Long-term stability of the Leksell Gamma Knife® Perfexion™ patient positioning system (PPS).

PURPOSE: To assess the long-term mechanical stability and accuracy of the patient positioning system (PPS) of the Leksell Gamma Knife(®) Perfexion™ (LGK PFX). METHODS: The mechanical stability of the PPS of the LGK PFX was evaluated using measurements obtained between September 2007 and June 2011. Three methods were employed to measure the deviation of the coincidence of the radiological focus point (RFP) and the PPS calibration center point (CCP). In the first method, the onsite diode test tool with single diode detector was used together with the 4 mm collimator on a daily basis. In the second method, a service diode test tool with three diode detectors was used biannually at the time of the routine preventive maintenance. The test performed with the service diode test tool measured the deviations for all three collimators 4, 8, and 16 mm and also for three different positions of the PPS. The third method employed the conventional film pin-prick method. This test was performed annually for the 4 mm collimator at the time of the routine annual QA. To estimate the effect of the patient weight on the performance of the PPS, the focus precision tests were also conducted with varying weights on the PPS using a set of lead bricks. RESULTS: The average deviations measured from the 641 daily focus precision tests were 0.1 ± 0.1, 0.0 ± 0.0, and 0.0 ± 0.0 mm, respectively, for the 4 mm collimator in the X (left/right of the patient), Y (anterior/posterior of the patient), and Z (superior/inferior of the patient) directions. The average of the total radial deviations as measured during ten semiannual measurements with the service diode test tool were 0.070 ± 0.029, 0.060 ± 0.022, and 0.103 ± 0.028 mm, respectively for the central, long, and short diodes for the 4 mm collimator. Similarly, the average total radial deviations measured during the semiannual measurements for the 4, 8, and 16 mm collimators and using the central diode were 0.070 ± 0.029, 0.097 ± 0.025, 0.159 ± 0.028 mm, respectively. The average values of the deviations as obtained from the five annual film pin-prick tests for the 4 mm collimator were 0.10 ± 0.06, 0.06 ± 0.09, and 0.03 ± 0.03 mm for the X, Y, Z stereotactic directions, respectively. Only a minor change was observed in the total radial deviations of the PPS as a function of the simulated patient weight up to 202 kg on the PPS. CONCLUSIONS: Excellent long-term mechanical stability and high accuracy was observed for the PPS of the LGK PFX. No PPS recalibration or any adjustment in the PPS was needed during the monitored period of time. Similarly, the weight on the PPS did not cause any significant disturbance in the performance of the PPS for up to 202 kg simulated patient weight.

Evaluation of set-up uncertainties with daily kilovoltage image guidance in external beam radiation therapy for gynaecological cancers.

AIMS: To assess the set-up uncertainty for gynaecological cancer patients treated with external beam radiation therapy using daily kilovoltage image guidance and to estimate set-up margins for treatment and factors that would predict higher set-up uncertainty. MATERIALS AND METHODS: Alignment data from daily two-dimensional kilovoltage planar images and three-dimensional kilovoltage cone beam images for 52 patients treated on a Varian 2300iX linear accelerator with On Board Imaging (OBI; version 1.4) capability were analysed. The mean displacements of translational shifts, population systematic errors and random errors were calculated. Using van Herk's formula, the clinical target volume (CTV) to planning target volume (PTV) margins for set-up uncertainties were calculated. The differences in set-up error were calculated with respect to the type of cancer, imaging type and body mass index (BMI). RESULTS: Population systematic and random errors were 1.1 mm, 2.3 mm, 2.3 mm and 3.9 mm, 5.0 mm, 3.5 mm in the anterior-posterior (AP), medial-lateral (ML) and superior-inferior (SI) directions, respectively, for the entire patient population. Using van Herk's formula, the CTV to PTV margins for set-up uncertainties were found to be 5.5, 9.1 and 8.3 mm in the AP, ML and SI directions respectively. The mean displacements in the AP, ML and SI directions for BMI ≥ 30 (28 patients) versus <30 (24 patients) were -0.1 mm, 0.9 mm and 1.0 mm versus -0.1 mm, 0.1 mm and 0.4 mm, respectively, (P = 0.02). CONCLUSIONS: Daily imaging helps to assess set-up uncertainty. The set-up margin for CTV to PTV was larger for patients with BMI ≥ 30 without image guidance and these patients would benefit more from daily image guidance.

