Biomedical subjects

W M Gregory

Publications and source records attributed to W M Gregory.

At least 19 recordsLinked to original sources

PubMed2005

Meta-analysis to evaluate the role of interferon in follicular lymphoma.

PURPOSE: To determine whether interferon (IFN) -alpha2, when given with or following chemotherapy, influences response rate, remission duration, and survival in newly diagnosed patients with follicular lymphoma. PATIENTS AND METHODS: Ten phase III studies evaluating the role of IFN-alpha2 in 1,922 newly diagnosed patients with follicular lymphoma were analyzed. Updated individual patient data were used to perform meta-analyses for response, survival, and remission duration. RESULTS: The addition of IFN-alpha2 to initial chemotherapy did not significantly influence response rate. An overall meta-analysis for survival showed a significant difference in favor of IFN-alpha2, but also showed significant heterogeneity between studies. Further analyses were carried out in order to explain this heterogeneity, and to define the circumstances in which IFN-alpha2 prolonged survival. The survival advantage was seen when IFN-alpha2 was given: (1) in conjunction with relatively intensive initial chemotherapy (2P = .00005), (2) at a dose >/= 5 million units (2P = .000002), (3) at a cumulative dose >/= 36 million units per month (2P = .000008), and (4) with chemotherapy rather than as maintenance therapy (P = .004). With regard to remission duration, there was also a significant difference in favor of IFN-alpha2, irrespective of the intensity of chemotherapy used, IFN dose, or whether IFN was given as a maintenance strategy or with chemotherapy. CONCLUSION: When given in the context of relatively intensive initial chemotherapy, and at a dose >/= 5 million units (>/= 36 x 10(6) units per month), IFN-alpha2 prolongs survival and remission duration in patients with follicular lymphoma.

Adolescent↗

PubMed2005

Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group.

PURPOSE: This phase III randomized trial compared two chemotherapy regimens, gemcitabine plus carboplatin and mitomycin, ifosfamide, and cisplatin, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). The regimens were compared with regard to effects on survival, response rates, toxicity, and quality of life. PATIENTS AND METHODS: Eligible patients had previously untreated stage IIIB or IV NSCLC suitable for cisplatin-based chemotherapy. Randomly assigned patients were to receive four cycles, each at 3-week intervals, of carboplatin area under the curve of 5 on day 1 plus gemcitabine 1,200 mg/m(2) on days 1 and 8 (GCa) or mitomycin 6 mg/m(2), ifosfamide 3g/m(2), and cisplatin 50 mg/m(2) on day 1 (MIC). RESULTS: Between February 1999 and August 2001, 422 patients (GCa, n = 212; MIC, n = 210) were randomly assigned in the United Kingdom. The majority of patients received the intended four cycles (GCa, 64%; MIC, 61%). There was a significant survival advantage for GCa compared with MIC (hazard ratio, 0.76; 95% CI, 0.61 to 0. 93; P = .008). Median survival was 10 months with GCa and 7.6 months with MIC (difference, 2.4 months; 95% CI, 1.0 to 4.0), and 1-year survival was 40% with GCa and 30% with MIC (difference, 10%; 95% CI, 3% to 18%). Overall response rates were similar (42% for GCa v 41% for MIC; P = .84). More thrombocytopenia occurred with GCa (P = .03), but this was not associated with increased hospital admission or fatality. GCa caused less nausea, vomiting, constipation, and alopecia and was associated with fewer admissions for administration and better quality of life. CONCLUSION: In patients with advanced NSCLC, GCa chemotherapy was shown to be a better-tolerated treatment that conferred a survival advantage over MIC.

Adult↗

PubMed2001

ChlVPP alternating with PABlOE is superior to PABlOE alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation/Central Lymphoma Group randomized controlled trial.

The purpose of this randomized trial was to compare the efficacy of 6 cycles of prednisolone, Adriamycin (doxorubicin), bleomycin, vincristine (Oncovin) and etoposide (PABlOE) with 3 cycles of PABIOE that alternate with 3 cycles of chlorambucil, vinblastine, procarbazine and prednisone (ChlVPP) in patients with advanced Hodgkin's disease. Between October 1992 and April 1996, 679 patients were entered onto the study. 41 of these did not match the protocol requirements on review and were excluded from further analysis, most of these being reclassified as NHL on histological review. Of the remaining 638 patients, 319 were allocated to receive PABIOE and 319 were allocated to receive ChlVPP/PABlOE. The complete remission (CR) rates were 78% and 64%, for ChlVPP/PABlOE and PABIOE respectively after initial chemotherapy (P< 0.0001). 124 patients were re-evaluated subsequently following radiotherapy to residual masses. The CR rates changed from 78% to 88% for ChlVPP/PABlOE and from 64% to 77% for PABlOE when re-evaluated in this manner (treatment difference still significant, P = 0.0002). The treatment associated mortality in the PABlOE arm was 2.2% (7 deaths), while there were no such deaths in the ChlVPP/PABlOE arm (P = 0.015). The failure-free survival was significantly greater in the ChlVPP/PABlOE arm (P< 0.0001) as was the overall survival (P = 0.01). The failure-free and overall survival rates at 3 years were 77% and 91% in the ChlVPP/PABlOE arm, compared with 58% and 85% in the PABIOE arm, respectively. These results indicate that ChlVPP alternating with PABIOE is superior to PABIOE alone as initial treatment for advanced Hodgkin's disease.

