Symptom control and quality of life in people with lung cancer: a randomised trial of two palliative radiotherapy fractionation schedules.

AIMS: To determine whether palliation of chest symptoms from a 10 Gy single fraction (regimen 1) was equivalent to that from 30 Gy in 10 fractions (regimen 2). MATERIALS AND METHODS: Patients with cytologically proven, symptomatic lung cancer not amenable to curative therapy, with performance status 0-3, were randomised to receive either 30 Gy in 10 fractions or a 10 Gy single fraction. Local symptoms were scored on a physician-assessed, five-point categorical scale and summed to produce a total symptom score (TSS). This, performance status, Hospital Anxiety and Depression (HAD) score and Spitzer's quality-of-life index were noted before treatment, at 1 month after treatment and every 2 months thereafter. Palliation was defined as an improvement of one point or more in the categorical scale. Equivalence was defined as less than 20% difference in the number achieving an improvement in the TSS. RESULTS: We randomised 149 patients and analysed 74 in each arm. According to the design criteria, palliation was equivalent between the two arms. TSS improved in 49 patients (77%) on regimen 1, and in 57 (92%) patients on regimen 2, a difference of 15% (95% confidence interval [CI] 3-28) in the proportion improving between the two regimens. A complete resolution of all symptoms was achieved in three (5%) on regimen 1, and in 14 (23%) patients on regimen 2 (P < 0.001), a difference in the proportion between the two regimens of 21% (95% CI 10-33). A significantly higher proportion of patients experienced palliation and complete resolution of chest pain and dyspnoea with regimen 2. No differences were observed in toxicity. The median survival was 22.7 weeks for regimen 1 and 28.3 weeks for regimen 2 (P = 0.197). CONCLUSIONS: Although this trial met the pre-determined criteria for equivalence between the two palliative regimens, significantly more patients achieved complete resolution of symptoms and palliation of chest pain and dyspnoea with the fractionated regimen.

Stage III carcinoma of cervix. The importance of increasing age and extent of parametrial infiltration.

The relative importance of a number of potential prognostic factors was analysed for a sequential group of 296 patients with stage III carcinoma of the cervix who had been treated in a mature prospective clinical trial. Using a log-rank analysis of survival curves generated by the life-table method increasing age (p = 0.05) and extent of parametrial infiltration (p = 0.001) were found to be significantly related to prognosis. These two factors were further demonstrated to be independent variables and, of the two, parametrial extension (p = 0.002) was more significant than increased age (p = 0.035). Involvement of the lower third of the vagina, the presence of bullous oedema and the histological differentiation of the disease were not prognostically significant in this study. It is suggested that tumour volume as defined by extent of parametrial infiltration is a sufficiently good prognostic factor to be incorporated into a revised staging system.

Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules.

BACKGROUND: The optimum dose and fractionation schedule for the palliative irradiation of painful bone metastases is controversial. PURPOSE: To compare the efficacy, side-effects and effect on quality of life of two commonly used radiotherapy schedules in the management of painful bone metastases. MATERIALS AND METHODS: In a prospective trial, 280 patients were randomised to receive either a single 10 Gy treatment or a course of 22.5 Gy in five daily fractions for the relief of localised metastatic bone pain. RESULTS: Response rates have been calculated from 240 assessable treated sites of pain. The overall response rates were 83.7% (single treatment) and 89.2% (five fractions). The complete response rates were 38.8% (single treatment) and 42.3% (five fractions). The median duration of pain control was 13.5 weeks (single treatment) and 14.0 weeks (five fractions). None of these differences was statistically significant. There were no differences between the groups in the effect of treatment on a variety of quality of life parameters. CONCLUSIONS: It is concluded that a single 10 Gy treatment is as effective as a course of 22.5 Gy in five fractions in the management of painful bone metastases.

Uterine sarcomas: a review of the Edinburgh experience from 1974 to 1992.

A retrospective review of patients treated for a uterine sarcoma in Edinburgh from 1974 to 1992 has been performed. Clinical details at presentation, tumour pathology, treatment and the outcome of treatment were all recorded. 82 patients' case notes were reviewed. 54 patients had died and 28 were alive (mean follow-up period 80.3 months). 39 patients had a malignant mixed mesodermal tumour, 12 patients had an endometrial stromal sarcoma, and 27 had a leiomyosarcoma. Using a modified FIGO staging retrospectively, 41 patients had Stage 1 disease, two patients had Stage 2, 16 patients had Stage 3, and 13 patients had Stage 4 disease. Definitive treatment of total abdominal hysterectomy and bilateral salpingo-oophorectomy was used in 69 patients, with 35 of these patients also receiving post-operative radiotherapy to the pelvis. 13 patients did not undergo surgery. Five of these patients received radical radiotherapy, three patients received palliative radiotherapy, and five patients were not treated. The overall median survival is 15 months and the 5-year actuarial survival is 31%. 25 of the 26 surviving patients had Stage 1 disease at presentation. Post-operative pelvic radiotherapy did not influence either survival or local tumour control. 51 of the 54 patients who relapsed had evidence of distant metastases. We conclude that total abdominal hysterectomy and bilateral salpingo-oophorectomy remains the treatment of choice for uterine sarcomas.

