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P Hoban

Publications and source records attributed to P Hoban.

13 recordsLinked to original sources
PubMed2001

Directional dependence in film dosimetry: radiographic and radiochromic film.

The trend towards conformal, intensity modulated radiotherapy treatments has established the need for a true integrating dosimeter. In traditional radiotherapy, radiographic film dosimetry is commonly used. The accuracy and reproducibility of film optical density as an indicator of dose is influenced by several variables, including the chemical processing conditions. As a result radiochromic film, with all the advantages of radiographic film but without the need for chemical processing, has increased in popularity, although the low-dose sensitivity of radiochromic film does remain a disadvantage for some experiments. Several studies have investigated the reproducibility of radiochromic film results, but none have specifically addressed the well-known directional dependence seen with traditional radiographic film. In this study, the directional dependence of radiographic (Kodak X-omat V) and radiochromic (Gafchromic) films were measured. It was found that both films over responded when exposed parallel to the central axis of the beam as opposed to perpendicular exposure. An attempt is made to explain the reason for the responses of both films in terms of spectral effects and the air gap between the phantom segments. Although radiographic film exposed parallel rather than perpendicular to the central axis of the beam exhibits a measured difference in film response at depth, this over response does not occur when the extent of the film is restricted to a small region at the centre of the phantom (in this case an air gap is not introduced across the phantom). This suggests that it is the air gap rather than the orientation of the film that is the cause of the over response. Furthermore, when film occupies a slice through the entire phantom an over response occurs for both radiographic and radiochromic film, indicating that spectral effects are not the cause.

Film Dosimetry↗
PubMed1999

Accounting for treatment delays when treating highly proliferative tumours.

This study was undertaken to investigate the possibility of increasing the dose per fraction or increasing the number of fractions to account for treatment delays occurring during radiotherapy treatments for highly proliferative tumours. The linear quadratic model with time was used to determine the difference in biological effective dose (BED) for the original schedule and the schedule including a treatment delay. Tables of extra fractions and extra dose per fraction required to account for a number of possible delays have been determined. It has been shown that for tumours with very short potential doubling times it is best to deliver the extra dose as an increase in dose per fraction rather than an increase in the number of fractions, while for tumours with moderately short potential doubling times (above 7 days) the reverse is true. The equivalent uninterrupted schedules, which would have delivered the same effects to the tumour, have also been determined.

Cell Division↗
PubMed1999

Perturbation of radiotherapy beams by radiographic film: measurements and Monte Carlo simulations.

Radiographic film is an established practical tool used in the measurement of the dose distribution for radiotherapy purposes. The accuracy and reproducibility of film optical density as an indicator of dose has been associated with several factors including photon energy, processing conditions and film plane orientation. Few studies have investigated the factors causing variability in film dosimetry, due to the difficulty of separating the individual contributions. The effect that a sheet of radiographic film in a water phantom has on its response to a 6 MV photon and a cobalt-60 teletherapy beam, when orientated perpendicular and parallel to the beam central axis, is reported. Monte Carlo generated spectra were used to calculate collision kerma (Kcoll) for water and film elements. Measured and calculated results indicate a potential over-response at 25 cm depth of the order of 14 +/- 2.4% and 18 +/- 6.0% respectively for 6 MV photons and 15 +/- 3.4% and 32 +/- 4.5% respectively for a cobalt beam. For film exposed parallel as compared to perpendicular to the central axis of the beam, the calculated results suggest an explanation in terms of the predominantly forward directed secondary electrons for the measured difference in film response at depth. It is proposed that the difference in response of the parallel as compared to perpendicular exposed film be due to the predominantly 'upstream' photon interactions giving rise to energy deposition in film. The simulations indicate that the variation with depth of relative energy imparted in film and water elements correlates with the observed variation in film response with depth.

Energy Transfer↗
PubMed1999

Standard effective doses for proliferative tumours.

