Patterns of local residual disease and local failure after intensity modulated/image guided radiation therapy for sinonasal tumors in dogs.

BACKGROUND: Most dogs with sinonasal tumors (SNT) treated with radiation therapy (RT) died because of local disease progression. HYPOTHESIS/OBJECTIVES: Our hypothesis is that the majority of local failure and residual disease would occur within the radiation field. ANIMALS: Twenty-two dogs with SNT treated with RT. METHODS: Retrospective cohort study. INCLUSION CRITERIA: dogs with SNT receiving 10 daily fractions of 4.2 Gy with intensity modulated radiation therapy (IMRT)/image guided radiation therapy (IGRT) and follow-up cone beam computed tomography (CBCT). Each CBCT was registered with the original radiation planning CT and the gross tumor volume (GTV) contoured. The GTV was classified as residual (GTVr) or a failure (GTVf). The dose statistic for each GTV was calculated with the original IMRT plan. For GTVf, failures were classified as "in-field," "marginal," or "out-field" if at least 95, 20-95, or less than 20% of the volume of failure was within 95% (D95) of the total prescription dose, respectively. RESULTS: There were 52 follow-up CBCT/CTs. Overall there was a GTVr for 20 dogs and GTVf for 16 dogs. The majority of GTVr volume was within the original GTV. GTVf analysis showed that 75% (12/16) were "in-field," 19% (3/16) were "marginal" and 6% (1/16) were "out-field." CONCLUSION AND CLINICAL IMPORTANCE: In-field failures are the main pattern for local recurrence, and there is evidence of radioresistant subvolumes within the GTV.

Clinical-dosimetric relationship between lacrimal gland dose and keratoconjunctivitis sicca in dogs with sinonasal tumors treated with radiation therapy.

BACKGROUND: Dogs with sinonasal tumor can develop keratoconjunctivitis sicca (KCS) after radiation therapy (RT). In humans, the incidence of xerophtalmia is associated with the mean radiation dose received by the ipsilateral lacrimal gland (LG). HYPOTHESIS/OBJECTIVES: The eyes receiving a higher mean LG dose are more likely to develop KCS. The aim of the study was to determine a starting threshold dose to use as dose constraint for intensity-modulated radiation therapy (IMRT). ANIMALS: Dogs with nasal tumors treated with RT between August 2013 and December 2016. METHODS: Case control retrospective study of dogs with sinonasal tumor treated with 42 Gray (Gy) in 10 fractions using IMRT. Dogs were included if development of KCS after RT was documented (cases) or adequate follow-up information with Schirmer tear test (STT) result for ≥6 months after RT was available (controls). Lacrimal glands were contoured and dose distribution was calculated using the original treatment plan to determine prescribed doses to LGs. RESULTS: Twenty-five dogs were treated with RT and 5 dogs (20%) developed KCS. Fifteen dogs met the inclusion criteria including 5 unilateral KCS and 10 control dogs, resulting in 5 KCS eyes and 25 control eyes. KCS developed at a median of 111 days (84-122) after 1st RT. The mean LG dose reached using a 4.2 Gy per fraction was 33.08 Gy (range: 23.75-42.33) for KCS eyes and 10.33 Gy (1.8-24.77) for control eyes (P < .001). The minimum LG mean dose for developing KCS was 23.75 Gy. No eyes that received a mean LG dose <20 Gy developed KCS versus 5/7 (71%) developed with >20 Gy. CONCLUSION AND CLINICAL IMPORTANCE: Contouring and applying a dose constraint on LGs should be performed when using IMRT in dogs with sinonasal tumors to reduce the risk of KCS.

A Novel 2D Probability Density Function Integrating the Rectal Motion and Wall Thickness in Prostate IMRT.

