Basic concepts and directions in the radiation therapy quality assurance processes of clinical trials.

The radiation therapy quality assurance of clinical trials is internationally recognized as a key factor to control the quality of radiotherapy for its impact on clinical trial's goals. Quality assessment may be performed at different levels and by different means, which are now quite standardized. The optimal radiation therapy quality assurance of clinical trials trade-off to maintain accrual rates, radiotherapy quality and optimize clinical trial research processes is yet to be defined. This article addresses current definitions, processes, limitations and directions.

Voice modulation, self-perception and motor branch of the superior laryngeal nerve.

OBJECTIVES: Vocal morbidity resulting from damage to the motor branch of the superior laryngeal nerve (SLN) after endocrine surgery is well known, but diagnosis is often delayed. The present study aimed to quantify these vocal changes acoustically (main objective), and correlate this with the vocal complaints of patients with suspected SLN motor impairment (secondary objective). MATERIAL AND METHODS: Thirty females patients with suspected injury of the SLN cricothyroid branch (CT-) were compared to 30 patients without postoperative vocal impairment (CT+) and to 30 control subjects. Mean, minimal and maximal fundamental frequencies (F0mean, F0min and F0max) and vocal range were measured on /e/ at high frequency, sirens (glissandi), a reading text, and minimal intonation pairs. Subjective vocal impairment was evaluated on the Voice Handicap Index (VHI). RESULTS: A lowering of F0mean associated with vocal range reduction by one fifth (in the reading text) seemed to be specific to CT- patients. Production of questions was affected, with differences in melodic curve and attack. Thyroidectomy within 2 months in itself (without suspected SLN cricothyroid branch injury) also affected these parameters, but to a lesser degree. CT- patients reported greater voice impairment than CT+ patients or controls (P=0.0004). CONCLUSION: Alterations in speech intonation, quantified on minimal pair test, and self-assessed vocal handicap (VHI) are tools that can easily be used in daily practice to screen for SLN motor branch lesion.

Hypofractionated stereotactic radiotherapy for challenging brain metastases using 36 Gy in six fractions.

PURPOSE: Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3cm in diameter) and limited in number, in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15cm3) or brain metastases located next to critical structures. MATERIAL AND METHODS: Patients with brain metastases treated with the 6×6Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated. RESULTS: Sixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N=5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity. CONCLUSION: The 6×6Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way.

A new Monte Carlo model of a Cyberknife® system for the precise determination of out-of-field doses.

In a previous work, a PENELOPE Monte Carlo model of a Cyberknife system equipped with fixed collimator was developed and validated for in-field dose evaluation. The aim of this work is to extend it to evaluate peripheral doses and to determine the precision of the treatment planning system (TPS) Multiplan in evaluating the off-axis doses. The Cyberknife® head model was completed with surrounding components based on manufacturer drawings. The contribution of the different head parts on the out-of-field dose was studied. To model the attenuation and the modification of particle energy caused by components not modelled, the photon transport was modified in one of the added components. The model was iteratively adjusted to fit dose profiles measured with EBT3 films and an ionization chamber for several collimator sizes. Finally, dose profiles were calculated using the two Multiplan TPS algorithms and were compared to our simulations. The contributions to out-of-field dose were identified as scattered radiation from the phantom and head leakage and scatter originating at the secondary collimator level. Particle transport in the additional pieces was modified to model this radiation. The maximum differences between simulated and measured doses are of 20.4%. Regarding the detector responses away from axis, EBT3 films and the Farmer chamber give similar response (less than 20% difference). The TPS Monte Carlo algorithm underestimates the doses away from axis more importantly for the smaller field sizes (up to 98%). Besides, RayTracing simplifies peripheral dose to a constant value with no inclusion of particle transport. A Monte Carlo model of a Cyberknife system for the determination of out-of-field doses up to 14 cm off-axis was successfully developed and validated for different depths and field sizes in comparison with measurements. This study also confirms that TPS algorithms do not model peripheral dose properly.

[Digital applicator by 3D printing in contact brachytherapy]. / Applicateur numérique par impression tridimensionnelle en curiethérapie de contact.

Brachytherapy of skin tumours uses custom applicators that are manufactured manually. The integration of 3D printing customization of applicators during hidh dose rate brachytherapy planning could allow a better skin conformation and a better reproducibility of the positioning and treatment. We present the technical implementation of this method for our first two patients. A provisional planning scanner was carried out to create a digital applicator. The creation of the digital applicator used successively several software programs. The first, commercial, was RhinocerosR 3D used via Grasshopper, an integrated open source plug-in. The 3D applicator was then exported to the commercial software Simplify3DR. A g-code format file was generated for the printer. A second scanner was made with a 3D applicator in place to plan the final treatment. The treatment was planned by reverse optimization. The applicator could be designed within 15 days. For patient A, it was noted that 95 % of the clinical target volume received at least 35.4Gy (63Gy EQD2). For patient B, 95 % of the clinical target volume received at least 36Gy (64.8Gy EQD2). The forecast and actual planimetry met the coverage criteria of D95. Contact brachytherapy with 3D bioimpression is feasible, after software training, for complex treatment lesions. This technique could be extended to other indications.

Retrospective evaluation of blood copper stable isotopes ratio 65 Cu/63 Cu as a biomarker of cancer in dogs.

Previous studies in humans with breast, colorectal or liver cancer showed that neoplasia was associated with a modification of the blood ratio between 65 Cu and 63 Cu (∂Cu). The aim of the present study was to compare the blood ∂Cu of dogs with cancer to healthy controls or dogs with non-oncologic disease. One hundred and seventeen dogs were included in the study (35 dogs with cancer, 33 dogs with non-neoplastic disease, and 49 healthy controls). The ∂Cu of dogs with cancer was significantly lower than the ratio of healthy controls (P < 0.0001) but not significantly different from dogs with non-oncologic disease. Six dogs with lymphoma were also evaluated after they achieved clinical remission and five out of six had an increase of ∂Cu. Further studies are warranted but these results suggest that ∂Cu could help in the diagnosis of cancer in a controlled clinical context, and may be a potential biomarker for the follow-up of cancer.

Influence of Zn2+ on the kinetic events that contribute to the 500-kDa dextran-sulfate-dependent activation of factor XII (Hageman factor).

The effect of zinc ions on kinetic and equilibrium steps that may contribute to the activation and subsequent autoactivation of human blood coagulation factor XII in the presence of 500-kDa dextran sulfate was studied. To analyze the results, the expression of the overall autoactivation constant that had been established from the model presented in a previous study was used. Comparison of the kinetics obtained at different levels of zinc, which included amounts lower than the residual concentration introduced by NaCl in the incubation mixture, suggested that the addition of Zn2+ up to 5 microM lowered the mean number of sites available for the binding of factor XII to the surface from 220 to 172 and increased the rate of the first-order activation of factor XII by one order of magnitude, from (1.6 +/- 0.4) x 10(-4) s(-1) to (8.0 +/- 0.4) x 10(-4) s(-1) in the presence of 550 nM dextran sulfate. Neither the factor XII/surface dissociation constant (1 microM), the apparent catalytic constant, nor the apparent Michaelis-Menten constant associated with the postulated multi-stage kinetic sequence were affected by the presence of zinc. Most experimental trends induced by the presence of zinc could be successfully interpreted by using the model, thus reinforcing its reliability under different conditions.