This study was undertaken to investigate the treatment schedules used clinically for highly proliferative tumours, particularly with reference to the effects of fraction size, fraction number and treatment duration. The linear quadratic model (with time component) is used here to compare non-standard treatment regimens (e.g. accelerated and hyperfractionated schedules), currently the focus of randomized trials, with each other and some common 'standard regimens'. To ensure easy interpretation of results, two parameters known as proliferative standard effective dose one (PSED1) and proliferative standard effective dose two (PSED2) have been calculated for each regimen. Graphs of PSED1 and PSED2 versus potential doubling time (Tp) have been generated for a range of fractionation regimens which are currently under trial in various randomized studies. From these graphs it can be seen that the highly accelerated schedules (such as CHART) only show advantages for tumours with very short potential doubling times. Calculations for most of the schedules considered showed at least equivalent tumour control expected for the trial schedule compared with the control arm used and these values agree quite well with clinical results. These calculations are in good agreement with clinical results available at present. The greater the PSED1 or PSED2 for the schedule considered the greater the tumour control, which can be expected. However, as has been seen with clinical trials, this higher cell kill also results in higher acute effects which have proved too great for some accelerated schedules to continue.

Cell Division↗
PubMed1999

Cytochrome P450 CYP2D6 genotypes: association with hair colour, Breslow thickness and melanocyte stimulating hormone receptor alleles in patients with malignant melanoma.

We previously identified associations between polymorphism in the cytochrome P450 CYP2D6 gene and outcome in several cancers. We have now examined the hypothesis that homozygosity for the mutant alleles, CYP2D6*4 and CYP2D6*3, is associated with susceptibility and outcome in malignant melanoma. Outcome was assessed by Breslow thickness. We first confirmed previous reports that these mutant alleles are associated with increased susceptibility to malignant melanoma. For example, the frequency of homozygosity for CYP2D6*4 was significantly greater (P = 0.006, chi-squared 1 d.f. = 7.4, odds ratio 2.2, 95% confidence interval 1.2, 3.9) in cases (9.1%) than in control individuals (4.3%). The frequency of homozygosity for the mutant alleles was next examined in the malignant melanoma cases grouped on the basis of characteristics associated with malignant melanoma risk. Homozygosity was significantly more common (P = 0.038) in cases with red/blonde hair than in those with brown/black hair. We found no associations between the CYP2D6 genotype and sex, skin type or eye colour. The possible association of CYP2D6 with outcome was assessed by comparing genotype frequencies in patients with tumours of Breslow thickness < 1.5 mm with those whose tumours were > or = 1.5 mm. In patients with red/blonde, but not brown or black hair, homozygosity for CYP2D6*4 was significantly associated with thicker lesions in a multivariate model (P = 0.036). We further examined the association of CYP2D6*4 homozygosity with red/blonde hair by classifying patients on the basis of homo- or heterozygosity for wild-type or val92met, asp294his or asp84glu melanocyte stimulating hormone receptor (MC1R) alleles. None of the nine patients with brown/black hair with the asp294his allele were homozygotes for CYP2D6*4. By contrast, in the patients with red/blonde hair, three of five cases with asp294his were homozygotes for the mutant CYP2D6 allele. The difference in the frequency of CYP2D6*4 homozygotes in the red/blonde cases with wild-type MC1R alleles compared with those with asp294his was significant (exact P = 0.029). No associations between val92his or asp84glu and CYP2D6 alleles were identified.

Cytochrome P-450 CYP2D6↗
PubMed1998

Susceptibility and outcome in oral cancer: preliminary data showing an association with polymorphism in cytochrome P450 CYP2D6.

