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Biomedical subjects

R Swindell

Publications and source records attributed to R Swindell.

At least 91 records · Page 5Linked to original sources
PubMed1990

Low-dose pituitary irradiation for acromegaly.

External radiotherapy has been used as primary treatment for acromegaly in 29 patients and in combination with surgery in 41 patients in whom growth hormone levels remained elevated postoperatively. Fourteen further patients who did not receive radiotherapy have also been studied, four of whom had undergone surgical treatment. Radiotherapy schedules consisted of 20 Gy in eight fractions over 11 days (n = 23) or 35-40 Gy in 15 fractions over 21 days (n = 47). Growth hormone hypersecretion was either unchanged or increased with time in non-irradiated patients. In those patients who underwent radiotherapy, the likelihood of the mean GH level during GTT falling to less than 5 mU/l was unaffected by the total dose of radiation administered. However, patients with a pre-radiotherapy GH level of less than 30 mU/l showed a significantly increased probability of achieving a post- radiotherapy GH level less than 5 mU/l (P = 0.002). Previous surgery, initial serum prolactin and the age or sex of the patient did not predict the successful outcome of radiotherapy. In view of the known dose dependency of radiation-induced hypopituitarism, lower radiation dose schedules (20 Gy; eight fractions in 11 days) can be used in acromegaly with some benefit, especially in younger patients. However, all patients should undergo operative removal of as much GH-secreting tissue as possible, in order to lower GH levels and increase the probability of achieving a cure following radiotherapy.

Acromegaly↗
PubMed1990

Five year follow-up and dose delivery analysis of cisplatin, iproplatin or carboplatin in combination with cyclophosphamide in advanced ovarian carcinoma.

Eighty eight patients with FIGO stage IIb/c (postoperative residual) or III/IV epithelial ovarian cancer were randomised to receive cycles of cyclophosphamide (600 mg/m2) with either iproplatin (240 mg/m2), cisplatin (100 mg/m2) or carboplatin (300 mg/m2). A total of six cycles were given at monthly intervals. Patients were well-balanced for major prognostic factors. There was no significant difference in overall response rate (iproplatin arm, 64.3%, cisplatin arm 72.7% and carboplatin arm 66.7%). There were more complete remissions on the carboplatin arm, 45.8% compared with 21.4% on iproplatin and 22.7% on cisplatin but the difference was not statistically significant (p = 0.11). With a median follow up of 50 months the median survival for the iproplatin arm is 18 months, for the cisplatin arm 19 months and for the carboplatin arm 24 months (p = 0.15). Toxicity was greatest with cisplatin and least with carboplatin. Myelotoxicity limited the dose delivery of iproplatin as measured by total dose, dose intensity and dose intensity product. Carboplatin is at least as effective and less toxic than cisplatin when used in conjunction with cyclophosphamide for the treatment of ovarian carcinoma, and this analogue has been selected for dose intensification studies in this tumour at the Christie Hospital.

Adult↗
PubMed1989

Expression of epidermal growth factor receptor (EGF-R) in non-small cell lung cancer. Use of archival tissue and correlation of EGF-R with histology, tumour size, node status and survival.

A total of 152 non-small cell lung cancers (NSCLC) were studied retrospectively to determine the relationship between epidermal growth factor receptor (EGF-R) status and the histological type, tumour size, nodal status and prognosis. EGF-R status was assessed on routinely embedded paraffin sections with an antibody to the cytoplasmic domain of the tumour (F4 antibody). EGF was demonstrated in all tumour types and every squamous and large cell carcinoma was positive for the antibody. Most tumours showed heterogeneity of staining. EGF expression was seen statistically more frequently in well differentiated tumours. Patients with 50% or more tumour cells showing positivity tended to have an improved survival but this result failed to reach statistical significance. There was no relationship between the size of the primary tumour or the lymph node status. Other cells, such as mucinous glands, bronchial epithelial cells and macrophages stained positively with the monoclonal antibody. EGF receptor status, with the antibodies presently available, adds little to help in either diagnosis or prognosis. Interpretation of data has to be guarded since the antibody was seen in some normal cells.

Carcinoma, Non-Small-Cell Lung↗
PubMed1989

A simple outpatient treatment with oral ifosfamide and oral etoposide for patients with small cell lung cancer (SCLC).

