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S Ashley

Publications and source records attributed to S Ashley.

At least 127 records · Page 7Linked to original sources

Improving the acceptability of high-dose radiotherapy by reducing the duration of treatment: accelerated radiotherapy in high-grade glioma.

Radiotherapy, although clearly beneficial in patients with high-grade glioma, is largely palliative, and a protracted course of treatment may not be the most appropriate approach in the context of limited survival. We therefore assessed the feasibility, toxicity and survival results of a short accelerated radiotherapy regimen given twice daily over a period of 3 weeks. A total of 116 patients with high-grade glioma were treated with radiotherapy in a prospective study using an accelerated fractionation regimen. The total dose of 55 Gy was given in 32-36 fractions of 1.72-1.53 Gy, twice daily 5 days a week, with a minimum 6 h interval between fractions. Toxicity was assessed using Karnofsky performance status scale and in the later part of the study with the Barthel index. Survival data were compared with a control group treated with 60 Gy in 30 daily fractions in a previous MRC study, matched for known prognostic factors. The median survival of 116 patients treated with accelerated radiotherapy was 10 months. Survival comparison of accelerated patients with matched controls treated with conventional fractionation demonstrated a hazard ratio of 1.13 (95% confidence interval 0.85-1.51; P = 0.39). Early treatment toxicity was acceptable, with only seven patients developing transient decrease in performance status. The accelerated radiotherapy regimen was logistically feasible and acceptable to patients, carers and staff. Treatment time was reduced without apparent increase in early toxicity and there was no loss of survival benefit. The effectiveness and convenience of a short accelerated regimen makes this a suitable alternative to a 6 week course of radiotherapy in patients with high-grade glioma. However, a full randomised trial comparing conventional and accelerated radiotherapy may be required as proof of equivalence.

Actuarial Analysis↗

Modifying the Barthel Performance Index Score for use in patients with brain tumours.

Performance status scores are useful tools in the management of patients with malignant disease. No specific performance index score exist, however, for patients with glioma. The Barthel Index, has been used in our department because it has been widely used in patients following stroke and found useful. This study aims to establish whether a modification of the Barthel Index would be more appropriate for patients with glioma and, if so, what modifications should be made. The opinions of multidisciplinary health workers and carers experienced in helping patients with glioma were established by questionnaire. Difficulty with speech and the presence of seizures were statistically ranked the most significant disability in terms of overall performance status. As these are not included in the Barthel Index a modification is justified. However, to include new categories in a performance index but avoid increasing its complexity, existing categories have to be omitted. Therefore, the second aim of this study was to establish which categories within the Barthel contribute least to a change in the total score. Three-hundred-and-thirty-three prospectively recorded Barthel scores were evaluated in 81 patients over 2 years and the individual categories evaluated by multifactor analysis. The sensitivity of the categories 'bowel function' and 'independence in grooming' to a change in the total score was less than 1%. In conclusion, substituting 'speech difficulties' and the presence of seizure in place of 'bowel function' and 'independence in grooming' from the Barthel Index will improve the specificity for patients with glioma without reducing the sensitivity or acceptability for the patients and research nurses who most often complete them.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Role of bisphosphonates in prevention and treatment of bone metastases from breast cancer.

Clinical research over the last decade has confirmed the helpful role of bisphosphonates in the management of patients with bone metastases secondary to breast cancer and other malignancies. This role is also expanding in myeloma and in the management of osteoporosis. Current clinical research in oncology is focusing on their potential for the prevention of skeletal complications of malignant disease and the development of bone metastases while basic researchers are developing compounds of higher potency and, perhaps, higher therapeutic efficacy. One of the earliest agents to be investigated, etidronate, is effective in the management of malignant hypercalcemia and, when used orally and intermittently, results in reduced bone loss in osteoporosis. However, it does not appear to reduce pain in patients with malignant disease. Clodronate has been shown to be an effective agent in the management of hypercalcemia and can be used as a single intravenous infection for this purpose. Clodronate is also effective in some patients in reducing bone pain and improving mobility. When used orally, it can, as can pamidronate, reduce the skeletal complications of breast cancer such as hypercalcemia, bone fractures and bone pain. It may have fewer gastrointestinal side effects than oral pamidronate. There is emerging evidence that bisphosphonates may delay or prevent the clinical appearance of bone metastases as well as reduce other skeletal complications. Trials of adjuvant bisphosphonates such as clodronate and pamidronate in operable breast cancer are currently under way in Europe and North America.