Stage IB cervical carcinoma: a clinical audit.

All patients with FIGO Stage IB cervical cancer registered with the Department of Clinical Oncology at the Western General Hospital, Edinburgh, during the 6 years from 1979 to 1984 have been reviewed, as part of a continuing programme of clinical audit. Of the 140 patients with Stage IB disease, 68 (49%) were treated by primary surgery of whom 44 (31%) also received adjuvant radiotherapy. Radical radiotherapy was the definitive treatment for 69 patients (49%). Three patients (2%) were not treated with curative intent. The crude 5-year survival rate for all cases was 72% and the cause-specific 5-year survival rate was 78%. Local tumour control at 5 years was 72%. There was no significant difference in outcome between the surgically treated and irradiated groups of patients. Age, histology and nodal status did not influence outcome. Irradiated patients with bulky tumours fared significantly worse than the other patients who received radical radiotherapy. Multivariate analysis of all patients revealed no significant independent prognostic variables. Primary surgery appears to confer no benefit over radical radiotherapy in terms of either survival or local control. Treatment-related late bladder and bowel morbidity was, however, significantly worse in irradiated patients.

Endometrial carcinoma: does the addition of intracavitary vault caesium to external beam therapy postoperatively result in improved control or increased morbidity?

A retrospective analysis of treatment for endometrial carcinoma is reported here. From 1987 to 1989, 138 patients were referred to the oncology department following total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer. Forty-seven patients were not prescribed postoperative radiotherapy; 31 had Stage I well differentiated adenocarcinoma with minimal myometrial invasion, while the remaining 16 patients were considered unfit for postoperative radiotherapy. There were no instances of local relapse amongst the 31 patients with minimal myometrial invasion. The remaining 91 patients all received external beam irradiation to the pelvis and, according to the preference of the individual therapist, 51 were prescribed additional intracavitary vault caesium-137. Patients receiving postoperative radiotherapy were analysed according to whether or not they received additional intracavitary vault caesium. The two groups were also analysed for incidence of vaginal vault recurrence and treatment related morbidity. In the group receiving additional intracavitary treatment more patients had Stage II or III disease (P < 0.05), and had greater depth of myometrial invasion (P < 0.05). Vaginal vault recurrence was not observed in patients receiving intracavitary therapy in addition to external beam therapy. Four patients (10%) receiving external beam therapy alone developed vaginal vault recurrence. The incidence of Kottmeier-Perez grade 2 or 3 bowel toxicity following treatment was significantly higher in those patients receiving combined treatment (18% vs. 2.5%; P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

A review of the pathology and management of uterine papillary serous carcinoma and correlation with outcome.

Uterine papillary serous carcinoma (UPSC) accounts for 10% of endometrial carcinomas but a higher proportion of deaths due to its aggressive nature and poor response to chemotherapy and radiotherapy. In order to add to the knowledge of UPSC in the literature and to review our local practices, we examined the pathology, medical records, and management of all cases of UPSC (67 patients) treated in South East Scotland over a 10-year period and also evaluated the prognostic significance of the percentage of UPSC in endometrial pipelle and hysterectomy specimens. Although only 63% of initial diagnostic biopsies were reported to contain UPSC, rereview of the cases revealed UPSC in 98.5% of the preoperative biopsies. The percentage of UPSC in the tumors did not affect the outcome. Stage, positive omentum, and treatment with external-beam +/- intracavitary radiotherapy were significantly correlated with overall survival and progression-free survival by univariate analysis, but only stage (P < 0.01) was correlated with outcome on multivariate analysis. Chemotherapy did not affect outcome. UPSC may be difficult to diagnose in preoperative biopsies, particularly when present as part of a mixed tumor. Even a small percentage of UPSC in a diagnostic biopsy or hysterectomy specimen is correlated with a poor prognosis. This study emphasizes the need of a cooperative, prospective study on this distinct uterine carcinoma.

Adenoid cystic carcinoma of the salivary glands.

