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J R Yarnold

Publications and source records attributed to J R Yarnold.

At least 19 recordsLinked to original sources
PubMed2002

Dose-position and dose-volume histogram analysis of standard wedged and intensity modulated treatments in breast radiotherapy.

The aim of this work was to evaluate the positional distribution of dose in a concise manner and to analyse dose-histogram results in tangential breast radiotherapy in 300 patients, randomized to standard wedged or intensity modulated radiotherapy (IMRT), for future correlation with clinical outcome data. A simple method for analysing the dose-position relationship in the treatment volume was used to compare the spatial distribution of dose in patients. The breast was divided into equal thirds (upper, middle and lower) and dose was assessed using three dose bands; 95-105%, >105-110% and >110% of the prescription dose. The effect of using IMRT on the dosimetry was assessed from dose-volume histogram data using the following parameters: percentage of the target volume receiving a dose less than 95%, greater than 105%, either less than 95% or greater than 105% of that prescribed; the mean dose; and the maximum dose. Doses greater than 105% were predominantly in the upper and lower regions of the breast in the standard wedged treatment. 96% of these patients received doses greater than 105% in the upper region of the breast and 70% received doses greater than 105% in the lower breast. Only 4% of patients allocated IMRT received doses greater than 105% in either region. Analysis of dose-volume histogram data showed that IMRT reduced the volume receiving a dose greater than 105% by a mean of 10.7% (p= or <0.001); the mean change in the volume receiving a dose less than 95% was 0.2% (p=0.63). Average mean plan dose was 101.6% for standard treatment and 99.6% for IMRT (p<0.001 for each compared with 100.0% ideal). The mean value of maximum dose was reduced from 111% to 106% in the group of patients randomized to IMRT. A simple method for describing the relationship between dose and position in the breast, which is helpful for the effective correlation of dosimetry and clinical effects, is reported. Further, application of IMRT to the tangential field irradiation of the breast has been demonstrated to reduce high dose regions in both volume and dose level without compromising either minimum dose coverage or mean dose delivered to the breast.

Breast Neoplasms↗
PubMed2001

Double-blind randomized phase II study of hyperbaric oxygen in patients with radiation-induced brachial plexopathy.

BACKGROUND: Radiation-induced brachial plexopathy (RIBP) is an untreatable complication of curative radiotherapy for early breast cancer, characterized by chronic neuropathic pain and limb paralysis. Hyperbaric oxygen (HBO2) therapy is known to promote healing of tissue rendered ischaemic by radiotherapy, but is untested in RIBP. METHODS: Thirty four eligible research volunteers suffering from RIBP were randomized to HBO2 or control group. The HBO2 group breathed 100% oxygen for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The control group accompanied the HBO2 group and breathed a gas mixture equivalent to breathing 100% oxygen at surface pressure. All volunteers and investigators, except the operators of the hyperbaric chamber and the trial statistician, were blind to treatment assignments. The warm sensory threshold, which measures the function of small sensory fibres, was selected as the primary endpoint. FINDINGS: Pre-treatment neurophysiological tests were grossly abnormal in the affected hand compared to the unaffected hand in both HBO2 and control groups, as expected, but no statistically significant differences were noted in either group at any time up to 12 months post-treatment. However, normalization of the warm sensory threshold in two of the HBO2 group was reliably recorded. Two cases with marked chronic arm lymphoedema reported major and persistent improvements in arm volume for at least 12 months after treatment with HBO2. IINTERPRETATION: There is no reliable evidence to support the hypothesis that HBO2 therapy slows or reverses RIBP in a substantial proportion of affected individuals, although improvements in warm sensory threshold offer some suggestion of therapeutic effect. Improvement in long-standing arm lymphoedema was not anticipated, and justifies further investigation.

Action Potentials↗
PubMed2000

Effect of local radiotherapy for bone pain on urinary markers of osteoclast activity.

Urinary markers of bone resorption, pyridinoline and deoxypyridinoline were measured before and at 4 weeks after radiotherapy for metastatic bone pain. An association was shown between relief of metastatic skeletal pain by radiotherapy and low marker concentrations before and after treatment, lending support to the hypothesis that relief of metastatic bone pain by radiotherapy relates to an effect on bone, rather than tumour physiology.

Amino Acids↗
PubMed2000

Evaluation of compensation in breast radiotherapy: a planning study using multiple static fields.

