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Biomedical subjects

R I Mackay

Publications and source records attributed to R I Mackay.

15 recordsLinked to original sources
PubMed2005

Quantitative analysis of patient-specific dosimetric IMRT verification.

Patient-specific dosimetric verification methods for IMRT treatments are variable, time-consuming and frequently qualitative, preventing evidence-based reduction in the amount of verification performed. This paper addresses some of these issues by applying a quantitative analysis parameter to the dosimetric verification procedure. Film measurements in different planes were acquired for a series of ten IMRT prostate patients, analysed using the quantitative parameter, and compared to determine the most suitable verification plane. Film and ion chamber verification results for 61 patients were analysed to determine long-term accuracy, reproducibility and stability of the planning and delivery system. The reproducibility of the measurement and analysis system was also studied. The results show that verification results are strongly dependent on the plane chosen, with the coronal plane particularly insensitive to delivery error. Unexpectedly, no correlation could be found between the levels of error in different verification planes. Longer term verification results showed consistent patterns which suggest that the amount of patient-specific verification can be safely reduced, provided proper caution is exercised: an evidence-based model for such reduction is proposed. It is concluded that dose/distance to agreement (e.g., 3%/3 mm) should be used as a criterion of acceptability. Quantitative parameters calculated for a given criterion of acceptability should be adopted in conjunction with displays that show where discrepancies occur. Planning and delivery systems which cannot meet the required standards of accuracy, reproducibility and stability to reduce verification will not be accepted by the radiotherapy community.

Film Dosimetry↗
PubMed2005

Intensity-modulated radiotherapy planning from limited anatomical information: is Sim-CT sufficient for planning women with breast cancer receiving intensity-modulated radiotherapy?

AIMS: To investigate intensity-modulated radiotherapy (IMRT) plans for women with carcinoma of the breast, using a small number of Sim-CT slices, thus avoiding changing the patient's position and potential problems with CT capacity. MATERIALS AND METHODS: Ten CT scans of women with breast cancer were obtained for use in the study. IMRT plans based on an open tangent pair and additional top-up segment fields were created using the full CT scan, and represented the gold standard treatment plan for comparison purposes. Five-slice CT simulator scans were artificially created by omitting intermediate slices from the full CT scans. Additionally, the intermediate CT slices were recreated via interpolation of the five slices using a standard interpolation algorithm. IMRT plans were created in the same way as for the full CT scans. To allow a suitable plan comparison to be made, the beam segments and monitor units were transferred to the full CT scans, and the dose distribution calculated. RESULTS: The interpolated five-slice plans showed no significant difference in the volume of tissue receiving dose outside the range 95-105%, compared with the IMRT plans created using the full CT data set (1.3 +/- 2.2%, P = 0.092). In contrast, the discrete slice CT simulator plans increased by 6.3 +/- 5.4%, P = 0.0054, showing a statistically significant difference in the dose distribution produced and a clinically inferior plan. CONCLUSIONS: Plans created using five discrete slice CT scans were inferior to full CT-derived IMRT treatment plans, and are therefore not acceptable for IMRT. However, interpolating five CT simulator slices provides adequate anatomical information to produce comparable IMRT plans to those created by full CT scans of the patient. This allows the introduction of IMRT for this patient group without the need to change treatment position to accommodate CT scanning.

Anatomy, Cross-Sectional↗
PubMed2005

Improving IMRT quality control efficiency using an amorphous silicon electronic portal imager.

An amorphous silicon electronic portal imaging device (EPID) has been investigated to determine its usefulness and efficiency for performing linear accelerator quality control checks specific to step and shoot intensity modulated radiation therapy (IMRT). Several dosimetric parameters were measured using the EPID: dose linearity and segment to segment reproducibility of low dose segments, and delivery accuracy of fractions of monitor units. Results were compared to ion chamber measurements. Low dose beam flatness and symmetry were tested by overlaying low dose beam profiles onto the profile from a stable high-dose exposure and visually checking for differences. Beam flatness and symmetry were also calculated and plotted against dose. Start-up reproducibility was tested by overlaying profiles from twenty successive two monitor unit segments. A method for checking the MLC leaf calibration was also tested, designed to be used on a daily or weekly basis, which consisted of summing the images from a series of matched fields. Daily images were coregistered with, then subtracted from, a reference image. A threshold image showing dose differences corresponding to > 0.5 mm positional errors was generated and the number of pixels with such dose differences used as numerical parameter to which a tolerance can be applied. The EPID was found to be a sensitive relative dosemeter, able to resolve dose differences of 0.01 cGy. However, at low absolute doses a reproducible dosimetric nonlinearity of up to 7% due to image lag/ghosting effects was measured. It was concluded that although the EPID is suitable to measure segment to segment reproducibility and fractional monitor unit delivery accuracy, it is still less useful than an ion chamber as a tool for dosimetric checks. The symmetry/flatness test proved to be an efficient method of checking low dose profiles, much faster than any of the alternative methods. The MLC test was found to be extremely sensitive to sudden changes in MLC calibration but works best with a composite reference image consisting of an average of five successive days' images. When used in this way it proved an effective and efficient daily check of MLC calibration. Overall, the amorphous silicon EPID was found to be a suitable device for IMRT QC although it is not recommended for dosimetric tests. Automatic procedures for low monitor unit profile analysis and MLC leaf positioning yield considerable time-savings over traditional film techniques.

