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P D Higgins

Publications and source records attributed to P D Higgins.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of bladder dose in intensity-modulated radiation therapy of the prostate.

Day-to-day variation in bladder and rectal filling affects prostate location and positioning accuracy. Systems using ultrasonic localization or gold seed placement are most often used to help correct for these changes. At some institutions, patients are instructed to empty their rectum and fill their bladders prior to treatment in an attempt to standardize the prostate location, displace small bowel out of the radiation field, and move some of the bladder wall away from the high-dose area. Although instructed to come to treatment with a full bladder, it is presumed that there is variability in bladder filling each day of treatment, depending on the amount of fluids consumed and time to treatment. We have reviewed daily bladder volumes on a subset of 5 prostate patients, all of them prescribed to receive 7560 cGy in 42 fractions, and have evaluated the dosimetric consequences of bladder volume changes from full to two-third or one-third filling. All of these patients' positions were verified daily with ultrasonic localization. Those measurements have been used to help analyze the actual treated bladder volumes for comparison with the treatment plan. We find that, in general, maximum filling only occurred on the initial simulation/image acquisition day and was typically smaller on all the following treatment days. Based on our dose-volume model, we estimate that average bladder daily doses were 8-50% higher than predicted by the initial intensity-modulation radiation therapy (IMRT) plan.

Dose-Response Relationship, Drug↗
PubMed2006

Dose uncertainty due to aperture effects in dynamic fields.

Dosimetry of intensity modulated radiation therapy requires accurate modeling of the beamlets that comprise each treatment segment. Planning systems such as Varian Eclipse and Philips Pinnacle recommend measuring dose distributions and output factors for fields as small as possible, generally down to at least 2 x 2 cm2. Conventionally, we perform these measurements for regular fields, defined by the secondary collimators. In practice, it is the multileaf collimation system (MLC) that defines the intensity map and provides dynamic dose modulation in either a moving window or segmented step-and-shoot mode. For this review we have only considered the latter delivery mode. Using this method, we have studied aperture motion effects on the dynamic collimator scatter (S(c)), total scatter (S(c,p)), and phantom scatter (S(p)) factors for various combinations of collimator settings (4 x 4-14 x 40 cm2) and dynamically stepped leaf gaps (0.1 to 1.0 cm) in comparison with those for static field factors. For two different Varian linear accelerators, we found similar results in a systematic dependence of collimator scatter on gap width and collimator setting. As the gap increases from 0.1 to 1.0 cm the dynamic collimator scatter factors converge from a maximum difference of about 30% toward the static field values. At the same time, there is no measurable difference between dynamic field phantom scatter factors and those conventionally obtained for static fields. Second, we evaluated the two planning systems as to how well they account for collimator scatter by attempting to mimic the dynamic apertures used above by planning and measuring dose distributions to several small, cylindrical targets for a similar range of fixed collimator settings. We found that the ratio of measured-to-planned doses as a function of target size were similar to the measured, dynamic S(c) data for the Varian Eclipse planning system, indicating underestimation of dose for targets smaller than 1 cm diameter, but were close to unity for the Philips Pinnacle system, suggestive of the underlying differences in the dose calculation algorithms. We discuss the measurements and results and potential impact on the dosimetry of small clinical targets.

Air↗
PubMed2003

In vivo diode dosimetry for routine quality assurance in IMRT.

Due to the complexity of IMRT dosimetry, dose delivery evaluation is generally done using a treatment plan in which the optimized fluence distribution has been transferred to a test phantom for accessibility and simplicity of measurement. The actual patient doses may be reconstructed in vivo through the use of electronic portal imaging devices or films, but the assessment of absolute dose from these measurements is time-consuming and complicated. In our clinic we have instituted the use of routine diode dosimetry for IMRT patients following the same procedure used for standard radiation therapy patients in which each new treatment field is checked at the start of treatment. For standard cases the dose at dmax is calculated as part of the monitor unit calculation. For the IMRT cases, the dose contribution to the dmax depth for each field is taken from the treatment plan. We found that about 90% of the diode measurements agreed to within +/- 10% of the planned doses (45/51 fields) and 63% (32/51 fields) achieved +/- 5% agreement. By using this direct in vivo method to verify the clinical doses delivered, we have been able to make a uniform startup procedure for all patients while simplifying our IMRT QA process.