Members of the cytochrome P450 and glutathione S-transferase supergene families are candidates for susceptibility and outcome in oral squamous cell cancer. We determined GSTM1, GSTM3, GSTT1, CYP1A1 and CYP2D6 genotypes in 100 Caucasian cases and 467 control individuals. The frequency of homozygosity for mutant CYP2D6 alleles was higher in the cases (P = 0.001, OR = 3.2, 95% CI = 1.6-6.5) than control individuals. In the cases, the frequency of homozygosity for mutant alleles was greater and that of homozygosity for wild-type CYP2D6 alleles was lower in those diagnosed at > or = 65 years (P = 0.009) than in those diagnosed at < or = 64 years. The older cases included relatively more women and patients who did not consume tobacco or alcohol. The association of CYP2D6 with outcome was assessed using the Cox's proportional hazards model. The time to first cervical node metastasis was shorter in heterozygotes and homozygotes for mutant CYP2D6 alleles compared with homozygotes for wild-type alleles after correction for age at diagnosis, gender, alcohol and tobacco consumption and tumour differentiation (P = 0.04, hazard ratio 3.6, 95% CI 1.1-12.5). The mechanism for the association of CYP2D6 alleles with susceptibility and outcome is unclear though the data are compatible with the view that homozygosity for mutant alleles confers impaired detoxication of an unknown carcinogen. No associations between GSTM1, GSTM3, GSTT1 or CYP1A1 genotypes and susceptibility or, time to node metastases were identified. We previously showed that CYP2D6 genotypes were not associated with susceptibility to squamous cell cancer in the pharynx or larynx. Therefore, the data presented suggest that susceptibility to squamous cell cancer in the various parts of the upper aerodigestive tract is associated with different genes and allelic variants.

Adult↗
PubMed1997

The gene for the naevoid basal cell carcinoma syndrome acts as a tumour-suppressor gene in medulloblastoma.

Individuals with naevoid basal cell carcinoma (Gorlin) syndrome are at increased risk of developing medulloblastoma in childhood. We have shown that approximately 5% of patients with Gorlin syndrome will develop this complication in the first few years of life, and in addition 10% of patients with medulloblastoma diagnosed at age 2 years or under have Gorlin syndrome. One out of three medulloblastomas occurring in patients with Gorlin syndrome was shown to have lost the wild-type allele on 9q, indicating that the Gorlin locus probably acts as a tumour suppressor in the development of this tumour. We have also confirmed this role in a basal cell carcinoma (BCC) from the same individual. Information from these families would suggest that Gorlin syndrome is more common than previously recognized and may not always be diagnosed on clinical grounds alone even in middle life.

Basal Cell Nevus Syndrome↗
PubMed1995

Alternate splicing produces a novel cyclin D1 transcript.

Using Northern blotting and PCR analysis of cDNA derived from a range of cell lines and tissues, alternate splicing of the cyclin D1 gene (CCND1) mRNA has been demonstrated. The variant transcript shows no splicing at the downstream exon 4 boundary, encoding a protein with an altered carboxy-terminal domain. Investigation of mRNA extracted from mononuclear cells, lung tumour and normal tissue suggests that both transcripts are invariably expressed. However, splicing to produce the two forms of mRNA is modulated, in the heterozygote, by a frequent A/G polymorphism located within the splice donor region of exon 4. Preliminary analysis of patients with resectable non-small cell lung cancer suggests that genotype is associated with shortened event free survival and greater risk of local relapse.

Aged↗
PubMed1995

Accounting for primary electron scatter in x-ray beam convolution calculations.

Fermi-Eyges electron-scattering theory has been incorporated into the primary dose calculation for external x-ray beam radiotherapy using the convolution method. Incorporating scattering theory into the convolution technique accounts for the density distribution between the interaction and deposition sites, whereas conventional convolution methods only consider the average density between these two points. As the lateral spread of electrons ejected from an interaction site depends on the density distribution, the energy deposition (and hence dose distribution) is predicted more accurately if scattering is accounted for. This new method gives depth dose curves which show better agreement with Monte Carlo calculations in a (slab inhomogeneity) lung phantom than a conventional convolution method, especially at high energies and small field sizes where lateral electronic disequilibrium exists at the central axis. For a 5 x 5-cm2 18-MV beam incident on the lung phantom, a reduction in the maximum error between the convolution and Monte Carlo depth dose curves from 5% to 2.5% is obtained when scattering theory is used in the primary dose calculation. Incorporating scattering theory into the convolution calculation increases the computation time of the primary dose by a factor of 3.