Analgesics, Non-Narcotic↗

Long-term follow-up of young children with brain tumors after irradiation.

PURPOSE: Young children with brain tumors are at high risk of developing late sequelae after curative radiotherapy. A retrospective study was undertaken to determine the frequency and severity of neurological deficits, endocrine dysfunction, and intellectual disabilities. METHODS AND MATERIAL: One hundred and fifty-six children age < or = 3 years were treated between 1952 and 1986 with radiotherapy. Of the 57 survivors, 47 had surgery, 12 chemotherapy and 24 children received cranio-spinal radiotherapy. Late radiation side effects were assessed with a clinical examination, blood tests and an interview. RESULTS: The median follow-up was 13 years and the actuarial survival at 5 and 10 years was 49% and 44%, respectively. No, or only a mild, handicap was noted in 24 patients, while 21 had moderately severe and 16 severe disabilities. Children with supratentorial tumors had more abnormal neurological findings compared to those with infratentorial malignancies (p < 0.001). Eighty percent of children had endocrine abnormalities, which were more marked in children with parasellar tumors (p < 0.001). Twenty-one children were mentally retarded. In a multivariate analysis epilepsy emerged as the only significant variable independently associated with poor cognitive function. CONCLUSION: Long-term morbidity was found to be disabling in 58% of the surviving children. These findings encourage the development of treatment strategies designed to reduce toxicity.

Adolescent↗

Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease.

PURPOSE: To analyze presentation variables that might indicate a high or low likelihood of success of the treatment of patients relapsing after initial radiotherapy of Hodgkin's disease in clinical Stages I or II who were staged with laparotomy. METHODS AND MATERIALS: Data were analyzed on 681 patients in the International Database on Hodgkin's Disease who were initially in clinical Stages I or II, who were staged with laparotomy, and who relapsed after initial treatment with irradiation alone. Factors analyzed for outcome after first relapse included initial stage, age, sex, histology, presentation (supra- vs. infradiaphragmatic), number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, lactate dehydrogenase, alkaline phosphatase, serum albumin, and hemoglobin. RESULTS: Only age and histology showed significant prognostic impact in univariate and multivariate analyses. The influence of age may perhaps be attributed to suboptimal treatment of some older patients. Patients with nodal relapse had a better prognosis than patients with extranodal relapse, probably indicating that the latter had more extensive disease at relapse. The length of the initial disease-free interval had no influence on prognosis after relapse. CONCLUSION: The decisive factors for outcome after initial treatment with irradiation alone are a) the factors predicting the risk of relapse after initial radiotherapy and b) the factors predicting outcome after relapse, that is, histologic subtype and extent of disease at relapse.

Adult↗

The management of histologically unverified presumed cerebral gliomas with radiotherapy.

PURPOSE: To define the natural history, and prognostic factors of patients with histologically unverified presumed gliomas diagnosed on CT or MR imaging, and treated with external beam radiotherapy. METHODS AND MATERIALS: Retrospective review of 111 adults with histologically unverified presumed cerebral glioma treated with radiotherapy between 1974 and 1990. Using CT or MRI criteria alone 41 were presumed low grade, 63 high grade gliomas and 7 were unclassified. Survival results were compared to a cohort of 82 adults with histologically verified low grade gliomas treated over the same period with surgery and radiotherapy. RESULTS: The 5 year survival probability of the whole cohort was 31%. Age, performance status, and the degree of contrast enhancement were independent prognostic factors for survival. Patients with presumed low grade glioma had a 5 year survival of 41% compared to 52% for patients with verified low grade glioma. After correction for prognostic factors no significant difference was found in the survival between patients with verified and unverified low grade tumors. One of 15 cases with subsequent histology, obtained at autopsy or salvage surgery, had nonglial pathology. CONCLUSION: Patients diagnosed on the basis of clinical features and imaging as having presumed glioma have similar natural history and clinical behavior after treatment with radiotherapy to those with histologically confirmed gliomas. However, the results should not be taken as justification for avoiding biopsy. A proportion of patients may have nonglial pathology and new more effective treatment strategies for patients with glial tumors can only evolve on the basis of full diagnostic information including pathology.

