Hybrid Cerenkov-scintillation detector validation using Monte Carlo simulations.

Objective.This study aimed at investigating through Monte Carlo simulations the limitations of a novel hybrid Cerenkov-scintillation detector and the associated method for irradiation angle measurements.Approach.Using Monte Carlo simulations, previous experimental irradiations of the hybrid detector with a linear accelerator were replicated to evaluate its general performances and limitations. Cerenkov angular calibration curves and irradiation angle measurements were then compared. Furthermore, the impact of the Cerenkov light energy dependency on the detector accuracy was investigated using the energy spectra of electrons travelling through the detector.Main results.Monte Carlo simulations were found to be in good agreement with experimental values. The irradiation angle absolute mean error was found to be less than what was obtained experimentally, with a maximum value of 1.12° for the 9 MeV beam. A 0.4% increase of the ratio of electrons having an energy below 1 MeV to the total electrons was found to impact the Cerenkov light intensity collected as a function of the incident angle. The effect of the Cerenkov intensity variation on the measured angle was determined to vary according to the slope of the angular calibration curve. While the contribution of scattered electrons with a lower energy affects the detector accuracy, the greatest discrepancies result from the limitations of the calculation method and the calibration curve itself.Significance.A precise knowledge of the limitations of the hybrid detector and the irradiation angle calculation method is crucial for a clinical implementation. Moreover, the simulations performed in this study also corroborate hypotheses made regarding the relations between multiple Cerenkov dependencies and observations from the experimental measurements.

External beam irradiation angle measurement using a hybrid Cerenkov-scintillation detector.

Objective.In this study, we propose a novel approach designed to take advantage of the Cerenkov light angular dependency to perform a direct measurement of an external beam irradiation angle.Approach.A Cerenkov probe composed of a 10 mm long filtered sensitive volume of clear PMMA optical fibre was built. Both filtered and raw Cerenkov signals from the transport fibre were collected through a single 1 mm diameter transport fibre. An independent plastic scintillation detector composed of 10 mm BCF12 scintillating fibre was also used for simultaneous dose measurements. A first series of measurements aimed at validating the ability to account for the Cerenkov electron energy spectrum dependency by simultaneously measuring the deposited dose, thus isolating signal variations resulting from the angular dependency. Angular calibration curve for fixed dose irradiations and incident angle measurements using electron and photon beams where also achieved.Main results.The beam nominal energy was found to have a significant impact on the shapes of the angular calibration curves. This can be linked to the electron energy spectrum dependency of the Cerenkov emission cone. Irradiation angle measurements exhibit an absolute mean error of 1.86° and 1.02° at 6 and 18 MV, respectively. Similar results were obtained with electron beams and the absolute mean error reaches 1.97°, 1.66°, 1.45° and 0.95° at 9, 12, 16 and 20 MeV, respectively. Reducing the numerical aperture of the Cerenkov probe leads to an increased angular dependency for the lowest energy while no major changes were observed at higher energy. This allowed irradiation angle measurements at 6 MeV with a mean absolute error of 4.82°.Significance.The detector offers promising perspectives as a potential tool for future quality assurance applications in radiotherapy, especially for stereotactic radiosurgery (SRS), magnetic resonance image-guided radiotherapy (MRgRT) and brachytherapy applications.

Comparative optic and dosimetric characterization of the HYPERSCINT scintillation dosimetry research platform for multipoint applications.

