Patients diagnosed with Neuroendocrine Tumors (NET) often are also diagnosed with Neuroendocrine Liver Metastases (NLM) during the course of their disease. NLM can cause significant morbidity and mortality, oftentimes much more than compared to patients with NET. Treatment options have been limited in the past, focusing on surgical resections, for which only a minority of patients are candidates. However, developments of new treatment modalities have progressed rapidly and patients with NLM now have significantly more options, including surgical-directed therapies; liver-directed therapies; and nonsurgical, non-liver-directed therapies. This review provides information about the roles of hepatic resection, orthotopic liver resection, radiofrequency ablation, hepatic artery embolization and hepatic artery chemoembolization, hepatic artery radioembolization and selective internal radiation therapy, peptide receptor radionuclide therapy, systemic chemotherapy, biotherapies including somatostatin analogs and interferon-α, vascular endothelial growth factor and mTOR targets, and microRNA-regulated pathways. Given these new options, the clinician can tailor therapy specific to the patient diagnosed with NLM, thereby giving the patient the best possible chance of prolonged survival.

Purpose/Objective: To assess the safety and efficacy of upfront treatment using bortezomib in combination with standard radiation therapy (RT) and temozolomide, followed by adjuvant bortezomib and temozolomide for up to 24 cycles in patients with newly-diagnosed glioblastoma multiforme (GBM). Patients and Methods: Twenty-four newly-diagnosed GBM patients were enrolled. Patients received standard external beam regional RT with concurrent temozolomide commencing 3–6 weeks after surgery, followed by adjuvant temozolomide and bortezomib for up to 24 cycles or until tumor progression. During RT, bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, 11, 29, 32, 36, and 39. Post RT, bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, and 11 every 4 weeks. Results: No unexpected adverse events occurred from the addition of bortezomib. Efficacy analysis showed median progression free survival (PFS) of 6.2 months (95% CI, 3.7–8.8) with promising PFS rates at 18 months and beyond compared to historical norms (25.0% at 18 and 24 months, 16.7% at 30 months). In terms of overall survival (OS), the median OS was 19.1 months (95% CI, 6.7–31.4) with improved OS rates at 12 months and beyond (87.5% at 12, 50.0% at 24, 34.1% at 36 throughout 60 months) compared to historical norms. Median PFS was 24.7 months (95% CI 8.5–41.0) in 10 MGMT methylated and 5.1 months (95% CI 3.9–6.2) in 13 unmethylated patients. The estimated median OS was 61 months in the methylated (the upper bound of 95% CI could not be reached) and 16.4 months (95% CI 11.8–21.0) in the unmethylated patients. Conclusion: Addition of bortezomib to current standard radio-chemotherapy in newly-diagnosed GBM patients was tolerable. The PFS and OS rates appeared promising with more benefit to MGMT methylated patients. Further clinical investigation is warranted in a larger cohort of patients.

Current findings suggest a potential role for the use of pre-operative F-FDOPA PET in suspected glioma. IncreasedF-FDOPA uptake may not only predict higher glioma grade, but also worse OS.

BACKGROUND AND PURPOSE: To investigate the association between pH-sensitive amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) and relative cerebral blood volume (CBV) measurements obtained from dynamic susceptibility contrast (DSC) perfusion MRI in patients with gliomas. MATERIALS AND METHODS: In this retrospective study, 90 patients were scanned between 2015 and 2018 (median age=50.3, male/female=59/31) with histologically confirmed gliomas. pH-weighting was obtained using CEST-EPI estimation of the magnetization transfer ratio asymmetry (MTRasym) at 3ppm and CBV was estimated using DSC-MRI. The voxel-wise correlation and patient-wise median value correlation between MTRasym at 3ppm and CBV within T2 hyperintense lesions and contrast enhancement lesions was evaluated using Pearson’s correlation analysis. RESULTS: General colocalization of elevated perfusion and high acidity was observed in tumors, with local intra-tumor heterogeneity. For patient-wise analysis, median CBV and MTRasym at 3ppm within T2 hyperintense lesions were significantly correlated (R=0.3180,P=0.0023), but not in areas of contrast enhancement (P=0.5231). The positive correlation in T2 hyperintense lesions remains within high grade (HGG, R=0.4128,P=0.0006) and in IDHWT gliomas (R=0.4300,P=0.0016), but not WHO II or in IDHMUT tumors. Both MTRasym at 3ppm and the voxel-wise correlation between MTRasym and CBV are higher in HGG compared to LGG in T2 hyperintense tumor (MTRasym:P=0.0176; Pearson’s correlation:P=0.0088). The same trend is held when comparing between IDH wild-type gliomas and IDH mutant gliomas (MTRasym:P=0.0368; Pearson’s correlation:P=0.0076). CONCLUSIONS: A positive linear correlation between CBV and acidity in areas of T2 hyperintense, non-enhancing tumor, but not enhancing tumor, were observed across patients. Local heterogeneity was observed within individual tumors.

Background Diffusion magnetic resonance (MR) characteristics are a predictive imaging biomarker for survival benefit in recurrent glioblastoma treated with anti-vascular endothelial growth factor (VEGF) therapy; however, its use in large volume recurrence has not been evaluated. Objective To determine if diffusion MR characteristics can predict survival outcomes in patients with large volume recurrent glioblastoma treated with bevacizumab or repeat resection. Methods A total of 32 patients with large volume (>20 cc or > 3.4 cm diameter) recurrent glioblastoma treated with bevacizumab and 35 patients treated with repeat surgery were included. Pretreatment tumor volume and apparent diffusion coefficient (ADC) histogram analysis were used to phenotype patients as having high (>1.24 μm2/ms) or low (<1.24 μm2/ms) ADCL, the mean value of the lower peak in a double Gaussian model of the ADC histogram within the contrast enhancing tumor. Results In bevacizumab and surgical cohorts, volume was correlated with overall survival (Bevacizumab: P = .009, HR = 1.02; Surgical: P = .006, HR = 0.96). ADCL was an independent predictor of survival in the bevacizumab cohort (P = .049, HR = 0.44), but not the surgical cohort (P = .273, HR = 0.67). There was a survival advantage of surgery over bevacizumab in patients with low ADCL (P = .036, HR = 0.43) but not in patients with high ADCL (P = .284, HR = 0.69). Conclusion Pretreatment diffusion MR imaging is an independent predictive biomarker for overall survival in recurrent glioblastoma with a large tumor burden. Large tumors with low ADCL have a survival benefit when treated with surgical resection, whereas large tumors with high ADCL may be best managed with bevacizumab.