PURPOSE: A method that uses electronic portal imaging to design intensity-modulated beams for compensation in breast radiotherapy was implemented using multiple static fields in a planning study. We present the results of the study to verify the algorithm, and to assess improvements to the dosimetry. METHODS AND MATERIALS: Fourteen patients were imaged with computed tomography (CT) and on a treatment unit using an electronic portal imager. The portal imaging data were used to design intensity-modulated beams to give an ideal dose distribution in the breast. These beams were implemented as multiple static fields added to standard wedged tangential fields. Planning of these treatments was performed on a commercial treatment planning system (Target 2, IGE Medical Systems, Slough, U.K.) using the CT data for each patient. Dose-volume histogram (DVH) analysis of the plans with and without multileaf collimator (MLC) compensation was carried out. This work has been used as the basis for a randomized clinical trial investigating whether improvements in dosimetry are correlated with the reduction of long-term side effects from breast radiotherapy. RESULTS: The planning analysis showed a mean increase in target volume receiving 95-105% of prescribed dose of 7.5% (range -0.8% to 15.9%) when additional MLC compensation was applied. There was no change to the minimum dose for all 14 patient data sets. The change in the volume of breast tissue receiving over 105% of prescribed dose, when applying MLC compensation, was between -1.4% and 11.9%, with positive numbers indicating an improvement. These effects showed a correlation with breast size; the larger the breast the greater the amount of improvement. CONCLUSIONS: The method for designing compensation for breast treatments using an electronic portal imager has been verified using planning on CT data for 14 patients. An improvement was seen in planning when applying MLC compensation and this effect was greater the larger the breast size.

Algorithms↗
PubMed2000

The delivery of intensity modulated radiotherapy to the breast using multiple static fields.

BACKGROUND AND PURPOSE: To develop a method of using a multileaf collimator (MLC) to deliver intensity modulated radiotherapy (IMRT) for tangential breast fields, using an MLC to deliver a set of multiple static fields (MSFs). MATERIALS AND METHODS: An electronic portal imaging device (EPID) is used to obtain thickness maps of medial and lateral tangential breast fields. From these IMRT deliveries are designed to minimize the volume of breast above 105% of prescribed dose. The deliveries are universally-wedged beams augmented with a set of low dose shaped irradiations. Dosimetric and planning QA of this method has been compared with the standard, wedged treatment and the corresponding treatment using physical compensators. Several options for delivering the MSF treatment are presented. RESULTS: The MSF technique was found to be superior to the standard technique (P value=0.002) and comparable with the compensated technique. Both IMRT methods reduced the volume of breast above 105% dose from a mean value of 12.0% of the total breast volume to approximately 2.8% of the total breast volume. CONCLUSIONS: This MSF method may be used to reduce the high dose volume in tangential breast irradiation significantly. This may have consequences for long-term side effects, particularly cosmesis.

Breast Neoplasms↗
PubMed2000

Increased collagen production in fibroblasts cultured from irradiated skin and effect of TGF beta(1)- clinical study.

Fibrosis in normal tissues is a common and dose-limiting late complication of radiotherapy at many cancer sites, but its pathogenesis is poorly understood. We undertook a controlled study of the effect of irradiation on the collagen production of fibroblasts cultured from skin biopsies taken from patients undergoing radiotherapy treatment. Eight weeks after a single 8 Gy fraction using 300 kV X-rays, five patients treated at the Royal Marsden Hospital underwent biopsy of the irradiated site and of the contralateral, unirradiated body site. Fibroblasts from irradiated and control, unirradiated sites were cultured in vitro, and collagen production rates were measured during a 48-hour incubation under standardized conditions and in the presence and absence of transforming growth factor beta(1)(TGF beta(1)), 1 ng/ml, using HPLC. Collagen production was elevated in cells cultured from irradiated skin; median collagen production rates 61.16 pmoles hydroxyproline/10(5)cells/hour in irradiated cells, 39.78 pmoles hydroxyproline/10(5)cells/hour in unirradiated cells, P = 0.016 (Mann-Whitney U-test). In fibroblasts from unirradiated sites, collagen production rates were increased by the addition of TGF beta(1); however, in three of the cell lines cultured from irradiated sites this effect of TGF beta(1)on collagen production was not observed.

Aged↗
PubMed1999

Lymphatic relapse in women with early breast cancer: a difficult management problem.