Humans↗
PubMed2001

Field equivalence for clinical electron beams.

The concept of field equivalence for electron beams is examined using a pencil beam theory applied to circular fields. It is shown that a circular field can be found for a field of any size, shape and energy for which the depth dose distribution is approximately equivalent. The usefulness of the concept in clinical dosimetry is discussed.

Electrons↗
PubMed2000

The role of radiosurgery for multiple brain metastases.

OBJECT: The authors evaluated the role of stereotactic radiosurgery (SRS) in patients with multiple brain metastases by analyzing prognostic factors that predict survival. METHODS: Between March 1991 and January 1999, 83 patients with multiple brain metastases underwent SRS in which they used a 6 mV linear accelerator. The median radiation dose of 15 Gy (range 6-50 Gy) was delivered to the 40 to 90% (median 87%) isodose line encompassing the target. Actuarial overall survival was calculated from the date of SRS by using the Kaplan-Meier method. Univariate comparisons of survival between different groups were performed using a log-rank test. All 83 patients were included in the calculation of overall survival. Actuarial overall survival was 22% at 1 year and 13% at 2 years, and a median survival of 5.4 months (range, 0.3-28.8 months) was demonstrated. Variables that predicted survival were Karnofsky Performance Scale (KPS) score, extracranial disease status, and the number of intracranial metastases. Median survival in patients with a KPS score greater than as compared with less than 70 was 9.1 and 2.7 months, respectively (p = 0.002). Median survival when comparing absence and presence of extracranial disease was 9.9 and 4.1 months, respectively (p = 0.02). Median survival in patients harboring two, three, or four or more lesions was 6.6 months, 5.4 months, and 2.7 months, respectively (p = 0.02). In patients with a KPS score greater than or equal to 70 and with three or fewer lesions, median survival was 7 months or longer. In patients with four or more lesions median survival was 7.4 months for those with no extracranial disease and 2.4 months for those with extracranial disease. Other variables tested (sex, histological tumor type, previous resection, location of metastases, treatment modality, and tumor status) did not influence outcome. CONCLUSIONS: The absence of extracranial disease, a KPS score greater than or equal to 70, and fewer number of metastases were shown to be significant predictors of longer survival. Stereotactic radiosurgery appears to be a reasonable therapeutic option in patients with up to three lesions when their KPS score is greater than or equal to 70, regardless of extracranial disease status. In those with four or more metastases, however, SRS should be limited to those with no extracranial disease.

Adult↗
PubMed1999

Single dose versus fractionated stereotactic radiotherapy for recurrent high-grade gliomas.

PURPOSE: To evaluate the efficacy of stereotactic radiotherapy (SRT) in patients with recurrent high-grade gliomas by comparing two different treatment regimens, single dose or fractionated radiotherapy. METHODS AND MATERIALS: Between April 1991 and January 1998, 71 patients with recurrent high-grade gliomas were treated with SRT. Forty-six patients (65%) were treated with single dose radiosurgery (SRS) and 25 patients (35 %) with fractionated stereotactic radiotherapy (FSRT). For the SRS group, the median radiosurgical dose of 17 Gy was delivered to the median of 50% isodose surface (IDS) encompassing the target. For the FSRT group, the median dose of 37.5 Gy in 15 fractions was delivered to the median of 85% IDS. RESULTS: Actuarial median survival time was 11 months for the SRS group and 12 months for the FSRT group (p = 0.3, log-rank test). Variables predicting longer survival were younger age (p = 0.006), lower grade (p = 0.0006), higher Karnofsky Performance Scale (KPS) (p = 0.0005), and smaller tumor volume (p = 0.02). Patients in the SRS group had more favorable prognostic factors, with median age of 48 years, KPS of 70, and tumor volume of 10 ml versus median age of 53 years, KPS of 60, and tumor volume of 25 ml in the FSRT group. Late complications developed in 14 patients in the SRS group and 2 patients in the FSRT group (p<0.05). CONCLUSION: Given that FSRT patients had comparable survival to SRS patients, despite having poorer pretreatment prognostic factors and a lower risk of late complications, FSRT may be a better option for patients with larger tumors or tumors in eloquent structures. Since this is a nonrandomized study, further investigation is needed to confirm this and to determine an optimal dose/fractionation scheme.