BACKGROUND AND PURPOSE: This study investigated the variations of rectal motion and wall thickness in prostate intensity-modulated radiotherapy using a novel 2D probability density function. To evaluate the impact of the position, thickness, and deformation of the rectum on the dose distribution in prostate intensity-modulated radiotherapy plans, probability density functions (pdf) of the deformation of rectal cross-section (DW), rectal dose distribution (RM), and changes in rectal wall thickness (TW) were used in the planning optimization. MATERIALS AND METHODS: The problem of approximating the product of a number of Gaussian mixture distributions arises in the number of parameters describing the specific mean value, standard deviation, and weight in every Gaussian. In this work, a pdf model has been developed which specifies the variability of the average rectal wall thickness. The model is based on the histogram of 587 randomly selected patients with prostate cancer. RESULTS: The average wall thicknesses were determined based on the rectal structure contours drawn on the planning CT image set of the patient. The pdf describing the variability of the rectal wall thickness (pdfTW) is represented as a three-mode Gaussian mixture of specific (µF,σF); (µPF,σPF) and (µE,σE) and individual weights (wF, wPF, and wE) representing full, partially full, and empty rectal states, respectively. CONCLUSION: A 2D Gaussian pdf of rectal motion and rectal thickness (2D pdfM&TW) function, as a product-mixture model of the pdf of the rectal motion (pdfM) and the pdfTW, was developed using published and experimental data, respectively, and presented mathematically. Using correlation values between the functions pdfM and pdfTW, the sensitivity of profiles and projections to the 2D pdfM&TW is numerically demonstrated.

Retrospective study of patients radiation dose during cardiac catheterization procedures.

OBJECTIVE: Cardiac catheterization procedures provide tremendous benefits to modern healthcare and the benefit derived by the patient should far outweigh the radiation risk associated with a properly optimized procedure. With increasing utilization of such procedures, there is growing concern regarding the magnitude and variations of dose to patients associated with procedure complexity and techniques parameters. Therefore, this study investigated radiation dose to patients from six cardiac catheterization procedures at our facility and suggest possible initial dose values for benchmark for patient radiation dose from these procedures. This initial benchmark data will be used for clinical radiation dose management which is essential for assessing the impact of any quality improvement initiatives in the cardiac catheterization laboratory. METHODS: We retrospectively analyzed the dose parameters of 1000 patients who underwent various cardiac catheterization procedures: left heart catheterization (LH), percutaneous coronary intervention (PCI), complex PCI, LH with complex PCI, LH with PCI and cardiac resynchronization therapy (CRT) pacemaker in our cardiac catheterization laboratories. Patient's clinical radiation dose data [kerma-area-product (KAP) and air-kerma at the interventional reference point (Ka,r)] and technique parameters (fluoroscopy time, tube potential, current, pulse width and number of cine images) along with demographic information (age, height and weight) were collected from the hospital's RIS (Synapse), Sensis/Syngo Dynamics and Siemens Sensis Stats Manager electronic database. Statistical analysis was performed with the IBM SPSS Modeler v. 18.1 software. RESULTS: The overall patient median age was 67.0 (range: 26.0-97.0) years and the median body mass index (BMI) was 28.8 (range: 15.9-61.7) kg/m2 . The median KAP for the LH, PCI, LH with complex PCI, complex PCI, LH with PCI and CRT-pacemaker procedures are 44.4 (4.1-203.2), 80.2 (18.9-208.5), 83.7 (48.0-246.1), 113.8 (60.9-284.5), 91.7 (6.0-426.0) and 51.1 (7.0-175.9) Gy-cm2 . The median Ka,r for the LH, PCI, LH with complex PCI, complex PCI, LH with PCI and CRT-pacemaker procedures are 701.0 (35.3-3794.0), 1384.7 (291.7-4021.8), 1607.0 (883.5-4448.3), 2260.2 (867.4-5311.9), 1589.3 (100.2-7237.4) and 463.8 (67.7-1695.9) mGy respectively. CONCLUSION: We have analyzed patient radiation doses from six commonly used procedures in our cardiac catheterization laboratories and suggested possible initial values for benchmark from these procedures for the fluoroscopy time, KAP and air-kerma at the interventional reference point based on our current practices. Our data compare well with published values reported in the literature by investigators who have also studied patient doses and established benchmark dose levels for their facilities. Procedure-specific benchmark dose data for various groups of patients can provide the motivation for monitoring practices to promote improvements in patient radiation dose optimization in the cardiac catheterization laboratories. ADVANCES IN KNOWLEDGE: We have investigated local patients' radiation doses and established benchmark radiation data which are essential for assessing the impact of any quality improvement initiatives for radiation dose optimization.

Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation.

Gold nanoparticles (AuNPs) are a focus of growing medical research applications due to their unique chemical, electrical and optical properties. Because of uncertain toxicity, "green" synthesis methods are emerging, using plant extracts to improve biological and environmental compatibility. Here we explore the biodistribution of green AuNPs in mice and prepare a physiologically-based pharmacokinetic (PBPK) model to guide interspecies extrapolation. Monodisperse AuNPs were synthesized and capped with epigallocatechin gallate (EGCG) and curcumin. 64 CD-1 mice received the AuNPs by intraperitoneal injection. To assess biodistribution, groups of six mice were sacrificed at 1, 7, 14, 28 and 56 days, and their organs were analyzed for gold content using inductively coupled plasma mass spectrometry (ICP-MS). A physiologically-based pharmacokinetic (PBPK) model was developed to describe the biodistribution data in mice. To assess the potential for interspecies extrapolation, organism-specific parameters in the model were adapted to represent rats, and the rat PBPK model was subsequently evaluated with PK data for citrate-capped AuNPs from literature. The liver and spleen displayed strong uptake, and the PBPK model suggested that extravasation and phagocytosis were key drivers. Organ predictions following interspecies extrapolation were successful for rats receiving citrate-capped AuNPs. This work lays the foundation for the pre-clinical extrapolation of the pharmacokinetics of AuNPs from mice to larger species.

Proposed expansion margins for planning organ at risk volume for lenses during radiation therapy of the nasal cavity in dogs and cats.

Radiation therapy protocols for the feline or canine nasal cavity can damage epithelial cells of the posterior pole of the lens and lead to the development of cataracts. Aims of this retrospective, descriptive study were to calculate movements of the lens during radiation therapy of the nasal cavity in a sample of cats and dogs, and to propose species-specific expansion margins for planning organ at risk volume (PRV) to minimize radiation doses to the lens. All included patients were immobilized with an indexed bite block and positioned in a vacuum positioning cushion for head irradiation. On-board cone beam CT (CBCT) imaging was used for patient alignment. Both ocular lenses were contoured on the therapeutic CBCTs. Coregistration (fusion) between the planning CT and CBCTs was used to measure the movements of the lens. Two measurements were made: the differences between the centroid point of each lens as well as the displacement of the coregistrations. A total of 496 different observations were recorded from 14 cats and 52 dogs. Using the displacement results, we calculated how often the lens would be within the lens-PRV contour. We proposed that an optimal expansion margin from the lens volume of 2 mm in cats and 3 mm in dogs may be necessary in generating PRV expansion for the lens. From our results, we expect the lens would therefore be within these proposed PRV expansions in 92% of the feline measurements and 95% of the canine measurements.

Dosimetric evaluation of whole-breast radiation therapy: clinical experience.