For the first time in a clinical study oral Ifosfamide was used: 65 elderly or unfit patients with small cell lung cancer (SCLC) were treated as outpatients with fractionated oral Ifosfamide and Etoposide. Forty patients (62%) had extensive stage (ED) disease. The median age of the patients was 66 years. In the 60 patients evaluable for response the objective response rate was 90% with a complete response (CR) rate of 32% and a partial response (PR) rate of 58%. The overall median survival of all 65 patients was 11 months (13 months for LD, 9.5 months for ED). In those patients with LD achieving a CR or a PR radiotherapy was given to the mediastinum. No prophylactic cranial irradiation was given. There was a rapid improvement in the responding patients' performance status and symptoms generally with the first treatment cycle. Overall haematological toxicity was mild, with intravenous antibiotics only being required in 4% of the courses and with only one treatment-related death from septicaemia. A higher than expected rate of CNS toxicity was seen (30%). This was generally mild and always fully reversible and consisted mainly of forgetfulness, occasionally hallucinations, nightmares and somnolence. In only one case did encephalopathy necessitate early termination of treatment. This raises the question of whether Ifosfamide metabolism differs quantitatively or qualitatively when given by the oral route as opposed to the usual intravenous route. We conclude that this simple outpatient based treatment gives a high response rate with rapid improvement in symptoms.

Administration, Oral↗
PubMed1989

Randomized trial comparing ciprofloxacin plus netilmicin versus piperacillin plus netilmicin for empiric treatment of fever in neutropenic patients.

To assess the efficacy of ciprofloxacin in neutropenic patients, we conducted a randomized prospective trial comparing the combination of ciprofloxacin and netilmicin against piperacillin plus netilmicin as an empiric treatment of fever in cancer patients with neutropenia. Of 214 evaluable episodes, 115 and 99 were randomly assigned to the ciprofloxacin and the piperacillin arms, respectively. The overall response rates were very similar (59 and 62% for the ciprofloxacin and piperacillin arms, respectively). The response for the gram-positive bacteremias was almost identical (around 40%); this low response was due in part to an outbreak of infection by a multiply resistant strain of Staphylococcus epidermidis (for which the ciprofloxacin MIC was greater than or equal to 128 micrograms/ml) which occurred during the second half of the trial. Among gram-negative bacteremias, 9 of 11 infections (82%) responded to the ciprofloxacin combination compared with 3 of 7 (43%) that responded to the piperacillin combination (P = 0.23). The incidences of persistent, profound neutropenia were comparable in both treatments, but the susceptibility of the gram-negative organism to ciprofloxacin and netilmicin was significantly higher than was susceptibility to the other combination. Ciprofloxacin was well tolerated, and patients were able to convert from intravenous to oral therapy in 64 of 115 episodes.

Administration, Oral↗
PubMed1989

A comparative study of the nodular and diffuse variants of lymphocyte-predominant Hodgkin's disease.

A clinical comparison of the nodular and diffuse variants of lymphocyte-predominant Hodgkin's disease (HD-LP) has shown them to be similar in all respects, including survival and relapse-free survival (RFS). In addition, they appear similar to mixed cellularity (MC) and nodular sclerosing Hodgkin's disease (HD-NS) with regard to clinical course. Thus, the reported phenotypic differences between nodular lymphocyte predominant Hodgkin's disease (HD-LP[N]) and other forms of the disease do not appear to be reflected in clinical behavior.

Adult↗
PubMed1988

Expression of differentiation antigens within human mammary tumours is related to response to endocrine therapy and survival.

Human mammary tumours which are histologically well differentiated are more likely to synthesize receptors for estrogen (ER) and progesterone (PR) and to respond to systemic endocrine therapy. The aim of this study was to explore the relationship between differentiation, receptors and endocrine responsiveness in more detail by relating the expression of putative differentiation antigens within tumours to ER, PR and response to treatment. Sections of the primary tumours of 160 patients with advanced evaluable breast cancer were immunostained with 2 monoclonal antibodies (MAbs) (HMFG1 and HMFG2) raised against putative differentiation antigens found on the membranes which surround the milk fat globule. Tumours were highly heterogeneous with respect to antigen expression. However, the number of cells which expressed the antigens was highly correlated with ER and PR concentrations and with response to endocrine therapy. In tumours where greater than or equal to 20% of cells expressed the antigen recognized by HMFG1, 73% responded to endocrine therapy; this was similar to the response predicted by ER (67%) and PR (73%). Expression of HMFG1 was correlated with survival from the start of endocrine therapy (p less than 0.0001) to the same degree as ER and PR. Patients with tumours which expressed ER, PR and HMFG1 had the highest response rate (87%) and survival (median 49 months); the response in tumours which expressed none of these phenotypes was 13% and the median survival of these patients was 9 months. These results suggest that cells which express differentiation antigens also express ER and PR. Differentiated cells within mammary tumours may therefore be the target cells for systemic hormone, and also the source of factors which control tumour growth.

