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Biomedical subjects

M I Saunders

Publications and source records attributed to M I Saunders.

At least 91 records · Page 5Linked to original sources
PubMed1991

Is control of the primary tumour worthwhile in non-oat cell carcinoma of the bronchus?

In the United Kingdom most patients with locally advanced non-small cell lung cancer are given treatment with palliative intent only, even when there is a good performance status and an absence of evidence for distant metastasis. It has, however, been shown that after radical radiotherapy prolonged survival can result, but only when complete regression of tumour is achieved. Research has, therefore, been directed toward an increase in primary tumour control. In pilot studies a combination of chemotherapy and radiotherapy has given improvement in tumour clearance and survival. Another approach has been to use a short intensive course of radiotherapy in which three treatments are given each day for 12 consecutive days--Continuous, Hyperfractionated, Accelerated Radiotherapy (CHART); an increase in local tumour control and survival has been shown in a comparison with the results achieved in previous cases. CHART and the combination of chemotherapy and radiotherapy are both the subject of multicentre randomized controlled trials in the United Kingdom. Patients with locally advanced non-small cell carcinoma of the bronchus should be considered for entry into these studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Lung function and radiation response.

This study investigated whether impaired respiratory function affected the response to radiotherapy. A prospective study was performed in which lung function, arterial oxygen and haemoglobin concentration were examined, before treatment with radical radiotherapy, in 141 patients with advanced non-small cell lung cancer and head and neck cancer. The findings were considered to reflect the physiological conditions present at the time of radiotherapy and these were related to acute normal tissue reactions and tumour control. Although 53% of the patients showed some impairment of lung function and 47% demonstrated a haemoglobin oxygen saturation below the normal range, oxygen partial pressure was below expected levels in fewer patients (27%) and total arterial oxygen content was below normal in only 12% of patients. No correlation was found between the tests performed and the severity of acute morbidity or with local tumour control. In the patients with carcinoma of the bronchus, there was a trend for incomplete tumour control to be associated with a lower haemoglobin level, but this did not reach statistical significance. In patients selected for curative radiotherapy, lung function would not appear to be an important factor influencing the response of normal tissues or tumour to irradiation.

Adult↗
PubMed1990

Continuous, hyperfractionated, accelerated radiotherapy (CHART) in non-small cell carcinoma of the bronchus.

Between January 1985 and December 1988, 62 patients with locally advanced carcinoma of the bronchus were treated by radiotherapy using continuous, hyperfractionated, accelerated radiotherapy (CHART). With this regime on each of 12 consecutive days 3 fractions were given with a time interval of 6 hr between each. Initially a dose fraction of 1.4 Gy was used and a total of 50.4 Gy was achieved in 23 patients. As tolerance was good, the dose increment was raised to 1.5 Gy and the total to 54 Gy in the subsequent 39 patients. Esophagitis was the only immediate complication, and although most patients were reduced to a fluid diet for a period, recovery was complete and only one patient required endo-esophageal tube feeding for a short time. The results observed so far have been assessed against those in a previous trial of a radiosensitizer in cases similarly accepted for treatment. Complete regression, as observed radiologically, was achieved by 42%; this can be compared with 15% of the previously treated series. At 1 year the survival probability was 64% compared with a previous 44% and at 2 years 34% compared with a previous 12%. A randomized controlled clinical trial is now planned.

Carcinoma, Bronchogenic↗
PubMed1990

The rationale for continuous, hyperfractionated, accelerated radiotherapy (CHART).

Continuous, hyperfractionated, accelerated radiotherapy (CHART) was devised to give the maximum chance of improving clinical radiotherapy and was based upon available radiobiological evidence. A pilot study, begun in 1985, has now included 210 patients. When comparison is made with previously treated cases, improved results have been seen in the two main groups included, that is, advanced head and neck and bronchial carcinomas. Multi-center randomized controlled clinical trials are planned.

Humans↗
PubMed1990

An audit of head and neck cancer treatment in a Regional Centre for Radiotherapy and Oncology.

All patients with head and neck cancer attending the Regional Centre for Radiotherapy and Oncology at Mount Vernon hospital during the 8-year period from 1 January 1980 to 31 December 1987 have been included in this review. The 545 patients presenting a new primary carcinoma without evidence for metastasis outside the locoregional area, who were treated primarily by radiotherapy are the subject of this present audit. The characteristics of the patients, of the tumours and of the treatment given have been related to outcome. Early tumours (T1 and T2 which were node-negative) showed a complete response (CR) rate of 94% whereas more advanced tumours (T1 and T2 with palpable lymph nodes) showed a CR of 59%. The probability of local tumour control at 5 years was 77% in those without nodes and 20% in those with nodes. For more advanced disease (T3 and T4 tumours), initial CR was 72% in node-negative disease and 32% when the nodes were positive. At 5 years, the probability of local tumour control fell to 37% and 0 respectively. CR, freedom from recurrence and survival were statistically significantly related to T stage, N stage and site of primary tumour. The results compare favourably with those reported by other institutions. The development of medical audit and its influence on treatment policy are considered.

Adolescent↗
PubMed1990

Smoking and mucosal reactions to radiotherapy.

The pattern of cigarette smoking of 41 patients receiving continuous, hyperfractionated, accelerated radiotherapy for locally advanced head and neck cancer was examined to determine any relationship with the duration of mucositis. The uniformity of the treatment given made it possible to perform an analysis of the factors influencing the duration of the mucositis. There was no correlation with age, sex or weight loss prior to treatment. A highly significant correlation was shown with smoking during and/or after treatment (p = 0.014) and with the volume of mucosa irradiated (p = 0.025). Both appeared to act independently. It is important to encourage patients to cease smoking totally, prior to radiotherapy, to minimize the duration of mucositis associated with radiotherapy.