Radiation therapy of the intact breast is the standard therapy for preventing local recurrence of early-stage breast cancer following breast conservation surgery. To improve patient standard of care, there is a need to define a consistent and transparent treatment path for all patients that reduces significance variations in the acceptability of treatment plans. There is lack of consistency among institutions or individuals about what is considered an acceptable treatment plan: target coverage vis-à-vis dose to organs at risk (OAR). Clinical trials usually resolve these issues, as the criteria for an acceptable plan within the trial (target coverage and doses to OAR) are well defined. We developed an institutional criterion for accepting breast treatment plans in 2006 after analyzing treatment data of approximately 200 patients. The purpose of this article is to report on the dosimetric review of 623 patients treated in the last 18 months to evaluate the effectiveness of the previously developed plan acceptability criteria and any possible changes necessary to further improve patient care. The mean patient age is 61.6 years (range: 25.2 to 93.0 years). The mean breast separation for all the patients is 21.0cm (range: 12.4 to 34.9cm), and the mean planning target volume (PTV_eval) (breast volume for evaluation) is 884.0cm(3) (range: 73.6 to 3684.6cm(3)). Overall, 314 (50.4%) patients had the disease in the left breast and 309 (49.6%) had it in the right breast. A total of 147 (23.6%) patients were treated using the deep inspiration breath-hold (DIBH) technique. The mean normalized PTV_eval receiving at least 92% (V92% PD) and 95% (V95% PD) of the prescribed dose (PD) are more than 99% and 97%, respectively, for all patients. The mean normalized PTV_eval receiving at least 105% (V105% PD) of the PD is less than 1% for all groups. The mean homogeneity index (HI), uniformity index (UI), and conformity index (CI) for the PTV_eval are 0.09 (range: 0.05 to 0.15), 1.07 (range: 0.46 to 1.11), and 0.98 (range: 0.92 to 1.0), respectively. Our data confirm the significant advantage of using DIBH to reduce heart dose when compared with the free-breathing technique. The p values analyses of the results for the V5Gy, V10Gy, V15Gy, V20Gy, and V30Gy for the heart comparing DIBH and free-breathing techniques are well less than 0.05 (i.e., p < 0.05). However, similar analyses for the lung give values greater than 0.05 (i.e., p > 0.05), indicating that there is no significant difference in lung dose comparing the 2 treatment techniques.

Cobalt-60 tomotherapy: clinical treatment planning and phantom dose delivery studies.

PURPOSE: Investigations have shown that a Cobalt-60 (Co-60) radioactive source has the potential to play a role in intensity modulated radiation therapy (IMRT). In this paper, Co-60 tomotherapy's conformal dose delivery potential is evaluated by delivering conformal dose plans on a cylindrical homogeneous phantom containing clinical structures similar to those found in a typical head and neck (H&N) cancer. Also, the clinical potential of Co-60 tomotherapy is investigated by generating 2D clinical treatment plans for H&N and prostate anatomical regions. These plans are compared with the 6 MV based treatment plans for modalities such as linear accelerator-based tomotherapy and broad beam IMRT, and 15 MV based 3D conformal radiation therapy (3DCRT). METHODS: For experimental validation studies, clinical and nonclinical conformal dose patterns were delivered on circular, homogeneous phantoms containing GafChromic film. For clinical planning study, dose calculations were performed with the EGSnrc Monte Carlo program, where a Theratronics 780C Co-60 unit and a 6 MV linear accelerator were modeled with a MIMiC binary multileaf collimator. An inhouse inverse treatment planning system was used to optimize tomotherapy plans using the same optimization parameters for both Co-60 and 6 MV beams. The IMRT and 3DCRT plans for the clinical cases were generated entirely in the Eclipse treatment planning system based on inhouse IMRT and 3DCRT site specific protocols. RESULTS: The doses delivered to the homogeneous phantoms agreed with the calculations, indicating that it is possible to deliver highly conformal doses with the Co-60 unit. The dose distributions for Co-60 tomotherapy clinical plans for both clinical cases were similar to those obtained with 6 MV based tomotherapy and IMRT, and much more conformal compared to 3DCRT plans. The dose area histograms showed that the Co-60 plans achieve the dose objectives for the targets and organs at risk. CONCLUSIONS: These results confirm that Co-60 tomotherapy is capable of providing state-of-the-art conformal dose delivery and could be used for the treatment of targets in both small and larger separation anatomical regions.

Foetal radiation dose and risk from diagnostic radiology procedures: a multinational study.