Adult↗
PubMed1988

Comparative toxicity of cisplatin, carboplatin (CBDCA) and iproplatin (CHIP) in combination with cyclophosphamide in patients with advanced epithelial ovarian cancer.

Sixty patients with FIGO stage IIb, IIc, III and IV ovarian cancer were entered into a randomized Phase III study of cyclophosphamide 600 mg/m2 with cisplatin 100 mg/m2, iproplatin 240 mg/m2 or carboplatin 300 mg/m2. Dose modifications were made according to renal function and myelotoxicity. The arms containing carboplatin (CBDCA) and iproplatin (CHIP) were not shown to be significantly different from the cisplatin containing arm with regard to response rate, duration of response and survival. Subjective toxicity showed that cisplatin and cyclophosphamide therapy was associated with more nausea and vomiting (P = 0.0005). The duration of vomiting showed a significant increase with successive courses of chemotherapy for the cisplatin containing arm only (P less than 0.003). The cyclophosphamide/CHIP combination caused significantly more diarrhoea (P less than 0.0006). Alopecia was more severe (P less than 0.02), and neurotoxicity was more common, in patients who received cyclophosphamide and cisplatin (paraesthesiae P = 0.0007, tinnitus P less than 0.00005, deafness P = 0.0018). All three combinations caused cumulative toxicity on haemoglobin (Hb) (P less than 0.001 for each treatment), leukocyte count (WCC) (P less than 0.0005 for each treatment), and platelet count (P less than 0.0005 for each treatment). The degree of fall in Hb for each course of therapy was greater in the cisplatin containing arm compared with the CHIP and CBDCA arms which were not significantly different from each other (P = 0.0005). For WCC the cisplatin/cyclophosphamide regimen was significantly less toxic than CHIP/cyclophosphamide, with CBDCA/cyclophosphamide falling between the two and not being significantly different from either (P = 0.0005). The CHIP containing arm caused more thrombocytopenia than the other arms which were of equal toxicity (P less than 0.0005). Serum creatinine showed a gradual significant overall rise with each course of cisplatin/cyclophosphamide therapy (P less than 0.0005), whereas the CBDCA arm showed no change and the CHIP arm showed a small fall in serum creatinine after most courses of therapy. This study showed that CHIP or CBDCA in combination with cyclophosphamide was less toxic than cisplatin/cyclophosphamide therapy with regard to alopecia, degree and duration of nausea and vomiting, renal toxicity, neurotoxicity and anaemia. The CHIP/cyclophosphamide regimen caused more thrombocytopenia and diarrhoea. The CHIP and CBDCA containing arms caused more leukopenia than the cisplatin containing regimen. Either iproplatin or carboplatin would be an acceptable alternative to cisplatin in chemotherapy regimens, and would result in reduced toxicity.

Aged↗
PubMed1988

The Christie hospital adjuvant tamoxifen trial--status at 10 years.

From November 1976 to June 1982, a randomised clinical trial was carried out at the Christie Hospital, Manchester, to test the clinical efficacy of tamoxifen (TAM) as an adjuvant to surgery for patients with operable breast carcinoma. Following surgery, premenopausal women were randomly allocated to have either TAM 20 mg day-1 for one year or an irradiation menopause (the previous standard treatment). Postmenopausal women had TAM 20 mg day-1 for one year or no further treatment (Controls). A total of 1005 patients were entered into the trial of whom 961 are evaluable at 10 years from the inception. At 10 years the analysis shows no significant difference in overall and disease free survival between premenopausal women given TAM or an irradiation menopause. For premenopausal node negative patients there would appear to be a trend in favour of the TAM treated patients with a 93% ten year survival vs. 82% for the irradiation menopause group (P = 0.09). When the disease free survival of all 961 patients is analysed, allowing for node status, then there is a marked trend in favour of the TAM treated patients (P = 0.07). Of the patients originally allocated to TAM 47% had an irradiation menopause on relapse and 73% of the postmenopausal control patients had TAM on relapse. The incidence of side effects and second primary tumours is discussed as well as the possible effects of varying the length of time over which adjuvant TAM is administered.