Adolescent↗
PubMed1989

Continuous, hyperfractionated, accelerated radiotherapy (CHART): an interim report upon late morbidity.

Continuous, hyperfractionated, accelerated radiotherapy (CHART) has given high levels of tumour control in advanced head and neck and bronchial carcinomas. In general, late changes have appeared less than after conventional radiotherapy but despite a prediction of reduced risk of spinal cord damage, two cases of radiation myelitis have presented. The possible causes are considered and a reduction in permitted spinal cord dose has been made.

Aged↗
PubMed1989

Cell proliferation and differentiation in squamous cancer.

Cellular differentiation is generally regarded as an important histological predictor of tumour behaviour. Verrucous carcinoma is a very well-differentiated tumour characterised by slow enlargement and an unsatisfactory response to radiotherapy. Tumour cell kinetic studies using the intravenous administration of bromodeoxyuridine (BrdUrd) before tumour sampling have shown these tumours to have high labelling indices and short duration of DNA synthesis. These values result in short potential cell doubling times of these tumours although they then have a well-differentiated appearance histologically. Study of 20 other squamous cell carcinomas has shown no relationship between grade and cell proliferation.

Bromodeoxyuridine↗
PubMed1989

Continuous hyperfractionated accelerated radiotherapy in locally advanced carcinoma of the head and neck region.

Shortening of the overall duration of radiotherapy would reduce the possibility repopulation of tumor during treatment. Most clinical trials of such accelerated radiotherapy have incorporated a split course to improve normal tissue tolerance. Any interruption, however, even for the week-end, may allow repopulation to occur. A scheme of radiotherapy has been used during which treatment was given 3 times per day on each of 12 consecutive days without interruption for the week-end. In a pilot study a significant improvement in survival and local tumor control has been achieved in 48 patients with head and neck tumors when comparison was made with a previously treated group. A randomized controlled clinical trial is planned.

Adult↗
PubMed1988

Radiation myelitis and survival in the radiotherapy of lung cancer.

A previous survey of patients who survived more than 6 months after radiotherapy for carcinoma of the bronchus using a 6 fraction regimen revealed a considerable incidence of radiation myelitis. In a further survey, in which the data bank has been increased from a total of 303 to 754 cases, analyses have confirmed that radiation myelitis occurs once a threshold dose of 33.5 Gy to the spinal cord has been reached. The incidence was positively related to the hemoglobin concentration, but not to the blood pressure at the time of radiotherapy. In the same group of patients survival was positively related to radiation dose, the hemoglobin concentration, and the systolic blood pressure. In other patients who were treated with 6 fractions, but who received a lower minimum tumor dose, either because this was planned or as a result of cord shielding, no relationship was shown between survival and radiation dose, hemoglobin concentration and systolic or pulse pressure. Radiosensitivity is dependent upon the oxygen concentration which, in normal tissues, is related to the hemoglobin concentration and in tumor to both the hemoglobin and the systolic blood pressure. The achievement of a threshold radiation dose appears essential before these prognostic factors become relevant.

Carcinoma, Bronchogenic↗
PubMed1988

Measurement of cell kinetics in human tumours in vivo using bromodeoxyuridine incorporation and flow cytometry.

The proliferative potential of human solid tumours, in vivo, was investigated using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry (FCM). Patients with solid tumours from a variety of sites were injected with 500 mg BrdUrd, intravenously, several hours prior to biopsy or surgical excision. The labelling index (LI), duration of S-phase (Ts) and thus the potential doubling time (Tpot) could be measured within 24 h of sampling. The results show that both the LI and Ts vary greatly between tumours (Ts ranges from 5.8 to 30.7 h). However, within this study of 26 evaluable patients, tumours of the same tissue origin tended to have similar Ts values. Melanomas had the shortest Ts (8.8 h), nine patients with head and neck cancer had Ts values ranging from 5.8 to 18.8 h (median 12.5 h). The longest Ts values (24 h) were found in lung and rectum. The estimates of Tpot ranged from only 3.2 days in an oat cell carcinoma to 23.2 days in a lymphoma. The striking feature of the study was that 38% of the tumours had a potential doubling time of 5 days or less. We found no relationship between proliferation and histopathological differentiation or DNA ploidy. It should now be possible to assess the prognostic significance of pretreatment cell kinetic measurements which may, in the future, aid in the selection of treatment schedules for the individual patient.

Bromodeoxyuridine↗
PubMed1988

Radiotherapy employing three fractions on each of twelve consecutive days.

In order to achieve the greatest advantage of accelerated hyperfractionated radiotherapy, treatment has been given 3 times each day for 12 consecutive days without a rest period. A total tumour dose of 50.4 Gy was well tolerated in a series of 38 patients with bronchial, head and neck and oesophageal carcinomas. A further 14 patients have now received an elevated dose of 54 Gy, again with satisfactory tolerance. The tumour responses at all these sites have been very promising and further work is proceeding.

Bronchial Neoplasms↗
PubMed1986

Hemoglobin, radiation, morbidity and survival.

Analyses concerned with a group of patients treated by radiotherapy for carcinoma of the bronchus give evidence to support the view that oxygen tension at the time of radiation therapy is important both in determining tumor control and radiation morbidity.

Female↗
PubMed1986

Concentrations achieved in human tumors after administration of misonidazole, SR-2508 and Ro 03-8799.

Misonidazole, SR-2508 and Ro 03-8799 have been given in sequence to patients before tumor sampling. Tumor concentrations of the three drugs have been measured and it has been possible to make prediction as to the likely advantage of the newer drugs over misonidazole. Based upon the three cases described here and 13 others given two drug combination, we suggest that in multifraction radiotherapy, both are likely to prove more than five times more efficient than misonidazole.

Aged↗