Complexity metrics for IMRT and VMAT plans: a review of current literature and applications.

Modulated radiotherapy with multileaf collimators is widely used to improve target conformity and normal tissue sparing. This introduced an additional degree of complexity, studied by multiple teams through different properties. Three categories of complexity metrics were considered in this review: fluence, deliverability and accuracy metrics. The first part of this review is dedicated to the inventory of these complexity metrics. Different applications of these metrics emerged. Influencing the optimizer by integrating complexity metrics into the cost function has been little explored and requires more investigations. In modern treatment planning system, it remains confined to MUs or treatment time limitation. A large majority of studies calculated metrics only for analysis, without plan modification. The main application was to streamline the patient specific quality assurance workload, investigating the capability of complexity metrics to predict patient specific quality assurance results. Additionally complexity metrics were used to analyze behaviour of TPS optimizer, compare TPS, operators and plan properties, and perform multicentre audit. Their potential was also explored in the context of adaptive radiotherapy and automation planning. The second part of the review gives an overview of these studies based on the complexity metrics.

Photoactivation of gold nanoparticles for glioma treatment.

Radiosensitization efficacy of gold nanoparticles (AuNPs) with low energy radiations (88 keV) was evaluated in vitro and in vivo on rats bearing glioma. In vitro, a significant dose-enhancement factor was measured by clonogenic assays after irradiation with synchrotron radiation of F98 glioma cells in presence of AuNPs (1.9 and 15 nm in diameter). In vivo, 1.9 nm nanoparticles were found to be toxic following intracerebral delivery in rats bearing glioma, whether no toxicity was observed using 15 nm nanoparticles at the same concentration (50 mg/mL). The therapeutic efficacy of gold photoactivation was determined by irradiating the animals after intracerebral infusion of AuNPs. Survival of rats that had received the combination of treatments (AuNPs: 50 mg/mL, 15 Gy) was significantly increased in comparison with the survival of rats that had received irradiation alone. In conclusion, this experimental approach is promising and further studies are foreseen for improving its therapeutic efficacy. FROM THE CLINICAL EDITOR: These investigators report that gold nanoparticles of the correct size can be used to enhance the effects of irradiation in the context of a glioma model. Since many of the glioma varieties are currently incurable, this or similar approaches may find their way to clinical trials in the near future.

Intracerebral delivery of carboplatin in combination with either 6 MV photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma.

BACKGROUND: The purpose of the present study was to compare side-by-side the therapeutic efficacy of a 6-day infusion of carboplatin, followed by X-irradiation with either 6 MV photons or synchrotron X-rays, tuned above the K-edge of Pt, for treatment of F98 glioma bearing rats. METHODS: Carboplatin was administered intracerebrally (i.c.) to F98 glioma bearing rats over 6 days using AlzetTM osmotic pumps starting 7 days after tumor implantation. Radiotherapy was delivered in a single 15 Gy fraction on day 14 using a conventional 6 MV linear accelerator (LINAC) or 78.8 keV synchrotron X-rays. RESULTS: Untreated control animals had a median survival time (MeST) of 33 days. Animals that received either carboplatin alone or irradiation alone with either 78.8 keV or 6 MV had a MeSTs 38 and 33 days, respectively. Animals that received carboplatin in combination with X-irradiation had a MeST of > 180 days with a 55% cure rate, irrespective of whether they were irradiated with either 78.8 KeV synchrotron X-rays or 6MV photons. CONCLUSIONS: These studies have conclusively demonstrated the equivalency of i.c. delivery of carboplatin in combination with X-irradiation with either 6 MV photons or synchrotron X-rays.

Monochromatic minibeams radiotherapy: from healthy tissue-sparing effect studies toward first experimental glioma bearing rats therapy.

PURPOSE: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. METHODS AND MATERIALS: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 × 5 × 4.8 mm(3) volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 × 8 × 7.8 mm(3) volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. RESULTS: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 ± 12.5 days versus 23.3 ± 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. CONCLUSIONS: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.