In diagnostic radiology examinations there is a benefit that the patient derives from the resulting diagnosis. Given that so many examinations are performed each year, it is inevitable that there will be occasions when an examination(s) may be inadvertently performed on pregnant patients or occasionally it may become clinically necessary to perform an examination(s) on a pregnant patient. In all these circumstances it is necessary to request an estimation of the foetal dose and risk. We initiated a study to investigate fetal doses from different countries. Exposure techniques on 367 foetuses from 414 examinations were collected and investigated. The FetDoseV4 program was used for all dose and risk estimations. The radiation doses received by the 367 foetuses ranges: <0.001-21.9 mGy depending on examination and technique. The associated probability of induced hereditary effect ranges: <1 in 200000000 (5 × 10(-9)) to 1 in 10000 (1 × 10(-4)) and the risk of childhood cancer ranges <1 in 12500000 (8 × 10(-8)) to 1 in 500 (2 × 10(-3)). The data indicates that foetal doses from properly conducted diagnostic radiology examinations will not result in any deterministic effect and a negligible risk of causing radiation induced hereditary effect in the descendants of the unborn child.

A survey of organ equivalent and effective doses from diagnostic radiology procedures.

The quantification of radiation risks associated with radiological examinations has been a subject of interest with the increased use of X-rays. Effective dose, which is a risk-weighted measure of radiation to organs in the body associated with radiological examination, is considered a good indicator of radiological risk. We have therefore investigated patient effective doses from radiological examinations. Organ and effective doses were estimated for 94 patients who underwent computed tomography examinations and for 338 patients who had conventional radiography examinations. The OrgDose (version 2) program was used for the estimation of effective doses. The tube potential ranges: 57 kVp to 138 kVp depending on the examination and patient size. The entrance surface doses have a wide range even for the same examination: 0.44-10.31 mGy (abdomen) and 0.66-16.08 mGy (lumbar spine) and the corresponding effective dose ranges 0.025-0.77 mSv and 0.025-0.95 mSv respectively. Effective dose for adult abdomen-pelvic CT examinations ranges 5.4-19.8 mSv with a mean of 13.6 mSv and for pediatrics ranges 2.1-5.5 mSv with a mean of 2.7 mSv. The mean effective dose for adult chest and head CT examinations are 7.9 and 1.8 mSv respectively and for pediatrics are 1.7 and 1.1 mSv.

Aperture superposition dose model versus pencil beam superposition dose model for a finite size Cobalt-60 source for tomotherapy deliveries.

PURPOSE: The finite size pencil beam (FSPB) superposition method is a commonly used dose calculation method in intensity modulated radiation therapy (IMRT). The FSPB model assumes that dose for a broad intensity modulated beam can be calculated by superposition of dose from small, pencil-like beams. However, this model is limited to point-like radiation sources and is not valid for finite size sources, such as a Cobalt-60 (Co-60) source of 2 cm diameter. In this paper, the authors present results that show the limitation of this model and propose an alternative model, namely the aperture superposition (AS) model, to calculate photon dose for intensity modulated beams arising from finite size radiation sources. METHODS: The AS model is based on adding beam apertures rather than pencil beams. Each aperture is defined as a series of adjacently opened leaves of a multileaf collimator with no closed leaves in between them. The apertures are calculated using the EGSnrc Monte Carlo program. The accuracy of the AS model was tested for dose calculations of fan beams, as encountered in tomotherapy treatment plans. The results were compared with the FSPB model and GafChromic film measurements. The measurements and simulations were performed for a clinical Theratronics T780C Co-60 unit with MIMiC binary multileaf collimator mounted on it. RESULTS: The comparisons between the AS model and film measurements show agreement better than 1.5% in the high dose regions and 3.7% in the low dose regions. On the contrary, film measurement comparisons to the FSPB model show that the FSPB model underestimates the dose by up to 7% for small field sizes such as 2 × 2 cm(2) and 20% for larger field sizes such as 20 × 2 cm(2). CONCLUSIONS: The results presented in this paper indicate that the AS model provides better accuracy than the FSPB model when calculating dose for fan beams from large radiation sources. The implementation of this model to the current treatment planning systems has the scope of advancing Co-60 based IMRT and tomotherapy.