The aim of this study was to review the ability to control symptoms of regional lymphatic relapse in women with early breast cancer. A retrospective study was made of 759 consecutive women presenting with stage 1 or 2 breast cancer treated by breast conserving surgery and radiotherapy between June 1984 and December 1994, 291 (38.3%) of whom were managed by a policy of observation on the lymphatic pathways. Patterns of lymphatic relapse, relapse management and morbidity caused by recurrent malignancy were reviewed from the case notes. The overall rate of relapse in the ipsilateral axilla and/or supraclavicular fossa was 76/759 (10%) at any time prior to death or last follow-up. 34 of 65 patients who relapsed in the axilla did so despite prior axillary surgery and/or radiotherapy. 41 of 76 patients with regional recurrence presented with symptoms, including lymphoedema, arm pain or sensory motor changes. These symptoms were poorly controlled by palliative surgery, radiotherapy or systemic therapy in 23 cases, including 12 who progressed to arm paralysis. Symptomatic control of patients with regional lymphatic relapse can be very difficult, even in women under regular surveillance in a multidisciplinary breast cancer clinic.

Adult↗
PubMed1999

A study testing the routine use of ultrasound measurements when selecting the electron energy for breast boost radiotherapy.

The determination of the depth of the tumour bed within the breast requiring an electron therapy boost dose is generally judged clinically and can be inconsistent between individual radiotherapists. High frequency ultrasound provides a reproducible, safe and quick method of measuring this depth. In order to improve current working practice at the Royal Marsden NHS Trust the routine use of ultrasound when planning breast boost radiotherapy was established. Fifty-three early stage postoperative breast cancer patients had both clinical and ultrasound assessments of boost depth performed. These measurements were converted into electron energy and compared. Measurements ranged from 0.8 cm to 4.9 cm and electron energy from 4 MeV to 15 MeV. As a direct result of the ultrasound measurements taken, 60% of patients had their electron energy changed from that chosen by the clinically assessed measurement. Overall, the energy was as likely to be increased as decreased. Breast size did not influence the need for change but patients with small breasts never required an increase in the energy from that chosen clinically. It was concluded that the use of ultrasound, once integrated into the planning process, can improve accuracy when selecting electron energy for patients receiving breast boost irradiation.

Breast Neoplasms↗
PubMed1998

Practical implementation of compensators in breast radiotherapy.

BACKGROUND AND PURPOSE: A method of using electronic portal imaging to design compensators for tangential breast irradiation has been developed. We describe how this has been implemented. MATERIALS AND METHODS: The compensator design method generates wedged and unwedged beam weights, in conjunction with templates for multiple lead-sheet compensators and pseudo-CT outlines. The latter describe the breast and lung profiles in a set of transverse slices. The layers of the compensator and pseudo-CT outlines are transferred to a treatment planning system for verification. The accuracy of the planning system for the high transmission blocks used to describe the compensators has been verified using a plotting tank system. Dose volume histogram data and transaxial and sagittal plan slices have been compared for both standard and compensated treatments for a sample set of five patients. RESULTS: The planning system predicted the dose at depths of 1.5 and 5 cm to within 2% for the compensators tested. The biggest source of discrepancy was a consequence of the planning system requiring blocks to have integer percentage transmission. For all patients studied, the compensated treatment resulted in a significant reduction in the percentage volume outside the 95-105% dose, with an average reduction of 10.2%. The percentage volume outside the 95-107% dose was also reduced by typically 3.4%. The implementation was found to yield a convenient automatic method of designing compensators using electronic portal imaging and verifying the results using a planning system. CONCLUSIONS: These results indicate that this method of implementation can be used in practice. The dosimetric accuracy of the treatment planning system is limited by the requirement that blocks should be of integer transmission, but this effect is small.

Breast Neoplasms↗
PubMed1998

The effectiveness of the routine clinic visit in the follow-up of breast cancer patients: analysis of a defined patient cohort.

The study aimed to identify the proportion of patients with relapse or a contralateral breast tumour who are diagnosed as a consequence of regular follow-up in a specialist breast clinic after breast conserving surgery and radiotherapy for early breast cancer. A retrospective review was undertaken of 490 consecutive patients entered into a randomized clinical trial of radiotherapy fractionation at a single institution. As part of the trial, patients were reviewed in a multidisciplinary breast clinic 3-monthly for the first 3 years, 6-monthly between 3 and 5 years and annually thereafter, with biennial mammography. For this study, information was retrieved from hospital records to ascertain: (a) whether patients were symptomatic at the time of relapse or contralateral breast tumour; and (b) whether they presented at a scheduled appointment or brought their appointment dates forward. The subsequent management of patients with relapse was reviewed to determine whether or not this may have been influenced favourably by a policy of regular follow-up. Twenty-one (44%) of the 48 patients with locoregional relapse were asymptomatic. Of these, 17 were detected by clinical examination (that is, directly as a result of a routine clinic attendance), while four were detected by routine mammography. Ten of the 17 patients diagnosed by clinical examination had successful surgery for locoregional relapse and all have remained disease free. Five of 17 developed distant metastases within 6 months and two others had skin nodules on the breast excised. Only three of the 67 patients with distant relapses were asymptomatic. Two of the 11 patients with contralateral breast tumours were asymptomatic and were diagnosed on routine mammography. The benefits and cost-effectiveness of less rigid approaches to follow-up of breast cancer patients needs to be evaluated in large prospective randomized trials.

