Brazilian Expert Consensus for NTRK Gene Fusion Testing in Solid Tumors.

Oncogenic neurotrophic tropomyosin receptor kinase gene fusions occur in less than 1% of common cancers. These mutations have emerged as new biomarkers in cancer genomic profiling with the approval of selective drugs against tropomyosin receptor kinase fusion proteins. Nevertheless, the optimal pathways and diagnostic platforms for this biomarker's screening and genomic profiling have not been defined and remain a subject of debate. A panel of national experts in molecular cancer diagnosis and treatment was convened by videoconference and suggested topics to be addressed in the literature review. The authors proposed a testing algorithm for oncogenic neurotrophic tropomyosin receptor kinase gene fusion screening and diagnosis for the Brazilian health system. This review aims to discuss the latest literature evidence and international consensus on neurotrophic tropomyosin receptor kinase gene fusion diagnosis to devise clinical guidelines for testing this biomarker. We propose an algorithm in which testing for this biomarker should be requested to diagnose advanced metastatic tumors without known driver mutations. In this strategy, Immunohistochemistry should be used as a screening test followed by confirmatory next-generation sequencing in immunohistochemistry-positive cases.

A multi-centre randomized controlled trial investigating Consolidation Chemotherapy with and without oxaliplatin in distal rectal cancer and Watch & Wait.

BACKGROUND: Neoadjuvant chemoradiation(nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait-WW). Consolidation chemotherapy(cCT) regimens using fluoropyrimidine-based with or without oxalipatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCT compared to fluoropirimidine alone regimens in terms of primary tumor response remains unclear. Since oxalipatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine + oxaliplatin) for patients with distal rectal cancer. METHODS: In this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54 Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine + oxaliplatin. Magnetic resonance(MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1 cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy(RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) may be enrolled in an organ-preservation program(WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Secondary endpoints are 3-year surgery-free survival, TME-free survival, distant metastases-free survival, local regrowth-free survival and colostomy-free survival. DISCUSSION: Long-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05000697; registered on August 11th, 2021.

Impact of cranial stereotactic radiotherapy associated with immunotherapy with nivolumab and ipilimumab on overall survival in patients with melanoma brain metastases: a real-world evidence

PurposeTo evaluate the impact of cranial stereotactic radiotherapy (SRT) on overall survival (OS) of melanoma brain metastases (MBM) patients treated with combined nivolumab and ipilimumab (CNI) in a contemporary and real-world setting.Methods/patientsThe study was performed by using TriNetX, a global health network dataset of electronic medical records from patients in 49 healthcare organizations. We queried for patients with specific terms between January 2016 and December 2020 and run a propensity score matching (PSM) analysis. OS was estimated by Kaplan–Meier and log-rank test was applied.ResultsAfter initial query and PSM, 114 patients were selected in each cohort. Median OS was 327 days in CNI and not reached in the CNI + SRT cohort, with OS probability of 54.4 and 40.9%, respectively (log-rank P = .0057). CNI + SRT was associated with significantly decreased mortality (HR, 0.57; 95% CI 0.377-0.853; proportionality P = .0034).ConclusionsThis real-world analysis showed that CNI + SRT led to an improvement in OS compared to CNI. (AU)

Impact of cranial stereotactic radiotherapy associated with immunotherapy with nivolumab and ipilimumab on overall survival in patients with melanoma brain metastases: a real-world evidence.

PURPOSE: To evaluate the impact of cranial stereotactic radiotherapy (SRT) on overall survival (OS) of melanoma brain metastases (MBM) patients treated with combined nivolumab and ipilimumab (CNI) in a contemporary and real-world setting. METHODS/PATIENTS: The study was performed by using TriNetX, a global health network dataset of electronic medical records from patients in 49 healthcare organizations. We queried for patients with specific terms between January 2016 and December 2020 and run a propensity score matching (PSM) analysis. OS was estimated by Kaplan-Meier and log-rank test was applied. RESULTS: After initial query and PSM, 114 patients were selected in each cohort. Median OS was 327 days in CNI and not reached in the CNI + SRT cohort, with OS probability of 54.4 and 40.9%, respectively (log-rank P = .0057). CNI + SRT was associated with significantly decreased mortality (HR, 0.57; 95% CI 0.377-0.853; proportionality P = .0034). CONCLUSIONS: This real-world analysis showed that CNI + SRT led to an improvement in OS compared to CNI.

Polyculture of bullfrog tadpoles and Nile tilapia fry.

Two experiments were carried out to test better stocking proportion according to animal size for tilapia (Oreochromis niloticus) and tadpole (Lithobates catesbeianus). The experiments were laid out in a completely randomized design with five treatments (in Experiment I) and four treatments (in Experiment II). In Experiment I, the treatments consisted of a tilapia monoculture; a 75% tilapia + 25% tadpole polyculture; a 50% tilapia + 50% tadpole; a 25% tilapia + 75% tadpole; and a tadpole monoculture. In Experiment II, the treatments were represented by a tilapia monoculture; a 12.5% tilapia + 87.5% tadpole polyculture; a 25% tilapia + 75% tadpole; and a tadpole monoculture. In the first trial, mortality rate differed significantly, with the polyculture treatments having almost 100% mortality of tadpoles. In the second experiment, after adjustments in the initial size of the species, there were significant differences between treatments, with the 12.5% tilapia + 87.5% tadpole polyculture and the tadpole monoculture providing the best results. Regardless of the chosen density, for a polyculture of Nile tilapia and bullfrog tadpoles, ideal conditions would be stocking tilapia fry weighing 50% of the weight initial tadpoles and the proportion of one tilapia for seven tadpoles.

Raman, IR, UV-vis and EPR characterization of two copper dioxolene complexes derived from L-dopa and dopamine.

The anionic complexes [Cu(L(1-))3](1-), L(-)=dopasemiquinone or L-dopasemiquinone, were prepared and characterized. The complexes are stable in aqueous solution showing intense absorption bands at ca. 605 nm for Cu(II)-L-dopasemiquinone and at ca. 595 nm for Cu(II)-dopasemiquinone in the UV-vis spectra, that can be assigned to intraligand transitions. Noradrenaline and adrenaline, under the same reaction conditions, did not yield Cu-complexes, despite the bands in the UV region showing that noradrenaline and adrenaline were oxidized during the process. The complexes display a resonance Raman effect, and the most enhanced bands involve ring modes and particularly the nuCC+nuCO stretching mode at ca. 1384 cm(-1). The free radical nature of the ligands and the oxidation state of the Cu(II) were confirmed by the EPR spectra that display absorptions assigned to organic radicals with g=2.0005 and g=2.0923, and for Cu(II) with g=2.008 and g=2.0897 for L-dopasemiquinone and dopasemiquinone, respectively. The possibility that dopamine and L-dopa can form stable and aqueous-soluble copper complexes at neutral pH, whereas noradrenaline and adrenaline cannot, may be important in understanding how Cu(II)-dopamine crosses the cellular membrane as proposed in the literature to explain the role of copper in Wilson disease.