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Biomedical subjects

J L Haybittle

Publications and source records attributed to J L Haybittle.

At least 19 recordsLinked to original sources
PubMed1992

Cardiac doses in post-operative breast irradiation.

Data were collected on radiation doses given to the heart and coronary arteries during primary breast irradiation in order to analyze factors which might be important in the aetiology of subsequent cardiac-related disease. Twenty eight patients with breast cancer were studied. Fourteen patients treated from 1957 to 1984 were studied retrospectively (group 1), and 14 treated from 1988 to 1989 were studied prospectively (group 2). All patients had stage I or II disease at presentation, and were under 70 years of age. None had chemotherapy as a primary form of treatment. Patients were given a computed tomography scan of the chest, and three-dimensional reconstruction was made of the heart, lung and body contour. Original dose distributions were super-imposed on these outlines, and doses to the total cardiac volume and three main coronary arteries were estimated using an alpha/beta ratio of 4 Gy. Nine out of 14 patients in group 1 had a mastectomy followed mainly by orthovoltage radiation with similar techniques used up until 1984. Thirteen out of 14 patients in group 2 had conservative surgery followed by a modern two- or four-field megavoltage technique. We found that for patients with left-sided tumours (n = 20), the heart volume irradiated to a minimum extrapolated target dose of 5 Gy is significantly decreased for patients treated with a modern technique (group 2) when compared with those treated with earlier techniques (group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Salvage surgery following irradiation with different fractionation regimes in the treatment of carcinoma of the laryngo pharynx: experience gained from a British Institute of Radiology study.

The 10-year follow-up of patients in a clinical trial involving the comparison of treatment by three fractions per week versus five fractions per week in radiotherapy of squamous carcinoma of the larynx and hypopharynx has now been completed. The trial involved an intake of 734 patients between 1966 and 1975. No statistically significant differences have been found between the two trial arms in terms of overall survival, age corrected survival, local recurrence, laryngectomy-free rates or effects on the normal tissues. Local recurrence was found in 320 of the 713 evaluable patients (45 per cent). Salvage laryngectomy was performed in 151 of the 320 patients with recurrence (47 per cent). Survival at 10 years for all node negative patients was 50 per cent in those patients without primary recurrence, compared with 40 per cent in those undergoing salvage laryngectomy.

Carcinoma, Squamous Cell↗
PubMed1992

LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial.

PURPOSE: The purpose of this randomized trial was to compare the efficacy of eight cycles of chlorambucil, vincristine, procarbazine, and prednisone (LOPP) with four cycles of LOPP that alternate with four cycles of etoposide, vinblastine, Adriamycin (doxorubicin; Familitalia Carlo Erba, Ltd, UK), and prednisone (EVAP) in patients with advanced Hodgkin's disease. PATIENTS AND METHODS: Between June 1983 and December 1989, 594 patients were entered onto the study. Of the 594, 295 patients were allocated to receive LOPP, and 299 were allocated to receive LOPP/EVAP. RESULTS: The complete remission (CR) rates were 57% and 64%, respectively, after initial chemotherapy (difference not significant [NS]), and 65% and 75%, respectively, after the subsequent administration of radiotherapy to residual masses (P less than .01). The procedure associated mortality in the LOPP and LOPP/EVAP arms was 1% and 3%, respectively. The actuarial CR relapse-free survival was significantly greater in the LOPP/EVAP arm (P less than .001) as was the overall survival (P less than .05). The CR relapse-free rate, disease-free survival (DFS) rate, and overall survival rate at 5 years were 52%, 32%, and 66%, respectively, in the LOPP arm, compared with 72%, 47%, and 75% in the LOPP/EVAP arm, respectively. CONCLUSION: These results indicate that LOPP and EVAP is superior to LOPP alone as initial treatment for advanced Hodgkin's disease.

Actuarial Analysis↗
PubMed1991

British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results.