Calibration↗
PubMed2001

The required number of treatment imaging days for an effective off-line correction of systematic errors in conformal radiotherapy of prostate cancer--a radiobiological analysis.

BACKGROUND AND PURPOSE: To use radiobiological modelling to estimate the number of initial days of treatment imaging required to gain most of the benefit from off-line correction of systematic errors in the conformal radiation therapy of prostate cancer. MATERIALS AND METHODS: Treatment plans based on the anatomical information of a representative patient were generated assuming that the patient is treated with a multi leaf collimator (MLC) four-field technique and a total isocentre dose of 72 Gy delivered in 36 daily fractions. Target position variations between fractions were simulated from standard deviations of measured data found in the literature. Off-line correction of systematic errors was assumed to be performed only once based on the measured errors during the initial days of treatment. The tumour control probability (TCP) was calculated using the Webb and Nahum model. RESULTS: Simulation of daily variations in the target position predicted a marked reduction in TCP if the planning target volume (PTV) margin was smaller than 4 mm (TCP decreased by 3.4% for 2 mm margin). The systematic components of target position variations had greater effect on the TCP than the random components. Off-line correction of estimated systematic errors reduced the decrease in TCP due to target daily displacements, nevertheless, the resulting TCP levels for small margins were still less than the TCP level obtained with the use of an adequate PTV margin of approximately 10 mm. The magnitude of gain in TCP expected from the correction depended on the number of treatment imaging days used for the correction and the PTV margin applied. Gains of 2.5% in TCP were estimated from correction of systematic errors performed after 6 initial days of treatment imaging for a 2 mm PTV margin. The effect of various possible magnitudes of systematic and random components on the gain in TCP expected from correction and on the number of imaging days required was also investigated. CONCLUSIONS: Daily variations of target position markedly reduced the TCP if small margins were used. Off-line correction of systematic errors can only partly compensate for these TCP reductions. The adequate number of treatment imaging days required for systematic error correction depends on the magnitude of the random component compared with the systematic component, and on the size of PTV margin used. For random components equal to or smaller than the systematic component, 3 consecutive treatment imaging days are estimated to be sufficient to gain most of the benefit from correction for current clinically used margins (6-10 mm); otherwise more days are required.

Humans↗
PubMed1999

The modelled benefits of individualizing radiotherapy patients' dose using cellular radiosensitivity assays with inherent variability.

OBJECTIVE: To model the increases in local tumour control that may be achieved, without increasing normal tissue complications, by prescribing a patient's dose based on cellular radiosensitivity measured using an assay possessing inherent variability. METHOD: Patient populations with varying radiosensitivity were simulated, based on measured distributions among cancer patients of the surviving fraction of their fibroblasts given a dose of 2 Gy in vitro (SF2). The dose-response curve for complications in the population was assessed using a formula relating SF2 to normal tissue complication probability (NTCP), by summing the data for the individuals. This curve was similar to clinically-derived dose-response curves. The effect of individualizing the patients' doses was explored, based on individual radiosensitivities measured by SF2, so that every patient had the same low (5%) value of NTCP. RESULTS: It was found that a significant gain (up to around 30%) in tumour control probability (TCP) was predicted for the population when the doses were individualized using a predictive assay result strongly correlated with NTCP. A greater gain in TCP was predicted when each of the individuals were assumed to have a higher sensitivity and the distribution of radiosensitivity in the population was widened to compensate. The gain in TCP was less (around 20%) when considering less-sensitive patients and a narrower distribution of radiosensitivities. The effect of assay variability and other factors that could affect the predictive power of the assay was simulated. Assay variability and an imperfect correlation between in vitro cell survival and tissue complications, rapidly increased the NTCP for the population when treated with individualized doses. However the individualized doses could be reduced so that NTCP declined to an acceptable level, but in this case the TCP for the population also declined. For example, when the assay variability was half the true variability in SF2, the gain in TCP was reduced to around 6%. Also, the predicted gains in population TCP were higher if tumour and normal tissue radiosensitivity were assumed to be correlated. In this case, and in the absence of assay variability, increases in population TCP of about 50% and 30% were predicted, depending on the assumed relative sensitivities of the individual patients compared with that of the population average. For practical application, the division of the patient population simply into three groups of high, average and low radiosensitivity was also examined. The three groups were treated with different doses and the NTCP for the population was kept below 5%. Although the gain in population TCP was less than that predicted with the full individualization, considerable gains of up to 20% were still predicted. This method of dividing the population was more resilient to assay variability and other factors that may affect complications in patients. The modelling suggests that small improvements in TCP (5-10%) may still be achievable even if the correlation between SF2 and late complications is lower at around - 0.4 to - 0.6, as reported in some clinical series. CONCLUSION: Modelling based on measured distributions of fibroblast radiosensitivity shows that improvements in tumour control rates may be achievable through the individualization of radiotherapy dose prescriptions of cancer patients, when assay variability is less than about 50% of the true variability in radiosensitivity, and with greater benefits if tumour and normal tissue radiosensitivity are correlated. Tripartite stratification of the population proved to be less sensitive to assay uncertainty, and can provide most of the benefits of the full individualization.