Adult↗
PubMed1998

Comparison between pulsed-field gel electrophoresis and the comet assay as predictive assays for radiosensitivity in fibroblasts.

The radiosensitivity of skin fibroblasts derived from patients as measured in vitro by a clonogenic survival assay appears to correlate with the risk of developing severe late reactions to radiation. Unfortunately, these assays are clinically impractical as a predictive test for radiosensitivity. The purpose of this study was to assess the utility of two possible surrogate assays for radiosensitivity, pulsed-field gel electrophoresis (PFGE) and single-cell gel electrophoresis (comet assay), both of which can be used to measure DNA double-strand breaks. Twenty-three nontransformed human fibroblast cell lines exhibiting a range of radiosensitivities were studied with both of these assays. The results were correlated with measurements of radiosensitivity obtained as part of a larger study examining the correlation between cellular radiosensitivity and clinical response. [2-(14)C]Thymidine-labeled confluent cultures were irradiated at 1.0 Gy/min with doses of 0 to 150 Gy. After allowing 4 h for repair at 37 degrees C, cells were trypsinized and aliquots were used for preparing slides for the comet assay. After neutral lysis and electrophoresis, the slides were stained with ethidium bromide and 50 comet moments were measured for each dose. The remainder of the cells were formed into agarose plugs and, after neutral lysis, were subjected to PFGE. The fraction of activity released (FAR) from the well was measured by scintillation counting of appropriate segments of each gel lane. Cellular radiosensitivity was measured with a standard clonogenic assay at a low dose rate of 1.2 cGy/min, and the dose that resulted in a surviving fraction of 0.01 (D0.01) was calculated. The slope of the plot of comet moment as a function of dose for each cell line did not correlate with D0.01 (R = 0.36, P > 0.1). In contrast, the slope of the FAR as a function of dose had a weak inverse correlation with D0.01 (R = 0.43 and P = 0.05) such that the more radiosensitive cell lines exhibited a steeper dose response for FAR. Although the correlation between the slope of the dose response for FAR and D0.01 was weak, refinement of the PFGE technique may provide a potentially useful predictive assay for radiosensitivity.

Breast↗
PubMed1997

Acute toxicity in pelvic radiotherapy; a randomised trial of conformal versus conventional treatment.

BACKGROUND: A prospective, randomized clinical trial to assess the effect of reducing the volume of irradiated normal tissue on acute reactions in pelvic radiotherapy accured 266 evaluable patients between 1988 and 1993. PURPOSE: This is the definitive analysis to assess the differences between the conformal and conventional arms of the trial. MATERIALS AND METHODS: In both arms, patients were treated with 6 MV X-rays using a 3-field technique (in all but 5 cases) consisting of an anterior and two wedged lateral or posterior oblique fields; in the conventional arm, rectangular fields were employed, whereas in the conformal arm, the fields were shaped with customized blocks drawn according to the beam's-eye-view of the target volume. The most common dosage was 64 Gy in 2-Gy fractions 5 times a week, although a subgroup (of ca. bladder patients) were treated with 30-36 Gy in once-a-week 6 Gy fractions. Each patients completed a comprehensive acute toxicity scoring questionnaire concentrating on bowel and bladder problems, tiredness and nausea, before the start of treatment, weekly during and for 3 weeks after the end of treatment and then monthly for a further 2 months. compliance was excellent. RESULTS: There were no differences between the patients in the two arms with respect to age, gender, tumour type (52% prostate, 41% bladder, 5% rectum, 2% other) fractionation/dosage, anterior field size, weight, or baseline symptoms. Substantial differences in normal-tissue volumes (rectum, bladder, etc.) were achieved: median high-dose volume (HDV) of 689 cm3 for the conformal technique versus 792 cm3 for the conventional. A clear pattern of an increase in symptoms during RT, followed by a decrease after RT, was observed for the patient group as a whole. However, a very extensive analysis has not revealed any (statistically) significant differences between the two arms in level of symptoms, nor in medication prescribed. The disparity between our findings and those of other, non-randomized studies is discussed. CONCLUSIONS: The data on late effects must be collected and analyzed before any definite conclusions can be drawn on the benefits of conformal therapy in the pelvis.