SU-E-T-07: Edema Induced Changes in Tumor Cell Survival Fraction and Tumor Control Probability in 131Cs Permanent Prostate Implant Patients.

PURPOSE: The purpose of this study is to estimate the effect of edema, developed during implant procedure, on tumor cell surviving fraction(SF) and tumor control probability(TCP) in the patients of prostate cancer who underwent 131 Cs permanent seed implants. METHODS: The impact of edema on SF and TCP, was calculated using LQ equation extended to account for exponential nature of edema decay, dose delivered to dematous prostate and inhomogeneous dose distribution. Where (1) S(D)=(1/V)Σi=1n [Vpi{1+M0 exp(-λe t)}Si (D)] Si (D)=exp[-αRi (0)∫0t [exp(- λt)/{1+M0 exp(-λe t)}τ/3]dt -ßq(t){Ri (0)∫0t [exp(-λt)/{1+M0 exp(-λe t)}τ/3]dt }2 ] and (2) TCP=exp[-ρVpS(D)] Following parameters, α=0.15Gy-1 , ß=0.05Gy-2 , α/ß=3.0Gy, Tp=42days, µ=61.6d-1 and ρ=1×106 are used to calculate SF and TCP for 31 patients of 131 Cs permanent seed implants for edema half lives(EHL) ranging from 4 days to 34 days and for edemas of magnitudes(M0 ) varying from 5% to 60% of the actual prostate volume. RESULTS: The dose reductions in 131 Cs implants varied from 1.1% (for EHL=4 days and M0 =5%) to 32.3% (for EHL= 34 days and M0 = 60%). These are higher than the dose reduction in 125 I implants, which vary from 0.3% (for EHL= 4 days and M0 = 5%) to 17.5% (for EHL= 34 days and M0 = 60%). As edema half life increased from 4 days to 34 days and edema magnitude increased from 5% to 60% the SF increased by 4.57 log, and the TCP decreased by 0.80. CONCLUSIONS: Compensation of edema induced increase in the SF and decrease in the TCP in 131 Cs seed implants should be carefully done by redefining seed positions with the guidance of post needle plans. The presented model in this study can be used to estimate the SF or the TCP for pre plan or real time permanent prostate implants using day 0 post implant CT images.

Poster - Thur Eve - 46: The upcoming international code of practice for small static photon field dosimetry.

The increased use of small photon fields in stereotactic and intensity-modulated radiotherapy has raised the need for standardizing the dosimetry of such fields using procedures consistent with those for conventional radiotherapy. An international working group, established by the IAEA in collaboration with AAPM and IPEM, is finalising a Code of Practice for the dosimetry of small static photon fields. Procedures for reference dosimetry in nonstandard machine specific reference (msr) fields are provided following the formalism of Alfonso et al. (Med. Phys. 35: 5179; 2008). Reference dosimetry using ionization chambers in machines that cannot establish a conventional 10 cm × 10 cm reference field is based on either a direct calibration in the msr field traceable to primary standards, a calibration in a reference field and a generic correction factor or the product of a correction factor for a virtual reference field and a correction factor for the difference between the msr and virtual fields. For the latter method, procedures are provided for determining the beam quality in non-reference conditions. For the measurement of field output factors in small fields, procedures for connecting large field measurements using ionization chambers to small field measurements using high-resolution detectors such as diodes, diamond, liquid ion chambers, organic scintillators and radiochromic film are given. The Code of Practice also presents consensus data on correction factors for use in conjunction with measured, detector-specific output factors. Further research to determine missing data according to the proposed framework will be strongly encouraged by publication of this document.

A simulation study of irregular respiratory motion and its dosimetric impact on lung tumors.

This study is aimed at providing a dosimetric evaluation of the irregular motion of lung tumors due to variations in patients' respiration. Twenty-three lung cancer patients are retrospectively enrolled in this study. The motion of the patient clinical target volume is simulated and two types of irregularities are defined: characteristic and uncharacteristic motions. Characteristic irregularities are representative of random fluctuations in the observed target motion. Uncharacteristic irregular motion is classified as systematic errors in determination of the target motion during the planning session. Respiratory traces from measurement of patient abdominal motion are also used for the target motion simulations. Characteristic irregular motion was observed to cause minimal changes in target dosimetry with the largest effect of 2.5% ± 0.9% (1σ) reduction in the minimum target dose (D(min)) observed for targets that move 2 cm on average and exhibiting 50% amplitude variations within a session. However, uncharacteristic irregular motion introduced more drastic changes in the clinical target volume (CTV) dose; 4.1% ± 1.7% reduction for 1 cm motion and 9.6% ± 1.7% drop for 2 cm. In simulations with patients' abdominal motion, corresponding changes in target dosimetry were observed to be negligible (<0.1%). Only uncharacteristic irregular motion was identified as a clinically significant source of dosimetric uncertainty.

