Radiobiological evaluation of organs at risk for electronic high-dose-rate brachytherapy in uveal melanoma: a radiobiological modeling study.

PURPOSE: The objective of this study was to examine feasibility of single- or hypo-fraction of high-dose-rate (HDR) electronic brachytherapy (eBT) in uveal melanoma treatment. MATERIAL AND METHODS: Biologically effective doses (BED) of organs at risk (OARs) were compared to those of iodine-125-based eye plaque low-dose-rate brachytherapy (125I LDR-BT) with vitreous replacement (VR). Single- or hypo-fractionated equivalent physical doses (SFEDs or HFEDs) for tumor were calculated from tumor BED of 125I LDR-BT using linear-quadratic (LQ) and universal survival curve (USC) models. BED OARs doses to retina opposite the implant, macula, optic disc, and lens were calculated and compared among SFED, HFED, and 125I LDR-BT. Electronic BT of 50 kVp was considered assuming dose fall-off as clinically equivalent to 125I LDR-BT. All OARs BEDs were analyzed with and without silicone oil VR. RESULTS: For a single-fraction incorporating VR, the median/interquartile range of LQ (USC)-based BED doses of the retina opposite the implant, macula, optic disc, and lens were 16%/1.2% (33%/4%), 35%/19.5% (64%/17.7%), 37%/19% (75%/17.8%), and 27%/7.9% (68%/23.2%) of those for 125I LDR-BT, respectively. SFED tumor values were 29.8/0.2 Gy and 51.7/0.5 Gy when using LQ and USC models, respectively, which could be delivered within 1 hour. SFED can be delivered within 1 hour using a high-dose-rate eBT. Even four-fraction delivery of HFED without VR resulted in higher OARs doses in the macula, optic disc, and lens (135 ~ 159%) than when using 125I LDR-BT technique. A maximum p-value of 0.005 was observed for these distributions. CONCLUSIONS: The simulation of single-fraction eBT, including vitreous replacement, resulted in significantly reduced OARs doses (16 ~ 75%) of that achieved with 125I LDR-BT.

Dose-rate considerations for the INTRABEAM electronic brachytherapy system: Report from the American association of physicists in medicine task group no. 292.

The purpose of this report is to provide detailed guidance on the dosimetry of the INTRABEAM® (Carl Zeiss Medical AG, Jena, Germany) electronic brachytherapy (eBT) system as it stands at the present time. This report has been developed by the members of American Association of Physicists in Medicine (AAPM) Task Group 292 and endorsed by the AAPM. Members of AAPM Task Group 292 on Electronic-Brachytherapy Dosimetry have reviewed pertinent publications and user manuals regarding the INTRABEAM system dosimetry and manufacturer-supplied dose calculation protocols. Formal written correspondence with Zeiss has also provided further clarification. Dose-rate calculations for the INTRABEAM system are highly dependent on choice of dosimetry protocol. Even with careful protocol selection, large uncertainties remain due to the incomplete characterization of the ionization chambers used for verification with respect to their energy dependence as well as manufacturing variations. There are two distinct sets of dose-rate data provided by Zeiss for the INTRABEAM system. One dataset (Calibration V4.0) is representative of the physical dose surrounding the source and the other dataset (TARGIT) has been adjusted to be consistent with a clinical trial named TARGIT (TARGeted Intraoperative RadioTherapy). The adjusted TARGIT doses are quite dissimilar to the physical doses, with differences ranging from 14% to 30% at the surface of a spherical applicator, depending on its diameter, and up to a factor of two at closer distances with the smaller needle applicators. In addition, ion chamber selection and associated manufacturing tolerances contribute to significant additional uncertainties. With these substantial differences in dose rates and their associated uncertainties, it is important for users to be aware of how each value is calculated and whether it is appropriate to be used for the intended treatment. If users intend to deliver doses that are the same as they were in 1998 at the onset of the TARGIT trial, then the TARGIT dose-rate tables should be used. The Calibration V4.0 dose rates may be more appropriate to use for applications other than TARGIT trial treatments, since they more closely represent the physical doses being delivered. Users should also be aware of the substantial uncertainties associated with the provided dose rates, which are due to beam hardening, chamber geometry, and selection of the point-of-measurement for a given ionization chamber. This report serves to describe the details and implications of the manufacturer-recommended dosimetry formalism for users of the INTRABEAM system.

Electronic intracavitary brachytherapy quality management based on risk analysis: The report of AAPM TG 182.

PURPOSE: The purpose of this study was to provide guidance on quality management for electronic brachytherapy. MATERIALS AND METHODS: The task group used the risk-assessment approach of Task Group 100 of the American Association of Physicists in Medicine. Because the quality management program for a device is intimately tied to the procedure in which it is used, the task group first designed quality interventions for intracavitary brachytherapy for both commercial electronic brachytherapy units in the setting of accelerated partial-breast irradiation. To demonstrate the methodology to extend an existing risk analysis for a different application, the task group modified the analysis for the case of post-hysterectomy, vaginal cuff irradiation for one of the devices. RESULTS: The analysis illustrated how the TG-100 methodology can lead to interventions to reduce risks and improve quality for each unit and procedure addressed. CONCLUSION: This report provides a model to guide facilities establishing a quality management program for electronic brachytherapy.