From 1979-1983, 299 patients with stage III or IV Hodgkin's disease (HD) were randomised to receive cyclical chemotherapy with MOPP (mustine, Oncovin, procarbazine, prednisone) or LOPP (Leukeran substituted for mustine). Two hundred and ninety patients were evaluable. There was no statistically significant difference between the complete remission (CR) rates (63% for MOPP, 57% for LOPP), percentage of patients remaining disease free at 5 years (38% for MOPP, 35% for LOPP) and overall survival at 5 years (65% for MOPP, 64% for LOPP). On multivariate analysis younger age, grade I histopathology, absence of systemic symptoms, and normal albumin level were favourable prognostic factors for survival. Acute toxicity in the form of nausea/vomiting, myelosuppression, and phlebitis were less with LOPP than MOPP. Deaths in both groups were usually due to disseminated Hodgkin's disease; there were no infective deaths in the absence of Hodgkin's disease. Second malignancies occurred in six patients treated with MOPP--three acute myeloid leukaemia (AML), one non-Hodgkin's lymphoma (NHL), two carcinomas (Ca); with LOPP, four second malignancies occurred (one AML, one NHL, two Ca). These long term results confirm that LOPP is as effective as MOPP, and less toxic, in the treatment of advanced Hodgkin's disease.

Adolescent↗
PubMed1991

Curability of breast cancer.

Three concepts of cure are defined--statistical, clinical and personal. The evidence for the curability of female breast cancer according to each of these concepts is examined. It is concluded that the presence of statistically or clinically cured groups of patients is not convincingly demonstrated in past series of treated patients, but that a quarter of such patients have experienced personal cure in that they died from some other cause without overt signs of breast cancer present. The level of personal cure in currently treated series of patients should be higher, mainly due to their more favourable stage distribution.

Breast Neoplasms↗
PubMed1991

The predictive value of histological classification into degrees of differentiation of squamous cell carcinoma of the larynx and hypopharynx compared with the survival of patients.

In the course of running two clinical trials between 1966 and 1985, data became available for 1315 patients, 713 in the first trial and 602 patients in the second trial, which has allowed comparison between histological findings in laryngeal and hypopharyngeal carcinoma, the observed survival and the tumour-free rates for these patients who were followed for up to 10 years. Extensive histopathology reviews have revealed over 98% agreement on tumour cell type between the initial report and that of the reviewer. Highly significant differences have been found for squamous cell carcinoma between the observed survival and the tumour-free rates for patients with well-differentiated and with anaplastic lesions. There was a statistically significant greater proportion of patients with well-differentiated tumours at larynx sites and in stage 1 when compared with patients with anaplastic tumours, but even when this was taken into account, multivariate analyses showed that tumour grading still made an independent significant contribution to the prediction of prognosis. For squamous cell carcinoma only very simple and rapidly assessed histopathological features need to be identified to classify tumours into the two grades employed in this study. The analyses have confirmed the prognostic significance of tumour grading in squamous cell carcinoma in the larynx and hypopharynx.

Carcinoma, Squamous Cell↗
PubMed1991

Final report on the second British Institute of Radiology fractionation study: short versus long overall treatment times for radiotherapy of carcinoma of the laryngo-pharynx.

The second British Institute of Radiology trial of dose fractionation in radiotherapy compared two groups of prospectively randomized patients with squamous carcinoma of the laryngo-pharynx; one group was treated in a short (less than or equal to 4 weeks) and the other in a long (greater than 4 weeks) overall time. Treatment in any one centre could be given, with no planned gap in the course of treatment, either as a conventional, daily (5 fractions per week regime) or as 3 fractions per week. A total of 611 patients were allocated to treatment, of whom nine have had to be excluded from the analysis for a lack of information. Patients were admitted to the trial from January 1976 to December 1985 and were followed up for a maximum of 10 years and a minimum of 3 years. A reduction in total dose was made for use in the short compared with the long treatment regime. This reduction in total dose varied between 18% and 22% depending on whether 5 fractions or 3 fractions per week regimes were used. Overall, no statistically significant differences have been found between the two arms of the trial. The patients treated with 5 fractions per week in a short overall treatment time showed fewer late normal tissue effects. An analysis based on stratification by age, stage and anatomical site gave a relative risk (short/long overall treatment time) for deaths of 1.23 with a 95% confidence interval from 0.96 to 1.59. Analyses stratified for stage and site gave relative risks with 95% confidence intervals of 1 x 10 (0.84-1.44) for local recurrences/tumour persistence, and 1.01 (0.70-1.45) for laryngectomies.

