Acyclovir achieves a lower concentration in African HIV-seronegative, herpes simplex virus 2-seropositive women than in non-African populations.

Acyclovir pharmacokinetics was evaluated in 68 HIV-seronegative, herpes simplex virus 2 (HSV-2)-seropositive African women, who received a single oral 400-mg dose of acyclovir, with plasma acyclovir concentrations measured over 8 h. Geometric mean peak concentration and area under the concentration-time curve were 0.31 µg/ml and 1.59 h · µg/ml, respectively, 54% and 52% lower than values from non-Africans. Lower acyclovir concentrations may partly explain the reduced acyclovir suppression of HSV-2 genital ulcer recurrence in HPTN 039 African women participants.

Clinical and virologic response to episodic acyclovir for genital ulcers among HIV-1 seronegative, herpes simplex virus type 2 seropositive African women: a randomized, placebo-controlled trial.

In a randomized trial among African women with recurrent genital herpes, episodic acyclovir therapy resulted in modestly greater likelihood of lesion healing (hazard ratio [HR] = 1.48, P = 0.098; mean, 5.1 vs. 6.0 days) and cessation of herpes simplex virus shedding (HR = 1.88, P = 0.008; mean, 3.0 vs. 5.0 days) compared with placebo, similar to results of studies in high-income countries (ClinicalTrials.gov registration NCT00808405).

Accuracy of dose measurements and calculations within and beyond heterogeneous tissues for 6 MV photon fields smaller than 4 cm produced by Cyberknife.

For the small radiation field sizes used in stereotactic radiosurgery, lateral electronic disequilibrium and steep dose gradients exist in a large portion of these fields, requiring the use of high-resolution measurement techniques. These relatively large areas of electronic disequilibrium make accurate dosimetry as well as dose calculation more difficult, and this is exacerbated in regions of tissue heterogeneity. Tissue heterogeneity was considered insignificant in the brain where stereotactic radiosurgery was first used. However, as this technique is expanded to the head and neck and other body sites, dose calculations need to account for dose perturbations in and beyond air cavities, lung, and bone. In a previous study we have evaluated EBT Gafchromic film (International Specialty Products, Wayne, NJ) for dosimetry and characterization of the Cyberknife radiation beams and found that it was comparable to other common detectors used for small photon beams in solid water equivalent phantoms. In the present work EBT film is used to measure dose in heterogeneous slab phantoms containing lung and bone equivalent materials for the 6 MV radiation beams of diameter 7.5 to 40 mm produced by the Cyberknife (Accuray, Sunnyvale, CA). These measurements are compared to calculations done with both the clinically utilized Raytrace algorithm as well as the newly developed Monte Carlo based algorithm available on the Cyberknife treatment planning system. Within the low density material both the measurements and Monte Carlo calculations correctly model the decrease in dose produced by a loss of electronic equilibrium, whereas the Raytrace algorithm incorrectly predicts an enhancement of dose in this region. Beyond the low density material an enhancement of dose is correctly calculated by both algorithms. Within the high density bone heterogeneity the EBT film measurements represent dose to unit density tissue in bone and agree with the Monte Carlo results when corrected to dose to unit density tissue in bone. We conclude that EBT film is an appropriate dosimeter for measuring dose in heterogeneous materials and these measurements agree with Monte Carlo calculations of dose as implemented in the Cyberknife treatment planning system.

Evaluation of GAFCHROMIC EBT film for Cyberknife dosimetry.