This study introduces the HYPERSCINT research platform (HYPERSCINT-RP100, Medscint Inc., Quebec, Canada), the first commercially available scintillation dosimetry platform capable of multi-point dosimetry through the hyperspectral approach. Optic and dosimetric performances of the system were investigated through comparison with another commercially available solution, the Ocean Optics QE65Pro spectrometer. The optical characterization was accomplished by measuring the linearity of the signal as a function of integration time, photon detection efficiency and spectral resolution for both systems under the same conditions. Dosimetric performances were then evaluated with a 3-point plastic scintillator detector (mPSD) in terms of signal to noise ratio (SNR) and signal to background ratio (SBR) associated with each scintillator. The latter were subsequently compared with those found in the literature for the Exradin W1, a single-point plastic scintillator detector. Finally, various beam measurements were realized with the HYPERSCINT platform to evaluate its ability to perform clinical photon beam dosimetry. Both systems were found to be comparable in terms of linearity of the signal as a function of the intensity. Although the QE65Pro possesses a higher spectral resolution, the detection efficiency of the HYPERSCINT is up to 1000 time greater. Dosimetric measurements shows that the latter also offers a better SNR and SBR, surpassing even the SNR of the Exradin W1 single-point PSD. While doses ranging from 1 to 600 cGy were accurately measured within 2.1% of the predicted dose using the HYPERSCINT platform coupled to the mPSD, the Ocean optics spectrometer shows discrepancies up to 86% under 50cGy. Similarly, depth dose, full width at half maximum region of the beam profile and output factors were all accurately measured within 2.3% of the predicted dose using the HYPERSCINT platform and exhibit an average difference of 0.5%, 1.6% and 0.6%, respectively.

Investigation of the quinine sulfate dihydrate spectral properties and its effects on Cherenkov dosimetry.

Recent studies have proposed that adding quinine to water while performing Cherenkov volumetric dosimetry improves the skewed percent depth dose measurement. The aim of this study was to quantify the ability of quinine to convert directional Cherenkov emission to isotropic fluorescence and evaluate its contribution to the total emitted light. Aqueous solutions of quinine were prepared with distilled water at various concentrations (0.01-1.2 g l-1). The solutions were irradiated with photon beams at 6 and 23 MV. The dependence of the light produced as a function of sample concentration was studied using a spectrometer with a fixed integration time. Spectral measurements of the luminescent solution and the blank solution (distilled water only) were taken to deconvolve the Cherenkov and quinine contribution to the overall emission spectrum. Using a CCD camera, intensity profiles were obtained for the blank and the 1.00 g l-1 solutions to compare them with the dose predicted by a treatment planning system. The luminescent intensity of the samples was found to follow a logarithmic trend as a function of the quinine concentration. Based on the spectral deconvolution of the 1.00 g l-1 solution, 52.4% ± 0.7% and 52.7% ± 0.7% of the signal in the visible range results from the quinine emission at 6 and 23 MV, respectively. The remaining fraction of the spectrum is due to the Cherenkov light that has not been converted. The fraction of the Cherenkov emission produced between 250 nm and 380 nm in the water and that was absorbed by the fluorophore reached 24.8% and 9.4% respectively at 6 and 23 MV. X-ray stimulated fluorescence of the quinine was then proven to be the principal cause to the increased total light output compared to the water-only signal. This new information reinforces the direct correlation of the solution intensity to the dose deposition.

Interest to consider re-challenging by cetuximab and platinum containing regimen in recurrent Head and Neck Cancer.

BACKGROUND: The EXTREME protocol is the standard of care for recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC) in first line. Beyond the first-line except immunotherapy, poor efficacy was reported by second-line chemotherapy. Re-challenge strategies based on a repetition of the first line with platinum and cetuximab regimens might have been an option to consider. METHODS: We performed a retrospective study in order to assess the efficacy of the cetuximab plus platinum doublet-based chemotherapy regimen in patients with R/M HNSCC progressing after at least 3 months of cetuximab maintenance (EXTREME protocol). We complete a retrospective review of all medical records from R/M HNSCC patients treated after 16 weeks with the EXTREME regimen and treated with a re-challenge strategy between January 2010 and December 2014 in our institution (Centre Paul Strauss, Strasbourg, France). RESULTS: 33 patients were identified. The re-challenged strategy provided an ORR in 33.3% of cases and a DCR of 69.6% of cases. The median OS and PFS observed from the second line were 11.2 months and 6.5 months for the subset re-challenged by EXTREME or PCC regimens respectively. The response rate between patients with a platin free interval within 3 and 6 months and greater than 6 months were equal. Drugs dose intensity were better with the PCC protocol than the EXTREME regimen used as a rechallenge. CONCLUSIONS: This study suggest re-challenging strategy by these regimens could be considered beyond the first line as an option when the platin free interval is greater than 3 months.