Adolescent↗

Hypofractionated radiotherapy as palliative treatment in poor prognosis patients with high grade glioma.

We report the palliative effectiveness of a hypofractionated radiotherapy regimen in patients with poor prognosis high grade glioma. Thirty-eight elderly, and/or disabled patients received radiotherapy to a dose of 30 Gy in 6 fractions over 2 weeks to a planning target volume defined by the enhancing tumour and a 2-cm margin. The median survival was 6 months with a 1-year survival rate of 23%. Treatment was without acute toxicity. One month after radiotherapy, functional status, assessed using a verbally administered Barthel index, improved in 38% and remained stable in a further 39% of surviving patients. At 3 months 39% of surviving patients had improved and a further 12% remained stable. We conclude that in the poor prognostic group of patients with high grade glioma hypofractionated partial brain radiotherapy is well tolerated, convenient and provides effective palliation in a proportion of patients. Comparison with conventional radiotherapy or symptomatic care alone require further evaluation in randomised studies.

Activities of Daily Living↗

Survival in patients with recurrent glioma as a measure of treatment efficacy: prognostic factors following nitrosourea chemotherapy.

The assessment of efficacy of treatment in patients with recurrent glioma is notoriously difficult, and survival is the most objective endpoint. Between 1970 and 1992, a cohort of 211 patients with recurrent glioma received nitrosourea-based chemotherapy at the time of disease progression. The median survival from the start of chemotherapy was 7 months, with 30% 1-year and 10% 2-year survival probabilities. One-year survival was 22% in 147 patients with recurrent high-grade astrocytoma, 41% in 37 patients with low-grade astrocytoma and 45% in 24 patients with oligodendroglioma. Age, histological grade and Karnofsky performance status (KPS) at recurrence were independent prognostic factors for survival on multivariate analysis. Based on patients' age, tumour grade and KPS, it was possible to define three distinct prognostic groups with 1-year survival probabilities of 60, 21 and 17% (P < 0.005). Response to chemotherapy was difficult to assess but correlated with prognostic subgroup, with highest response rate (46%) in the most favourable group and lowest (13%) in the poor prognostic group. In patients with recurrent glioma, patient and tumour parameters are the major determinants of outcome which are identical to prognostic factors at the time of primary diagnosis. They can be used to provide prognostic information for the individual patient, and to stratify patients particularly in trials assessing the efficacy of novel treatments.

Adolescent↗

Percutaneous laser recanalisation of femoropopliteal occlusions using continuous wave Nd-YAG laser and sapphire contact probe delivery system.

A conventional continuous wave Nd-YAG medical laser system delivered by transparent sapphire tipped optical fibres was used for percutaneous recanalisation of 32 chronic femoropopliteal occlusions in 27 patients (19 men, eight women; median age 68 years, range 46-83 years). Twenty-four patients had severe intermittent claudication and three had critical ischaemia. The median occlusion length was 8 cm (range 3-35 cm) and lesions were not negotiable by guidewire. Laser energy was delivered at powers of 10-15 Watts using intermittent 1 second emissions (mean total energy 315 Joules, range 30-1015]). The sapphire tips used were 1.8 to 3.0 mm diameter. After laser recanalisation adjunctive balloon dilatation was necessary to widen the resulting lumen. All patients received anti-platelet therapy. Initial clinical success was achieved in 22 limbs (69%) with symptomatic relief and increase in mean (+/- S.D.) ankle-brachial pressure ratio from 0.52 (+/- 0.25) to 0.80 (+/- 0.21) [Mann-Whitney U, p < 0.001]. Recanalisation was unsuccessful in all calcified lesions (four cases). There was a high incidence of vessel perforation (28%) and wall dissection (25%). Emergency surgery was not required after failed procedures. The median follow-up was 12 months (range 6-20 months). By 6 months, 15 of 22 successfully recanalised lesions (68%) had reoccluded. The cumulative primary patency at 1 year was only 12%. These disappointing results do not support routine use of this system. Clearly, modifications of the laser/delivery system or the technique, or both, are required. The aim should be to achieve sole laser recanalisation without concomitant balloon dilatation.