Adult↗
PubMed1991

Normal tissue reactions in the British Institute of Radiology Study of 3 fractions per week versus 5 fractions per week in the treatment of carcinoma of the laryngo-pharynx by radiotherapy.

The radiobiological data obtained from a multicentre clinical trial of the British Institute of Radiology, which compared the treatment of carcinoma of the laryngo-pharynx by 3 fractions per week (3F/wk) with 5 fractions per week (5F/wk) radiotherapy, have been studied. The trial involved an intake of 734 patients between 1966 and 1975. The number of fractions, overall treatment time and total doses used by different treatment centres ranges from 9 to 40 fractions, 18 to 70 days and 3880 to 7800 cGy, respectively. An 11-13% reduction in the total radiation dose was applied for treatments with 3F/wk as compared with 5F/wk in centres treating over 6 weeks and 3 weeks, respectively. All patients were followed for 10 years from the start of treatment. Different types of early and late normal-tissue reactions were investigated, ranging from a low percentage incidence of perichondritis to 95% for slight early reactions. Greater than 80% of the late normal-tissue reactions seen were observed within the first year after the start of treatment, and 96% were observed within the first 5 years. There was no statistically significant difference in the normal-tissue event-free rates between the 3F/wk and 5F/wk treatment groups. This finding did not differ when different major treatment centres were studied separately. For a number of end-points, alpha/beta ratios and N- and T-exponents of a modified nominal standard dose (NSD) formula have been calculated.

Adult↗
PubMed1990

Recruitment, follow-up and analysis times in clinical trials of cancer treatment: a case study.

A study has been made of the way in which the number of events available for analysis in a clinical trial was dependent on the recruitment period, the maximum follow-up time on individual patients and the length of time between the start of the trial and its analysis. The events considered were deaths, local recurrences and late radiation effects on normal tissue in patients treated for cancer of the laryngo-pharynx by two different fractionation regimes. The relationship is demonstrated between the number of events and the 95% confidence intervals that can be placed on differences between results in the two arms of the trial. It was found, in this particular trial, that no significant improvement in precision was gained by following up patients beyond 5 years or carrying out the analysis later than 2 years after the end of recruitment. The results are discussed in the context of the initial design of clinical trials, particularly those in which the aim is to test therapeutic equivalence.

Clinical Trials as Topic↗
PubMed1990

Final report of the general clinical results of the British Institute of Radiology fractionation study of 3F/wk versus 5F/wk in radiotherapy of carcinoma of the laryngo-pharynx.

The 10 year follow-up of a clinical trial involving the comparison of 3F/wk versus 5F/wk in radiotherapy of squamous cell carcinoma of the larynx and hypopharynx has now been completed. The trial involved an intake of 734 patients between 1966 and 1975. The classification of all patients has been revised to conform with the latest TNM publication. A reduction in total dose was made for 3F/wk compared with 5F/wk. This varied between 13% and 11% in centres treating over 3 weeks and 6 weeks, respectively. No statistically significant differences have been found between the two arms (3F/wk versus 5F/wk) of the trial in any of the main group analyses. A number of sub-group analyses relating to survival, tumour-free and laryngectomy-free rates and to the comparison of acute or late normal-tissue radiation damage have also been performed. No differences have been found that could be considered to be statistically significant in relation to the particular sub-group. Previous interim reports suggested minor differences in sub-group analyses between the 3F/wk and 5F/wk regimes in this trial; these have diminished now that the full follow-up data are available. This trial has provided evidence on which clinicians may base their choice between either a 3F/wk fractionation regime or a conventional 5F/wk treatment protocol in the treatment of carcinoma of the laryngo-pharynx.

Carcinoma, Squamous Cell↗
PubMed1990

The predictive value of tumor classification compared with results of the British Institute of Radiology fractionation trial in the treatment of laryngopharyngeal carcinoma.

