Search PubMed⌕ Search

Biomedical subjects

J R Yarnold

Publications and source records attributed to J R Yarnold.

At least 37 records · Page 2Linked to original sources

Design of compensators for breast radiotherapy using electronic portal imaging.

A novel method of designing intensity modulated beams (IMBs) to achieve compensation in external beam radiotherapy of the breast, without the need for CT scans, is presented. The design method comprises three parts: (1) an electronic portal image is used to generate a map of radiological thickness; (2) this map is then used to obtain an estimate of the breast and lung outline; (3) a TMR-based dose calculation algorithm is then used to determine the optimum beam profile to achieve the best dose distribution. The dose distributions calculated for IMBs were compared with those calculated for the use of simple wedges. The results for two patients studied indicate that the dose inhomogeneity for IMBs is +/- 5%, compared with a value of +/- 10% for a wedged plan. The uncertainty in radiological thickness measurement corresponds to a dosimetric error of +/- 2%. Other errors associated with outline estimation are typically less than 2%, with a largest value of +5% for one of the patients who had a large and highly asymmetrical breast. The results for the two patients studied suggest that the uncertainties in the method are significantly smaller than the improvement in dose uniformity produced.

Algorithms↗

Non-surgical management of early breast cancer in the United Kingdom: the role and practice of radiotherapy. Clinical Audit Sub-committee of the Faculty of Clinical Oncology, Royal College of Radiologists, and the Joint Council for Clinical Oncology.

This paper reports on the delivery of radiotherapy to the primary site and lymphatic pathways in the management of early stage breast cancer. Radiotherapists were clear that their aim of locoregional radiotherapy was to reduce local recurrence. However, variation in policies for delivery were seen: 80% of radiotherapists did not always give radiotherapy routinely following wide local excision as part of breast conserving management; instead they withheld it selectively for a number of reasons. Only 66% routinely used breast boosts. There was a range of indications for giving radiotherapy to the lymphatic pathways; there was also variation in the management of incompletely or marginally excised primary tumours. Most sources of variation in the practice of radiotherapy in the management of women with early stage breast cancer appeared to arise from scientific uncertainty. However, organizational issues influenced many decisions. These scientific uncertainties and organizational issues are best addressed in the context of multidisciplinary breast clinics.

Breast Neoplasms↗

Non-surgical management of early breast cancer in the United Kingdom: radiotherapy fractionation practices. Clinical Audit Sub-committee of the Faculty of Clinical Oncology, Royal College of Radiologists, and the Joint Council for Clinical Oncology.

A national survey of British radiotherapy schedules used in women with early breast cancer was undertaken to document variation in treatment practices and to consider its clinical significance. Although the variation is considerable, the analysis suggests that the majority of schedules in use are very similar in terms of treatment intensity when allowance is made for fraction size and overall time. Half the respondents used one of three dosage schedules, which probably differ very little in terms of late normal-tissue effects and tumour control from a conventional schedule giving 50 Gy in daily 2 Gy fractions. Eighty-two percent of respondents were using schedules that are equivalent to a dose of between 45 Gy and 50 Gy in 2 Gy fractions. The study suggests that the protocols in use by a minority of respondents may be unduly conservative or aggressive, and it leads to the proposal that oncologists should set up trials comparing commonly used schedules as a matter of urgency.

Breast↗

Estimating the volume of lung irradiated during tangential breast irradiation using the central lung distance.

The aim of this study was to evaluate the central lung distance (CLD) as a surrogate for the volume of lung irradiated during tangential breast radiotherapy. 20 women underwent a planning computed tomography (CT) scan and three-dimensional (3D) treatment planning for both breasts. The field size was perturbed in a systematic manner to give a number of plans with the CLD increasing from 0 to 30 mm. The volume of lung irradiated was determined directly using dose-volume histograms of the lung and correlated with the known CLD. The results indicate that absolute and percentage lung volumes increase with increasing CLD according to a quadratic relationship which is different for both left and right lungs. It is concluded that while there is no substitute for a 3D plan and a lung dose-volume histogram calculation, CLD may be used as a guide to the volume of lung included within the tangential fields used for breast radiotherapy.

Breast Neoplasms↗

Cellular radiosensitivity and DNA damage in primary human fibroblasts.