Single magnetic resonance imaging vs magnetic resonance imaging/computed tomography planning in cervical cancer brachytherapy.

AIMS: To compare differences in dose to the target volume and organs at risk (OARs) for ring and tandem brachytherapy using individualised magnetic resonance imaging (MRI)/computed tomography-based three-dimensional treatment plans for each application vs plans based on a single scan for all fractions. MATERIALS AND METHODS: The study was carried out in 10 patients with carcinoma of the uterine cervix, treated with external beam radiotherapy and five fractions of high dose rate brachytherapy. Planning was carried out using MRI for the first fraction and computed tomography for each of the four subsequent fractions. The MRI-based plan was taken as the reference and the single-plan procedure was calculated by using the weights from the reference plan to calculate the dose distribution for each subsequent computed tomography-based plan. The high-risk clinical target volume (HRCTV) and OARs were delineated as per GEC-ESTRO guidelines. Total doses from external beam radiotherapy and brachytherapy were summated and normalised to a 2 Gy fraction size. RESULTS: The mean D(90) for the HRCTV was 81.9 Gy when using one plan and 84 Gy when using individual treatment plans. Similarly, the mean D(2 cc) was 75.68 Gy vs 74.99 Gy for the bladder, 55.84 Gy vs 56.56 Gy for the rectum and 64.8 Gy vs 65.5 Gy for the sigmoid. Ring rotation was identified in three patients, resulting in a change in dwell positions, which otherwise could have led to either a high bladder dose or suboptimal coverage of the HRCTV. CONCLUSIONS: Our study has shown that a single-plan procedure achieved acceptable dosimetry in most patients. However, the individualised plan improved dosimetry by accounting for variations in applicator geometry and the position of critical organs.

Four-dimensional computed tomography-based respiratory-gated whole-abdominal intensity-modulated radiation therapy for ovarian cancer: a feasibility study.

This study assesses the feasibility and implementation of respiratory-gated whole-abdominal intensity-modulated radiation therapy (RG-WAIMRT). Three patients were treated with RG-WAIMRT. The planning target volume (PTV1) included the entire peritoneal cavity and a pelvic boost field was created (PTV2). The dose prescribed was 30 Gy to PTV1 and 14.4 Gy to PTV2. For comparison, a conventional three-dimensional (3D) plan was generated for each patient. In the WAIMRT plan, an average of 90% of PTV1 received 30 Gy compared to 70% for the conventional 3D plan. The percent volume receiving 30 Gy (V(30)) for liver averaged 54% (WAIMRT) vs 43% (3D). The percent volume receiving 20 Gy (V(20)) for kidneys averaged 19% vs 0%, and the mean V(20) for bone marrow was 74% vs 83%, respectively. Major acute toxicities were anemia (grade 2: 1/3), leukopenia (grade 3: 2/3 patients), and thrombocytopenia (grade 2: 1/3 patients, grade 3: 1/3 patients). One patient could not complete the whole-abdomen field after 19.5 Gy because of persistent nausea. No major subacute toxicity has been reported. WAIMRT demonstrated superior target coverage and reduced dose to bone marrow, with a slightly increased dose to liver and kidneys. WAIMRT is a novel and feasible technique for ovarian cancer treatment.

Comparison of the IAEA TRS-398 and AAPM TG-51 absorbed dose to water protocols in the dosimetry of high-energy photon and electron beams.

