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Biomedical subjects

D V Ash

Publications and source records attributed to D V Ash.

At least 37 records · Page 2Linked to original sources
PubMed1991

Interstitial brachytherapy: past-present-future.

This article summarizes and reviews the development of brachytherapy from 1930 to 1990. Its purpose is to highlight the immense contribution made to its underlying science and clinical practice by Dr. Frank Ellis, who has been personally involved with it, in theory and in practice, for that whole half-century. A remarkable achievement in itself, but so much the more when it is seen beside his contributions to other aspects of radiation in the service of man. The early use of solid sources leads on to a discussion of manual afterloading and iridium. This leads on to a quick survey of the development of dosimetry. Thereafter clinical indications are briefly discussed and some published results tabulated. Lastly, some pointers to possible future development and benefits are discussed. Mention is also made of some continuing unresolved problems where new work could help to establish the most appropriate use of brachytherapy.

Brachytherapy↗
PubMed1991

Radiotherapy after conservative surgery for breast cancer: selective use of iridium-192 wire boost to tumour bed in high risk patients.

The results of treatment for 51 patients referred for radiotherapy after local excision of an 'early' breast carcinoma are reviewed. The patients were considered to be at particularly high risk of local recurrence due to the presence of one or more adverse histological features, most commonly microscopic involvement of resection margins. The patients received a course of whole-breast irradiation (40 Gy in 15 fractions over 3 weeks) but instead of following this with a routine photon or electron tumour-bed boost (15 Gy in five fractions) these patients received an iridium-192 wire implant, giving a tumour-bed boost of 25 Gy over approximately 3 days. After a median follow-up of 38 months, five patients have recurred locally within the breast, giving an actuarial breast recurrence-free survival of 87.8% at 8 years. Four patients have died of metastatic breast cancer, none of whom had uncontrolled local disease. Cosmesis was good or excellent in 76% of cases. The presence of microscopic tumour at resection margins or other adverse histological features is not, therefore, necessarily an indication for further surgery, as a good level of local control can still be achieved with radiotherapy providing a relatively high-dose tumour-bed boost is employed using an iridium-192 wire implant.

Adult↗
PubMed1991

Assessing quality of life in patients treated for advanced head and neck cancer.

A pilot study was undertaken to determine which measures of Quality of Life (QL) would be of most use in the follow-up of patients participating in clinical trials of treatments for head and neck cancer. A total of 96 non-randomized patients who had been treated for head and neck cancer either by surgery (three patients), radiotherapy (54 patients), or combined modality therapy (39 patients) completed a detailed questionnaire assessing a wide range of QL parameters. All participating patients were clinically disease-free. It was found that questions relating to quality of speech, ability to eat, levels of energy and activity, and aspects of psychological wellbeing detected the largest effects on QL. The level of QL impairment was consistently greater in those patients treated by surgery plus radiotherapy as compared to those treated by radiotherapy alone. Eleven patients were interviewed in their own homes and the findings generally supported the conclusions drawn from the questionnaire responses. The interviews also demonstrated that impairment of arm movement amongst some surgically treated patients detracted from QL by causing difficulties in performing everyday selfcare and domestic tasks. This study has provided the basis for a QL assessment to be incorporated into a randomized trial of radiotherapy alone versus surgery plus radiotherapy in the treatment of advanced head and neck cancer. The findings suggest that QL impairment is greater for patients who have surgery in addition to radiotherapy as primary treatment but this may be acceptable if a clear survival advantage is demonstrated.

Combined Modality Therapy↗
PubMed1991

In vivo measurement of the optical interaction coefficients of human tumours at 630 nm.

The light distribution within a treatment volume is determined by the source geometry (e.g. superficial or interstitial illumination) and the optical interaction coefficients of the irradiated tissue. We have measured the energy fluence rate at various points within tumours undergoing irradiation with 630 nm light for photodynamic therapy for several source geometries. The relative positions of source and detector fibres were determined using CT scanning techniques. The results of the measurements were then applied to solutions of the diffusion theory which allowed the determination of the absorption coefficient (sigma a = 30.5 +/- 16 m-1), the reduced scattering coefficient (sigma' s = 941 +/- 735 m-1), the effective attenuation coefficient (sigma eff = 261 +/- 49 m-1) and the build-up coefficient which relates surface irradiance to the energy fluence rate at depth (k = 1.6 +/- 0.6). Knowledge of these coefficients allows the transmission of light through tissue to be predicted and hence the optical dosimetry of subsequent treatments to be planned more effectively.

Breast Neoplasms↗
PubMed1990

The response of a rodent fibrosarcoma to superficial/interstitial photochemotherapy, chemotherapy or radiotherapy.