Aged↗

Phase I study of mitozantrone, methotrexate and mitomycin with granulocyte colony-stimulating factor (filgrastim) in patients with advanced breast cancer.

The combination of mitozantrone, methotrexate and mitomycin (3M) gives a response rate of around 50% in patients with advanced breast cancer. The predominant toxicity is haematological. In this study, previously untreated patients were given 3M with increasing doses of mitozantrone (7-14 mg m-2) with recombinant human granulocyte colony-stimulating factor (metHuG-CSF) (filgrastim) to prevent marrow toxicity. Doses administered were 7 mg m-2 mitomycin i.v. 6 weekly, methotrexate i.v. 35 mg m-2 (maximum 50 mg) 3 weekly and mitozantrone i.v. 3 weekly as follows: 7 mg m-2, six patients (group 1); 10 mg m-2, six patients (group 2); 12 mg m-2, six patients (group 3); 14 mg m-2, six patients (group 4); all on day 1 for six cycles at the assigned dose. All patients received filgrastim (Amgen 0.3 mg ml-1) at a dose of 5 micrograms kg-1 subcutaneously daily on days 4-17 of each cycle. All treatment was given on an out-patient basis. A total of 24 patients were entered into the study. The median age was 63 years (range 48-75). ECOG performance status was 0 in ten, 1 in 11 patients and 2 in three patients. Locoregional disease alone was present in seven patients. The remainder had one or more sites of metastases. The actual dose administered to the 24 patients was as follows. The six patients in group 1 all completed six courses of treatment as per protocol. In group 2, three patients completed six courses, two stopped because of toxicity after one and four courses and one had progressive disease after one course. In group 3, three patients completed and three stopped early because of progressive disease. In group 4, two patients completed, one progressed after four courses and three responding patients stopped treatment because of toxicity. The maximum tolerated dose of mitozantrone in the 3M combination was 12 mg m-2. The use of filgrastim with increasing doses of chemotherapy prevents neutropenia, but other toxicities, namely thrombocytopenia and lethargy, then become dose limiting.

Aged↗

Peripheral blood involvement in non-Hodgkin's lymphoma detected by clonal gene rearrangement as a biological prognostic marker.

Peripheral blood from 67 patients with non-Hodgkin's lymphoma was examined at initial diagnosis for the presence of circulating lymphoma cells by DNA hybridisation using immunoglobulin and T-cell receptor gene probes. Clonal gene rearrangement was found in 31% (21/67) of patients and correlated with clinical stage, histological grade and bone marrow involvement. Clinical stage and the presence of lymphoma cells in peripheral blood were prognostic factors for progression-free survival in all patients on univariate analysis, but the detection of lymphoma cells was not independent of stage. It was also not a significant predictor for survival. In patients with intermediate- and high-grade lymphoma, the detection of lymphoma cells in peripheral blood was a significant prognostic factor for progression-free survival (PFS) and survival only on univariate analysis. The 3-year PFS was 17% in patients with circulating lymphoma cells compared with 75% if these were absent (P < 0.05). The presence of lymphoma cells in peripheral blood is associated with extensive disease and may be a biological marker of poor disease control. Sensitive techniques of detection should form part of large prospective studies in non-Hodgkin's lymphoma.

Adult↗

Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen.

PURPOSE: To investigate the efficacy and toxicity of continuous infusion fluorouracil (5-FU) with every-3-weeks epirubicin and cisplatin (ECF) in advanced breast cancer in a phase II study. PATIENTS AND METHODS: Forty-three patients with metastatic (n = 29) or locally advanced/inflammatory (n = 14) breast cancer were treated with 5-FU 200 mg/m2/d via a Hickman line using an ambulatory pump for 6 months with epirubicin 50 mg/m2 intravenously (IV) and cisplatin 60 mg/m2 IV every 3 weeks, for eight courses. RESULTS: The overall response rate (complete plus partial) was 84% (95% confidence interval [Cl], 76% to 96%), with a complete response rate of 24% (95% Cl, 9% to 40%) in patients with metastatic disease and 36% (95% Cl, 11% to 61%) in patients with locally advanced disease. The main World Health Organization [WHO] grade 3 or 4 toxicities included leukopenia, emesis, and alopecia. CONCLUSION: Infusional ECF is a highly active regimen in advanced breast cancer and warrants evaluation in high-risk early breast cancer.

