Evaluation of quality of life and psychiatric morbidity in patients with malignant tumours of the skull base.

In general, patients with malignant tumours of the skull base have a poor prognosis. Treatment may have a disfiguring physical and disabling mental effect on patients. To evaluate the effect of treatment on physical and mental quality of life in patients with skull base malignancy, we conducted a cross-sectional patient survey of 18 patients treated for such tumours, using the University of Washington (version 4) quality of life questionnaire and the hospital anxiety and depression scale. The total quality of life score (median value) was 980 (550-1125). Patients with anterior skull base malignancy scored lower than those with lateral skull base malignancy (p=0.003). In general, the worst individual domain scores were: mood (64 per cent); activity (69 per cent); and, specifically for patients with anterior skull base malignancy, taste (54 per cent, p=0.004) and anxiety (60 per cent, p=0.034). One-third of skull base cancer patients were at risk of suffering from mental distress and psychiatric morbidity (indicated as a score of more than seven on the hospital anxiety and depression scale).

Dermatomyositis in association with transitional cell carcinoma of the bladder.

There is a well-recognized association between the inflammatory dermatomyopathy, dermatomyositis, and underlying visceral malignancy in adults. It is most commonly found in association with malignancies arising in the lung, breast and stomach. We report a case found in association with transitional cell carcinoma of the bladder, a site where there have only been a handful of previous reports.

Sensitivity of human squamous cell carcinoma of the larynx to fractionated radiotherapy.

Data obtained for the response of tumours from two multicentre clinical trials of the British Institute of Radiology have been combined and studied. Both trials involved patients with laryngopharyngeal carcinoma. There were 734 patients in the first trial, recruited between 1965 and 1975, and 611 patients in the second trial, recruited between 1975 and 1985. Observed survival and tumour-free rates for all patients are calculated. T-class and the nodal status of the patient at the start of the treatment were important factors in the determination of both observed survival and tumour-free rates. Overall treatment time was an important factor in determining the recurrence of tumour. The longer the overall treatment time the greater was the chance of tumour recurrence. The linear-quadratic (LQ) model was used in the analysis of the tumour recurrence data for a large group of patients with laryngeal tumours without nodal involvement. A small alpha/beta ratio of 0.94 Gy was obtained for T3 tumours while that of T2 tumours was negative, -10.5 Gy. The value for T1 tumours was higher at 23 Gy. However, use of the LQ model with a time component increased the alpha/beta ratios to 26.0 +/- 27.20 Gy, 18.0 +/- 12.33 Gy and 13.38 +/- 5.40 Gy for T1, T2 and T3 tumours, respectively. The time component, the gamma/alpha ratios, for these tumours were 0.15 +/- 0.27 Gy/day, 0.81 +/- 0.18 Gy/day and 0.76 +/- 0.15 Gy/day, respectively.

Carcinoma of the cervix uteri: an assessment of the relationship of tumour proliferation to prognosis.

The aim of this study was to ascertain whether assessing the growth fraction of cervical carcinoma of 28 patients, using antibody Ki-67, would be of value in clinical practice. The results showed no relationship between growth fraction and age, clinical stage, lymph node involvement or short term (3-5 years) survival.

Reduction in the diameter of human hairs following irradiation.

A measurable reduction in hair diameter was observed in human hairs following single exposures to gamma-rays, 250 KeV X-rays, 8 MV photons and 10 MV electrons in the range 2.9-14.0 Gy. The data from the different types of radiation were pooled and fitted by linear regression with a slope of 2.34 +/- 0.42% Gy-1. There was approximately 2.4% reduction in hair diameter per Gy exposure. It would appear that the measurement of damage to the matrix cells of growing human hairs exhibits potential for use in biological dosimetry, especially in cases of non-uniform overexposure.

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.

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.

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.

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.

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.

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.

Discrepancy between curettage and hysterectomy histology in patients with stage 1 uterine malignancy.

Histology reports of endometrial curettage and hysterectomy specimens were compared in patients with stage 1 uterine malignancy. In 63 of 117 (54%) the tumour grade or type reported in the curettage specimen differed from that described in the hysterectomy specimen; the grading was as likely to be more as less well differentiated at hysterectomy. The differences were not related to endometrial sampling technique or pre-operative intracavity radiotherapy. The results suggest that if decisions about patient management continue to be based on histological grading of tumours in endometrial curettage samples, unnecessary morbidity will be caused to some patients and inadequate treatment will be given to others.

Ten years experience with a chemotherapy regime for ovarian cancer.

In the period between January 1973 and September 1982, 57 patients with advanced epithelial ovarian cancer were treated with a chemotherapy regime of methotrexate, thiotepa, and vincristine. A 5-year survival rate of 24.1% was obtained. The chemotherapy regime was based on the mode of drug action and information gained from experimental work on fresh explant cultures of human tumor. The regime was well tolerated and the survival rate is similar to results obtained from other regimes recently reported.

The influence of pelvic lymph node disease on survival for stage I and II carcinoma of the cervix.

Two hundred and eighteen patients were referred to the Oxford Radiotherapy Department in the 5 years 1973-77 with stages I and II tumours of the uterine cervix. One hundred and eighty-one underwent pre-operative intracavitary radiotherapy followed by Wertheim hysterectomy and pelvic lymphadenectomy. Twenty-three per cent of these patients had metastatic disease in pelvic lymph nodes. Fifty-five per cent of patients with positive pelvic nodes died of carcinoma of the cervix compared with 9% of negative node cases. Prognostic factors are discussed and management of carcinoma of the cervix reviewed.

Treatment of multiple superficial transitional cell carcinoma of the bladder with intravesical yttrium-90.

Thirty-eight patients with extensive multiple superficial transitional cell carcinoma of the bladder which could not be controlled endoscopically were treated with intravesical yttrium-90. Nineteen are alive at between 1 and 9 years. Short-term control of the disease was achieved in most patients. In those followed up for at least 3 years, 48% remained alive and well and 36% avoided cystectomy or other major treatment.

Interstitial radiotherapy in treatment of superficial tumours of the lower alveolar ridge.

An adaptation of a routine afterloading implant technique for local irradiation of small tumours of the lower alveolar ridge is described. The methods the authors have used for radiation dosimetry are explained and some clinical results in 12 such lesions are presented. The technique has the advantage that the need for mandibular resection may be avoided, although this procedure is still available if the primary treatment fails.