Eighty-two patients with adenoid cystic carcinoma treated by a radical course of radiotherapy are reviewed. In 44 cases the tumour arose in the major salivary glands and, of these, 77% had an incomplete surgical excision and 23% had only a tumour biopsy before radiotherapy. Thirty-eight tumours arose in the minor salivary glands and, of these, 18% had an incomplete surgical excision and 82% a biopsy only before treatment. Primary tumour control was achieved in 67% of patients at 5 years. The local control was significantly better in patients who had an incomplete surgical excision: 86% compared with 37% at 5 years. The local control of tumours arising in the major salivary glands is significantly better than that of tumours arising in the minor glands, but this difference is explained by more patients with major gland tumours having had incomplete surgery. For patients treated after only a biopsy, local tumour control was achieved in 37%, demonstrating the radioresponsiveness of this type of carcinoma. No difference in survival was demonstrated in patients with major or minor gland tumours. Despite local tumour control, 43% of patients with major gland tumours died from metastatic disease. The commonest cause of death of patients with minor gland tumours was local failure.

Lack of correlation between differentiation status and response to radiation of three murine squamous cell carcinomas.

The gross growth rate, histology, cellular kinetics, and in situ radiobiological response have been measured for three murine, keratinising squamous cell carcinomas that differed in their degree of differentiation. Growth rate was fastest in the least-differentiated tumour, slowest in the best-differentiated. However, the kinetics of the compartment of undifferentiated cells that are likely to be radiotherapeutically important, were the same for the three lines. There was no correlation between degree of differentiation and intrinsic or apparent radiosensitivity as measured by the growth delay assay. The radiobiologically best-oxygenated tumour was that which has the largest stromal component and this was not the best-differentiated tumour.

A clinical trial of two conceptually different radical radiotherapy treatments in stage III carcinoma of the cervix.

Two hundred and ninety-six consecutive patients under the age of 70 years and having Stage III carcinoma of the cervix were randomised to receive one of two radical radiotherapy techniques. The first was a small-field, wedged, inhomogeneous 3-week X-ray treatment, followed by two radical radium insertions delivering 80% of a radical intracavity dose. The second was a 4-week homogeneous, large-field X-ray technique, supplemented by a single intracavitary insertion giving 50% of a radical intracavitary dose. Mature 5-year survival rates for the two techniques were 38.6% and 40.3% respectively (p = 0.76). Corrected 5-year results were 44.5% and 45% (p = 0.8). The time to pelvic recurrence and the sites of pelvic recurrence were not significantly different. The rate of major morbidity was eight out of 148 in the first group and five out of 148 in the second. This large, prospective, randomised trial failed to identify any significant advantage to two conceptually different techniques which explored different volumes, fractionation and balance between X-ray therapy and intracavitary therapy. The overall results remain very satisfactory when compared with recently published European results.

Early stage cervical cancer: psychosocial and sexual outcomes of treatment.

Eighty-three women, mean age 45 years, successfully treated by surgery (S) or radiotherapy (RT) for stage 1b cervical cancer were assessed a mean of 97 weeks post treatment. Forty to 50% reported persistent tiredness, lack of energy and weight gain. Sixty per cent had not resumed their full premorbid functional status. Mean scores for anxiety and depression were higher than general population means and this sample scored higher for psychological distress than published data quoted for disease free cancer patients. These women reported many concerns about cervical cancer, most commonly fear of recurrent disease (91%). More than one-third blamed themselves for the disease. There were no significant differences in functional outcome or psychological status between treatment groups or by age or time since treatment. Psychological distress scores were significantly correlated with physical complaints (P < 0.001) and functional outcomes (P < 0.02). For the 61 women who were sexually active, sexual function post-treatment was rated as significantly poorer than subjectively recalled premorbid sexual function (P < 0.005). RT treated patients were more likely to report pain on intercourse and loss of enjoyment. Psychological as well as physical problems were highly correlated with sexual outcome (P < 0.01) 44% were unable to talk adequately with their partners about their experience. The majority felt they needed more information about cervical cancer, its treatment and how to help themselves rehabilitate. Forty-nine per cent would have liked to have had counselling. Even with the same physical morbidity the functional, emotional and sexual status of these women could be improved by giving more attention to their psychological and sexual concerns.

Cisplatinum and prednimustine, an active regimen for advanced epithelial ovarian cancer.

80 patients with advanced epithelial ovarian carcinoma were treated for 6 months with cisplatinum and prednimustine following initial surgery. Response to treatment was assessed by second-look surgery. The objective response rate was 69% with 38% achieving a complete response for up to 55 months. The toxicity of this regimen was acceptable. Statistically, de-bulking or partial de-bulking had a significant beneficial effect on the likelihood of a complete response. The best survival figures were associated with maximum de-bulking. The combination of cisplatinum and prednimustine is a new and active regimen for operable advanced epithelial ovarian carcinoma.