Adult↗

Laser angioplasty.

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Angioplasty, Balloon↗

Vertical banded gastroplasty for the treatment of morbid obesity.

Prospective evaluation of 114 obese patients (96 women, 18 men) undergoing vertical banded gastroplasty over a 5-year period was undertaken. The age range was 17-58 (median 37) years, median weight 119.3 (range 79-216) kg, mean(s.d.) proportion of excess body-weight 104.1 (34.9) per cent and median body mass index (BMI) 44.8 (range 33.2-77.7) kg/m2. Three gastric outlet stoma circumferences were used: 5.5 cm (31 patients), 5.0 cm (28) and 4.75 cm (55). A total of 109 patients (95.6 per cent) were available for follow-up. At 1 year after operation, 54 patients (59 per cent) had lost greater than 50 per cent of excess body-weight. No patient lost less than 25 per cent of excess body-weight, and the median BMI was 32.5 (range 21.3-47.8) kg/m2. The operative mortality rate was zero, but three patients (2.6 per cent) with gastric leakage required surgical revision. Vertical banded gastroplasty is a relatively safe and simple procedure that produces significant and sustained weight reduction in the majority of morbidly obese patients.

Adolescent↗

Craniopharyngioma--a long-term results following limited surgery and radiotherapy.

Between 1950 and 1986 173 patients with craniopharyngioma were treated at the Royal Marsden Hospital with external beam radiotherapy either alone or following surgery. Four patients had complete tumour excision, 21 subtotal and 78 partial resection, 14 had biopsy alone, 34 aspiration alone and 22 had no surgery directed at tumour eradication. Seventy-seven (45%) were children (aged < 16 years). The 10 and 20 year progression-free survival (PFS) rates were 83% and 79%. There were no independent prognostic factors for PFS. The 10 and 20 year survival rates were 77% and 66% at a median follow-up of 12 years. After adjustment for mortality in the normal population, age and technique of radiotherapy (which corresponded with era of treatment) were significant independent prognostic factors for survival. The risk of death (corrected for mortality from natural causes and controlling for radiotherapy technique) for age groups 16-39 and > or = 40 was 0.58 and 0.40 respectively, relative to a risk of 1.0 for the age group < 16 years. Survival and PFS were not influenced by the extent of surgical excision. Visual field defect improved after radiotherapy in 36% of patients (38/106) and visual acuity in 30% (27/91). No patient developed radiation optic neuropathy. We conclude that limited surgery and radiotherapy achieve excellent long-term tumour control and survival with low morbidity.

Adolescent↗

Ploidy and proliferative index in medulloblastoma: useful prognostic factors?

Paraffin sections from 32 patients with primary medulloblastoma were analysed by flow cytometry for DNA ploidy and proliferative index to assess the value of these measurements in determining prognosis. Twenty-seven samples were informative. Of these 27 patients, 8 had had a total resection. The tumors were diploid in 13 patients and aneuploid in 14. Neither ploidy nor S-phase fraction were prognostic factors for survival, even when considered in conjunction with the type of surgery performed. This is in contrast to other published data, emphasising the need for large multicentre studies of biological prognostic factors in this rare tumour.

Adolescent↗

EPIC: an effective low toxicity regimen for relapsing lymphoma.

We have treated 40 patients was relapsed or resistant lymphoma with the combination of Etoposide, Prednisolone, Ifosfamide and Cisplatin (EPIC). Complete response was obtained in 11 patients (28%) with an overall response of 58%. The presence of bulky disease (P < 0.005), elevated LDH serum levels (P < 0.005), response to prior chemotherapy (P < 0.01) and B symptoms (P < 0.005) were significantly associated with response. However on multivariate analysis only the presence of bulky disease and of B symptoms were independent adverse factors for response and for survival. The regimen was well tolerated with myelosuppression being the most common toxicity. Leucopenia < or 1,000 microliters-1 and thrombocytopenia < or = 25,000 microliters-1 developed in 27% and 4% of cycles respectively. There were no treatment related deaths. The EPIC regimen has equivalent activity to other reported cisplatin based regimens used in the treatment of recurrent lymphoma, but is associated with lower treatment related morbidity and mortality.

Adult↗