H Mota

Bio-nanotechnology and photodynamic therapy—State of the art review

Photodynamic therapy (PDT) and bio-nanotechnology (NT) show striking similarities in clinical design and mechanistics. The PDT paradigm of photosensitizer application, light activation and singlet oxygen generation does in fact occur on the nanoscale level as does the resultant outcomes. NT has the ability to explain as well as modify each of the critical steps of PDT particularly photosensitizer design and delivery, light source miniaturization and optimization, location and intensity of the photodynamic reaction as well as offering a far greater insight into dosimetry and mechanisms of action. This review will explore the current and potential future interactions and modifications NT may have on PDT.

Clinical PD/PDT in North America: An historical review

The healing properties of light have been appreciated for thousands of years. However, the harnessing of light energy to create a rigorous and reliable means to diagnose and treat human disease is only a relatively recent phenomenon. Despite outstanding results from ancient history and subsequent reemergence and refinement of this knowledge over the last 100 years, it took again the hand of serendipity to open the modern age of Photodiagnosis and Photodynamic Therapy. Based on the prescience and perseverance of a handful, the under appreciated observations of tumor fluorescence and photodynamic action have been brought to a worldwide audience. This review highlights the development of clinical Photodiagnosis and Photodynamic Therapy, emphasizing the significant events and milestones taking place in North America.

Image-guided radiation therapy: current and future directions

Since its discovery, ionizing radiation has been a cornerstone of cancer treatment. In step with technological advances, radiation therapy has strived to increase its therapeutic ratio. With the advent of 3D and cross-sectional imaging, and the ability to modulate the radiation beam, the current age of radiation oncology was initiated, promising better tumor control rates with fewer side effects. However, these ever more precise and conformal treatments have also revealed the importance of accounting for organ and tumor motion. Efforts to understand and compensate for the uncertainties caused by movement are required to ensure accurate conformal radiation therapy. This review will explore the current and future directions of image-guided radiation therapy, whose goal is to increase the accuracy of radiotherapy.

Determination of absorbed dose in water at the reference point d(r0, theta0) for an 192Ir HDR brachytherapy source using a Fricke system.

A ring-shaped Fricke device was developed to measure the absolute dose on the transverse bisector of a Ir192 high dose rate (HDR) source at 1cm from its center in water, D(r0,θ0). It consists of a polymethylmethacrylate (PMMA) rod (axial axis) with a cylindrical cavity at its center to insert the Ir192 radioactive source. A ring cavity around the source with 1.5mm thickness and 5mm height is centered at 1cm from the central axis of the source. This ring cavity is etched in a disk shaped base with 2.65cm diameter and 0.90cm thickness. The cavity has a wall around it 0.25cm thick. This ring is filled with Fricke solution, sealed, and the whole assembly is immersed in water during irradiations. The device takes advantage of the cylindrical geometry to measure D(r0,θ0). Irradiations were performed with a Nucletron microselectron HDR unit loaded with an Ir192 Alpha Omega radioactive source. A Spectronic® 1001 spectrophotometer was used to measure the optical absorbance using a 1mL quartz cuvette with 1.00cm light pathlength. The PENELOPE Monte Carlo code (MC) was utilized to simulate the Fricke device and the Ir192 Alpha Omega source in detail to calculate the perturbation introduced by the PMMA material. A NIST traceable calibrated well type ionization chamber was used to determine the air-kerma strength, and a published dose-rate constant was used to determine the dose rate at the reference point. The time to deliver 30.00Gy to the reference point was calculated. This absorbed dose was then compared to the absorbed dose measured by the Fricke solution. Based on MC simulation, the PMMA of the Fricke device increases the D(r0,θ0) by 2.0%. Applying the corresponding correction factor, the D(r0,θ0) value assessed with the Fricke device agrees within 2.0% with the expected value with a total combined uncertainty of 3.43% (k=1). The Fricke device provides a promising method towards calibration of brachytherapy radiation sources in terms of D(r0,θ0) and audit HDR source calibrations.

Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic optimization

A number of patients with lung cancer receive either palliative or curative high-dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an expected potential consequence of HDR, we have calculated the radial dose distribution for an Ir-192 HDR source, rigorously examined the dose and prescription points recommended by the American Brachytherapy Society (ABS), and performed a radiobiological-based analysis. The radial dose rate of a commercially available Ir-192 source was calculated with a Monte Carlo simulation. Based on the linear quadratic model, the estimated palliative, curative and blood vessel rupture radii from the center of an Ir-192 source were obtained for the ABS recommendations and a series of customized HDR prescriptions. The estimated radius at risk for blood vessel perforation for the ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some situations reduce this radius to 4 mm. The estimated blood perforation radius is generally smaller than the palliative radius. Optimized and individualized endobronchial HDR prescriptions are currently feasible based on our current understanding of tumor and normal tissue radiobiology. Individualized prescriptions could minimize complications such as fatal hemoptysis without sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the use of CT imaging to better assess the relationship between the catheter and blood vessels promise to be useful strategies for increasing the therapeutic index of this treatment modality. Prospective trials employing treatment optimization algorithms are needed.

Quality assurance of HDR 192Ir sources using a Fricke dosimeter.

A prototype of a Fricke dosimetry system consisting of a 15 x 15 x 15 cm3 water phantom made of Plexiglas and a 11.3-ml Pyrex balloon fitted with a 0.2 cm thick Pyrex sleeve in its center was created to assess source strength and treatment planning algorithms for use in high dose rate (HDR) 192Ir afterloading units. In routine operation, the radioactive source is positioned at the end of a sleeve, which coincides with the center of the spherical balloon that is filled with Fricke solution, so that the solution is nearly isotropically irradiated. The Fricke system was calibrated in terms of source strength against a reference well-type ionization chamber, and in terms of radial dose by means of an existing algorithm from the HDRs treatment planning system. Because the system is based on the Fricke dosimeter itself, for a given type and model of 192Ir source, the system needs initial calibration but no recalibration. The results from measurements made over a 10 month period, including source decay and source substitutions, have shown the feasibility of using such a system for quality control (QC) of HDR afterloading equipment, including both the source activity and treatment planning parameters. The benefit of a large scale production and the use of this device for clinical HDR QC audits via mail are also discussed.

On the need for quality assurance in superficial kilovoltage radiotherapy

External auditing of beam output and energy qualities of four therapeutic X-ray machines were performed in three radiation oncology centres in northeastern Brazil. The output and half-value layers (HVLs) were determined using a parallel-plate ionisation chamber and high-purity aluminium foils, respectively. The obtained values of absorbed dose to water and energy qualities were compared with those obtained by the respective institutions. The impact on the prescribed dose was analysed by determining the half-value depth (D(1/2)). The beam outputs presented percent differences ranging from -13 to +25%. The ratio between the HVL in use by the institution and the measurements obtained in this study ranged from 0.75 to 2.33. Such deviations in HVL result in percent differences in dose at D(1/2) ranging from -52 to +8%. It was concluded that dosimetric quality audit programmes in radiation therapy should be expanded to include dermatological radiation therapy and such audits should include HVL verification.

Determination of absorbed dose in water at the reference point D(r{sub 0},{theta}{sub 0}) for an {sup 192}Ir HDR brachytherapy source using a Fricke system