Adolescent↗

PubMed2001

Applied kinesiology for treatment of women with mastalgia.

To determine whether an applied kinesiology technique was of benefit to women with breast pain, an open pilot study was conducted in which 88 newly presenting women with self-rated moderate or severe mastalgia were treated by applied kinesiology. This involved a hands-on technique consisting of rubbing a series of 'lymphatic reflex points' while touching painful areas of the breasts. The women were predominantly pre-menopausal, and patients with both cyclical and non-cyclical pain were included in the study. Patients' self-rated pain scores, both before and immediately after applied kinesiology were compared, together with a further score 2 months later. Immediately after treatment there was considerable reduction in breast pain in 60% of patients with complete resolution in 18%. At the visit after 2 months, there was a reduction in severity, duration and frequency of pain of 50% or more in about 60% of cases (P<0.0001). This preliminary study suggests that applied kinesiology may be an effective treatment for mastalgia, without side-effects and merits testing against standard drug therapies.

Journal Article↗

PubMed2000

Identification of long-term survivors in primary breast cancer by dynamic modelling of tumour response.

Although clinical response to primary chemotherapy in stage II and III breast cancer is associated with a survival advantage, it is the degree of pathological response in the breast and ipsilateral axilla that best identifies patients with a good long-term outcome. A mathematical model of the initial response of 39 locally advanced tumours to anthracycline-based primary chemotherapy has been previously shown to predict subsequent clinical tumour size. This model allows for the possibility of primary resistant disease, the presence of which should therefore be associated with a worse outcome. This study reports the application of this model to an additional five patients with locally advanced breast cancer, as well as to 63 patients with operable breast cancer, and confirms the biological reality of the model parameters for these 100 breast cancers treated with primary anthracycline-based chemotherapy. The tumours that responded to chemotherapy had higher cell-kill (P < 0.0005), lower resistance (P < 0.0001) and slower tumour regrowth (P < 0.002). Furthermore, ER-negative tumours had higher cell-kill (P < 0.05), as compared with ER-positive tumours. All patients with a pathological complete response had zero resistance according to the model. Furthermore, the long-term implication of chemo-resistant disease was demonstrated by survival analysis of these two groups of patients. At a median follow-up of 3.7 years, there was a statistically significantly worse survival for the 37 patients with locally advanced breast cancer identified by the model to have more than 8% primary resistant tumour (P < 0.003). The specificity of this putative prognostic indicator was confirmed in the 63 patients presenting with operable disease where, at a median follow-up of 7.7 years, those women with a resistant fraction of greater than 8% had a significantly worse survival (P < 0.05). Application of this model to patients treated with neoadjuvant chemotherapy may allow earlier identification of clinically significant resistance and permit intervention with alternative non-cross-resistant therapies such as taxoids.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

A randomized British National Lymphoma Investigation trial of CHOP vs. a weekly multi-agent regimen (PACEBOM) in patients with histologically aggressive non-Hodgkin's lymphoma.

BACKGROUND: Between 1987 and 1991, the British National Lymphoma Investigation randomized 459 patients with non-Hodgkin's lymphoma with a large-cell component to either CHOP or the PACEBOM regimen. PATIENTS AND METHODS: Four hundred fifty-nine eligible patients were included in this trial, four hundred one with diffuse large-cell lymphoma and fifty-eight with diffuse mixed-cell lymphoma according to the Working Formulation. Two hundred twenty-six patients were randomized to receive CHOP and two hundred thirty-three to receive PACEBOM. The two arms of the trial were well balanced for all potential prognostic factors. RESULTS: The complete remission rate with PACEBOM was 64% and with CHOP 57% (NS). At eight years, the actuarial cause specific survival (CSS) in the PACEBOM arm is 59% compared to 49% in the CHOP arm (P = 0.09). Patients < 50 years of age fared significantly better in the PACEBOM arm both for CSS and overall survival (P = 0.002) and the CSS was also significantly improved in stage IV disease (P = 0.02). CONCLUSIONS: The mature data from this trial suggest that an etoposide-containing multi-agent weekly regimen can be superior to CHOP.

