Dosimetric predictors of toxicity in a randomized study of short-course vs conventional radiotherapy for glioblastoma.

Purpose: There is no consensus on appropriate organ at risk (OAR) constraints for short-course radiotherapy for patients with glioblastoma. Using dosimetry and prospectively-collected toxicity data from a trial of short-course radiotherapy for glioblastoma, this study aims to empirically examine the OAR constraints, with particular attention to left hippocampus dosimetry and impact on neuro-cognitive decline.

Methods And Materials: Data was taken from a randomized control trial of 133 adults (age 18-70 years; ECOG performance score 0-2) with newly diagnosed glioblastoma treated with 60 Gy in 30 (conventional arm) versus 20 (short-course arm) fractions of adjuvant chemoradiotherapy (ClinicalTrials.

A Novel Composite Biomarker Panel For Detection Of Early Stage Non-small Cell Lung Cancer.

Purpose: To investigate a novel composite methodology of using targeted serum microRNAs (micro ribonucleic acid; miRNA) and urine metabolites for the accurate detection of early stage non-small cell lung cancer (NSCLC).

Methods: Consecutively consenting NSCLC patients and matched control subjects were recruited to provide samples of serum for miRNA and/or urine for metabolite analyses. Serum miRNA levels were measured using quantitative real-time reverse-transcription with exogenous control, and the comparative delta cycle threshold (CT) method was used to calculate relative miRNA expression of two targeted miRNAs (miR-21 and miR-223).

A Phase II Multi-institutional Clinical Trial Assessing Fractionated Simultaneous In-Field Boost Radiotherapy for Brain Oligometastases.

Purpose/Objective Published preclinical and phase I clinical trial data suggest that fractionated lesional radiotherapy with 60 Gy in 10 fractions can serve as an alternative approach to single fraction radiosurgical boost for brain oligometastases.  Methods and Materials A phase II clinical trial (NCT01543542) of a total of 60 Gy in 10 fractions of lesional (one to three) radiotherapy (given simultaneously with whole-brain helical tomotherapy with 30 Gy in 10 fractions) was conducted at five institutions. We hypothesized that fractionated radiotherapy would be considered unsuitable if the median overall survival (OS) was degraded by two months or if six-month intracranial control (ICC) and intracranial lesion (ILC) were inferior by 10% compared with the published RTOG 9508 results.

Non-small cell lung cancer detection using microRNA expression profiling of bronchoalveolar lavage fluid and sputum.

Aim: To assess if miRNA expression profiling of bronchoalveolar lavage (BAL) fluid and sputum could be used to detect early-stage non-small cell lung cancer (NSCLC).

Materials And Methods: Hierarchical cluster analysis was performed on the expression levels of 5 miRNAs (miR-21, miR-143, miR-155, miR-210, and miR-372) which were quantified using RNA reverse transcription and quantitative real-time polymerase chain reaction in sputum and BAL samples from NSCLC cases and cancer-free controls.

Results: Cluster analysis of the miRNA expression levels in BAL samples from 21 NSCLC cases and sputum samples from 10 cancer-free controls yielded a diagnostic sensitivity of 85.

Dose-escalated Hypofractionated Intensity-modulated Radiation Therapy With Concurrent Chemotherapy for Inoperable or Unresectable Non-Small Cell Lung Cancer.

Purpose: The local control of inoperable non-small cell lung cancer (NSCLC) using standard radiotherapy (RT) doses is inadequate. Dose escalation is a potential strategy to improve the local control for patients with NSCLC; however, the optimal dose required for local control in this setting is unknown.

Methods And Materials: Patients with unresectable or inoperable stage II/III NSCLC with ECOG≤1 received 48 Gy in 20 daily fractions using intensity-modulated radiotherapy, followed by 1 of 3 boost dose levels: 16.

Layered gadolinium-based nanoparticle as a novel delivery platform for microRNA therapeutics.

Specific expression patterns of microRNA (miRNA) molecules have been linked to cancer initiation, progression, and metastasis. The accumulating evidence for the role of oncogenic or tumor-suppressing miRNAs identified the need for nano-scaled platform that can help deliver nucleotides to modulate miRNAs. Here we report the synthesis of novel layered gadolinium hydroxychloride (LGdH) nanoparticles, a member of the layered double hydroxide (LDH) family, with physiochemical properties suitable for cell uptake and tracing via magnetic resonance (MR) imaging.

A Phase I Study of Tomotherapy in Patients With Primary Benign and Low-grade Brain Tumors: Late Toxicity and Quality of Life.

Objectives: To evaluate longitudinal quality of life and late neurotoxicity (>12 mo) of tomotherapy in patients with primary benign and low-grade brain tumors.

Methods: Between January 2006 and October 2009, 49 patients with brain tumors were treated with tomotherapy at 2 radiotherapy centers in Canada. The median age of the patients was 51.

The biodistribution and pharmacokinetic evaluation of choline-bound gold nanoparticles in a human prostate tumor xenograft model.

Purpose: Gold nanoparticles (GNPs) have attracted significant attention in the treatment of cancer due to their potential as novel radiation enhancers, particularly when functionalized with various targeting ligands. The aim of this study was to assess the biodistribution and pharmacokinetic characteristics of a novel choline-bound GNP (choline-GNP) stabilized with polyethelenimine (PEI).

Methods: Choline bound to 27 nm diameter GNPs was characterized using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR).

Sputum microRNA profiling: a novel approach for the early detection of non-small cell lung cancer.