PURPOSE: To evaluate the relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts to decide whether the initial or residual DNA damage levels are the more predictive of normal tissue cellular radiosensitivity. METHODS AND MATERIALS: Five primary human nonsyndromic and two primary ataxia telangiectasia fibroblast strains grown in monolayer were studied. Cell survival was assessed by clonogenic assay. Irradiation was given at high dose rate (HDR) 1-2 Gy/min. DNA damage was measured in stationary phase cells and expressed as fraction released from the well by pulsed-field gel electrophoresis (PFGE). For initial damage, cells were embedded in agarose and irradiated at HDR on ice. Residual DNA damage was measured in monolayer by allowing a 4-h repair period after HDR irradiation. RESULTS: Following HDR irradiation, cell survival varied between SF2 0.025 to 0.23. Measurement of initial DNA damage demonstrated linear induction up to 30 Gy, with small differences in the slope of the dose-response curve between strains. No correlation between cell survival and initial damage was found. Residual damage increased linearly up to 80 Gy with a variation in slope by a factor of 3.2. Cell survival correlated with the slope of the dose-response curves for residual damage of the different strains (p = 0.003). CONCLUSION: The relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts of differing radiosensitivity is closest with the amount of DNA damage remaining after repair. If assays of DNA damage are to be used as predictors of normal tissue response to radiation, residual DNA damage provides the most likely correlation with cell survival.

Cell Survival↗

The use of ultrasound to measure breast thickness to select electron energies for breast boost radiotherapy.

Ultrasound has been used in 30 patients to measure breast thickness as a means of selecting the most appropriate electron energy for the boost in breast conservation radiotherapy. When compared with electron energies selected on the basis of clinical examination, the target volume was underdosed in 21/30 patients. A major problem in the placement of an electron boost is the demarcation of the target volume.

Breast↗

The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity.

A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts.

Adult↗

The relationship between cellular radiation sensitivity and tissue response may provide the basis for individualising radiotherapy schedules.

There is a wide variation in normal tissue reactions to radiotherapy and in many situations the severity of these reactions limits radiotherapy dose. Clinical fractionation studies carried out in Gothenburg have demonstrated that a large part of the spectrum of normal tissue reactions is due to differences in individual normal tissue sensitivity. If this variation in normal tissue reactions is due to differences in intrinsic cellular radiosensitivity, it should be possible to predict tissue response based on measurement of cellular sensitivity. Here we report the initial results of a study aimed at establishing whether a direct relationship exists between cellular radiosensitivity and tissue response. Ten fibroblasts strains, including four duplicates, were established from a group of patients in the Gothenburg fractionation trials who had received radiotherapy following mastectomy. Skin doses were measured and both acute and late skin changes were observed following radiotherapy. Right and left parasternal areas were treated with different dose fractionation schedules. Clonogenic assays were used to assess intrinsic cellular radiosensitivity, and all experiments were carried out without prior knowledge of the clinical response, or which strains were duplicates. Irradiation was carried out using 60Co gamma-rays at high dose-rate (HDR) of 1-2 Gy/min and low dose-rate (LDR) of 1 cGy/min. A spectrum of sensitivity was seen, with SF2 values of 0.17-0.28 at HDR and 0.25-0.34 at LDR, and values of D0.01 of 5.07-6.38 Gy at HDR and 6.43-8.12 Gy at LDR. Comparison of the in vitro results with the clinical normal tissue effects shows a correlation between cellular sensitivity and late tissue reactions, which is highly significant with p = 0.02. A correlation between cellular sensitivity and acute effects was noted in the left-sided parasternal fields, but not the right. This is thought to be coincidental, and without biological significance. Our results suggest that cellular sensitivity might form the basis for the development of an assay system capable of predicting late normal tissue effects to curative radiotherapy, which might allow dose escalation in some patients. Increased local control and cure, with unchanged or improved normal tissue complications, could result from such individualised radiotherapy prescriptions.

Breast Neoplasms↗

Invited review: tangential breast irradiation--rationale and methods for improving dosimetry.