The International Atomic Energy Agency (IAEA TRS-398) and the American Association of Physicists in Medicine (AAPM TG-51) have published new protocols for the calibration of radiotherapy beams. These protocols are based on the use of an ionization chamber calibrated in terms of absorbed dose to water in a standards laboratory's reference quality beam. This paper compares the recommendations of the two protocols in two ways: (i) by analysing in detail the differences in the basic data included in the two protocols for photon and electron beam dosimetry and (ii) by performing measurements in clinical photon and electron beams and determining the absorbed dose to water following the recommendations of the two protocols. Measurements were made with two Farmer-type ionization chambers and three plane-parallel ionization chamber types in 6, 18 and 25 MV photon beams and 6, 8, 10, 12, 15 and 18 MeV electron beams. The Farmer-type chambers used were NE 2571 and PTW 30001, and the plane-parallel chambers were a Scanditronix-Wellhöfer NACP and Roos, and a PTW Markus chamber. For photon beams, the measured ratios TG-51/TRS-398 of absorbed dose to water Dw ranged between 0.997 and 1.001, with a mean value of 0.999. The ratios for the beam quality correction factors kQ were found to agree to within about +/-0.2% despite significant differences in the method of beam quality specification for photon beams and in the basic data entering into kQ. For electron beams, dose measurements were made using direct N(D,w) calibrations of cylindrical and plane-parallel chambers in a 60Co gamma-ray beam, as well as cross-calibrations of plane-parallel chambers in a high-energy electron beam. For the direct N(D,w) calibrations the ratios TG-51/TRS-398 of absorbed dose to water Dw were found to lie between 0.994 and 1.018 depending upon the chamber and electron beam energy used, with mean values of 0.996, 1.006, and 1.017, respectively, for the cylindrical, well-guarded and not well-guarded plane-parallel chambers. The Dw ratios measured for the cross-calibration procedures varied between 0.993 and 0.997. The largest discrepancies for electron beams between the two protocols arise from the use of different data for the perturbation correction factors p(wall) and p(dis) of cylindrical and plane-parallel chambers, all in 60Co. A detailed analysis of the reasons for the discrepancies is made which includes comparing the formalisms, correction factors and the quantities in the two protocols.

Experimental determination of depth-scaling factors and central axis depth dose for clinical electron beams.

Depth-scaling factors rho(eff) for clear polystyrene and polymethylmethacrylate (PMMA) phantoms have been determined experimentally as a function of nominal electron-beam energy in the range 6 to 22 MeV. Values of rho(eff) have been calculated from the ratio rho(eff) = R(wat)(50) / R(med)(50), where R(wat)(50) and R(med)(50) are the measured depths of 50% ionization in electron solid water and plastic (clear polystyrene and PMMA) phantoms, respectively. Measurements were made using an Attix chamber in an electron solid water phantom, a Holt chamber in a clear polystyrene phantom, and a Markus chamber in a PMMA phantom. The average value of measured rho(poly)(eff) was found to be 0.999 +/- 0.009. This is higher than the value of 0.975 recommended by Task Group 25 (TG-25) of the American Association of Physicists in Medicine (AAPM) by 2.5%. Depending on energy, the maximum differences between the AAPM TG-25-recommended and the measured values lie in the range 1% to 3.5%. Similarly, the average value of measured rho(PMMA)(eff) was found to be 1.168 +/- 0.023. This is higher than the AAPM TG-25-recommended value of 1.115, by 5%. Depending on energy, the maximum differences between the AAPM TG-25-recommended and the measured values lie in the range 3% to 8%. Central axis depth dose curves in water were generated for 6, 15, and 20 MeV electron beams from measured depth-ionization data in PMMA and clear polystyrene phantoms following the recommendations of the AAPM TG-25 report and using both TG-25-recommended and experimentally determined values of depth-scaling factors rho(eff). For both phantoms, either the TG-25-recommended value or the experimentally determined values of rho(eff) yielded agreement to within about 2 mm among all depth doses in water at the depths of clinical relevance.

An investigation of a model of percentage depth dose for irregularly shaped fields.

A significant component of the total dose delivered to tumor and surrounding tissue during a radiation treatment arises from the scattering of the primary beam. Accounting for this component accurately and efficiently is a necessity. In this study we investigate a method for calculating the phantom-scatter contributions to the total dose by simple summation of scatter dose from a set of individual triangles that span an irregular field. The calculation of phantom scatter is based on a two-parameter model, which is applicable to regions where electron equilibrium is established. The two physical parameters are the dose-averaged linear attenuation coefficient and the beam-hardening coefficient. The advantage of this model is that it is a natural method when an irregular field is shaped by a multi-leaf collimator (MLC). Accuracy is not compromised by the triangulation since the irregular field is defined by the straight edges of the MLC leaves. The model predicts the percent depth dose with acceptable accuracy for any arbitrary shape of fields. We report on results for 6- and 18-MV photon beams and for a number of irregularly shaped fields.