Growth and dose-response curves were established for a subcutaneously implanted isogenic fibrosarcoma in BD9 rats after treatment with photochemotherapy (PCT), using Photofrin II or polyhaematoporphyrin with superficial or interstitial 630 nm light, cyclophosphamide or gamma-irradiation. Tumour response to PCT increased with dose up to 200 J.cm-2 for superficial light or 200 J for interstitial light but no further response occurred after higher light doses. The maximum response after interstitial treatment was significantly greater than after superficial treatment where only a small margin of normal tissue was treated. The incidence of necrosis in the overlying skin was significantly less after interstitial than superficial light suggesting a better therapeutic ratio after interstitial than superficial PCT. Tumour response increased with the diameter of the treatment field after superficial light supporting the possibility of a tumour bed effect associated with PCT. The largest tumour that could be effectively treated with a single optical fibre was 12 mm. The dose-response curves for interstitial PCT and cyclophosphamide were similar but ionizing irradiation produced increasing tumour response throughout the range of doses used (5 to 30 Gy) and the maximum response was greater after radiotherapy than after PCT or chemotherapy suggesting that in this tumour model interstitial PCT is as effective as cyclophosphamide but less effective than radiotherapy.

Animals↗
PubMed1989

The use of simultaneous radiotherapy and 5-flurouracil in patients with inoperable squamous cell lung cancer.

Over a 2-year period, 17 patients with histologically proven squamous cell carcinoma of the bronchus, assessed as inoperable or incurable on surgical or medical grounds, were treated with palliative radiotherapy and a concurrent 120-h infusion of 5-flurouracil, at a dosage of 1 g/day. The treatment was found to be well tolerated with no major toxicity. The degree of palliation and survival obtained was found to be no different to that of a historical matched control group, treated with radiotherapy alone, with median survival in the two groups of 35 weeks and 42 weeks respectively (log rank test P greater than 0.69). We conclude that although a non-toxic treatment regime, no benefit was obtained by the addition of 5-flurouracil to palliative radiotherapy.

Aged↗
PubMed1989

Evaluation of response following irradiation of juvenile angiofibromas.

Ten cases of angiofibroma treated by irradiation are reported. Relief of symptoms occurred by the end of treatment in eight patients. Objective regression was much slower, six having visible disease for greater than 6 months and four for at least 1 year. Only one was symptomatic. Radiological resolution lagged behind clinical improvement and was complete in only one of three asymptomatic patients evaluated by computed tomography (CT) at between 2 and 3 years after treatment. The significance of these residual masses seen on CT is unclear.

Adolescent↗
PubMed1988

An evaluation of the palliative role of radiotherapy in inoperable carcinoma of the bronchus.

Ninety-six patients with inoperable carcinoma of the bronchus were entered into a prospective study of the effectiveness of palliative radiotherapy. The median survival of the group as a whole was 38 weeks. Major symptoms such as cough, dyspnoea and haemoptysis were well controlled at 3 months and 6 months follow-up. There was no significant effect on performance status. Dysphagia and tiredness occurred in 81% of patients, but were classed as mild in 41% and 47% respectively, lasting less than 4 weeks in 86%. There was no correlation between the radiotherapy dose received and symptom control. Fourteen per cent of patients were dead within approximately 3 months of treatment and were unlikely to have benefited from therapy. Careful selection of patients for palliative radiotherapy is recommended.

Adenocarcinoma↗
PubMed1987

Short term morbidity and cosmesis following lumpectomy and radical radiotherapy for operable breast cancer.

One hundred and eighty-four patients with T0-T2, N0-N1b, M0 breast cancer were treated by local excision and radical radiotherapy. Short-term morbidity and cosmetic assessment are reported after a median follow-up of 21 months. At 1 year 80% of women considered the cosmetic result very good or excellent, whereas only 63% of their consultants gave a similar assessment. Mild or moderate arm oedema developed in 22% of patients, radiation pneumonitis in 9% and oesophagitis in 11%. Mild discomfort in the treated breast was reported by 39% and moderate by 17%. Oedema of the breast was noted in 20%. It is too early to comment on long term disease control or final cosmetic result but to date the morbidity has been considered acceptable and measures to reduce it further are being implemented.

Adult↗
PubMed1984

Priorities for computed tomography and lymphography in the staging and initial management of Hodgkin's disease.

Thirty-five patients with Hodgkin's disease were staged with the aid of chest radiographs, bipedal lymphograms and computed tomography (CT) scans. Computed tomographic findings altered management in only two patients (6%) by indicating enlargement of their radiotherapy fields. After lymphography, five patients (14%) were changed from Stage II (clinical and CT staging) to Stage III, so altering their management. Because either technique may show more extensive disease, CT and lymphography are complementary. Computed tomography should be performed initially. If it reveals no abnormality in the lymphogram area, lymphography, too, should be undertaken. Inverted Y fields are easier to visualise and design from lymphograms than from CT sections.

Combined Modality Therapy↗
PubMed1983

A method for integrating computed tomography into radiotherapy planning and treatment.

