Evaluating the geometric and dosimetric impact of applying anisotropic CTV to PTV margins in image-guided post-prostatectomy radiation therapy.

INTRODUCTION: Guidelines for clinical target volume (CTV) to planning target volume (PTV) margins in post-prostatectomy radiation therapy (PPRT) are varied and often not clearly defined. Assessment of appropriateness of margins is commonly measured on prevalence of geographic miss. METHODS: Cone-beam CT (CBCT) images (n = 92) for 10 PPRT patients were incorporated to provide on-treatment information on the appropriateness of six different CTV expansion margins in terms of geographic miss and change in dose-volume statistics for CTV, rectum and bladder. Uniform margins included 10 mm, 5 mm, 10 mm + 5 mm posteriorly and 5 mm + 3 mm posteriorly. In addition, two anisotropic margins were evaluated by separating the superior and inferior portions of the CTV before expansion. Treatment plans were created for each PTV retrospectively. RESULTS: The frequency of geographic miss was the smallest for the large uniform expansions but resulted in the highest organ-at-risk (OAR) doses. Geographic miss in the smaller uniform and anisotropic PTVs was more prevalent but commonly to a small volume < 1% of CTV. When averaged over all CBCT fractions, V95% dose for all CTV margins remained > 99%. The anisotropic expansions generated smaller irradiated target volumes and consequently saw up to 7.3% reduction in bladder dose when compared with similar uniform expansion margins. CONCLUSION: Supplementing the incidence of geographic miss with dosimetric information on target coverage and OAR doses provides more informed assessment of the appropriateness of different CTV expansion margins. Our study extends the evaluation of anisotropic margins for PPRT.

Radiotherapy quality assurance in the TROG 12.01 randomised trial and its impact on loco-regional failure.

Introduction: There is no consensus as to what specifically constitutes head and neck cancer radiotherapy quality assurance (HNC RT QA). The aims of this study are to (1) describe the RT QA processes used in the TROG 12.01 study, (2) review the RT QA processes undertaken for all patients with loco-regional failure (LRF), and (3) provide prospective data to propose a consensus statement regarding the minimal components and optimal timing of HNC RT QA. Materials and methods: All patients undergoing RT QA in the original TROG 12.01 study were included in this substudy. All participating sites completed IMRT credentialling and a clinical benchmark case. Real-time (pre-treatment) RT QA was performed for the first patient of each treating radiation oncologist, and for one in five of subsequent patients. Protocol violations were deemed major if they related to contour and/or dose of gross tumour volume (GTV), high dose planning target volume (PTVhd), or critical organs of risk (spinal cord, mandible, and brachial plexus). Results: Thirty HNROs from 15 institutions accrued 182 patients. There were 28 clinical benchmark cases, 27 pre-treatment RT QA cases, and 38 post-treatment cases. Comprehensive RT QA was performed in 65/182 (36%) treated patients. Major protocol violations were found in 5/28 benchmark cases, 5/27 pre-treatment cases, and 6/38 post-treatment cases. An independent review of all nine LRF cases showed major protocol violations in four of nine cases. Conclusion: Only pre-treatment RT QA can improve patient outcomes. The minimal components of RT QA in HNC are GTVs, PTVhd, and critical organs at risk. What constitutes major dosimetric violations needs to be harmonised.

eXaSkin: A novel high-density bolus for 6MV X-rays radiotherapy.