Aged↗
PubMed1997

Dosimetric evaluation of compensation in radiotherapy of the breast: MLC intensity modulation and physical compensators.

BACKGROUND AND PURPOSE: Electronic portal images may be used to design the compensation required to maximise dose uniformity in the breast from opposed tangential beams. MATERIALS AND METHODS: Four methods of implementing the desired compensation have been studied: a simple wedge, a physical compensator in conjunction with a wedge; one open field plus four shaped multi-leaf-collimated (MLC) fields, and one wedged field in conjunction with three shaped MLC fields. Evaluation was performed using thermoluminescent dosimeters (TLDs) placed inside a phantom which was designed to mimic the human breast. The measured results are compared with both the prediction of the in-house compensation design software and with the dose predicted by the GE Target II planning system. The implications of each method for the time taken to plan and deliver treatment were analysed. RESULTS: The dose inhomogeneity, as measured at seven points in the central plane was greatest for the simple wedge (root mean square (rms) = 4.5%) compared to an open field plus four shaped MLC fields (rms = 2.2%), a wedged field plus three shaped MLC fields (rms = 3.3%), and the physical compensator (rms = 2.4%). The times required to plan and prepare these treatments varied considerably. The standard wedged treatment required under 15 min; both MLC-based and the physical compensator treatments required approximately 50 min. Differences of treatment delivery times were up to 8 min. CONCLUSIONS: These results indicate that the dose inhomogeneity can be reduced by beam intensity modulation designed using EPIDs.

Breast↗
PubMed1997

Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) and the European Organization for Research and Treatment of Cancer (EORTC)

Prophylactic cranial irradiation (PCI) reduces the risk of cranial metastasis in small cell lung cancer (SCLC), but the magnitude and value of this reduction, the risks of radiation morbidity and whether PCI influences survival are unclear. We conducted a randomised trial in patients with limited-stage SCLC who had had a complete response to induction therapy. Initially, patients were randomised equally to (1) PCI 36 Gy in 18 daily fractions, (2) PCI 24 Gy in 12 fractions and (3) no PCI; subsequently, to increase the rate of accrual, randomisation was to clinicians' choice of PCI regimen versus no PCI (at a 3:2 ratio). The endpoints were appearance of brain metastases, survival, cognitive function, and quality of life (QoL). Three hundred and fourteen patients (194 PCI, 120 No PCI) were randomised. In the revised design, the most commonly used PCI regimens were 30 Gy in 10 fractions and 8 Gy in a single dose. With PCI, there was a large and highly significant reduction in brain metastases (HR = 0.44, 95% CI 0.29-0.67), a significant advantage in brain-metastasis-free survival (HR = 0.75, 95% CI 0.58-0.96) and a non-significant overall survival advantage (HR = 0.86, 95% CI 0.66-1.12). In both groups, there was impairment of cognitive function and QoL before PCI and additional impairment at 6 months and 1 year, but no consistent difference between the two groups and thus no evidence over 1 year of major impairment attributable to PCI. PCI can safely reduce the risk of brain metastases. Further research is needed to define optimal dose and fractionation and to clarify the effect on survival. Patients with SCLC achieving a complete response to induction therapy should be offered PCI.

Adult↗
PubMed1995

Correlation of breast dose heterogeneity with breast size using 3D CT planning and dose-volume histograms.

The aim of this study was to evaluate the effect of breast size on dose heterogeneity. Twenty women underwent a planning CT scan of the thorax. A three-dimensional treatment plan was devised for each patient using a standard technique of isocentric medial and lateral wedged tangential fields. Three-dimensional dose distributions were derived using an equivalent path length (EPL) inhomogeneity correction and cumulative dose-volume histogram (DVH) data calculated for the breast. Analysis of the DVHs for each patient reveals that 0.2-23.8% of the breast received an absorbed dose outside the desired 95-105% of that prescribed at the isocentre. The degree of dose heterogeneity was most strongly correlated with breast volume (r = 0.70, 95% confidence interval (C.I.) 0.37-0.87). There was also a positive correlation for breast dose heterogeneity versus brassière (bra) cup size (Spearman rank correlation rho = 0.62), breast area (r = 0.39, 95% C.I. -0.06-0.71) and chest wall separation (r = 0.31, 95% C.I. -0.15-0.66). We conclude that breast size is an important determinant of dose heterogeneity within the breast.

Anthropometry↗