AAPM's TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams.

A protocol is prescribed for clinical reference dosimetry of external beam radiation therapy using photon beams with nominal energies between 60Co and 50 MV and electron beams with nominal energies between 4 and 50 MeV. The protocol was written by Task Group 51 (TG-51) of the Radiation Therapy Committee of the American Association of Physicists in Medicine (AAPM) and has been formally approved by the AAPM for clinical use. The protocol uses ion chambers with absorbed-dose-to-water calibration factors, N(60Co)D,w which are traceable to national primary standards, and the equation D(Q)w = MkQN(60Co)D,w where Q is the beam quality of the clinical beam, D(Q)w is the absorbed dose to water at the point of measurement of the ion chamber placed under reference conditions, M is the fully corrected ion chamber reading, and kQ is the quality conversion factor which converts the calibration factor for a 60Co beam to that for a beam of quality Q. Values of kQ are presented as a function of Q for many ion chambers. The value of M is given by M = PionP(TP)PelecPpolMraw, where Mraw is the raw, uncorrected ion chamber reading and Pion corrects for ion recombination, P(TP) for temperature and pressure variations, Pelec for inaccuracy of the electrometer if calibrated separately, and Ppol for chamber polarity effects. Beam quality, Q, is specified (i) for photon beams, by %dd(10)x, the photon component of the percentage depth dose at 10 cm depth for a field size of 10x10 cm2 on the surface of a phantom at an SSD of 100 cm and (ii) for electron beams, by R50, the depth at which the absorbed-dose falls to 50% of the maximum dose in a beam with field size > or =10x10 cm2 on the surface of the phantom (> or =20x20 cm2 for R50>8.5 cm) at an SSD of 100 cm. R50 is determined directly from the measured value of I50, the depth at which the ionization falls to 50% of its maximum value. All clinical reference dosimetry is performed in a water phantom. The reference depth for calibration purposes is 10 cm for photon beams and 0.6R50-0.1 cm for electron beams. For photon beams clinical reference dosimetry is performed in either an SSD or SAD setup with a 10x10 cm2 field size defined on the phantom surface for an SSD setup or at the depth of the detector for an SAD setup. For electron beams clinical reference dosimetry is performed with a field size of > or =10x10 cm2 (> or =20x20 cm2 for R50>8.5 cm) at an SSD between 90 and 110 cm. This protocol represents a major simplification compared to the AAPM's TG-21 protocol in the sense that large tables of stopping-power ratios and mass-energy absorption coefficients are not needed and the user does not need to calculate any theoretical dosimetry factors. Worksheets for various situations are presented along with a list of equipment required.

Changes in the size and location of kidneys from the supine to standing positions and the implications for block placement during total body irradiation.

PURPOSE: The use of total body irradiation (TBI) as a conditioning regimen for bone marrow transplantation often calls for partial transmission kidney blocks. These blocks are frequently designed based on the location of the kidneys during the abdominal computerized tomography (CT) scan. At our institution, TBI patients are treated in the standing position. As the kidneys can shift with different patient positions, a study was undertaken to evaluate the magnitude of the changes in the size and location of the kidneys from the supine CT position to the upright treatment position. METHODS AND MATERIALS: Intravenous contrast was administered to 15 patients. The patients were initially positioned supine on a simulator table and then positioned upright immediately in front of the image intensifier. PA radiographs were obtained with the patients in both positions. Changes in the size of the kidneys and their location relative to the vertebral bodies were noted. RESULTS: In going from the supine to upright position, all the kidneys shifted inferiorly between 0.5 cm and 7.5 cm with an average of 3.6 cm. Most of the kidneys also shifted in the transverse dimension and incurred a change in width. The range of the transverse shift was from 0.9 cm in the lateral direction to 4.9 cm medially. The maximum width broadening was 1.2 cm and the maximum decrease in width was 1.8 cm. CONCLUSIONS: When compared to the supine position, patients in the upright position show a dramatic inferior shift of the kidneys with other obvious, but less predictable, changes. For TBI treatments delivered in the upright position, kidney blocks should not be designed on the basis of supine abdominal CT scans.

Roles of replication protein A and DNA-dependent protein kinase in the regulation of DNA replication following DNA damage.