PURPOSE: To evaluate eXaSkin, a novel high-density bolus alternative to commercial tissue-equivalent Superflab, for 6MV photon-beam radiotherapy. MATERIALS AND METHODS: We delivered a 10 × 10 cm2 open field at 90° and head-and-neck clinical plan, generated with the volumetric modulated arc therapy (VMAT) technique, to an anthropomorphic phantom in three scenarios: with no bolus on the phantom's surface, with Superflab, and with eXaSkin. In each scenario, we measured dose to a central planning target volume (PTV) in the nasopharynx region with an ionization chamber, and we measured dose to the skin, at three different positions within the vicinity of a neck lymph node PTV, with MOSkin™, a semiconductor dosimeter. Measurements were compared against calculations with the treatment planning system (TPS). RESULTS: For the static field, MOSkin results underneath the eXaSkin were in agreement with calculations to within 1.22%; for VMAT, to within 5.68%. Underneath Superflab, those values were 3.36% and 11.66%. The inferior agreement can be explained by suboptimal adherence of Superflab to the phantom's surface as well as difficulties in accurately reproducing its placement between imaging and treatment session. In all scenarios, dose measured at the central target agreed to within 1% with calculations. CONCLUSIONS: eXaSkin was shown to have superior adaptation to the phantom's surface, producing minimal air gaps between the skin surface and bolus, allowing for accurate positioning and reproducibility of set-up conditions. eXaSkin with its high density material provides sufficient build-up to achieve full skin dose with less material thickness than Superflab.

Characterization of an organic semiconductor diode for dosimetry in radiotherapy.

PURPOSE: The development of novel detectors for dosimetry in advanced radiotherapy modalities requires materials that have a water equivalent response to ionizing radiation such that characterization of radiation beams can be performed without the need for complex calibration procedures and correction factors. Organic semiconductors are potentially an ideal technology in fabricating devices for dosimetry due to tissue equivalence, mechanical flexibility, and relatively cheap manufacturing cost. The response of a commercial organic photodetector (OPD), coupled to a plastic scintillator, to ionizing radiation from a linear accelerator and orthovoltage x-ray tube has been characterized to assess its potential as a dosimeter for radiotherapy. The radiation hardness of the OPD has also been investigated to demonstrate its longevity for such applications. METHODS: Radiation hardness measurements were achieved by observing the response of the OPD to the visible spectrum and 70 keV x rays after pre-exposure to 40 kGy of ionizing radiation. The response of a preirradiated OPD to 6-MV photons from a linear accelerator in reference conditions was compared to a nonirradiated OPD with respect to direct and indirect (RP400 plastic scintillator) detection mechanisms. Dose rate dependence of the OPD was measured by varying the surface-to-source distance between 90 and 300 cm. Energy dependence was characterized from 29.5 to 129 keV with an x-ray tube. The percentage depth dose (PDD) curves were measured from 0.5 to 20 cm and compared to an ionization chamber. RESULTS: The OPD sensitivity to visible light showed substantial degradation of the broad 450 to 600 nm peak from the donor after irradiation to 40 kGy. After irradiation, the spectral shape has a dominant absorbance peak at 370 nm, as the acceptor better withstood radiation damage. Its response to x rays stabilized to 30% after 35 kGy, with a 0.5% difference between 770 Gy increments. The OPD exhibited reproducible detection of ionizing radiation when coupled with a scintillator. Indirect detection showed a linear response from 25 to 500 cGy and constant response to dose rates from 0.31 Gy/pulse to 3.4 × 10-4  Gy/pulse. However, without the scintillator, response increased by 100% at low dose rates. Energy independence between 100 keV and 1.2 MeV advocates their use as a dosimeter without beam correction factors. A dependence on the scintillator thickness used during a comparison of the PDD to the ionizing chamber was identified. A 1-mm-thick scintillator coupled with the OPD demonstrated the best agreement of ± 3%. CONCLUSIONS: The response of OPDs to ionizing radiation has been characterized, showing promising use as a dosimeter when coupled with a plastic scintillator. The mechanisms of charge transport and trapping within organic materials varies for visible and ionizing radiation, due to differing properties for direct and indirect detection mechanisms and observing a substantial decrease in sensitivity to the visible spectrum after 40 kGy. This study proved that OPDs produce a stable response to 6-MV photons, and with a deeper understanding of the charge transport mechanisms due to exposure to ionizing radiation, they are promising candidates as the first flexible, water equivalent, real-time dosimeter.

Characterization of a plastic dosimeter based on organic semiconductor photodiodes and scintillator.