External beam therapy (EBT) GAFCHROMIC film is evaluated for dosimetry and characterization of the CyberKnife radiation beams. Percentage depth doses, lateral beam profiles, and output factors are measured in solid water using EBT GAFCHROMIC film (International Specialty Products, Wayne, NJ) for the 6 MV radiation beams of diameter 5 to 60 mm produced by the CyberKnife (Accuray, Sunnyvale, CA). The data are compared to those measured with the PTW 60008 diode and the Wellhofer CC01 ion chamber in water. For the small radiation field sizes used in stereotactic radiosurgery, lateral electronic disequilibrium and steep dose gradients exist in a large portion of these fields, requiring the use of high-resolution measurement techniques. For small beams, the detector size approaches the dimensions of the beam and adversely affects measurement accuracy in regions where the gradient varies across the detector. When film is the detector, the scanning system is usually the resolution-limiting component. Radiographic films based upon silver halide (AgH) emulsions are widely used for relative dosimetry of external radiation treatment beams in the megavoltage energy range, because of their good spatial resolution and capability to provide integrated dosimetry over two dimensions. Film dosimetry, however, has drawbacks due to its steep energy dependence at low photon energies as well as film processor and densitometer artifacts. EBT radiochromic film, introduced in 2004 specifically for IMRT dosimetry, may be a detector of choice for the characterization of small radiosurgical beams, because of its near-tissue equivalence, radiation beam energy independence, high spatial resolution, and self developing properties. For radiation beam sizes greater than 10 mm, the film measurements were identical to those of the diode and ion chamber. For the smaller beam diameters of 7.5 and 5 mm, however, there were differences in the data measured with the different detectors, which are attributed to their different spatial resolution and non-water-equivalence.

Comparison of the epson expression 1680 flatbed and the vidar VXR-16 dosimetry PRO film scanners for use in IMRT dosimetry using gafchromic and radiographic film.

Intensity-modulated radiotherapy (IMRT) treatment plan verification is often done using Kodak EDR2 film and a Vidar Dosimetry PRO film digitizer. However, since many hospitals are moving towards a filmless environment, access to a film processor may not be available. Therefore, we have investigated a newly available Gafchromic EBT film for IMRT dosimetry. Planar IMRT dose distributions are delivered to both EBT and EDR2 film and scanned with the Vidar VXR-16 as well as an Epson Expression 1680 flatbed scanner. The measured dose distributions are then compared to those calculated with a Pinnacle treatment planning system. The IMRT treatments consisted of 7-9 6 MV beams for treatment of prostate, head and neck, and a few other sites. The films were analyzed using FilmQATM (3cognition LLC) software. Comparisons between measured and calculated dose distributions are reported as dose difference (DD) (pixels within +/-5%), distance to agreement (DTA) (3 mm), as well as gamma values (y) (dose= +/-3%, dist. =2 mm). Using EDR2 with the Vidar scanner is an established technique and agreement between calculated and measured dose distributions was better than 90% in all indices (DD, DTA, and gamma). However, agreement with calculations deteriorated reaching the lower 80% for EBT film scans with the Vidar scanner in logarithmic mode. The EBT Vidar scans obtained in linear mode showed an improved agreement to the upper 80% range, but artifacts were still observed across the scan. These artifacts were very distinct in all EBT scans and can be attributed to the way the film is transported through the scanner. In the Epson scanner both films are rigidly immobilized and the light source scans over the film. It was found that the Epson scanner performed equally well with both types of film giving agreement to better than 90% in all indices.

TG-69: radiographic film for megavoltage beam dosimetry.

TG-69 is a task group report of the AAPM on the use of radiographic film for dosimetry. Radiographic films have been used for radiation dosimetry since the discovery of x-rays and have become an integral part of dose verification for both routine quality assurance and for complex treatments such as soft wedges (dynamic and virtual), intensity modulated radiation therapy (IMRT), image guided radiation therapy (IGRT), and small field dosimetry like stereotactic radiosurgery. Film is convenient to use, spatially accurate, and provides a permanent record of the integrated two dimensional dose distributions. However, there are several challenges to obtaining high quality dosimetric results with film, namely, the dependence of optical density on photon energy, field size, depth, film batch sensitivity differences, film orientation, processing conditions, and scanner performance. Prior to the clinical implementation of a film dosimetry program, the film, processor, and scanner need to be tested to characterize them with respect to these variables. Also, the physicist must understand the basic characteristics of all components of film dosimetry systems. The primary mission of this task group report is to provide guidelines for film selection, irradiation, processing, scanning, and interpretation to allow the physicist to accurately and precisely measure dose with film. Additionally, we present the basic principles and characteristics of film, processors, and scanners. Procedural recommendations are made for each of the steps required for film dosimetry and guidance is given regarding expected levels of accuracy. Finally, some clinical applications of film dosimetry are discussed.

Stereotactic radiosurgery-radiotherapy: Should Monte Carlo treatment planning be used for all sites?