Adolescent↗
PubMed1999

Kinetics of mammary clonogenic cells and rat mammary cancer induction by X-rays or fission neutrons.

Following the hormonal treatment of rats with high prolactin levels and glucocorticoid deficiency (Prl+/Glc-) for 48 days (Day +48), total recoverable mammary DNA was increased by more than sevenfold, tritiated thymidine uptake by nearly fourfold, and total mammary clonogens by about fivefold. Irradiation with 4, 40, and 80 cGy X-rays on Day +48 increased total mammary carcinomas per rat-day-at-risk linearly with dose, and 40 and 80 cGy significantly decreased first carcinoma latency. A dose of 40 cGy X-rays before hormone treatment (Day -1) yielded tumor latencies and frequencies insignificantly different from unirradiated controls but significantly different from those when the dose was given on Day +48. Total carcinomas per rat-day-at-risk were fitted better by a function of dose to the power 0.4 than by a linear function after exposure to 1, 10. and 20 cGy fission neutrons, and 10 and 20 cGy significantly shortened the time to appearance of the first cancer. In contrast to results with X-rays, 10 cGy neutrons on Day -1 yielded tumor frequencies and latencies insignificantly different from 10 cGy neutrons on Day +48. The carcinogenic action of X-rays, but not of neutrons, was thus influenced by total clonogen numbers and/or proliferation rates.

Animals↗
PubMed1998

Patient selection criteria for the treatment of brain metastases with stereotactic radiosurgery.

In this study we evaluate prognostic factors that predict local-regional control and survival following stereotactic radiosurgery (SRS) in patients with brain metastasis and establish guidelines for patient selection. Our evaluation is based on 73 patients with brain metastasis treated with SRS at the University of Minnesota between March 1991 and November 1995. The ability of stereotactic radiosurgery to improve local control in patients with brain metastases is confirmed in our study in which only 6 of 62 patients failed locally after SRS, with an actuarial local progression-free survival of 80% at 2 years. Variables that predicted worse prognosis were larger tumor size (p = 0.05) for local progression-free survival and multiplicity of metastasis (p = 0.03) and infratentorial location of metastases (p = 0.006) for regional progression-free survival. Absence of extracranial disease, KPS > or = 70, and single intracranial metastasis were significant predictors of longer survival. Patients who fulfill all three criteria will survive longer after SRS (MS = 17.7 months) and will most likely benefit from the increase local control in the brain achieved by SRS. Survival in patients who do not meet any of these criteria is very poor (MS = 1.5 months), and these patients are less likely to benefit from this treatment. Careful selection of patients for SRS is warranted.

Adult↗
PubMed1998

Calculation of depth dose and dose per monitor unit for irregularly shaped electron fields.

A new dosimetric quantity, the lateral build-up ratio (LBR), has been introduced to calculate depth dose distribution for any shaped field. Factors to account for change in incident fluence with collimation are applied separately. The LBR data for a small circular field are used to extract radial spread of the pencil beam, sigma(r), as a function of depth and energy. By using the relationship between LBR, sigma(r), energy and depth, a formalism is developed to calculate dose per monitor unit for any shaped field. Criteria for lateral scatter equilibrium are also developed which are useful in clinical dosimetry.

Algorithms↗
PubMed1997

Cost-benefit analysis of 3D conformal radiation therapy.

