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Biomedical subjects

W M Gregory

Publications and source records attributed to W M Gregory.

At least 55 records · Page 3Linked to original sources
PubMed1993

The hormonal milieu and prognosis in operable breast cancer.

Evidence is presented from those studies which have shown that the timing of surgery affects the prognosis of premenopausal women with operable breast cancer. Those undergoing surgery at a time of unopposed oestrogen (days 3-12) had a significantly worse prognosis than those who had operations at other phases of the menstrual cycle. This was also borne out by another study that indicated that progesterone levels at the time of surgery had prognostic significance, with node positive patients in the luteal phase (progesterone > 1.5 ng/ml) having a significantly better outcome. A meta-analysis has shown a highly significant heterogeneity of results, which do not overall show an effect. Possible reasons for this heterogeneity are discussed together with the need for prospective studies.

Breast Neoplasms↗
PubMed1992

An inter-observer and intra-observer variability study on the diagnosis of lymph node biopsy specimens.

One hundred lymph node biopsy specimens were examined on two separate occasions by seven pathologists differing in experience in lymphoreticular pathology. Neither history nor immunohistochemistry was provided and the study, therefore, focused on morphological interpretation alone. The participants evaluated each case using a constructed response form in which the confidence with which they entered each response was also entered. Agreement on various points, between pathologists, between the two rounds, and with the referring centre was assessed. Whilst there was a high level of agreement over a diagnosis of benign vs. malignant and non-Hodgkin lymphoma vs. Hodgkin's disease, there was considerably less agreement over both T vs. B cell phenotype and high vs. low grade. The lack of agreement over grade, an evaluation which is usually made independent of immunohistochemistry, is particularly important, because of the relevance to selection of treatment. Proliferation markers may be more appropriate determinants of treatment choice.

Biopsy↗
PubMed1992

Doxorubicin in advanced breast cancer: influence of schedule on response, survival and quality of life.

The influence of scheduling of doxorubicin on response, survival and quality of life was assessed in a randomised trial in patients with advanced breast cancer, none of whom had previously received cytotoxic chemotherapy for advanced disease. 28 patients received 75 mg/m2 doxorubicin every 3 weeks for four courses (arm 1) and 31 patients received 25 mg/m2 weekly for 12 courses (arm 2). Response rates and median time to progression were similar in the two arms and median survival was 8 months in both arms. However, amongst patients receiving treatment every 3 weeks, psychological distress measured using the Rotterdam symptom checklist fell significantly over the course; no such change was observed in those treated weekly. Physical symptoms related to cancer improved during treatment similarly for both groups.

Adult↗
PubMed1992

Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials.

PURPOSE: A meta-analysis was performed to compare survival after treatment with melphalan and prednisolone (M + P) with that after combination chemotherapy (CCT) in patients with multiple myeloma. METHODS: Meta-analysis was performed on 18 published trials comprising 3,814 patients comparing M + P with CCT. Two-year survival percentages with observed and expected deaths at 2 years were calculated for each trial, and the overview methodology was applied to these figures. RESULTS: Overall results from the 18 trials suggest that there is no difference in efficacy between the two treatments. This finding, however, masks a highly significant correlation between 2-year survival rates for M + P-treated patients in individual studies and the difference between the M + P and CCT 2-year survival rates for that study (r = .69; P = .0008). In separate overviews, those studies with a high M + P 2-year survival rate showed a survival difference in favor of M + P (P = .02), whereas those with a low rate suggested a difference in favor of CCT (P V .07). Comparison of the 2-year survival rates in the M + P treatment arms of each of the studies with available data showed an inverse correlation between survival and the proportion of patients with either poor performance status (P less than .001) or immunoglobulin A (IgA) M band (P = .02). CONCLUSIONS: These results imply that M + P is superior for patients with an intrinsically good prognosis and inferior for those patients with a poor prognosis. If reliable prognostic factors can be established for this disease, they could be used to select therapy for individual patients.

Actuarial Analysis↗
PubMed1991

Timing of surgery during menstrual cycle and survival of premenopausal women with operable breast cancer.

Timing of operation in relation to menstrual phase might affect outlook in premenopausal women with operable breast cancer. We examined the records of 249 such women treated between 1975 and 1985, and compared overall and recurrence-free survival in those whose operation was 3-12 days after their last menstrual period (LMP) (group 1, n = 75) with those in whom it was 0-2 or 13-32 days after LMP (group 2, n = 174). Overall and recurrence-free survival were greatly reduced in group 1 women (p less than 0.001 for both). Actuarial survival at 10 years was 54% in group 1 versus 84% in group 2. This effect was independent of other factors, was of much the same importance as nodal status in multivariate analysis, was largely confined to histologically node-positive cases, seemed to be greater in women with small tumours (less than or equal to 2 cm), and was seen in patients with oestrogen-receptor positive and negative tumours. Thus phase of menstrual cycle at operation is of great importance for long-term outlook in premenopausal women with breast cancer.

