Biomedical subjects

Stanley H Benedict

Publications and source records attributed to Stanley H Benedict.

5 recordsLinked to original sources

PubMed2005

Stereotactic body radiation therapy of lung tumors: preliminary experience using normal tissue complication probability-based dose limits.

OBJECTIVES: To assess the feasibility and toxicity of stereotactic body radiotherapy (SBRT) for patients with locally advanced or metastatic tumors in lung. METHODS: Twenty-five tumors in 17 patients were treated. All treatments were delivered in 3 daily fractions of 9 to 15 Gy per fraction. Normal tissue complication probability (NTCP) calculations (using the Lyman model) were performed to facilitate dose prescription, and doses were prescribed with a maximum allowable NTCP risk of pneumonitis of up to 20%, not to exceed 15 Gy per fraction. Planning target volumes were designed to allow for respiratory variation in tumor location. RESULTS: The median dose prescribed was 35 Gy (range, 24 to 45 Gy). Twenty-three of 25 tumors remained controlled at median follow-up of 14 months. Four patients experienced grade 1-2 acute toxicity. Late toxicity developed in 2 patients who received treatment to peri-hilar tumors, including one patient in whom bronchial stenosis developed with complete occlusion and lobar atelectasis 6 months after treatment. No patient had grade 3 or 4 radiation pneumonitis. CONCLUSIONS: SBRT prescribed within the confines of NTCP-restricted dosing on this protocol resulted in no radiation pneumonitis. Tissues other than lung parenchyma which are unaccounted for by NTCP may be dose-limiting when performing hypofractionated SBRT in the lung.

Adult↗

PubMed2005

Intracranial stereotactic positioning systems: Report of the American Association of Physicists in Medicine Radiation Therapy Committee Task Group no. 68.

Intracranial stereotactic positioning systems (ISPSs) are used to position patients prior to precise radiation treatment of localized lesions of the brain. Often, the lesion is located in close proximity to critical anatomic features whose functions should be maintained. Many types of ISPSs have been described in the literature and are commercially available. These are briefly reviewed. ISPS systems provide two critical functions. The first is to establish a coordinate system upon which a guided therapy can be applied. The second is to provide a method to reapply the coordinate system to the patient such that the coordinates assigned to the patient's anatomy are identical from application to application. Without limiting this study to any particular approach to ISPSs, this report introduces nomenclature and suggests performance tests to quantify both the stability of the ISPS to map diagnostic data to a coordinate system, as well as the ISPS's ability to be realigned to the patient's anatomy. For users who desire to develop a new ISPS system, it may be necessary for the clinical team to establish the accuracy and precision of each of these functions. For commercially available systems that have demonstrated an acceptable level of accuracy and precision, the clinical team may need to demonstrate local ability to apply the system in a manner consistent with that employed during the published testing. The level of accuracy and precision required of an individual ISPS system is dependent upon the clinical protocol (e.g., fractionation, margin, pathology, etc.). Each clinical team should provide routine quality assurance procedures that are sufficient to support the assumptions of accuracy and precision used during the planning process. The testing of ISPS systems can be grouped into two broad categories, type testing, which occurs prior to general commercialization, and site testing, performed when a commercial system is installed at a clinic. Guidelines to help select the appropriate tests as well as recommendations to help establish the required frequency of testing are provided. Because of the broad scope of different systems, it is important that both the manufacturer and user rigorously critique the system and set QA tests appropriate to the particular device and its possible weaknesses. Major recommendations of the Task Group include: introduction of a new nomenclature for reporting repositioning accuracy; comprehensive analysis of patient characteristics that might adversely affect positioning accuracy; performance of testing immediately before each treatment to establish that there are no gross positioning errors; a general request to the Medical Physics community for improved QA tools; implementation of weekly portal imaging (perhaps cone beam CT in the future) as a method of tracking fractionated patients (as per TG 40); and periodic routine reviews of positioning accuracy.

Equipment Failure Analysis↗

PubMed2004

Stereotactic body radiation therapy. Rationale, techniques, applications, and optimization.