BACKGROUND: The potential of 3D conformal radiation therapy to improve the efficacy of radiotherapy is one of the most important technical advances in recent years. The potential benefit of improved local control from dose escalation must be weighed against the potential cost of increased complications to normal tissue. METHOD AND RESULTS: We evaluated the cost-benefit of 3D conformal radiation therapy in terms of the benefit to tumor cure weighed against the cost of complications to normal tissue. Assessment of current data shows that problems remain in adequately defining variables that contribute to both the tumor cure probability (benefit) and normal tissue complication probability (cost). For tumor cure probability, identifying the dose escalation needed for cure for the most tumor sites as well as precisely defining tumor volume remain problematic. For normal tissue complication probability, inadequate clinical data on toxicity to normal tissue for different tumor sites continue to make it difficult to use methods that estimate complications, such as dose-volume histograms as proposed by Lyman, to the clinical setting. CONCLUSION: 3D conformal radiation therapy is a promising new technology that may substantially improve the efficacy of radiation therapy. More clinical research, however, is needed to recognize the costs and benefits of this new technology: 1. Tumor control probability: More information is needed on the accurate definition of the target volume as well as on the amount of radiation necessary to cure different tumor sites. 2. Normal tissue complication probability: Methods for determining toxicity to normal tissue are needed. Current calculations based on various models are insufficient.

Cost-Benefit Analysis↗
PubMed1997

Blocked field effects on collimator scatter factors.

In routine dosimetry we assume separability of the collimator (Sc) and phantom (Sp) scatter components that together comprise the total scatter factor (Sc,p). In practice, the addition of blocking also affects the photon fluence attributable to the treatment head and flattening filter in a complicated way. The reduced aperture blocks out some of the head scatter contribution, while the block and tray add back secondary scatter. In the following we present techniques for directly measuring the aperture effect on Sc in air or in a full-scatter phantom. The change in Sc is found to be a scaleable quantity that can be modelled as a simple linear fit to the ratio of projected open-to-blocked equivalent square fields. Measurements have been made for 6, 18 and 24 MV photon beams on one Varian 2500 and two Varian 2100c accelerators. Results indicate a progressive loss of collimator scatter contribution with increased field blocking that is amplified with increasing energy. Block and tray scatter only contribute significantly to Sc for large fields and treatment distances of 80 cm or less. Application of these corrections in monitor unit calculations is presented.

Least-Squares Analysis↗
PubMed1996

DP-2, a heterodimeric partner of E2F: identification and characterization of DP-2 proteins expressed in vivo.

E2F is a heterodimeric transcription factor that regulates the expression of genes at the G1/S boundary and is composed of two related but distinct families of proteins, E2F and DP. E2F/DP heterodimers form complexes with the retinoblastoma (Rb) protein, the Rb-related proteins p107 and p130, and cyclins/cdks in a cell cycle-dependent fashion in vivo. E2F is encoded by at least five closely related genes, E2F-1 through -5. Here we report studies of DP-2, the second member of the DP family of genes. Our results indicate that (i) DP-2 encodes at least five distinct mRNAs, (ii) a site of alternative splicing occurs within the 5' untranslated region of DP-2 mRNA, (iii) at least three DP-2-related proteins (of 55, 48, and 43 kDa) are expressed in vivo, (iv) each of these proteins is phosphorylated, and (v) one DP-2 protein (43 kDa) carries a truncated amino terminus. Our data also strongly suggest that the 55-kDa DP-2-related protein is a novel DP-2 isoform that results from alternative splicing. Thus, we conclude that DP-2 encodes a set of structurally, and perhaps functionally, distinct proteins in vivo.

Alternative Splicing↗
PubMed1995

Three-dimensional conformal pancreas treatment: comparison of four- to six-field techniques.

PURPOSE: We compare practical conformal treatment approaches to pancreatic cancer using 6 and 18 MV photons and contrast those approaches against standard techniques. METHODS AND MATERIALS: A four-field conformal technique for treating pancreas cancer has been developed using nonopposed 18 MV photons. This approach has been extended to 6 MV photon application by the addition of one to two fields. These techniques have been optimized to increase sparing of normal liver and bowel, compared with opposed-field methods, to improve patient tolerance of high doses. In this study we compare these techniques in a simulated tumor model in a cylindrical phantom. Dose-volume analysis is used to quantify differences between the conformal, nonopposed techniques with conformal, opposed field methods. This model is also used to evaluate the effect of 1-2 cm setup errors on dose-volume coverage. RESULTS: Dose-volume analysis demonstrates that five-to-six field conformal treatments using 6 MV photons provides similar or better dose coverage and normal tissue sparing characteristics as an optimized 18 MV, four-field approach when 1-2 cm margins are included for setup uncertainty. All approaches using nonopposed beam geometry provide significant reduction in the volume of tissue encompassed by the 30-50% isodose surfaces, as compared with four-field box techniques. CONCLUSIONS: Three-dimensional (3D) conformal treatments can be designed that significantly improve dose-volume characteristics over conventional treatment designs without costing unacceptable amounts of machine time. Further, deep intraabdominal sites can be adequately accessed and treated on intermediate energy machines with a relatively moderate increase in machine time.