Adolescent↗

PubMed1997

A randomized trial of five versus eight courses of cisplatin or carboplatin in advanced epithelial ovarian carcinoma. A North Thames Ovary Group Study.

BACKGROUND: There is no clear data on the optimum number of courses of platinum chemotherapy required for treating advanced ovarian cancer. A prospective randomised trial was performed to compare five with eight courses of either carboplatin 400 mg/m2 or cisplatin 75 mg/m2 given four-weekly to patients with stage IC-IV ovarian cancer. PATIENTS AND METHODS: 225 patients were entered into the study and 233 were eligible for randomisation: 118 to five courses and 115 to eight courses. In each randomisation, half the patients received carboplatin and half received cisplatin. RESULTS: The mean number of courses received on the five arm was 4.74 and on the eight arm, 6.42, an increase of 35%. The median survival for all patients was 24 months with the median survival for the 156 patients with stage 3 disease being 21 months. No difference was detected in survival (P = 0.53) or time to progression from initial surgery (P = 0.29) between the two arms of the trial. False-negative calculations based on a multivariate analysis show that the trial currently has 95% power for excluding a difference of 10% in favour of the eight course arm at three years. CONCLUSION: There is insufficient evidence at the present time to justify more than five courses of first-line single agent platinum chemotherapy in the management of advanced ovarian cancer.

Adolescent↗

PubMed1997

Body weight and vascular invasion in post-menopausal women with breast cancer.

To examine the relationship between body weight and vascular invasion (VI) around tumours in post-menopausal women with operable breast cancer, a retrospective study was conducted of 393 patients treated in a breast unit between 1987 and 1991. Weight was measured at the time of diagnosis. Vascular invasion was recorded as being present or absent. Vascular invasion was seen in slightly more of the 50 perimenopausal patients than in the 343 post-menopausal women (44% vs 36%). In the tumour specimens from post-menopausal patients weighing <50 kg, VI was observed in 11% compared with 45% of those weighing more than 80 kg (P= 0.02). Furthermore, the 5-year survival of those with VI was 74% compared with 91% for those without (P < 0.0001). Menopausal status and body weight may influence survival in patients with breast cancer, possibly as a result of the presence of unopposed circulating oestrogens at the time of surgery. Oestrogens may alter cohesiveness of breast cancer cells and modulate secretion of proteases, thereby influencing invasive potential. Excision of tumours in such an environment may have a deleterious impact on survival.

Analysis of Variance↗

PubMed1997

Cautionary tales of survival analysis: conflicting analyses from a clinical trial in breast cancer.

Data from a completed randomized trial in breast cancer are used to demonstrate and quantify the variation in estimated survival curves and log-rank statistics at different times throughout a trial. False 'plateaux' are common, as are wide fluctuations in chi2 values obtained from the log-rank test when there are few events. We show how analyses conducted at different times can demonstrate different effects. Long follow-up is often necessary to allow correct interpretation of results. We discuss the assumption of proportional hazards and the consequences of making that assumption inappropriately. We show how checking whether hazards are proportional can help in avoiding erroneous conclusions.

Breast Neoplasms↗

PubMed1996

Mental health of hospital consultants: the effects of stress and satisfaction at work.

BACKGROUND: Burnout and psychiatric morbidity among gastroenterologists, surgeons, radiologists, and oncologists in the UK have been estimated by means of a questionnaire-based survey. The relationship between consultants' mental health and their job stress and satisfaction, as well as their job and demographic characteristics, were also examined. METHODS: Psychiatric morbidity was estimated using the 12-item General Health Questionnaire. The three components of burnout-emotional exhaustion, depersonalization, and low personal accomplishment-were assessed using the Maslach Burnout Inventory. Job stress and satisfaction were measured using study-specific questions. FINDINGS: Of 1133 consultants, 882 (78%) returned questionnaires. The estimated prevalence of psychiatric morbidity was 27%, with no significant differences between the four specialist groups. Radiologists reported the highest level of burnout in terms of low personal accomplishment. Job satisfaction significantly protected consultants' mental health against job stress. Three sources of stress were associated with both burnout and psychiatric morbidity; feeling overloaded, and its effect on home life; feeling poorly managed and resourced; and dealing with patients' suffering. Burnout was also associated with low satisfaction in three domains: relationships with patients, relatives and staff; professional status/esteem; intellectual stimulation. In addition, being aged 55 years or less and being single were independent risk factors for burnout. Burnout was also more prevalent among consultants who felt insufficiently trained in communication and management skills. INTERPRETATION: Consultants' mental health is likely to be protected against the high demands of medical practice by maintaining or enhancing job satisfaction, and by providing training in communication and management skills.

Adult↗

PubMed1996

Prognosis of patients with breast cancers up to 1 cm in diameter.