Dosimetry of interface region near closed air cavities for Co-60, 6 MV and 15 MV photon beams using Monte Carlo simulations.

Underdosing of treatment targets can occur in radiation therapy due to electronic disequilibrium around air-tissue interfaces when tumors are situated near natural air cavities. These effects have been shown to increase with the beam energy and decrease with the field size. Intensity modulated radiation therapy (IMRT) and tomotherapy techniques employ combinations of multiple small radiation beamlets of varying intensities to deliver highly conformal radiation therapy. The use of small beamlets in these techniques may therefore result in underdosing of treatment target in the air-tissue interfaces region surrounding an air cavity. This work was undertaken to investigate dose reductions near the air-water interfaces of 1x1x1 and 3x3x3 cm(3) air cavities, typically encountered in the treatment of head and neck cancer utilizing radiation therapy techniques such as IMRT and tomotherapy using small fields of Co-60, 6 MV and 15 MV photons. Additional investigations were performed for larger photon field sizes encompassing the entire air-cavity, such as encountered in conventional three dimensional conformal radiation therapy (3DCRT) techniques. The EGSnrc/DOSXYZnrc Monte Carlo code was used to calculate the dose reductions (in water) in air-water interface region for single, parallel opposed and four field irradiations with 2x2 cm(2) (beamlet), 10x2 cm(2) (fan beam), 5x5 and 7x7 cm(2) field sizes. The magnitude of dose reduction in water near air-water interface increases with photon energy; decreases with distance from the interface as well as decreases as the number of beams are increased. No dose reductions were observed for large field sizes encompassing the air cavities. The results demonstrate that Co-60 beams may provide significantly smaller interface dose reductions than 6 MV and 15 MV irradiations for small field irradiations such as used in IMRT and tomotherapy.

The role of Cobalt-60 in modern radiation therapy: Dose delivery and image guidance.

The advances in modern radiation therapy with techniques such as intensity-modulated radiation therapy and image-guided radiation therapy (IMRT and IGRT) have been limited almost exclusively to linear accelerators. Investigations of modern Cobalt-60 (Co-60) radiation delivery in the context of IMRT and IGRT have been very sparse, and have been limited mainly to computer-modeling and treatment-planning exercises. In this paper, we report on the results of experiments using a tomotherapy benchtop apparatus attached to a conventional Co-60 unit. We show that conformal dose delivery is possible and also that Co-60 can be used as the radiation source in megavoltage computed tomography imaging. These results complement our modeling studies of Co-60 tomotherapy and provide a strong motivation for continuing development of modern Cobalt-60 treatment devices.

Practical and clinical considerations in Cobalt-60 tomotherapy.

Cobalt-60 (Co-60) based radiation therapy continues to play a significant role in not only developing countries, where access to radiation therapy is extremely limited, but also in industrialized countries. Howver, technology has to be developed to accommodate modern techniques, including image guided and adaptive radiation therapy (IGART). In this paper we describe some of the practical and clinical considerations for Co-60 based tomotherapy by comparing Co-60 and 6 MV linac-based tomotherapy plans for a head and neck (HandN) cancer and a prostate cancer case. The tomotherapy IMRT plans were obtained by modeling a MIMiC binary multi-leaf collimator attached to a Theratron-780c Co-60 unit and a 6 MV linear accelerator (CL2100EX). The EGSnrc/BEAMnrc Monte Carlo (MC) code was used for the modeling of the treatment units with the MIMiC collimator and EGSnrc/DOSXYZnrc code was used for beamlet dose data. An in-house inverse treatment planning program was then used to generate optimized tomotherapy dose distributions for the H and N and prostate cases. The dose distributions, cumulative dose area histograms (DAHs) and dose difference maps were used to evaluate and compare Co-60 and 6 MV based tomotherapy plans. A quantitative analysis of the dose distributions and dose-volume histograms shows that both Co-60 and 6 MV plans achieve the plan objectives for the targets (CTV and nodes) and OARs (spinal cord in HandN case, and rectum in prostate case).