An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses.

For decades the field of radiation oncology has sought to improve the therapeutic ratio through innovations in physics, chemistry, and biology. To date, technological advancements in image guided beam delivery techniques have provided clinicians with their best options for improving this critical tool in cancer care. Medical physics has focused on the preferential targeting of tumors while minimizing the collateral dose to the surrounding normal tissues, yielding only incremental progress. However, recent developments involving ultra-high dose rate irradiation termed FLASH radiotherapy (FLASH-RT), that were initiated nearly 50 years ago, have stimulated a renaissance in the field of radiotherapy, long awaiting a breakthrough modality able to enhance therapeutic responses and limit normal tissue injury. Compared to conventional dose rates used clinically (0.1-0.2 Gy/s), FLASH can implement dose rates of electrons or X-rays in excess of 100 Gy/s. The implications of this ultra-fast delivery of dose are significant and need to be re-evaluated to appreciate the fundamental aspects underlying this seemingly unique radiobiology. The capability of FLASH to significantly spare normal tissue complications in multiple animal models, when compared to conventional rates of dose-delivery, while maintaining persistent growth inhibition of select tumor models has generated considerable excitement, as well as skepticism. Based on fundamental principles of radiation physics, radio-chemistry, and tumor vs. normal cell redox metabolism, this article presents a series of testable, biologically relevant hypotheses, which may help rationalize the differential effects of FLASH irradiation observed between normal tissue and tumors.

Pharmacological Ascorbate as a Means of Sensitizing Cancer Cells to Radio-Chemotherapy While Protecting Normal Tissue.

Chemoradiation has remained the standard of care treatment for many of the most aggressive cancers. However, despite effective toxicity to cancer cells, current chemoradiation regimens are limited in efficacy due to significant normal cell toxicity. Thus, efforts have been made to identify agents demonstrating selective toxicity, whereby treatments simultaneously sensitize cancer cells to protect normal cells from chemoradiation. Pharmacological ascorbate (intravenous infusions of vitamin C resulting in plasma ascorbate concentrations ≥20 mM; P-AscH-) has demonstrated selective toxicity in a variety of preclinical tumor models and is currently being assessed as an adjuvant to standard-of-care therapies in several early phase clinical trials. This review summarizes the most current preclinical and clinical data available demonstrating the multidimensional role of P-AscH- in cancer therapy including: selective toxicity to cancer cells via a hydrogen peroxide (H2O2)-mediated mechanism; action as a sensitizing agent of cancer cells to chemoradiation; a protectant of normal tissues exposed to chemoradiation; and its safety and tolerability in clinical trials.

Quality assurance for nonradiographic radiotherapy localization and positioning systems: report of Task Group 147.

New technologies continue to be developed to improve the practice of radiation therapy. As several of these technologies have been implemented clinically, the Therapy Committee and the Quality Assurance and Outcomes Improvement Subcommittee of the American Association of Physicists in Medicine commissioned Task Group 147 to review the current nonradiographic technologies used for localization and tracking in radiotherapy. The specific charge of this task group was to make recommendations about the use of nonradiographic methods of localization, specifically; radiofrequency, infrared, laser, and video based patient localization and monitoring systems. The charge of this task group was to review the current use of these technologies and to write quality assurance guidelines for the use of these technologies in the clinical setting. Recommendations include testing of equipment for initial installation as well as ongoing quality assurance. As the equipment included in this task group continues to evolve, both in the type and sophistication of technology and in level of integration with treatment devices, some of the details of how one would conduct such testing will also continue to evolve. This task group, therefore, is focused on providing recommendations on the use of this equipment rather than on the equipment itself, and should be adaptable to each user's situation in helping develop a comprehensive quality assurance program.

Radiation therapy plan checks in a paperless clinic.

Traditional quality assurance checks of a patient's radiation therapy plan involve printing out treatment parameters from the treatment planning system and the "record and verify" (R&V) system and visually checking the information for one-to-one correspondence. In a paperless environment, one can automate this process through independent software that can read the treatment planning data directly and compare it against the parameters in the R&V system's database. In addition to verifying the data integrity, it is necessary to check the logical consistency of the data and the accuracy of various calculations. The results are then imported into the patient's electronic medical record. Appropriate workflows must be developed to ensure that no steps of the QA process are missed. This paper describes our electronic QA system (EQS), consisting of in-house software and workflows. The EQS covers 3D conformal and intensity modulated radiation therapy, electrons, stereotactic radiosurgery, total body irradiation, and clinical set ups with and without virtual simulation. The planning systems handled by our EQS are ADAC Pinnacle and Varian FASTPLAN, while the R&V systems are LANTIS and VARIS. The improvement in our plan check process over the paperless system is described in terms of the types of detected errors. The potential problems with the implementation and use of the EQS, as well as workarounds for data that are not easily accessible through electronic means, are described.