Exposure of mammalian cells to DNA damage-inducing agents (DDIA) inhibits ongoing DNA replication. The molecular mechanism of this inhibition remains to be elucidated. We employed a simian virus 40 (SV40) based in vitro DNA replication assay to study biochemical aspects of this inhibition. We report here that the reduced DNA replication activity in extracts of DDIA-treated cells is partly caused by a reduction in the amount of replication protein A (RPA). We also report that the dominant inhibitory effect is caused by the DNA-dependent protein kinase (DNA-PK) which inactivates SV40 T antigen (TAg) by phosphorylation. The results demonstrate that RPA and DNA-PK are involved in the regulation of viral DNA replication after DNA damage and suggest that analogous processes regulate cellular DNA replication with the DNA-PK targeting the functional homologues of TAg.

A generalized film technique for the verification of vertex fields used in the treatment of brain tumors.

With the availability of commercial three-dimensional (3D)-treatment planning systems, more and more treatment plans call for the use of noncoplanar conformal beams for the treatment of brain tumors. However, techniques for the verification of many noncoplaner beams, such as vertex fields which involve any combination of gantry, collimator, and table angles, do not exist. The purpose of this work is to report on the results of an algorithm and a technique that have been developed for the verification of noncoplanar vertex fields used in the treatment of brain tumors. This technique is applicable to any geometric orientation of the beam, i.e., a beam orientation that consists of any combination of gantry, table, and collimator rotations. The method consists of superimposing a central plane image of a correctly magnified vertex field on a lateral or oblique field port film. To achieve this, the 3D coordinates of the projection of the isocenter onto the film for lateral (or oblique) as well as the vertex fields are determined and then appropriately matched. Coordinate transformation equations have been developed that enable this matching precisely. A film holder has been designed such that a film cassette can be secured rigidly along the side rails of the treatment table. The technique for taking a patient treatment setup verification film consists of two steps. In the first step, the gantry, table, and collimator angles for the lateral (or oblique) field are set and the usual double exposures are made; the first exposure corresponds to that of the treatment portal with the isocenter clearly identified and the second one a larger radiation field so that the peripheral anatomy is visible on the film. In the next step, the gantry, table, and collimator angles are positioned for the vertex field and the table is moved laterally and vertically and the film longitudinally to a position that will enable precise matching of the isocenter on the film. A third exposure is then taken with the vertex portal. What is seen on the film is a superposition of a central plane image of the vertex field onto the image of the lateral or oblique field. This technique has been used on 60 patients treated with noncoplanar fields for brain tumors. In all of these cases, the coincidence of the projection of the isocenter for the lateral (or oblique) and the vertex fields was found to be within 3 mm.

Experimental determination of fluence correction factors at depths beyond dmax for a Farmer type cylindrical ionization chamber in clinical electron beams.

Recently, it has been recommended that electron beam calibrations be performed at a new reference depth [Burns et al., Med. Phys. 23, 383 (1996)] given by dref = 0.6R50-0.1 cm, where R50 is the depth of 50% depth dose. In order to calibrate electron beams at dref with a Farmer type cylindrical ionization chamber, the values of the perturbation correction factors Pwall and Pfl at dref are required. Using a parallel plate Holt chamber as a reference chamber, the product PwallPfl has been determined for a 6.1-mm-diameter PTW cylindrical ionization chamber at dref as a function of R50 of clinical electron beams (6 < or = nominal energy E < or = 22 MeV). Assuming that Pwall for the PTW chamber is unity in electron beams, the measured Pfl values ranged from 0.96 to 0.98 as the energy is increased. These results are in close agreement with recently reported calculated values. Determination of dref requires the knowledge of R50. A relation between I50 and R50 is given in the IAEA Protocol [TRS No. 277 (IAEA, Vienna, 1987), pp. 1-98] for broad beams at SSD = 100 cm. It has been shown experimentally that the equation R50 = 1.029 x I50-0.063 cm, derived by Ding et al. [Med. Phys. 22, 489 (1995)] from Monte Carlo simulations of realistic clinical electron beams, can be used satisfactorily to obtain R50 from I50, where I50 is the depth of 50% ionization. The largest difference between the measured value of R50 and that calculated by using the above equation has been found to be about 1 mm at 22 MeV.

Differential dose delivery using a nondocking applicator for intraoperative radiation therapy.