A ring-shaped Fricke device was developed to measure the absolute dose on the transverse bisector of a Ir192 high dose rate (HDR) source at 1cm from its center in water, D(r0,θ0). It consists of a polymethylmethacrylate (PMMA) rod (axial axis) with a cylindrical cavity at its center to insert the Ir192 radioactive source. A ring cavity around the source with 1.5mm thickness and 5mm height is centered at 1cm from the central axis of the source. This ring cavity is etched in a disk shaped base with 2.65cm diameter and 0.90cm thickness. The cavity has a wall around it 0.25cm thick. This ring is filled with Fricke solution, sealed, and the whole assembly is immersed in water during irradiations. The device takes advantage of the cylindrical geometry to measure D(r0,θ0). Irradiations were performed with a Nucletron microselectron HDR unit loaded with an Ir192 Alpha Omega radioactive source. A Spectronic® 1001 spectrophotometer was used to measure the optical absorbance using a 1mL quartz cuvette with 1.00cm light pathlength. The PENELOPE Monte Carlo code (MC) was utilized to simulate the Fricke device and the Ir192 Alpha Omega source in detail to calculate the perturbation introduced by the PMMA material. A NIST traceable calibrated well type ionization chamber was used to determine the air-kerma strength, and a published dose-rate constant was used to determine the dose rate at the reference point. The time to deliver 30.00Gy to the reference point was calculated. This absorbed dose was then compared to the absorbed dose measured by the Fricke solution. Based on MC simulation, the PMMA of the Fricke device increases the D(r0,θ0) by 2.0%. Applying the corresponding correction factor, the D(r0,θ0) value assessed with the Fricke device agrees within 2.0% with the expected value with a total combined uncertainty of 3.43% (k=1). The Fricke device provides a promising method towards calibration of brachytherapy radiation sources in terms of D(r0,θ0) and audit HDR source calibrations.

SU‐FF‐T‐147: Improved Calibration Method of EDR Films for IMRT‐QA

Purpose: Due to film processing variation and the optical density not being linear with the dose, a full calibration has to be obtained for every IMRT‐QA with film. We are proposing the application of a linearization method and the use of a single dose calibration EDR film for relative and absolute dose measurement in IMRT‐QA. Method and Materials: The linearization method was studied for the EDR films using 6, 10 and 15 MV photon beams. The films were developed in a Konica film processor, then scanned with a Vidar VXR‐16 scanner and analyzed using RIT‐114 version 4.1. A standard 30‐point calibration curve was obtained with the 6 MV beam. Using the method developed in a previous paper, a curve fitting was obtained for a sigmoid expression modulated by a 3rd degree polynomial: ApparentDose = b (1+ a 1 x + a 2 x 2 + a 3 x 3 ) [ log ( m )− log ( m − x )] ; where x is the net optical density, m is the net saturation density, b, a1, a2 and a3 are parameters of the model. Results: A value of 1870.1945 was obtained for b that is a parameter related to the dose unit. The net saturation density was 3.5587 for our system. The parameters a1, a2 and a3 are, respectively, −0.4551, 0.1167, −0.0134. For every IMRT‐QA a spreadsheet is used to obtain a 70 point calibration curve for RIT, using only one exposed film developed together with the composed and enface films, obtaining <5% uncertainty. Conclusion: Some softwares are available to make film dosimetry in IMRT QA less cumbersome, however daily calibration still remains a time consuming procedure. Absolute dosimetry requires a full calibration every time film is used. The linearization method presented here is being used in our department for isodose comparison and for absolute measurement at calculation point. The overall time is reduced while obtaining uncertainty comparable to the existing methods.

Verificação do fator de calibração e indicador da qualidade do feixe de aceleradores lineares

A quality assurance program is a mandatory prerequisite for obtaining the high level of accuracy required for radiotherapy. This paper reports the results of part of the routine quality control tests for linear accelerators at the National Cancer Institute, Brazil, performed monthly over a period of two years. These tests included dose output and beam quality indicator. The results were compared with the guidelines of the AAPM TG-40 protocol. The results for the photon beams have shown dose output variations of up to 12%; for electron beams, the largest deviation found was 10%. The fluctuations observed in the beam quality indicator for the electron beams were greater than for the photon beams. These results strongly emphasize the importance of a quality assurance program in radiotherapy services in order to allow prompt corrections of the dose delivered to the patient.