Gallium-68 DOTATATE provides physiologic imaging and assists in disease localization for somatostatin receptor (SSTR) positive neuroendocrine tumor (NET) patients. However, questions regarding usefulness of gallium- 68 DOTATATE imaging in identifying the primary site in neuroendocrine tumors (NETS) of unknown primary, correlation of NET grade with median Standardized Uptake Value (SUV) and effects of long acting somatostatin analog on gallium-68 DOTATATE imaging quality needs to be evaluated. A single institution retrospective review of the first 200 NET patients with gallium-68 DOTATATE imaging from Dec 2016 to Dec 2017 was conducted. Questions related to NETs of unknown primary, correlation of Standardized Uptake Value (SUV) to Ki-67 (which signifies proliferation rate), the effects of long-acting systemic somatostatin analog (SSA) on SUV were part of our data analysis. From these 200 patients, 59.5% (119) were females, 40.5% (81) were males; the median age was 62 years. The following primary tumor sites were identified small bowel-37.5%; pancreas-18.5%; bronchial-14%; colon-3.5%; rectum-2%; appendix-1.5%; adrenal-0.5%; prostate-0.5%; others-3% and unknown primary-19%. Mean hepatic SUV of the lesion with the greatest radiolabeled uptake in 96 patients was similar irrespective to exposure to long acting SSA. Patients exposed to long acting SSA had mean SUV of 31.3 vs 27.8 for SSA naïve patients. The difference was not statistically significant. Gallium-68 DOTATATE imaging seems to distinguished G3 NET from G1/G2 based on mean SUV, and also identified the primary tumor site in 17 of 38 (45%) patients with unknown primary. Systemic exposure to long acting SSA does not appear to influence mean SUV of gallium-68 DOTATATE scan.Metronomic chemotherapy refers to the minimum biologically effective doses of a chemotherapy agent given as a continuous regimen without extended rest periods. Drug repurposing is defined as the use of an already known drug for a new medical indication, different from the original one. In oncology the combination of these two therapeutic approaches is called “Metronomics”. The aim of this work is to evaluate the therapeutic effect of cyclophosphamide in a metronomic schedule in combination with the repurposed drug losartan in two genetically different mice models of triple negative breast cancer. Our findings showed that adding losartan to metronomic cyclophosphamide significantly improved the therapeutic outcome. In both models the combined treatment increased the mice’s survival without sings of toxicity. Moreover, we elucidated some of the mechanisms of action involved, which include a decrease of intratumor hypoxia, stimulation of the immune response and remodeling of the tumor microenvironment. The remarkable therapeutic effect, the lack of toxicity, the low cost of the drugs and its oral administration, strongly suggest its translation to the clinical setting in the near future.Primary mediastinal large B-cell lymphoma (PMBL), a distinct mature B-cell lymphoma, expresses CD20 and has recently been successfully treated with the combination of a type I anti-CD20 monoclonal antibody, rituximab, with multiple combination chemotherapy regimens. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody (mAb), recognizing a unique CD20 extracellular membrane epitope with enhanced antibody dependent cellular cytotoxicity (ADCC) vs rituximab. We hypothesize that obinutuzumab vs rituximab will significantly enhance in-vitro and in-vivo cytotoxicity against PMBL. PMBL cells were treated with equal dose of obinutuzumab and rituximab for 24 hours (1-100 μg/ml). ADCC were performed with ex-vivo expanded natural killer cells at 101 E T ratio. Mice were xenografted with intravenous injections of luciferase expressing Karpas1106P cells and treated every 7 days for 8 weeks. Tumor burden was monitored by IVIS spectrum system. Compared with rituximab, obinutuzumab significantly inhibited PMBL cell proliferation (p = 0.01), promoted apoptosis (p = 0.05) and enhanced ADCC (p = 0.0002) against PMBL. Similarly, in PMBL xenografted NOD scid gamma mice, obinutuzumab significantly enhanced survival than rituximab when treated with equal doses (p = 0.05). Taken together our results suggest that obinutuzumab significantly enhanced natural killer cytotoxicity, reduced PMBL proliferation and prolonged the overall survival in humanized PMBL xenografted NOD scid gamma mice.

Metastatic brain disease continues to have a dismal prognosis. SKL2001 Previous studies achieved a reduction of local recurrence rates by aggressively resecting the peritumoral zone (supramarginal resection) or using 5-aminolaevulinic acid (5-ALA) fluorescence. The aim of the present study is to assess whether the use of 5-ALA has an impact on local recurrence or survival compared to conventional white light microscopic tumor resection.

We included consecutive patients who underwent surgical resection of brain metastases. Two groups were compared In the “white light” group, resection was performed with conventional microscopy. In the 5-ALA group, fluorescence guided peritumoral resection was additionally performed after standard microscopic resection. In-brain recurrence and mortality were compared between groups.

= 175 patients were included in the study. All baseline parameters were similarly distributed with no significant difference between surgical groups. Local in-brain recurrence occurred in 21/175 patients (12%) with a rate of 15/119 (12.6%) in the white light and 6/56 (10.7%) in the 5-ALA group (

= 0.720). The use of 5-ALA influenced neither in-brain recurrence (OR 0.59 [CI = 95% 0.18; 1.99],

= 0.40) nor mortality (OR 0.71 [CI = 95% 0.27; 1.85],

= 0.49).

The use of 5-ALA did not result in lower in-brain recurrence or mortality compared to the use of white light microscopy. The most prominent predictors of survival remain favorable preoperative performance status, a low tumor diameter and the absence of multiple cerebral lesions.

The use of 5-ALA did not result in lower in-brain recurrence or mortality compared to the use of white light microscopy. The most prominent predictors of survival remain favorable preoperative performance status, a low tumor diameter and the absence of multiple cerebral lesions.