Stereotactic body radiation therapy (SBRT) is a rapidly evolving cancer treatment method in which concepts and techniques previously developed for brain tumor radiosurgery are adapted to eradicate tumors elsewhere in the body. The spatial accuracy, conformality, and steep radiation dose gradients of radiosurgery, which have been critical to its success in the treatment of intracranial tumors, are applied in SBRT to treat a variety of extracranial tumors. Early results demonstrate excellent response rates and low toxicity with a variety of hypofractionated dose regimens and localization/immobilization techniques. This article provides an overview of the rationale and results of SBRT for specific indications, descriptions of some methods of treatment delivery, and discussion of potential areas of future investigation.

Brain Neoplasms↗

PubMed2002

The effects of pentoxifylline on the survival of human glioma cells with continuous and intermittent stereotactic radiosurgery irradiation.

PURPOSE: In linac-based stereotactic radiosurgery, treatment is delivered intermittently via multiple individual small radiotherapy arcs. The time lapses between the individual arcs permit greater damage repair and increased tumor cell survival in comparison with continuous irradiation. Because pentoxifylline (PTX) has been reported to prevent radiation-induced cell cycle arrest at the G2/M checkpoint, where damage repair is critically linked to cell survival, we hypothesized that PTX would exert a favorable radiosensitization effect by reducing the recovery observed during intermittent stereotactic radiosurgery. METHODS AND MATERIALS: The human glioma cell line T98G was used to study the effects of continuous vs. intermittent irradiation with or without PTX. Cell cycle patterns were studied using flow cytometry. Clonogenic assays of single cells and spheroid outgrowth assays provided a quantitative measure of PTX-mediated radiosensitization. The PTX effect upon cells in low oxygen conditions was also studied in vitro after enzymatic oxygen scavenging. RESULTS: Flow Cytometry: T98G cells exposed to both continuous and intermittent irradiation exhibit similar arrest at the G2/M checkpoint. The addition of 2 mM PTX significantly reduced the radiation-induced G2/M block in both irradiation schemes. Clonogenic Assays: The same PTX concentration applied before a continuous dose of 12 Gy, two intermittent doses of 6 Gy, or three intermittent doses of 4 Gy, all given within a 1-h interval, consistently caused radiosensitization. The drug enhancement ratios for PTX were 1.5, 2.7, and 6.0 for the continuous and two different intermittent dose schedules, respectively. Adding PTX after irradiation yielded lower enhancement ratios than pre-irradiation application. A similar pattern was observed after total doses of 4, 6, 9, or 12 Gy, as well. In low oxygen conditions, PTX was seen to have the same effects as in normoxic conditions. Spheroid Outgrowth Assays: The in vitro PTX effects were replicated in the spheroid outgrowth assays. CONCLUSION: In human glioma cells, PTX abrogates the radiation-induced G2/M block observed after either continuous radiation exposure or intermittent exposures modeling clinical linac-based radiosurgery. The PTX-mediated reduction of the G2/M block translates into radiosensitization, most notably during intermittent exposures, and is presumably a consequence of diminished DNA damage repair at the G2/M checkpoint, though other contributing effects cannot be ruled out. The radiosensitization effect of PTX is sustained under low oxygen conditions. These results support consideration of the clinical evaluation of PTX to enhance the efficacy of linac-based radiosurgery involving intermittent irradiation through multiple arcs.

Cell Survival↗

PubMed2002

Clinical application of intensity-modulated radiotherapy for locally advanced cervical cancer.

Intensity-modulated radiotherapy (IMRT) offers technical advantages over conventional external beam radiotherapy (CXRT) that might prove clinically advantageous in the management of gynecologic malignancies. Especially in the case of locally advanced cervical cancer, IMRT provides an opportunity to improve the therapeutic ratio by allowing a selective combination of normal tissue dose reduction and/or concomitant integrated boost dose to the tumor. The clinical and biologic rationale for IMRT in this setting is presented here, and pertinent technical considerations such as the delineation of relevant clinical and planning target volumes are discussed. The capacity for IMRT-mediated normal tissue sparing is illustrated by example and review of the literature. Furthermore, for a small cohort of patients with locally advanced or recurrent cervical cancer treated with concomitant integrated boost IMRT and concurrent chemotherapy, preliminary clinical observations of toxicity and tumor response are presented. Concomitant integrated boost IMRT appears clinically tolerable and efficacious in this setting, and formal clinical investigation is warranted as a means of exploiting the fraction-size dependence of radiosensitizers in common clinical use.

Female↗