BACKGROUND AND PURPOSE: Measurement of dose delivery is essential to guarantee the safety of patients undergoing medical radiation imaging or treatment procedures. This study aimed to evaluate the ability of organic semiconductors, coupled with a plastic scintillator, to measure photon dose in clinically relevant conditions, and establish its radiation hardness. Thereby, proving organic devices are capable of being a water-equivalent, mechanically flexible, real-time dosimeter. MATERIALS AND METHODS: The shelf-life of an organic photodiode was analyzed to 40 kGy by comparison of the charge-collection-efficiency of a 520 nm light emitting diode. A non-irradiated and pre-irradiated photodiode was coupled to a plastic scintillator and their response to 6 MV photons was investigated. The dose linearity, dose-per-pulse dependence and energy dependence was characterized. Finally, the percentage depth dose (PDD) between 0.5 and 20 cm was compared with ionization chamber measurements. RESULTS: Sensitivity to 6 MV photons was (190 ± 0.28) pC/cGy and (170 ± 0.11) pC/cGy for the non-irradiated and pre-irradiated photodiode biased at -2 V. The response was independent of the dose-per-pulse between 0.031 and 0.34 mGy/pulse. An energy dependence was found for low keV energies, explained by the energy dependence of the scintillator which plateaued between 70 keV and 1.2 MeV. The PDD was within ±3% of the ionization chamber. CONCLUSION: Coupling an organic photodiode with a plastic scintillator provided reliable measurement of a range of photon energies. Dose-per-pulse and energy independence advocate their use as a dosimeter, specifically image-guided treatment without beam-quality correction factors. Degradation effects of organic semiconducting materials deteriorate sensor response but can be stabilized.

An algorithmic approach to single-probe Cherenkov removal in pulsed x-ray beams.

PURPOSE: The removal of Cherenkov light in an optical dosimetry system is an important process to ensure accurate dosimetry without compromising spatial resolution. Many solutions have been presented in the literature, each with advantages and disadvantages. We present a methodology to remove Cherenkov light from a scintillator fiber optic dosimeter in a pulsed megavoltage x-ray beam using the temporal waveform across the pulse. METHODS: A sample waveform of Cherenkov light can be measured by exposing only the fiber to the beam. By assuming that the Cherenkov waveform closely matches the intensity of incident radiation, this waveform can be convoluted with the instantaneous scintillation response function to generate an expected scintillation signal. By finding the least-squares fit between these two functions and the experimental data, the estimated Cherenkov contribution can be subtracted off the net signal. This can be applied for arbitrarily complex Cherenkov waveforms (within the 2 ns timing resolution of the data acquisition), and in fact, the results suggest more fluctuations in the waveforms provide a better fit to data. RESULTS: Four beam profiles for different field sizes and energies were found with this method. They closely matched references data measured with ionization chamber with average differences across the beam no more than 4%. Noisy waveforms are assumed to be the primary cause of differences between the analyzed scintillator and IC results. We propose methods for improving the results and optimizing the data acquisition and analysis processes. CONCLUSIONS: These results demonstrate that it is possible and effective with a single probe to use function fitting of expected data to experimental to remove a complicated Cherenkov signal from the net light signal in pulsed-beam optical dosimetry.

Temporal separation of Cerenkov radiation and scintillation using a clinical LINAC and artificial intelligence.

Convolutional neural network (CNN) type artificial intelligences were trained to estimate the Cerenkov radiation present in the temporal response of a LINAC irradiated scintillator-fiber optic dosimeter. The CNN estimate of Cerenkov radiation is subtracted from the combined scintillation and Cerenkov radiation temporal response of the irradiated scintillator-fiber optic dosimeter, giving the sole scintillation signal, which is proportional to the scintillator dose. The CNN measured scintillator dose was compared to the background subtraction measured scintillator dose and ionisation chamber measured dose. The dose discrepancy of the CNN measured dose was on average 1.4% with respect to the ionisation chamber measured dose, matching the 1.4% average dose discrepancy of the background subtraction measured dose with respect to the ionisation chamber measured dose. The developed CNNs had an average time of 3 ms to calculate scintillator dose, permitting the CNNs presented to be applicable for dosimetry in real time.

