Author Correction: Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery.

Effective drug delivery is restricted by pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery.

National Cancer Institute Workshop on Proton Therapy for Children: Considerations Regarding Brainstem Injury.

Purpose: Proton therapy can allow for superior avoidance of normal tissues. A widespread consensus has been reached that proton therapy should be used for patients with curable pediatric brain tumor to avoid critical central nervous system structures. Brainstem necrosis is a potentially devastating, but rare, complication of radiation.

Somatic Mutations Drive Distinct Imaging Phenotypes in Lung Cancer.

Tumors are characterized by somatic mutations that drive biological processes ultimately reflected in tumor phenotype. With regard to radiographic phenotypes, generally unconnected through present understanding to the presence of specific mutations, artificial intelligence methods can automatically quantify phenotypic characters by using predefined, engineered algorithms or automatic deep-learning methods, a process also known as radiomics. Here we demonstrate how imaging phenotypes can be connected to somatic mutations through an integrated analysis of independent datasets of 763 lung adenocarcinoma patients with somatic mutation testing and engineered CT image analytics.

Nanoparticle-based brachytherapy spacers for delivery of localized combined chemoradiation therapy.

Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits.

Methods And Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy.

New potential for enhancing concomitant chemoradiotherapy with FDA approved concentrations of cisplatin via the photoelectric effect.

We predict, for the first time, that by using United States Food and Drug Administration approved concentrations of cisplatin, major radiosensitization may be achieved via photoelectric mechanism during concomitant chemoradiotherapy (CCRT). Our analytical calculations estimate that radiotherapy (RT) dose to cancer cells may be enhanced via this mechanism by over 100% during CCRT. The results proffer new potential for significantly enhancing CCRT via an emerging clinical scenario, where the cisplatin is released in-situ from RT biomaterials loaded with cisplatin nanoparticles.

Single-tube, highly parallel mutation enrichment in cancer gene panels by use of temperature-tolerant COLD-PCR.

Background: Multiplexed detection of low-level mutations presents a technical challenge for many technologies, including cancer gene panels used for targeted-resequencing. Analysis of mutations below approximately 2%-5% abundance in tumors with heterogeneity, samples with stromal contamination, or biofluids is problematic owing to increased noise from sequencing errors. Technologies that reduce noise via deep sequencing unavoidably reduce throughput and increase cost.

Radiation dose enhancement of gadolinium-based AGuIX nanoparticles on HeLa cells.

Unlabelled: Radiation dose enhancement of high-Z nanoparticles is an active area of research in cancer therapeutics. When kV and MV energy photon beams interact with high-Z nanoparticles in a tumor, the release of secondary electrons can injure tumor cells, leading to a higher treatment efficacy than radiation alone. We present a study that characterizes the radiation dose enhancing effects of gadolinium-based AGuIX nanoparticles on HeLa cells.

Facile Synthesis of PEGylated PLGA Nanoparticles Encapsulating Doxorubicin and its In Vitro Evaluation as Potent Drug Delivery Vehicle.

The advent of nanotechnology has bolstered a variety of nanoparticles based platforms for different biomedical applications. A better understanding for engineering novel nanoparticles for applications in cancer staging and therapy requires careful assessment of the nanoparticle's physico-chemical properties. Herein we report a facile synthesis method for PEGylated PLGA nanoparticles encapsulating anti-cancer drug doxorubicin for cancer imaging and therapy.

Beam quality and dose perturbation of 6 MV flattening-filter-free linac.

The aim of this study is twofold: (a) determination of the spectral differences for flattening-filter-free (FFF) versus standard (STD) linac under various clinical conditions, (b) based on an extensive list of clinically important beam configurations, identification of clinical scenarios that lead to higher macroscopic dose perturbations due to the presence of high-Z material. The focus is on dose enhancement due to contrast agents including high-Z elements such as gold or gadolinium. EGSnrc was used to simulate clinical beams under various irradiation conditions: open/IMRT/spit-IMRT fields, in/out-off-field areas, different depths and field sizes.

The effect of flattening filter free delivery on endothelial dose enhancement with gold nanoparticles.

Purpose: The aim of this study is to quantify and to compare the dose enhancement factor from gold nanoparticles (AuNP) to tumor endothelial cells for different concentrations of AuNP, and clinical MV beam configurations.

Methods: Tumor endothelial cells are modeled as slabs measuring 10 × 10 × 2 μm. A spherical AuNP is simulated on the surface of the endothelial cell, within the blood vessel.

A stochastic model of cell survival for high-Z nanoparticle radiotherapy.

Purpose: The authors present a stochastic framework for the assessment of cell survival in gold nanoparticle radiotherapy.

Methods: The authors derive the equations for the effective macroscopic dose enhancement for a population of cells with nonideal distribution of gold nanoparticles (GNP), allowing different number of GNP per cell and different distances with respect to the cellular target. They use the mixed Poisson distribution formalism to model the impact of the aforementioned physical factors on the effective dose enhancement.

Impact of beam quality on megavoltage radiotherapy treatment techniques utilizing gold nanoparticles for dose enhancement.

This study determines the optimal clinical scenarios for gold nanoparticle dose enhancement as a function of irradiation conditions and potential biological targets using megavoltage x-ray beams. Four hundred and eighty clinical beams were studied for different potential cellular or sub-cellular targets. Beam quality was determined based on a 6 MV linac with and without a flattening filter for various delivery conditions.

SU-E-T-408: Enhancing Stereotactic Radiosurgery for Neovascular Age-Related Macular Degeneration, Using Gold Nanoparticles.

Purpose: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss for people over the age of 60 in the United States. In this study the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance stereotactic radiosurgery for neovascular AMD is investigated.

Methods: Analytic calculations were carried out to estimate the nucleus dose enhancement factor (nDEF) due to photon-induced photo- /Auger electrons from AuNP targeting neovascular AMD endothelial cells (EC).

A modification of flattening filter free linac for IMRT.

Purpose: This study investigates the benefits of a modified flattening filter free (FFF) linac over the standard (STD) linac equipped with the flattening filter. Energy and angular spread of the electron beam of the FFF linac were modified. Modification of FFF beam parameters is explored to maximize the monitor unit efficiency and to minimize the head scatter in IMRT delivery for large target volumes or targets lying away from the central axis.

Noninvasive detection of EGFR T790M in gefitinib or erlotinib resistant non-small cell lung cancer.

Purpose: Tumors from 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer patients that develop resistance to gefitinib or erlotinib will contain a secondary EGFR T790M mutation. As most patients do not undergo repeated tumor biopsies we evaluated whether EGFR T790M could be detected using plasma DNA.

Experimental Design: DNA from plasma of 54 patients with known clinical response to gefitinib or erlotinib was extracted and used to detect both EGFR-activating and EGFR T790M mutations.

Experimental evaluation of the accuracy of skin dose calculation for a commercial treatment planning system.

This work investigates the accuracy of skin dose calculations using the Eclipse treatment planning system. Skin dose was measured using micro-MOSFETs for a range of irradiation conditions (open fields, physical wedges, dynamic wedges, different SSDs) for 6MV and 10MV beams, and compared with the mean dose calculated to a 2mm thick "skin" structure for semi-cylindrical phantoms (representative of a neck or breast). Agreement between the calculated and measured skin dose values was better than +/-20% for 95% of all measured points (both 6MV and 10MV x-ray spectra).