In Vitro Evaluation of Notch Inhibition to Enhance Efficacy of Radiation Therapy in Melanoma.

Purpose: The scope of radiation therapy is limited in melanoma. Using in vitro melanoma models, we investigated a Notch signaling inhibitor as a radiosensitizer to explore its potential to improve the efficacy of radiation therapy to widen the clinical application of radiation therapy in melanoma.

Methods And Materials: Melanoma cell lines A375, SKMEL28, and G361 were grown using standard tissue culture methods.

The Targeting of RNA Polymerase I Transcription Using CX-5461 in Combination with Radiation Enhances Tumour Cell Killing Effects in Human Solid Cancers.

An increased rate of cellular proliferation is a hallmark of cancer and may be accompanied by an increase in ribosome biogenesis and dysregulation in rRNA synthesis. In this regard, CX-5461 has been developed as a novel RNA polymerase I inhibitor and is currently in Phase I/II clinical trials for solid and hematological malignancies. In the present study, interactions between CX-5461 and single-dose X-ray exposure were assessed using isobologram analysis using MTS assay and drug-induced cell death was assessed using flow cytometric, confocal microscopy and Western blot analysis.

Textural analysis and lung function study: Predicting lung fitness for radiotherapy from a CT scan.

Objective: This study tested the hypothesis that shows advanced image analysis can differentiate fit and unfit patients for radical radiotherapy from standard radiotherapy planning imaging, when compared to formal lung function tests, FEV1 (forced expiratory volume in 1 s) and TLCO (transfer factor of carbon monoxide).

Methods: An apical region of interest (ROI) of lung parenchyma was extracted from a standard radiotherapy planning CT scan. Software using a grey level co-occurrence matrix (GLCM) assigned an entropy score to each voxel, based on its similarity to the voxels around it.

Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial.

Purpose: Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination.

Patients And Methods: Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses.

Biological effects of static magnetic field exposure in the context of MR-guided radiotherapy.

The clinical introduction of MRI-guided radiotherapy has prompted consideration of the potential impact of the static magnetic field on biological responses to radiation. This review provides an introduction to the mechanisms of biological interaction of radiation and magnetic fields individually, in addition to a description of the magnetic field effects on megavoltage photon beams at the macroscale, microscale and nanoscale arising from the Lorentz force on secondary charged particles. A relatively small number of scientific studies have measured the impact of combined static magnetic fields and ionising radiation on biological endpoints of relevance to radiotherapy.

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence.

Patients And Methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.

Clinical applications of textural analysis in non-small cell lung cancer.

Lung cancer is the leading cause of cancer mortality worldwide. Treatment pathways include regular cross-sectional imaging, generating large data sets which present intriguing possibilities for exploitation beyond standard visual interpretation. This additional data mining has been termed "radiomics" and includes semantic and agnostic approaches.

Improving the efficiency of image guided brachytherapy in cervical cancer.

Brachytherapy is an essential component of the treatment of locally advanced cervical cancers. It enables the dose to the tumor to be boosted whilst allowing relative sparing of the normal tissues. Traditionally, cervical brachytherapy was prescribed to point A but since the GEC-ESTRO guidelines were published in 2005, there has been a move towards prescribing the dose to a 3D volume.

High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial.

Unlabelled: FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal FGFR2 amplification have a high response rate to the selective FGFR inhibitor AZD4547, whereas cancers with subclonal or low-level amplification did not respond. Using cell lines and patient-derived xenograft models, we show that high-level FGFR2 amplification initiates a distinct oncogene addiction phenotype, characterized by FGFR2-mediated transactivation of alternative receptor kinases, bringing PI3K/mTOR signaling under FGFR control.