Adult↗
PubMed1988

Prognostic factors for survival in stage IIIB and IV Hodgkin's disease: a multivariate analysis comparing two specialist treatment centres.

A multivariate analysis of prognostic factors was carried out on 301 patients with clinical or pathological stage III/IV Hodgkin's disease treated using the same combination chemotherapy (MVPP) at two centres (Christie Hospital, Manchester, 151 patients, St. Bartholomew's Hospital, London, 150 patients). There were no significant difference in CR or relapse free and overall survival at 5 and 10 years between the two groups. Cox analysis of the Christie data alone produced four significant factors for survival - age, sex, lymphocyte count and stage. The latter three factors showed the same trend for the St. Bartholomew's Hospital patients but failed to reach statistical significance. Analysis of the combined data showed all four factors to be of importance in predicting survival. Three different prognostic groups were identified which separated patients with good, intermediate or poor prognosis in both centres. The good prognostic group included patients aged less than 45 years, lymphocyte count greater than 0.75 x 10(9) l-1 and female patients with stage IIIB disease (5 year survival 85%). The rest were of poorer prognosis with male stage IV patients faring particularly badly (5 year survival 40%). Problems associated with the use of multivariate analysis to produce useful prognostic groupings in patients from different centres, are discussed.

Age Factors↗
PubMed1987

Endocrine therapy for advanced carcinoma of the breast: effect of tumor heterogeneity and site of biopsy on the predictive value of progesterone receptor estimations.

This study was carried out to assess the influence of site of biopsy and tumor heterogeneity upon the value of progesterone receptor (PR) measurements for prediction of response of patients with advanced carcinoma of the breast to tamoxifen or ovarian ablation. One hundred eighty-one assessable patients were studied. Sixty-nine % of responders and 31% of nonresponders were PR positive. The times to progression and survival were not significantly different for responders whether they were receptor positive or receptor negative. PR was measured on operable primary tumors (97), inoperable primary tumors (59), and secondary deposits (69). The proportion of responders who had PR-positive biopsies from these sites was 59%, 88%, and 61%, respectively, and the proportion of PR-positive nonresponders was 30%, 27%, and 42%, respectively. Ten to 12 separate PR measurements were made on seven tumors, and in four of them, there were PR-positive and PR-negative areas which could account for false positive and false negative results. We conclude that the optimum prediction of response was seen when the biopsy was performed on inoperable primary tumors. Errors in prediction of response at this site were, in part, explained by within-tumor heterogeneity of PR; the greater errors in prediction when measurements were made on operable primary tumors or on secondary deposits are presumed to be related to the additional effects of change in receptor status with time and between-tumor-site heterogeneity, respectively.

Biopsy↗
PubMed1987

Endocrine therapy for advanced carcinoma of the breast: relationship between the effect of tamoxifen upon concentrations of progesterone receptor and subsequent response to treatment.

In some cell lines and tumors of mammary origin, tamoxifen causes an increase of progesterone receptor (PR) as a result of its partial estrogen agonist activity. In this study we have assessed the effect of tamoxifen on PR in patients with advanced carcinoma of the breast in order to test if those with a rise in PR are more likely to respond to endocrine therapy. PR was measured before and a median of 13 days after treatment with tamoxifen in a group of 52 patients with either locally advanced (n = 28) or recurrent (n = 24) carcinoma of the breast. Controls were a group of patients with operable disease who had two biopsies with no intervening tamoxifen (n = 51) or with intervening tamoxifen (n = 58). In the test group PR was higher in the second biopsy than the first in 21 patients, and 19 of these responded to continued endocrine therapy (90%). In the remaining 31 patients PR was either lower in the second biopsy (n = 19) or was negative in both biopsies (n = 12), and 11 of the total of 31 patients (35%) responded to continued endocrine therapy. The prediction of response and time to progression was better when both biopsies were taken into account than either the first or the second alone. The prediction of survival was similar for the group selected by an increase in the second biopsy and the group with PR present in the second biopsy. The controls without tamoxifen showed a marked variation in the level of PR in the first and second biopsies, suggesting heterogeneity of PR across the tumors studied. However, the PR level was significantly higher in the second biopsy in the controls given tamoxifen and in the test group compared with those with no intervening treatment (p = 0.031). This study indicates that some effect of tamoxifen upon PR can be demonstrated in human mammary tumors in vivo and that, by taking a second biopsy for PR estimation during treatment with tamoxifen, a more precise indication of subsequent response is obtained. The value of a single estimation of PR before treatment on secondary deposits is limited, and if one biopsy only is performed, it is of greater predictive value if taken after a few days treatment with tamoxifen.