Actuarial Analysis↗
PubMed1991

A mathematical model relating response durations to amount of subclinical resistant disease.

A mathematical model is presented which seeks to determine, from examination of the response durations of a group of patients with malignant disease, the mean and distribution of the resistant tumor volume. The mean tumor-doubling time and distribution of doubling times are also estimated. The model assumes that in a group of patients there is a log-normal distribution both of resistant disease and of tumor-doubling times and implies that the shapes of certain parts of an actuarial response-duration curve are related to these two factors. The model has been applied to data from two reported acute leukemia trials: (a) a recent acute myelogenous leukemia trial was examined. Close fits were obtained for both the first and second remission-duration curves. The model results suggested that patients with long first remissions had less resistant disease and had tumors with slower growth rates following second line treatment; (b) an historical study of maintenance therapy for acute lymphoblastic leukemia was used to estimate the mean cell-kill (approximately 10(4) cells) achieved with single agent, 6-mercaptopurine. Application of the model may have clinical relevance, for example, in identifying groups of patients likely to benefit from further intensification of treatment.

Humans↗
PubMed1991

The relationship between c-erbB-2 expression, S-phase fraction and prognosis in breast cancer.

The relationship between c-erbB-2 gene expression (assessed immunohistochemically), S-phase fraction (SPF) and prognosis has been analysed in 172 women with primary breast cancer. c-erbB-2 staining was independent of age, tumour size, number of nodes involved, tumour grade and DNA ploidy, but was more common in oestrogen receptor (ER) negative tumours (P = 0.02) and progesterone receptor (PgR) negative tumours (P = 0.03). A weak correlation between c-erbB-2 staining and SPF was observed (r = 0.18). Amongst women with node negative disease, SPF was significantly related to relapse free survival (RFS, P = 0.04) while c-erbB-2 staining was not (P = 0.2). In contrast, both SPF (P = 0.002) and c-erbB-2 staining (P = 0.016) provided significant prognostic information on RFS for women with node positive disease. Multivariate analysis showed that c-erbB-2 staining and SPF gave independent information on RFS for women with node positive disease.

Breast Neoplasms↗
PubMed1990

Attitudes to chemotherapy: comparing views of patients with cancer with those of doctors, nurses, and general public.

OBJECTIVE: To compare responses of patients with cancer with those of a matched control group, cancer specialists, general practitioners, and cancer nurses in assessing personal cost-benefit of chemotherapy. DESIGN: Prospective study of consecutively recruited patients with cancer and other groups by questionnaire; half of the patients received the questionnaire again three months after starting treatment. SETTING: A medical oncology ward of a London teaching hospital. SUBJECTS: 106 Patients with newly diagnosed solid tumours referred to the unit for consideration of treatment with cytotoxic chemotherapy, 100 of whom were able to complete the questionnaire. 100 Matched controls, 315 cancer doctors (238 radiotherapists and 77 medical oncologists), 1500 randomly chosen general practitioners, and 1000 randomly chosen cancer nurses. MAIN OUTCOME MEASURES: Percentage chance of cure, prolonging life, or palliation of symptoms required to make treatment worth while with two hypothetical chemotherapy treatments, with severe and mild side effects respectively. RESULTS: Respondents to the questionnaire comprised 100 patients, 100 controls, 60 (78%) medical oncologists, 88 (37%) radiotherapists, 790 (53%) general practitioners, and 303 (30%) cancer nurses. Most patients were willing to accept intensive chemotherapy for a very small chance of benefit. The median benefit required to make the hypothetical intensive treatments worth while for patients compared with controls were: for chance of a cure (range 1 to 100%) 1% v 50%, for prolonging life (range three months to five years) 12 months v 24-60 months, and for relief of symptoms (range 1 to 100%) 10% v 75% respectively. There were no significant differences in the responses of the 50 patients completing the questionnaire on a second occasion. Doctors and nurses were less likely to accept radical treatment for minimal benefit compared with the patients (median scores 10-50%, 12-24 months, and 50-75%, for chance of cure, prolonging life, and relief of symptoms respectively). Significantly more patients than controls accepted treatments giving the minimal benefit for each category (cure 53.1 v 19.0%, 67.0 v 35.0%; prolonging life 42.1 v 10.0%, 53.0 v 25.0%; relief of symptoms 42.6 v 10.0%, 58.7 v 19.0% for intensive and mild treatments respectively, p less than 0.001) as was the case for comparison of patients with other groups. CONCLUSION: Patients with cancer are much more likely to opt for radical treatment with minimal chance of benefit than people who do not have cancer, including medical and nursing professionals. This could be taken into account when discussing treatment options with patients and their relatives.