[Pharmacist involvement in supporting care in patients receiving oral anticancer therapies: A situation report in French cancer centers]. / Implication du pharmacien dans l'accompagnement des patients sous anticancéreux oraux : état des lieux dans les centres de lutte contre le cancer (CLCC).

INTRODUCTION: The increasing prescription of oral anticancer therapies has significantly changed inpatient care to outpatient care. This transformation requires an excellent coordination between different professionals to ensure healthcare channel security. METHOD: We performed a prospective study in 18 French cancer centers from March to April 2016. The aim of this study was to identify resources deployed to support patients receiving oral anticancer therapies and to assess pharmacist's involvement. RESULTS: More than half of the centers have developed patient education program and/or practice pharmaceutical consultations. In total, 54.5% have deployed an oral anticancer drugs program and the pharmacist is involved in multidisciplinary teams. In total, 44.4% of the centers have developed hospital-to-community coordination actions but all of them highlight the time-consuming character of those programs. DISCUSSION: Administrative burdens are seriously hindering patient education program's development. Multidisciplinary consultations can offer an attractive alternative because of easy implementation modalities. Finally, hospital-to-community coordination actions seem hard to implement and require harmonization of communication practices, and need more technical and financial means.

Erlotinib: another candidate for the therapeutic drug monitoring of targeted therapy of cancer? A pharmacokinetic and pharmacodynamic systematic review of literature.

Erlotinib is currently marketed at fixed standard dosage against pancreatic cancer and non-small-cell lung carcinoma. However, erlotinib pharmacokinetics (PK) is characterized by significant variability that may affect efficacy and tolerability. The aim of this review is to assess evidence that would justify therapeutic drug monitoring (TDM) and provide key information for the interpretation of erlotinib plasma concentrations. Literature was systematically reviewed to evaluate the standard criteria defining the potential clinical usefulness of TDM. Assessment was focused on the existence of unpredictable and wide PK variability and of consistent PK-pharmacodynamic relationships. PK parameters actually show marked variability (apparent clearance estimated to 4.85 ± 4.71 L/h, elimination half-life to 21.86 ± 28.35 hours, and apparent volume of distribution to 208 ± 133 L). Many covariates influence these parameters (CYP3A4 inducers or inhibitors, food, age, liver impairment), but most sources of variability still have to be identified. Some studies have demonstrated a relationship between exposure to erlotinib and clinical outcomes or skin toxicity. Erlotinib activity and target concentrations furthermore depend on tumor characteristics (eg, mutations on epidermal growth factor receptor and on K-ras). These results are in favor of TDM in addition to treatment adjustment for tumor biomarkers, but prospective clinical trials validating its clinical benefits are lacking. This review provides all the relevant information available to assist clinical interpretation of erlotinib plasma measurements. PK percentile curves and consideration to covariates yield information on whether a concentration measured is expected, whereas half maximal inhibitory concentration values determined in vitro provide preliminary insights on target concentration values to reach. Eventually, dosage adaptation might be considered in patients with intolerable toxicity because of excessive plasma levels or conversely nonresponse imputable to insufficient exposure.

Study of the scale formation mechanism on gold modified with an alkanethiol monolayer.

Scaling is a problem in many industrial processes. To control and minimize it, it is important to understand the dynamics of the scale formation. In this paper, the scale formation was examined on two kinds of gold surfaces. One was a pure metallic gold surface, and the other was a gold surface modified with an alkanethiol self-assembled monolayer. A series of surface characterization experiments were performed to ensure a good understanding of the gold-thiol bond stability in a caustic solution.