Aged↗
PubMed1987

DNA analysis by flow cytometry, response to endocrine treatment and prognosis in advanced carcinoma of the breast.

The relationship between DNA content of mammary cancer and subsequent response to endocrine therapy was studied in 136 patients with advanced disease. All were treated with tamoxifen or ovarian ablation as first-line systemic therapy after relapse and were evaluable for response according to UICC criteria. DNA characterisation by flow cytometry was used on formalin fixed paraffin-embedded samples of tumour. Tumours were grouped according to DNA index into diploid (n = 52, 38%), 'tetraploid' (n = 46, 34%) and 'other DNA-aneuploid' (n = 38, 28%). The highest proportion of oestrogen receptor positive tumours (ER + ve) was found in the 'tetraploid' tumours (38/46, 85%, Chi-square = 8.53, P less than 0.02), and response rates, (SD + PR + CR), were 26/52 (50%), 34/46 (74%), and 15/38 (39%) respectively (Chi-square = 10.88, P less than 0.005). Patients with diploid or 'tetraploid' tumours survived longer and stayed in remission longer than those with 'other DNA-aneuploid' tumours. We suggest that 'tetraploid' or 'near tetraploid' human mammary tumours may comprise a distinct group of endocrine responsive tumours within the overall group of aneuploid tumours. The conventional interpretation of DNA histograms, grouping into diploid and aneuploid, may be masking important features of some tumour groups.

Adult↗
PubMed1987

Evaluation of desmin as a diagnostic and prognostic marker of childhood rhabdomyosarcomas and embryonal sarcomas.

The diagnostic and prognostic relevance of desmin expression in 80 rhabdomyosarcomas (RMS) and 5 embryonal sarcomas (ES) was examined using a peroxidase anti-peroxidase staining procedure. Fifty-nine RMS but only one ES stained for desmin (P less than 0.05). The maximum percentage of desmin containing cells was 49 in RMS compared with only 1% in ES. Desmin positivity correlated inversely with survival (P less than 0.02) in that RMS with high proportions of desmin positive cells were associated with poorer prognoses than those containing fewer desmin positive cells. If the degree of expression of desmin is related to myogenic differentiation, then our results indicate that poorly differentiated RMS tend to have a better prognosis than the well differentiated tumours. One possible explanation is that the poorly differentiated RMS respond better to chemotherapy than to well differentiated RMS. A multivariant analysis incorporating desmin staining, treatment, histology, age and gender revealed that the two most significant independent prognostic factors were treatment and histology.

Desmin↗
PubMed1987

Effect of spinal irradiation on growth.

Standing height, sitting height, and leg length were measured in 79 patients (aged 16-30 years), who had been given craniospinal irradiation (n = 37) or cranial irradiation (n = 42) in childhood for a brain tumour and had completed their growth. Their measurements were compared with established standards for sitting height and leg length in British children (aged 16-18 years). To examine the effects of spinal irradiation on spinal growth independent of growth hormone deficiency we analysed the leg length (LL) minus sitting height (SH) standard deviation score (SDS) and used the cranial group as controls. There was an overall significant difference between the median craniospinal LL-SH SDS (1.98) and the median cranial LL-SH SDS (0.545). Within the craniospinal group there was a significant correlation with age at treatment, but there was no such correlation for the cranial group. After splitting age at treatment into three groups (0 less than 5, 5 less than 10, and 10-15 years) there was a significant difference between the LL-SH SDS of the craniospinal and cranial groups for each of the age ranges. In conclusion, spinal irradiation has a profound effect on spinal growth and the younger the child is when given irradiation the greater the subsequent skeletal disproportion. Our most conservative figures indicate that the eventual loss in height is 9 cm when irradiation is given at 1 year, 7 cm when given at 5 years, and 5.5 cm when given at 10 years.

Adolescent↗