PURPOSE: Although treatment of a field within a field to deliver a boost dose is quite common with external photon beam radiation therapy, the same is not always true with electron beam radiation or in intraoperative radiation therapy (IORT). The purpose of this work is to report the results and details of a new technique developed to treat a field within a field in intraoperative radiation therapy. METHODS AND MATERIALS: This technique makes use of the nondocking IORT system currently used at our institution. Treatment is given in two segments: the large field is first treated by using standard circular lucite cones; the second dose segment is delivered using a new circular brass cone designed to fit concentrically within the large lucite cone. RESULTS: Central axis depth dose, surface dose, output factors, and two-dimensional beam profiles have been measured for a 7 cm inner diameter (i.d.) flat lucite cone and 3.8 and 5 cm i.d. flat brass cones for electron beam energies ranging from 4-22 MeV. For different clinical target volumes, summed dose distributions differentially weighted in both energy and dose are presented. CONCLUSIONS: A simple technique for delivering differential dose in intraoperative radiation therapy is presented. The technique provides a method for escalating dose to higher values for a defined target volume.

Respiration-induced motion of the kidneys in whole abdominal radiotherapy: implications for treatment planning and late toxicity.

PURPOSE: Whole abdominal radiotherapy (WAR) has potential utility in the management of several malignancies. The limited radiation tolerance of the kidneys is an important consideration in the design of WAR fields. Although renal blocking is standard for WAR, few guidelines exist in the literature to factor respiration-induced kidney motion into the design of these blocks. METHODS: Radiographs were obtained to measure kidney excursion under forced respiratory conditions in eight patients (14 visualized kidneys). Intravenous contrast was administered and AP films were obtained at maximum inspiration and expiration. Renal excursion was measured relative to a horizontal reference line at the bottom of the L3 vertebral body. The kidney position on the actual treatment simulation film was also determined using this technique. Treatment isodose distributions through the kidneys were obtained for a sample patient using phantom measurements and two blocking schemes: AP/PA and PA only. These provided quantification of the actual dose received by the kidney in a typical WAR treatment. RESULTS: In the worst case scenario, the left kidney block required an additional 10 mm above and 15 mm below the renal silhouette on the simulation film in order to account for all phases of respiration. The corresponding values for the right kidney were 2 mm and 19 mm, respectively. The dose received by the kidney under the center of the block was 20% of prescribed using AP/PA blocks and 50% of prescribed using PA blocks only. However, portions of 'blocked' kidney received up to 90% of the prescribed dose with either technique. CONCLUSIONS: Although kidney motion under forced respiratory conditions is not representative of typical treatment conditions, the data highlight the possibility of renal movement during treatment. This is particularly important in light of the significant dose (20 to 50%) delivered to the kidney under the center of the kidney block of typical treatments. Given the potential for overdosage of this critical organ, careful prospective documentation of renal function is warranted in patients receiving WAR.

Evidence for activities inhibiting in trans initiation of DNA replication in extract prepared from irradiated cells.

We have previously shown that replication in vitro of plasmids containing the Simian virus 40 (SV40) origin of replication is reduced when an extract of irradiated cells is used (Wang et al., Radiat. Res. 142, 169-175, 1995). We proposed that the observed reduction in the overall replication activity is due to a reduction in the efficiency of initiation events, and that it is caused by the induction or activation by ionizing radiation of a factor(s) that inhibits DNA replication in trans. Here, we extend these studies and provide evidence that the reduced replication activity of an extract prepared from irradiated cells is not the result of a nonspecific inactivation of proteins or of an increase in the requirement for SV40 large tumor antigen (TAg), the only noncellular protein required for in vitro DNA replication. Mixing experiments demonstrate the presence of a dominant inhibitory activity(ies) in the extract of irradiated cells that efficiently stalls replication in reactions assembled using extract of nonirradiated cells. The inhibitory activity is a stable, nondialyzable molecule. Studies of kinetics suggest that the inhibitory activity(ies) affects the initiation steps of DNA replication and acts, at least partly, by modifying TAg, the key initiation protein of SV40 ori DNA replication. It is likely that the same inhibitory activity(ies) regulates cellular DNA replication by modifying the cellular homologues of TAg. Purification and characterization of this inhibitory activity(ies) will contribute to our understanding of the mechanism developed by the cell to regulate DNA replication after exposure to ionizing radiation and will define a checkpoint operating in S phase. Genetic evidence for a checkpoint in S phase distinct from the checkpoints operating in G1 and G2 phase has been reported in yeast.