Antineoplastic Agents↗
PubMed1990

Using mathematical models to estimate drug resistance and treatment efficacy via CT scan measurements of tumour volume.

A previously described mathematical model designed to evaluate resistance and tumour-kill for individual patients, and to predict changing tumour sizes, has been applied to patients with small cell lung cancer. The model requires tumour volume measurements, and these were obtained via computed tomography scans of the chest. The model fitted the data well, and was able to predict later tumour volumes using earlier ones, as well as suggesting times at which to change or abandon treatment for individual patients. The model gave estimates for resistance and tumour-kill which may provide additional useful outcome measures for clinical trials, and help in the design of future studies.

Drug Resistance↗
PubMed1989

A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer.

Etoposide is an increasingly used and well-tolerated drug in cancer medicine. Its cytotoxic action is phase-specific and it has demonstrated schedule dependency in both in vitro and animal studies, but clinical evidence of the importance of drug scheduling is uncertain. The two administration schedules of etoposide that have been compared in this randomized study of 39 patients with previously untreated extensive small-cell lung cancer treated with single-agent etoposide were 500 mg/m2 as a continuous intravenous (IV) infusion over 24 hours or five consecutive daily 2-hour infusions each of 100 mg/m2. Both regimens were repeated every 3 weeks, for a maximum of six cycles. Patients received combination chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VAC) or radiotherapy on failure to respond or at relapse, depending on their Karnofsky performance status. The same therapy was used in both arms of the study. All patients are evaluable for response to etoposide. In the 24-hour arm, two patients achieved a partial remission, resulting in an overall response rate of 10%. In the 5-day schedule, 16 patients had a partial response and one had a complete remission, producing an overall response rate of 89%, which was significantly superior to that in the 24-hour arm (P less than .001). The median duration of remission to etoposide in the 5-day arm was 4.5 months. Bone marrow toxicity was similar in both schedules. Etoposide pharmacokinetics were measured in all patients, and total areas under the concentration versus time curves (AUCs) were equivalent in both regimens. This study has clearly demonstrated the importance of etoposide scheduling in humans, and the superiority of five daily infusions over a 24-hour continuous infusion. The response rate to single-agent etoposide using an efficacious schedule in extensive small-cell lung cancer has been determined to be in excess of 80%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

The prognostic value of Ki67 immunostaining in non-Hodgkin's lymphoma.

The monoclonal antibody Ki67 recognizes an antigen expressed in all phases of the cell cycle except Go. It has been used in 141 biopsies from 138 patients with non-Hodgkin's lymphoma to identify proliferating cells in histological sections. A Ki67 index (the number of Ki67 positive tumour cells divided by the sum of Ki67 positive and negative tumour cells) has been derived by counting 1000 cells in each case. A correction for the presence of non-tumour cells has been incorporated by counting non-tumour cells in serial sections stained with a panel of other antibodies. A very strong correlation between a low Ki67 index (less than 20 per cent) and low grade histology and a high Ki67 index (greater than 20 per cent) and high grade histology was found (Chi2 = 98.0). Ninety-one patients could be analysed for survival and those with low grade lymphoma (n = 38) who had a relatively high Ki67 index (greater than 5 per cent) had a worse survival than those with an index of less than 5 per cent (p less than 0.05). In contrast, there was a trend for those patients with high grade disease with a very high Ki67 index (greater than 80 per cent) to have a better survival than those with a lower index (less than 80 per cent). The patients with high grade disease who achieved complete remission or good partial remission and had a Ki67 index of less than 80 per cent were more likely to relapse than those with an index of greater than 80 per cent (p less than 0.04). These findings could not be explained by the effect of other prognostic factors such as age, stage, or serum albumin. While the use of Ki67 immunostaining has potential drawbacks, it appears to be a simple and reproducible method of determining a tumour proliferative index which provides relevant clinical data.

Antibodies, Monoclonal↗
PubMed1988

Adjusting survival curves for imbalances in prognostic factors.

A new method for comparing the survival of two or more groups of patients adjusting for factors distributed unevenly between the groups is presented. This is a development of previous methods, and provides a graphical counterpart to Mantel's adjusted chi-square statistic. The method can be used to retrospectively stratify for prognostic factors, and to provide additional validation and interpretation of multivariate results, including those based on Cox's proportional hazards model. Like Mantel's adjusted chi-square statistic, the method adjusts at every event, based on the numbers of patients still at risk in each of the groups, and is thus able to show up time-dependent effects: factors can be seen to be relevant during certain periods of the study only. The method presented thus allows curves to be drawn as they would have been expected to look, had the prognostic factors been evenly distributed between the groups.

Antineoplastic Combined Chemotherapy Protocols↗