Purpose: MicroRNAs (miRNAs) post-transcriptionally regulate hundreds of gene targets involved in tumorigenesis thereby controlling vital biological processes, including cellular proliferation, differentiation and apoptosis. MiRNA profiling is an emerging tool for the potential early detection of a variety of malignancies. This study was conducyed to assess the feasibility and methodological robustness of quantifying sputum miRNAs, employing quantitative real-time polymerase chain reaction (RT-qPCR) and cluster analysis on an optimized miRNA profile as a novel approach for the early detection of non-small cell lung cancer (NSCLC).

Distribution of effervescent inhalable nanoparticles after pulmonary delivery: an in vivo study.

Background: Effervescent inhalable nanoparticles (NPs) have previously been shown to be a promising alternative to conventional lung cancer treatment in animals. This study investigates the biodistribution of effervescent inhalable NPs after a single dose administration via pulmonary route in lung cancer-bearing mice.

Methods & Results: Whole-body autoradiography and confocal laser-scanning microscopy (CLSM) were used to investigate the distribution of inhalable NPs loaded in an effervescent microcarrier.

Pulmonary delivery of inhalable nanoparticles: dry powder inhalers.

Pulmonary administration of inhalable nanoparticles (NPs) is an emerging area of interest. Dry powder inhalers may offer particular advantages for pulmonary administration of NPs. This article reviews research performed on the formulation of inhalable NPs as dry powder to achieve deep-lung deposition and enhance NP redispersibility.

Inhalable nanoparticles, a non-invasive approach to treat lung cancer in a mouse model.

Doxorubicin-loaded nanoparticles (NPs) were incorporated into inhalable effervescent and non-effervescent carrier particles using a spray-freeze drying technique. The prepared inhalable powders were tested in a tumor bearing Balb/c mouse model. Control mice were treated with blank inhalable NPs, inhalable lactose powder containing free doxorubicin, and intravenous injections of a suspension of doxorubicin NPs, doxorubicin solution, or saline solution.

Microcalorimetric method to assess phagocytosis: macrophage-nanoparticle interactions.

This study evaluated the use of isothermal microcalorimetry (ITMC) to detect macrophage-nanoparticle interactions. Four different nanoparticle (NP) formulations were prepared: uncoated poly(isobutyl cyanoacrylate) (PIBCA), polysorbate-80-coated PIBCA, gelatin, and mannosylated gelatin NPs. Changes in NP formulations were aimed to either enhance or decrease macrophage-NP interactions via phagocytosis.

Secondary cytotoxicity mediated by alveolar macrophages: a contribution to the total efficacy of nanoparticles in lung cancer therapy?

Local treatment of lung cancer using inhalable nanoparticles (NPs) is an emerging and promising treatment option. The aim of this study was to investigate the activation of alveolar macrophages by poly (isobutyl cyanoacrylate) (BIPCA) NPs and the consequences of this activation on H460 lung cancer cells. A methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to determine the primary cytotoxicity, that is, the immediate and direct cytotoxicity of doxorubicin (DOX)-loaded NPs on both cell lines.

Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial.

Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer.

Methods And Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received.

Formulation and in vivo evaluation of effervescent inhalable carrier particles for pulmonary delivery of nanoparticles.

The purpose of this study was to evaluate the safety of a new inhalable effervescent carrier preparation containing model nanoparticles. Spray-freeze drying was used to prepare inhalable powders containing butylcyanoacrylate nanoparticles. The particle size of the nanoparticles before incorporation into the effervescent carrier and after dissolving the carrier powder was measured using laser light scattering.

Targeted delivery of nanoparticles for the treatment of lung diseases.

Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems.

Formulation and cytotoxicity of doxorubicin loaded in self-assembled bio-polyelectrolyte microshells.

A bio-polyelectrolyte microshell composed of alginate sodium (ALG) and chitosan (CHI) was fabricated by electrostatic layer-by-layer (LbL) self-assembly technique. The resulting ALG-CHI microshells were found to be able to effectively load anti-cancer drug doxorubicin (DOX) in the interior of the shells under modest conditions without addition of other reagents, as demonstrated by confocal laser scanning microscopy (CLSM). The mass of DOX loaded in one capsule of four alginate/chitosan layers (i.

Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles.

Regional drug delivery via dry powder inhalers offers many advantages in the management of pharmaceutical compounds for the prevention and treatment of respiratory diseases. In the present study, doxorubicin (DOX)-loaded nanoparticles were incorporated as colloidal drug delivery system into inhalable carrier particles using a spray-freeze-drying technique. The cytotoxic effects of free DOX, carrier particles containing blank nanoparticles or DOX-loaded nanoparticles on H460 and A549 lung cancer cells were assessed using a colorimetric XTT cell viability assay.

Toxicity and outcome results of RTOG 9311: a phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma.

Purpose: To evaluate prospectively the acute and late morbidities from a multiinstitutional three-dimensional radiotherapy dose-escalation study for inoperable non-small-cell lung cancer.

Methods And Materials: A total of 179 patients were enrolled in a Phase I-II three-dimensional radiotherapy dose-escalation trial. Of the 179 patients, 177 were eligible.

Results of a phase I study to dose escalate using intensity modulated radiotherapy guided by combined PET/CT imaging with induction chemotherapy for patients with non-small cell lung cancer.

Intensity modulated radiation therapy (IMRT) guided by PET/CT imaging with respiratory gating was employed to dose escalate in patients with non-small cell lung cancer (NSCLC), using accelerated fractionation with induction chemotherapies. One patient developed a grade 5 pneumonitis and the study was halted at 84 Gy in 35 fractions.

Formulation and characterization of spray-dried powders containing nanoparticles for aerosol delivery to the lung.

Spray-drying is a common practice of powder preparation for a wide range of drugs. Spray-dried powders can be used to deliver particles to the lungs via a dry powder inhaler (DPI). The present study investigated the feasibility of developing a platform for aerosol delivery of nanoparticles.