Algorithms↗
PubMed1992

The influence of age, size, pubertal status and renal factors on urinary growth hormone excretion in normal children and adolescents.

Overnight urinary growth hormone (GH) excretion was measured in 528 schoolchildren (aged 4-16 years) whose heights and weights were between the third and 97th centiles. Urinary GH increased significantly with age, reaching a maximum in boys at 15-years-old and in girls at 13-years-old. Peak levels were five and three times higher in boys and girls respectively than in 4-year-olds. Maximum urinary GH excretion was seen at breast stages 3 and 4 in girls and at genital stage 4 in boys followed by a decline in both sexes at stage 5. Boys excreted more GH than girls during prepubertal and pubertal years. During prepubertal years there were fluctuations of urinary excretion of GH with age. Height, weight and pubertal status predicted 31% of the variability of urinary excretion of GH, and urinary excretion of creatinine, albumin and N-acetylglucosaminidase (NAG) predicted 52% of the variability. The importance of establishing sound age and sex-related reference ranges for urinary growth hormone is stressed before application of this test to children with growth disorders.

Adolescent↗
PubMed1979

Down syndrome: prevalence at birth, mortality and survival. A 17-year study.

Analysis of comprehensive records over a period of 15 yr permits calculation of the total prevalence of Down Syndrome in an industrial city. The prevalence at birth is shown to have fallen from 1.70 per 1000 births in the period 1961--65 to 0.84 per 1000 births in 1971--75. The fall in prevalence can be shown to be largely due to a change in distribution of maternal age. An earlier increase in the number of Down Syndrome children is shown to reflect a greatly improved survival in the first 5 yr of life to a continuing level of 81%. The number of Down Syndrome children is unlikely to increase much even with increase of birth rate unless older mothers have further pregnancies. For these reasons the policies of amniocentesis of older women and termination of affected pregnancies will have progressively less effect on the number of affected children if this demographic trend continues. A further effect is that special schools will have a proportionately greater burden as the younger children being admitted have less prospect of development and may be more demanding of staff than Down Syndrome children.

Actuarial Analysis↗
PubMed1979

The epidemiology of severe mental handicap.

Prevalence studies of severe mental handicap in an industrial area in the North West area of the United Kingdom have shown a marked increase between 1961 and 1977, with the hint of a reduction in the most recent years. Further analysis of causes of severe mental handicap shows that the prevalence of Down Syndrome is decreasing, certain causes remain constant in prevalence, and perinatal metabolic causes are shown to be increasing through a period of 15 yr ending in 1975. While improved survival of children influences the total prevalence, high mortality in some conditions makes the analysis of prevalence at birth more significant in considering changes in the pattern of aetiology. These studies are fundamental to the formulation of policies of prevention of severe mental handicap, whether these be social or dependent solely on health care services.

Adolescent↗
PubMed1974

Pertussis agglutinins in vaccinated children: better response with adjuvant.

Children were immunized with a single batch of pertussis vaccine, either adsorbed on aluminium hydroxide or plain. With a primary course of three injections, adsorbed vaccine produced higher titres of pertussis agglutinins in the serum than did plain vaccine. There was no obvious difference in response between those who received the three doses at intervals of 1-2 months, starting at 3-4 months of age, and those in whom the third dose was delayed until about 6 months after the second, but the number of children in each group was small.

Adjuvants, Pharmaceutic↗
PubMed1971

Agglutinin response to pertussis vaccination in the child.

Children were immunized with plain pertussis vaccine made by three manufacturers in 1967. After a primary course of three injections at monthly intervals, starting at 3-4 months of age, the agglutinin response was poor. Even after a "booster" dose, given five months later, not all of the vaccines had stimulated a response to all three pertussis agglutinogens. A further investigation with current vaccines of different kinds administered according to more than one schedule is recommended.

Animals↗