Humans↗
PubMed1993

A Monte Carlo technique to establish the water/tissue equivalence of phantom materials.

The quality of phantom materials is crucial for accurate dosimetry in radiotherapy. A wide range of factors such as density, electron density and elemental composition can influence the radiation properties, and hence the absorbed dose, of materials. New materials can be tested by direct measurements which requires considerable time and the availability of relatively large amounts of the material. Alternatively, the dosimetric properties of a proposed phantom material can be compared to those of water or tissue using Monte Carlo calculations. The aim of this study was to evaluate the use of a Monte Carlo technique for the investigation of the water/tissue equivalence of phantom materials. The material used for this investigation was Standard Dosimetry Agarose (SDA) gel, which is useful in MRI dosimetry. Depth doses in gel and water were calculated for mono-energetic electron beams of 6, 12 and 20 MeV, and photon beams of 60 keV and 6 MV. For each radiation quality the depth dose distributions are in close agreement.

Models, Structural↗
PubMed1992

Loss of heterozygosity mapping in Wilms tumor indicates the involvement of three distinct regions and a limited role for nondisjunction or mitotic recombination.

Loss of heterozygosity (LOH) for polymorphic markers is a frequently occurring event in some tumors, reflecting the role of allele loss in the development of these tumors. We have determined LOH in 38 cases of Wilms tumor for the 2 known loci on chromosome arm 11p and for a newly detected locus on chromosome arm 16q. Only 7 of the 38 tumors studied showed reduction to homozygosity of 11p13 markers. In 4 of these tumors, reduced expression of WT1 and WIT1, genes located at 11p13 and implicated in Wilms tumorigenesis, was noted. However, this was also found in 2 of 7 tumors showing LOH exclusively of 11p15 markers and in 15 of the remaining 24 tumors in which there was no LOH for 11p markers. This suggests that events not involving mitotic recombination or chromosome nondisjunction are the most common mechanisms for mutations at the 11p Wilms tumor locus. We also noted that mitotic recombination involving 11p15 loci occurred in addition to reduced expression of the 11p13 locus genes in 2 tumors, suggesting a possible interaction between these 2 loci. In addition, LOH for 16q markers was observed in 6 tumors. In one case this was coincident with reduction of WT1 and WIT1 gene expression, and in 3 other cases it occurred in addition to 11p LOH. This indicates that an additional locus on 16q is likely to be involved in Wilms tumorigenesis.

Adolescent↗
PubMedDate not supplied

Dosimetry of 6-MV x-ray beam penumbra.

The measurement of x-ray beam dose profiles in the penumbral region, using silicon diode, ionization chamber, TLD, and film dosimetry, has been investigated for a 6-MV beam defined by independent collimators. Penumbral width (80%-20%) at dmax, as measured by diode, film, and TLD was found to be 3.6, 3.6, and 3.4 mm, respectively. These results reflect the relative sensitive widths of each of the measurement systems (2.5, 2.0, and 1.0 mm, respectively). An empirical forming function was used to relate the penumbral shape measured with a finite-sized detector to that which would be measured with a point detector, the width of the point detector penumbra calculated from the diode penumbra is 3.4 mm, indicating that the TLD rods are a good approximation to a point detector. An alternative method of determining the width of a point detector penumbra is to extrapolate the penumbral widths obtained using two or more detectors of sensitive width. With this method, using Farmer and RK ionization chambers, a point detector penumbra width of 3.1 mm is obtained. An EGS4 Monte Carlo simulation, where a point source was assumed, gave a penumbral width of 2.8 mm. Negligible differences between the penumbra of beams defined by symmetric and asymmetric collimators was observed.

Biophysical Phenomena↗