PURPOSE: To evaluate a Monte Carlo (MC) treatment planning system for CyberKnife treatments of cranial and extracranial lesions and determine whether it is necessary for all treatment sites. Dose distributions are compared to those calculated with a ray-tracing algorithm. Maximum doses and dose-volume histograms for the target and selected critical structures are analyzed. METHODS AND MATERIALS: The CyberKnife is used for stereotactic radiosurgery-radiotherapy of intracranial lesions (91) as well as stereotactic body radiotherapy for lesions in the spine (24), lung (58), and pelvis (36). The Multiplan system is an inverse treatment planning system which uses an effective path length (EPL) algorithm (sometimes referred to as ray-trace) for dose calculations. In addition, an MC algorithm became clinically available in late 2007. RESULTS: The maximum doses calculated by the EPL to targets in the lung were uniformly larger than the doses calculated by MC by up to a factor of 1.32. In addition, large differences in target and critical organs' dose coverage were observed. In general, more beams traversing larger distances through low density lung are associated with larger differences. For other sites such as brain and pelvis targets the differences in maximum doses and tumor coverage were generally less than 5% between the 2 calculation methods. CONCLUSIONS: The MC algorithm should be consistently used for treatment plans of lung lesions and lesions near large air cavities, but the faster EPL algorithm is adequate for treatment sites with less tissue heterogeneity.

Comparison of planned dose distributions calculated by Monte Carlo and Ray-Trace algorithms for the treatment of lung tumors with cyberknife: a preliminary study in 33 patients.

PURPOSE: To compare dose distributions calculated using the Monte Carlo algorithm (MC) and Ray-Trace algorithm (effective path length method, EPL) for CyberKnife treatments of lung tumors. MATERIALS AND METHODS: An acceptable treatment plan is created using Multiplan 2.1 and MC dose calculation. Dose is prescribed to the isodose line encompassing 95% of the planning target volume (PTV) and this is the plan clinically delivered. For comparison, the Ray-Trace algorithm with heterogeneity correction (EPL) is used to recalculate the dose distribution for this plan using the same beams, beam directions, and monitor units (MUs). RESULTS: The maximum doses calculated by the EPL to target PTV are uniformly larger than the MC plans by up to a factor of 1.63. Up to a factor of four larger maximum dose differences are observed for the critical structures in the chest. More beams traversing larger distances through low density lung are associated with larger differences, consistent with the fact that the EPL overestimates doses in low-density structures and this effect is more pronounced as collimator size decreases. CONCLUSIONS: We establish that changing the treatment plan calculation algorithm from EPL to MC can produce large differences in target and critical organs' dose coverage. The observed discrepancies are larger for plans using smaller collimator sizes and have strong dependency on the anatomical relationship of target-critical structures.

Dosimetric verification of intensity modulated radiation therapy of 172 patients treated for various disease sites: comparison of EBT film dosimetry, ion chamber measurements, and independent MU calculations.

Three independent dose verification methods for intensity modulated radiation therapy (IMRT) were evaluated. Planar IMRT dose distributions were delivered to EBT film and scanned with the Epson Expression 1680 flatbed scanner. The measured dose distributions were then compared to those calculated with a Pinnacle treatment planning system. The IMRT treatments consisted of 7 to 9 6-MV beams for different treatment sites. The films were analyzed using FilmQA (3cognition LLC, Great Neck, NY) software. Comparisons between measured and calculated dose distributions are reported as dose difference (DD) (pixels within +/- 5%), distance to agreement (DTA) (3 mm), as well as gamma values (gamma) (dose = +/- 3%, distance = 2 mm). Point dose measurements with an ion chamber at isocenter were compared to dose calculated at that point. An independent monitor units (MUs) calculation program was also used for verification. For the film dose distributions, DD values varied from 92% to 97%, with head-and-neck and lung treatments showing lower values. Gamma varied from 93% to 98%, and DTA was well above 99%. The isocenter dose measurements deviated from 0.008 to 0.028 from the calculated dose. The larger deviations were attributed to high-dose gradients at the isocenter. RadCalc MU calculations gave differences from 0.027 to 0.079. The larger differences observed were for beams crossing large areas of heterogeneous tissue and were attributed to the limitations of the simple path-length correction method employed in RadCalc. In conclusion, the 3 independent verification methods for each IMRT patient at our institution demonstrated very good agreement between measurements and calculations and gave us the confidence that our IMRT treatments are delivered accurately.