A technique is described for accurate localisation and radiotherapy treatment planning for a wide range of intrathoracic, abdominal and pelvic tumours. It allows the patient to proceed in one step from a single examination by computed tomography (CT) to treatment and avoids the need for separate treatment simulation. Compatible laser-beam positioning systems between the CT scanner and treatment-machine rooms ensure accurate reproduction of patient position, so that CT data are directly applicable to treatment. The use of appropriate skin markers, which appear on the CT scan, allows accurate measurements of the distance of the centre of the planned volume from a tattoo placed on the patient at the time of the scan, and ensures that the planned treatment fields are accurately directed.

Abdominal Neoplasms↗
PubMed1983

Radiation treatment planning for bladder cancer: a comparison of cystogram localisation with computed tomography.

A comparison has been made between the target volumes of radical radiotherapy treatment plans produced with the aid of marker cystograms, and target volumes derived from computed tomography (CT) scans in 60 patients with bladder cancer. This has demonstrated inadequacies of the cystograms due to the inability to delineate extravesical spread of tumour and, as many patients with bladder cancer had a significant residual urine, emptying the bladder by catheterisation may have given a false impression of the shape and size of the target volume. Analysis of the results showed that cystographic localisation resulted in serious underdosage of the tumour in 18% of patients and failure to include all the bladder in 37%. Conventionally produced target volumes showed potentially significant discrepancies in 85% of patients when compared with target volumes delineated by CT.

Humans↗
PubMed1980

Causes of apparent low levels of misonidazole in human tumours.

Although the concentration of misonidazole measured in human tumours may appear to be only 50--70% of the corresponding blood level, the concentration within the intra- and extracellular fluid of the tumour may be nearer 100% of the blood level. Causes for these apparent low levels of drug which have been investigated are: 1. Presence of fat in the tissue. 2. Presence of non-cellular material in the tissue. 3. Degradation of the drug by anaerobic metabolism after biopsy. An in vitro experiment to test the partitior fractionation study of the distribution of misonidazole showed that it is distributed mainly in the fluid compartment of the cell and that overall drug levels in tissue are related to the fluid content of the tissue. Serial measurements of misonidazole on tissue after removal from the body have shown that breakdown of the drug occurs when the tissue becomes anoxic. These results suggest that the concentration of misonidazole present within tumour cells is higher than the overall level measured for the tissue and that the enhancement ratio to be expected may therefore be higher also.

Adipose Tissue↗
PubMed1980

Growth delay studies in patients with multiple metastases.

Patients with multiple measurable metastases can be used as their own perfectly matched controls to study the effect of different treatments on their metastases. Response to treatment may be assessed by sequential measurement of the regression and regrowth of the metastases and by assessment of the growth delay produced by each treatment. Three patients are described who have been studied in this way to investigate the addition of misonidazole to radiation. The results suggest that it is possible to obtain quantitative data that will discriminate between relatively small doses of radiation and provide interesting clinical information on tumour response. The problems of the method and its possible applications are discussed.

Clinical Trials as Topic↗
PubMed1979

The quantitative response of human tumours to radiation and misonidazole.

Eleven patients with measurable subcutaneous or pulmonary metastases were selected for a study of the effectiveness of the radiosensitizer misonidazole (MIS). Evaluable data were obtained in 6 patients and radiosensitization demonstrated in 5. Patients were irradiated either before or after MIS, and each patient acted as his own control. Response to treatment in 5 cases was assessed in terms of growth delay, and radiation doses were selected in expectation of enhancement ratios of 1.2 to 1.5. In 1 case evidence of sensitization was obtained from differential tumour clearance from 2 areas of skin irradiated before or after MIS. Results in 4/5 growth-delay studies indicated enhancement ratios ranging from 1.1 to greater than 1.5. An enhancement ratio of 1.3 was measured in a case of squamous carcinoma treated by a 10-fraction course of irradiation. Evidence of sensitization was obtained in breast carcinoma, osteosarcoma, leiomyosarcoma, prostatic carcinoma and synoviosarcoma. The results of this study support the view that MIS may improve the radiotherapeutic management of a wide range of tumours, although more extensive data are required to identify those categories of disease in which greatest benefit will be obtained, and to indicate the optimum radiation schedule.

Adolescent↗
PubMed1979

Distribution of misonidazole in human tumours and normal tissues.

Levels of misonidazole in human tumours, normal tissues and blood have been measured in patients given a 1g oral dose of drug before surgery or biopsy. The results show that 50--70% of the blood level was found in a wide range of tumours and that similar levels were found in adjacent normal tissues. Good penetration of drug was achieved within tumours, and up to 90--100% of the blood level was found in the necrotic cyst fluid at the centre of some tumours. CSF studies showed free diffusion into the CNS, which was confirmed by finding 50--70% of the blood level within brain tumours. A delay of passage of drugs into the CSF was noted, which was not found for drug diffusion into bile and saliva.

Brain Neoplasms↗