Humans↗
PubMed1995

Deconvolution of detector size effect for small field measurement.

Parametrization of the small fields employed in stereotactic applications is a painstaking process involving extensive film dosimetry to achieve acceptable beam edge definition. Use of cylindrical or spherical detectors for profile measurements would simplify data acquisition but add a volume averaging artifact to beam edge definition. We demonstrate a simple approach to unfolding the chamber size artifact from measured small beam profiles using typical cylindrical chambers. In comparison with film measurements we have found good agreement when the detector response function is deconvoluted from the measured profiles, although the amount of correction needed is fairly minimal for the detectors studied.

Film Dosimetry↗
PubMed1993

Sp-1 binds promoter elements regulated by the RB protein and Sp-1-mediated transcription is stimulated by RB coexpression.

The retinoblastoma (RB) protein is implicated in transcriptional regulation of at least five cellular genes, including c-fos, c-myc, and transforming growth factor beta 1. Cotransfection of RB and truncated promoter constructs has defined a discrete element (retinoblastoma control element; RCE) within the promoters of each of these genes as being necessary for RB-mediated transcription control. Previously, we have shown that RCEs form protein-DNA complexes in vitro with three heretofore unidentified nuclear proteins and mutation of their DNA-binding site within the c-fos RCE results in an abrogation of RCE-dependent transcription in vivo. Here, we demonstrate that one of the nuclear proteins that binds the c-fos, c-myc, and transforming growth factor beta 1 RCEs in vitro is Sp-1 and that Sp-1 stimulates RCE-dependent transcription in vivo. Moreover, we show that Sp-1-mediated transcription is stimulated by the transient coexpression of RB protein. We conclude from these observations that RB may regulate transcription in part by virtue of its ability to functionally interact with Sp-1.

3T3 Cells↗
PubMed1991

The dose distribution surrounding 192Ir and 137Cs seed sources.

Dose distributions in water have been measured using LiF thermoluminescent dosimeters for 192Ir seed sources with stainless steel and with platinum encapsulation to determine the effect of differing encapsulation. The dose distribution has also been measured for a 137Cs seed source. In addition, dose distributions surrounding these sources have been calculated using the EGS4 Monte Carlo code and have been compared to the measured data. The two methods are in good agreement for all three sources. Tables are given which describe the dose distribution surrounding each source as a function of distance and angle. In addition, specific dose constants have been determined from results of Monte Carlo simulation. This work has confirmed the utility of the EGS4 Monte Carlo code in modelling 192Ir and 137Cs seed sources to obtain brachytherapy dose distributions.

Brachytherapy↗
PubMed1991

Influence of detector size in photon beam profile measurements.

Correction is necessary to account for the detector size in clinical dosimetry of photon and electron beams. This correction is due to the absorbed dose gradient present in a finite-size detector. Further corrections are necessary when the detector and phantom materials are not the same. These corrections are due to the perturbation in the charged-particle fluence. Generally these corrections are applied to measurements along the central axis of the beam. Cross beam profile measurements, however, are not usually corrected for detector size. The ionization profile is also usually assumed to be equivalent to the absorbed dose profile. We have corrected the ionization chamber size effect by two approaches: extrapolation of measurements to zero detector size and deconvolution of measurements using a simple model for the detector response function. We have measured absorbed dose profiles to water using a small water-equivalent plastic scintillation detector. Film profile measurements were also studied. The ionization profile corrected for detector size and absorbed dose profile were not equal, probably due to loss of charged-particle equilibrium in the beam edges. For ionization chamber measurements, knowledge of the charged-particle spectrum is needed to convert ionization to absorbed dose to water. This is not necessary for relative absorbed dose measurements under charged-particle equilibrium. Film has been shown to be a straightforward and reliable method for cross beam profile measurements.

Film Dosimetry↗