In recent years there have been great advances and innovations in all technical aspects of radiotherapy, including three dimensional (3D) computer planning, patient immobilization, radiation delivery and treatment verification. Despite this progress, the technique of tangential breast irradiation has changed little over this period and has not exploited these advances. There is increasing evidence that dose inhomogeneity within the breast is greater than at other anatomical sites, especially in women with large breasts. This paper is a review of the factors contributing to poor dosimetry in the breast, the clinical consequences of an inhomogeneous dose distribution, and how breast dosimetry could be improved by considering each of the stages from planning to accurate treatment delivery. It also highlights the particular problem of women with large breasts who may be more likely to have a poorer cosmetic outcome after a fractionated course of radiotherapy than women with small/medium-sized breasts, and supports the clinical impression that such women are also more likely to have greater dose inhomogeneity when 3D treatment plans are examined. Preliminary data from our current computed tomography (CT) planning study are presented to support these observations.

Breast↗

Prediction of normal-tissue tolerance to radiotherapy from in-vitro cellular radiation sensitivity.

The success of radiotherapy depends on the total radiation dose, which is limited by the tolerance of surrounding normal tissues. Since there is substantial variation among patients in normal-tissue radiosensitivity, we have tested the hypothesis that in-vitro cellular radiosensitivity is correlated with in-vitro normal-tissue responses. We exposed skin fibroblast cell lines from six radiation-treated patients to various doses of radiation and measured the proportions surviving. There was a strong relation between fibroblast sensitivity in vitro and normal-tissue reactions, especially acute effects. Assessment of radiosensitivity could lead to improved tumour cure rates by enabling radiation doses to be tailored to the individual.

Breast Neoplasms↗

Weight gain after primary surgery for breast cancer--effect of tamoxifen.

Changes in body weight have been studied in 92 consecutive patients with primary breast cancer from the time of initial diagnosis and treatment. Sixty patients receiving tamoxifen were compared with 32 controls receiving no hormone treatment. Weight gain was seen in both groups, but was greater in the group receiving tamoxifen. Premenopausal women receiving tamoxifen had greater weight gain than postmenopausal women on tamoxifen therapy.

Adult↗

Selective avoidance of lymphatic radiotherapy in the conservative management of early breast cancer.

In view of the morbidity and potential mortality associated with routine post-operative lymph node radiotherapy in women with early stage breast cancer, an attempt has been made to select patients in whom radiotherapy can be withheld. Three hundred and forty-seven consecutive patients treated wide local excision plus or minus axillary surgery have been evaluated. Only 20% were subsequently given radiotherapy to regional nodes. Relapse in the axilla, the supraclavicular fossa or at both these sites have occurred in 16 patients so far, 12 of whom were successfully treated. Systemic relapse was seen in eight of these patients occurring with one exception before or within 3 months of node relapse. Only four have persisting symptoms as a result of nodal relapse. So far, a policy involving selective lymphatic radiotherapy in women treated for early breast cancer appears justified.

Axilla↗

Cosmetic and functional outcomes of breast conserving treatment for early stage breast cancer. 1. Comparison of patients' ratings, observers' ratings, and objective assessments.

The cosmetic and functional results of breast conserving therapy were evaluated in a sample of 76 patients with early stage breast cancer, treated by wide local excision, axillary dissection and postoperative radiotherapy between 1975 and 1985. A comparison was made between patients' ratings, independent ratings by two observers (an oncology nurse and a radiation oncologist) and objective measurements. In approximately 40% of the cases, moderate to large differences in the appearance of the treated versus the untreated breast were reported by patients and clinical observers alike. When evaluated on an individual level, the observers' ratings showed relatively high inter-rater agreement (kappa = 0.64), but low levels of concordance were found between the patients' and observers' ratings (kappa < 0.10). Approximately half of the patients reported limited arm or shoulder function, generally mild in nature. Compared to the patients', the observers' ratings of arm edema were significantly lower, indicating 20% mild and 5% more severe swelling. Objective measures of cosmesis and function correlated moderately with the observers' and patients' ratings. Both cosmetic and functional results were found to be significantly related to time elapsed since treatment, with patients treated longer ago exhibiting more problems. The cosmetic and functional outcomes were not related to the patients' age. The results suggest that the patients' opinion can provide important additional information in the evaluation of cosmetic and functional results of breast conserving treatment.

Adult↗