Data from a clinical trial involving 734 patients have shown the value and the deficiencies of the current Union Internationale Contre le Cancer's tumor, node, and metastasis classification system for prognostic purposes. The tumor-category classification provides a good discriminant for both nodal involvement and survival; however, the previous node classification system only discriminated between node-negative and node-positive patients, as nodal fixity was not found to be a discriminator. The current anatomical site classification is ambiguous for some laryngeal and pharyngeal subsites, and modifications to the present system based on prognostic values are proposed. A difference in patient age between tumor categories has been shown, and various differences in incidence and survival data for the sexes have been demonstrated. Differences in observed and expected survival rates are related to continued late deaths from tumor. Multivariate analyses have shown that stage grouping is the most powerful prognostic discriminator, followed by anatomical site and age.

Adult↗
PubMed1989

Postoperative radiotherapy and late mortality: evidence from the Cancer Research Campaign trial for early breast cancer.

OBJECTIVE: To identify any excess mortality caused by adjuvant radiotherapy for early breast cancer. DESIGN: Prospective randomised clinical trial. Two thousand subjects needed for study to have a 90% chance of detecting a difference in survival rate of 7% with 95% significance. Patients were followed up until June 1988, giving follow up of 158-216 months. SETTING: A multicentre trial mainly drawing patients from centres in the United Kingdom. PATIENTS: 2800 Women presenting with clinical stage I or II carcinoma of the breast from June 1970 to April 1975. INTERVENTIONS: One group of women (n = 1376) had simple mastectomy followed by immediate postoperative radiotherapy (1320 to 1510 rets). The remaining women (n = 1424) had simple mastectomy with subsequent careful observation of the axilla, radiotherapy being delayed until there was obvious progression or recurrence of disease locally. END POINT: Increased mortality in patients treated with radiotherapy from causes other than breast cancer. MEASUREMENTS AND MAIN RESULTS: Survival was measured from time of first treatment to death or last follow up. Deaths from any cause and from specified causes were counted as events. Comparison over the whole follow up showed a slight excess mortality in the group treated with radiotherapy (relative risk 1.04; 95% confidence interval 0.94 to 1.15). The relative risk of death from breast cancer was 0.97 (0.87 to 1.08) but that of death from other causes was 1.37 (1.09 to 1.72), the increase mainly being in women who had had tumours of the left breast (1.61 (1.17 to 2.24)) and had been treated with orthovoltage (1.85 (1.27 to 2.71)). Analysis of causes of death after five years showed a relative risk of 2.11 (1.25 to 3.59) for new malignancies and of 1.65 (1.05 to 2.58) for cardiac disease, the increase in cardiac mortality being most pronounced in patients who had had tumours of the left breast and whose treatment had included orthovoltage radiation (relative risk 2.67 (1.28 to 5.55)). CONCLUSIONS: Adjuvant radiotherapy after simple mastectomy for early breast cancer produces a small excess late mortality from other cancers and cardiac disease. The risk has to be balanced against the higher risk of local recurrence when immediate postoperative radiotherapy is not given. The balance has to be assessed for each patient, and for many patients radiotherapy will still be desirable in the initial treatment of their early breast cancer.

Breast Neoplasms↗
PubMed1989

First interim progress report on the second British Institute of Radiology Fractionation Study: short versus long overall treatment times for radiotherapy of carcinoma of the laryngopharynx.

Preliminary data from a second British Institute of Radiology Fractionation Trial comparing short (less than or equal to 4 weeks) and long (greater than 4 weeks) overall treatment times are reported. The intake of patients ran from January, 1975 to December, 1985 when 611 patients with carcinoma of the laryngo-pharynx were registered in this prospective, randomized, multicentre clinical trial. No significant differences have, so far, been demonstrated between the two arms of the trial with respect to observed survival rates, tumour-free or laryngectomy-free rates. Further long-term follow-up is continuing.

Clinical Trials as Topic↗
PubMed1988

Long-term survival experience of female patients with genital cancer.

Survival analyses of patients with cancer of the cervix uteri, corpus uteri or ovary registered at Cambridge in 1960-1979 show that, although the long-term survivors had mortality rates similar to those of a normal age-matched population and might therefore be considered 'statistically cured', their risk of dying from their original cancer was still much higher than normal. Death rates from other cancers were slightly increased in cervix patients but not in corpus and ovary. At all three sites there was no evidence that deaths from non-malignant causes were increased. Only in cancer of the ovary was survival significantly better for patients registered in 1970-1979 than for patients registered in 1960-1969.

Adult↗