Temporal separation of Cerenkov radiation and scintillation using artificial neural networks in Clinical LINACs.

The irradiation of scintillator-fiber optic dosimeters by clinical LINACs results in the measurement of scintillation and Cerenkov radiation. In scintillator-fiber optic dosimetry, the scintillation and Cerenkov radiation responses are separated to determine the dose deposited in the scintillator volume. Artificial neural networks (ANNs) were trained and applied in a novel single probe method for the temporal separation of scintillation and Cerenkov radiation. Six dose profiles were measured using the ANN, with the dose profiles compared to those measured using background subtraction and an ionisation chamber. The average dose discrepancy of the ANN measured dose was 2.2% with respect to the ionisation chamber dose and 1.2% with respect to the background subtraction measured dose, while the average dose discrepancy of the background subtraction dose was 1.6% with respect to the ionisation chamber dose. The ANNs performance was degraded when compared with background subtraction, arising from an inaccurate model used to synthesise ANN training data.

Investigation of the radiation dose from cone-beam CT for image-guided radiotherapy: A comparison of methodologies.

Four methodologies were evaluated for quantifying kilovoltage cone-beam computed tomography (CBCT) dose: the Cone-Beam Dose Index (CBDI), IAEA Report 5 recommended methodology (IAEA), the AAPM Task Group 111 methodology (TG111), and the current dose metric; the Computed Tomography Dose Index (CTDI) on two commercial Varian cone-beam CT imaging systems; the Clinac iX On-Board Imager (OBI); and the TrueBeam X-ray Imaging system (XI). The TG111 methodology measured the highest overall dose (21.199 ± 0.035 mGy OBI and 22.420 ± 0.002 XI for pelvis imaging) due to the full scatter of the TG111 phantom and was within 5% of CTDI measurements taken using a full scatter TG111 phantom and 30-cm film strips. CBDI measured the second highest overall dose, within 10% of the TG111, with IAEA measuring the third highest dose. For head CBCT protocols, CBDI measured the highest dose, followed by IAEA. The CTDI method measured lowest across all scan modes highlighting its limitations for CBCT dosimetry. The XI imaging system delivered lower doses for head and thorax scan modes and similar doses to the OBI system for pelvis scan modes due to additional beam hardening filtration in the XI system. The TG111 method measured the highest dose in the center of a CBCT scan during image guidance procedures; however, CBDI provided a good approximation to TG111 with existing CTDI equipment and may be more applicable clinically.

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer.

PURPOSE: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. PATIENTS AND METHODS: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. RESULTS: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. CONCLUSIONS: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.

A multi-institutional dosimetry audit of rotational intensity-modulated radiotherapy.

BACKGROUND: Rotational IMRT (VMAT and Tomotherapy) has now been implemented in many radiotherapy centres. An audit to verify treatment planning system modelling and treatment delivery has been undertaken to ensure accurate clinical implementation. MATERIAL AND METHODS: 34 institutions with 43 treatment delivery systems took part in the audit. A virtual phantom planning exercise (3DTPS test) and a clinical trial planning exercise were planned and independently measured in each institution using a phantom and array combination. Point dose differences and global gamma index (γ) were calculated in regions corresponding to PTVs and OARs. RESULTS: Point dose differences gave a mean (±sd) of 0.1±2.6% and 0.2±2.0% for the 3DTPS test and clinical trial plans, respectively. 34/43 planning and delivery combinations achieved all measured planes with >95% pixels passing γ<1 at 3%/3mm and rose to 42/43 for clinical trial plans. A statistically significant difference in γ pass rates (p<0.01) was seen between planning systems where rotational IMRT modelling had been designed for the manufacturer's own treatment delivery system and those designed independently of rotational IMRT delivery. CONCLUSIONS: A dosimetry audit of rotational radiotherapy has shown that TPS modelling and delivery for rotational IMRT can achieve high accuracy of plan delivery.