Tumor Heterogeneity of Fibroblast Growth Factor Receptor 3 (FGFR3) Mutations in Invasive Bladder Cancer: Implications for Peri-Operative anti-FGFR3 Treatment

Background: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. Patients: and methods We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201).Results: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type.Conclusions: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting

Critical Contribution of Mesoporosity to the Stability of Zeolitic Catalysts for Oleate Isomerization in Continuous Flow Reactor

Two types of hierarchical micro-mesoporous materials, as prepared from the zeolites with structure of 10-MR (10-membered rings) ferrierite and 12-MR faujasite Y, have been tested as catalysts of isomerization of methyl oleate in continuous flow conditions. The catalysts have been characterized by X-ray diffraction (XRD), nitrogen physisorption, transmission electron microscopy (TEM), NH3 thermal programmed desorption (TPD), and 27Al MAS NMR. The reaction products have been identified by GC–MS and MALDI–TOF/TOF–MS, quantified by GC–FID, and their cold-flow properties for use as diesel biofuel have been evaluated by differential scanning calorimetry (DSC). The preparations of catalysts by recrystallization in cetyltrimethylammonium (CTA) solution have produced different structural mesoporosity in the two kinds of zeolites, with filling of previous mesopores in faujasite and opening of a bottle-necked negative-crystal mesoporosity in ferrierite. This last type of material has remarkably improved the stability of the isomerization reactions, with 98&nbsp;wt% conversion of methyl oleate and 55% selectivity of branched monoenoic fatty esters upon 8&nbsp;h time-on-flow, an uncommon result among the literature available on the continuous-flow experiments. The better results obtained on ferrierite catalysts, with crystallization points on the average 8&nbsp;°C lower than for faujasite catalysts, have confirmed the shape selectivity of ferrierite structure for alkene isomerization reactions

FDG PET-CT demonstration of metastatic neuroendocrine tumor of prostate

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: FDG PET-CT is generally not suitable for diagnosing prostate cancer because of low glycolysis of the tumor cells. Neuroendocrine differentiation of the prostate cancer is often associated with early visceral metastasis and dismal prognosis, which is resulted from changed metabolic and regulatory pathways. Case presentation: A case is reported in this paper that FDG PET-CT demonstrates intense uptake of neuroendocrine tumor of the prostate and multiple metastases. Conclusion: There is high glycolysis and strong FDG-avidity of neuroendocrine tumor of the prostate, which is similar to that of high grade of neuroendocrine tumor in other tissue and organs. In some selected cases of prostate neuroendocrine cancer, whole body FDG PET-CT may be helpful for detection of metastatic disease. Background Positron emission tomography (PET) is a new imaging modality which has been widely used for detection o

Multi-center assessment of lymph-node density and nodal-stage to predict disease-specific survival in patients with bladder cancer treated by radical cystectomy

BACKGROUND:Prognostic tools in pathological-node (pN) patients after radical cystectomy (RC) are needed.OBJECTIVES:To evaluate the prognostic impact of lymph node (LN)-density on disease-specific survival (DSS) in patients with bladder cancer (BC) undergoing RC with pelvic lymph node dissection.METHODS:We analyzed a multi-institutional cohort of 1169 patients treated with upfront RC for cT1-4aN0M0 urothelial BCat nine centers. LN-densitywas calculated as the ratio of the number of positive LNs×100% to the number of LNs removed. The optimal LN-density cut-off value was defined by creating a time-dependent receiver operating characteristic (ROC) curve in pN patients. Univariable and multivariable Cox’ regression analyses were used to assess the effect of conventional Tumor Nodes Metastasis (TNM) nodal staging system, LN-density and other LN-related variables on DSS in the pN-positive cohort.RESULTS:Of the 1169 patients, 463 (39.6%) patients had LN-involvement. The area under the ROC curve was 0.60 and the cut-off for LN-density was set at 20%, 223 of the pN-positive patients (48.2%) had a LN-density ≥ 20%. In multivariable models, the number of LN-metastases (HR 1.03, p = 0.005) and LN-density, either as continuous (HR 1.01, p = 0.013) or as categorical variable (HR 1.37, p = 0.014), were independently associated with worse DSS, whereas pN-stage was not.CONCLUSIONS:LN-density ≥ 20% was an independent predictor of worse DSS in BC patients with LN-involvement at RC. The integration of LN-density and other LN-parameters rather than only conventional pN-stage may contribute to a more refined risk-stratification in BC patients with nodal involvement.Development and application of statistical models for medical scientific researc

Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer

Because only 16% of patients with metastatic cervical cancer are alive 5 years after diagnosis, the Gynecologic Oncology Group (GOG) has carefully designed and conducted many phase II studies to identify promising drugs. Cisplatin has emerged as the most active single agent with overall response rates of 19%. Recent phase III trials have documented response rates of 27% and 39% when cisplatin has been combined with either paclitaxel or topotecan, respectively. The comparison of cisplatin to cisplatin plus topotecan in GOG-179 has yielded the first study to show a statistically significant impact on the overall response rate, median progression-free survival, and median survival, with all outcome measures favoring the two-drug regimen. Despite these encouraging results, however, most of the responses are partial and of short duration. The need for novel combinations and the implementation of active biologic agents is implicit. The accumulated data in this disease setting, as evidenced by the experience of the GOG, are presented in this review