, the enrichment of K5NdLi2F10 nanoparticles in tumor site due to the enhanced permeability and retention effect was confirmed. The systematic studies of toxicity, bio-distribution and in-vivo dynamic imaging suggest that these materials give high biocompatibility and low toxicity. These NIR-emitting nanoparticles with high quantum efficiency, high penetration and low toxicity might facilitate tumor identification in deep tissues more sensitively.

Pinoline and N-acetylserotonin reduce glutamate-induced lipid peroxidation in retinal homogenates.

Glutamate is a neurotransmitter associated with oxidative retinal disorders. Pinoline (PIN) and N-acetylserotonin (NAS) are newly identified neural protectors. We investigated the glutamate-induced lipid peroxidation (LPO) and the protective effects of PIN and NAS in the retina. Porcine retinal homogenates were treated with different concentrations of glutamate. The malondialdehyde (MDA) level per unit weight of protein was quantified spectro-photometrically as an index of LPO. The glutamate concentration that induced a significant increase in retinal MDA was determined. The glutamate-treated retinal homogenate was then co-incubated with 5 different concentrations (0, 35.7, 71.5, 143 and 286 microM) of PIN, NAS or their combinations (concentration corresponding to 25, 50 and 75% of protection). Glutamate induced a significant dose-dependent increase in retinal MDA (p<0.0001). Co-incubation with PIN or NAS significantly suppressed the glutamate-induced MDA (p<0.01) in a dose-dependent manner (p<0.0001). The concentrations to inhibit 50% of LPO were 132.8 and 98.6 microM for PIN and NAS, respectively. In summary, elevated glutamate induced retinal LPO. Both PIN and NAS suppressed the glutamate-induced LPO and a synergic protection was evident after incubation in PIN/NAS mixtures.

Correlation of the response of recurrent malignant gliomas treated with interferon alpha with tumor interferon alpha gene content.

Malignant gliomas are treated by combining surgery and radiation with chemotherapy. Cure is rare and utilizing information arising from our improved understanding of brain tumor biology may be of value. Interferon alpha (IFNalpha) treatment as restorative immunotherapy has been utilized in malignant gliomas in the past. Interferon alpha/beta gene presence is variable in these tumors. The relationship between response to IFNalpha therapy and gene status has not been assessed prospectively. Patients with recurrent malignant gliomas were treated with 8-week courses of IFNalpha. Clinical and laboratory toxicity was assessed and response determined by MRI scans. Tumor interferon alpha/beta gene content was measured. Toxicities included fourteen grade 3/4 neuro-motor events, and eleven grade 3 neuro-cortical events. Rapid tolerance developed and with dose reductions few doses were missed. Three individuals with glioblastoma multiforme demonstrated a partial response. Median time to progression was 24.6 (+/-17.6) weeks for all glioblastomas. The correlation between longer time to progression and lower tumor IFNalpha gene content as measured here was significant. A minority of patients with recurrent malignant gliomas will respond to IFNalpha therapy at starting doses of 20 Mu/m(2) and above. These doses are associated with significant toxicity. A relationship between the tumor IFNalpha gene status and tumor response to therapy may be present. With current improved understanding of IFNalpha toxicities and ability to measure tumor IFNalpha function, this therapy warrants further evaluation for identifying patients whose tumors are likely to be responsive to IFNalpha therapy.

Intraoperative angiography during aneurysm surgery: a prospective evaluation of efficacy.

OBJECT: Indications for intraoperative angiography during aneurysm surgery remain unclear. To define its use, the authors report the results of a prospective study in which this modality was used in all patients undergoing surgery for intracranial aneurysms. METHODS: Intraoperative angiography was performed prospectively in the surgical treatment of 517 consecutive aneurysms regardless of the lesion's location, size, or complexity. In 64 (12.4%) of 517 aneurysms intraoperative angiography findings prompted a change in surgical treatment. Residual aneurysm (47%) was the most frequent finding leading to clip revision. In 44% of cases, intraoperative angiography revealed vessel compromise. Surgery for aneurysms of the proximal internal carotid artery (ICA) was the most frequently altered, with lesions located at the superior hypophyseal artery (SHA) and clinoidal region having the highest revision rates, eight (40%) of 20 and eight (44%) of 18, respectively. Aneurysm size predicted the need for revision; giant aneurysms (> 24 mm) underwent revision in nine (29%) of 31 cases, whereas large aneurysms (15-24 mm) were revised in 12 (22%) of 54 cases. In a multivariate logistic regression model, factors related to increased revision rates included the SHA and clinoidal locations, as well as giant and large size. Ninety-five patients underwent both intraoperative and postoperative angiography. Five discrepancies were noted (95% accuracy); four were flow-related and one involved a previously unrecognized residual aneurysm. Complications attributable to intraoperative angiography occurred in 0.4% of cases. CONCLUSIONS: Proximal ICA location and large aneurysm size significantly predicted revision of surgery following intraoperative angiography. Unexpected findings, even in less complex locations, are frequently identified on intraoperative angiography. Low complication rates, high accuracy, and the unexpected need for clip readjustments favor a more widespread use of intraoperative angiography.