Investigation of an efficient source design for Cobalt-60-based tomotherapy using EGSnrc Monte Carlo simulations.

Recent investigations demonstrate a strong potential for Cobalt-60 (Co-60)-based tomotherapy. Reported work suggests that Co-60-based tomotherapy offers a clinically and commercially viable alternative to megavoltage x-ray-based tomotherapy. Tomotherapy applications use a combination of intensity-modulated fan beams to deliver highly conformal radiotherapy. However, conventional Co-60 units are designed to give large uniform rectangular fields using an isotropic radioactive source in a cylindrical geometry. Such cylindrical source geometry likely provides a sub-optimal use of the radioactivity within the source volume for tomotherapy applications due to a significant loss of radiated energy outside the fan beam collimation system. To investigate a more efficient source geometry suitable for Co-60 tomotherapy applications, a computer code was written to model an isotropic source in a 6-faced polyhedron geometry such as cube, parallelepiped, prism and truncated pyramid. This code was integrated with the existing EGSnrc/BEAMnrc Monte Carlo (MC) code. The integrated source code was thoroughly tested, validated and used to investigate the energy spectra, radiation output and self-shielding properties of various rectangular-shaped (RS) Co-60 sources. Fan beam dose profiles were calculated for various cylindrical and RS Co-60 sources for a range of source-to-axis distances (SAD), multi-leaf collimator-to-isocentre distances (CID) and modified collimator systems. Fringe and penumbra distances were analysed for the simulated dose profiles. Our results demonstrate that clinically acceptable fringe and penumbra distances can be achieved by a careful selection of SAD, CID, source shape and dimensions and modified collimator system. Significant overall gain in radiation output of the 20 x 1 cm(2) fan beams can be achieved by an optimal selection of the source geometry for a given active volume of Co-60. The overall gain includes the effects of change in packing density (accounting for self-absorption) and change in source shape.

Radiation-induced craniofacial bone growth inhibition: efficacy of cytoprotection following a fractionated dose regimen.

BACKGROUND: Severe craniofacial growth disturbances are noted in 66 to 100 percent of children with head and neck cancers who received radiotherapy during their growing years. The authors have previously demonstrated the prevention of radiation-induced craniofacial bone growth inhibition following single-dose orthovoltage radiation to the orbitozygomatic complex in an infant rabbit model through the administration of the cytoprotective agent amifostine (WR-2721) before radiation treatment. The purpose of this study was to investigate the efficacy of cytoprotection using a fractionated dose regimen that better approximates the clinical application of radiation therapy. METHODS: Thirty 7-week-old male New Zealand rabbits were randomized into three groups (n = 10), each receiving six fractions of orthovoltage radiation to the right orbitozygomatic complex: group C, sham irradiation control; group F35, total dose of 35 Gy; and group F35A, total dose of 35 Gy with administration of amifostine 200 mg/kg intravenously 20 minutes before each fraction. Bone growth was evaluated up to skeletal maturity (age 21 weeks) with serial radiographs and computed tomography scans for cephalometric analysis, bone volume, and bone density measurements. RESULTS: Fractionated radiation resulted in significant (p < 0.05) bone growth inhibition compared with sham radiation in 16 of 21 cephalometric parameters measured and significantly (p < 0.05) reduced bone volume of the rabbit orbitozygomatic complex. Pretreatment with amifostine before each radiation fraction prevented growth deformities in four cephalometric parameters and significantly (p < 0.05) attenuated these effects in another seven parameters compared with radiated animals. Bone volumes were also significantly (p < 0.05) improved in F35A animals compared with F35 animals. CONCLUSIONS: This study establishes that fractionation of orthovoltage radiation does not prevent the development of growth disturbances of the rabbit craniofacial skeleton and also demonstrates that preirradiation administration of amifostine is highly effective in the prevention and attenuation of radiation-induced craniofacial bone growth inhibition.