The prognosis of patients with tumours measuring up to 1 cm diameter was examined. 336 patients treated at Guy's Hospital between 1975 and 1994 were reviewed. Of these, 103 (31%) were lymph node-positive, with approximately one third of these having one node involved, one third two to three nodes and one third four nodes or more. A similar proportion of those with palpable and impalpable tumours had axillary node involvement. Patients with axillary node involvement had a significantly worse prognosis and those node-positive patients with impalpable cancers had a significantly worse outcome compared with node-positive palpable cases. When patients were subdivided on a basis of nodal status and age (< or = 50 or > 50), node-positive women aged > 50 fared significantly better than younger women. These data suggest the need to know accurately the axillary nodal status of patients with small breast cancers, whether symptomatic or detected by screening. This knowledge will allow women with curable cancers to be identified together with those who have a worse prognosis and who will be likely to benefit from systemic adjuvant therapy.

Age Factors↗

PubMed1996

Inadequacy of iridium implant as sole radiation treatment for operable breast cancer.

In order to avoid a prolonged course of external irradiation as part of breast conservation therapy, 27 patients received an iridium implant to the primary tumour bed as sole radiation treatment. Surgery was standardised comprising tumourectomy and axillary clearance. Using a rigid implant afterloading with iridium192 wires, 55 Gy was delivered on a continuous basis over 5 days. After 6 years median follow-up, relapse of cancer within the treated breast has occurred in 10 of the 27 patients (37%). Compared with historical controls treated by similar surgery and iridium192 implant (20 Gy) with external radiotherapy (46 Gy), there was a significantly increased breast relapse rate in those treated by iridium implant alone. However, the incidence of distant metastases and overall survival was similar. Thus, a continuous iridium192 implant delivering 55 Gy in 5 days is not an effective means of achieving local control in patients with operable breast cancer.

Brachytherapy↗

PubMed1996

Variations in the management and survival of women under 50 years with breast cancer in the South East Thames region.

A retrospective, population-based study was undertaken to determine variations in the management of women aged less than 50 years with primary breast cancer in different hospital settings and the influence of these variations on survival. A total of 1757 women who were resident in the South East Thames Health Region aged less than 50 years at the time of diagnosis of breast cancer and who presented during a 5 year period (January 1984 to December 1988) were recorded by the Thames Cancer Registry. The hospitals at which primary surgery was undertaken were categorised as teaching or non-teaching hospitals. The non-teaching hospitals were grouped according to the mean number of patients treated annually during the study period (< or = 2, 3-9, > or = 10 each year). The following factors were compared between these groups: age, extent of disease, tumour morphology, extent of primary surgery (mastectomy vs less than mastectomy), use of axillary surgery (any vs none) and use of systemic adjuvant therapy. Survival rates for the different groups were compared. Registration rates did not differ significantly between health districts. A total of 1485 (85%) women underwent surgery in over 90 different hospitals. In 1324 (86%) of these cases the surgery was undertaken in a total of 42 NHS hospitals within SE Thames Health Region or in seven teaching hospitals in adjacent regions. Mastectomy rates decreased from 52% in 1984 to 28% in 1988 (P<0.0001), but were consistently higher in teaching hospitals (P=0.01). The use of any form of axillary surgery decreased from 49% to 36% over the 5 year period (P=0.003), with significantly lower rates of axillary surgery being performed in non-teaching hospitals (P<0.0001). The proportion of cases recorded as having non-specific morphology was higher in nonteaching than in teaching hospitals (P<0.0001). On multivariate analysis survival was significantly (P<0.001) influenced by stage and tumour histology. Among patients who underwent surgery, the type of hospital in which this was undertaken did not appear to influence survival significantly. This analysis of routine cancer registry data indicates that patients were widely dispersed in a large number of different hospitals and that there were marked variations in practice according to the type of hospital to which patients presented. The treatments provided were frequently at variance with those recommended at a consensus conference held during the study period, particularly in relation to the use of axillary surgery and adjuvant systemic therapy. The way in which services are currently provided may hamper the delivery of appropriate management and comprehensive support. These data thus have implications for the purchasing and provision of services for this common condition.

Adult↗

PubMed1996

Mathematical modelling of tumour response in primary breast cancer.

Although breast cancer is perceived to be relatively chemosensitive, cytotoxic drug therapy only leads to cure in the adjuvant setting. In advanced disease, primary resistance and inadequate cell kill may be important in determining the lack of a durable response to cytotoxics, but for an individual patient's tumour there is no consistent way of determining the importance of these two factors. An adaptation of Skipper's log cell kill model of tumour response to chemotherapy was applied to serial tumour measurements of 46 locally advanced primary breast carcinomas undergoing neoadjuvant chemotherapy. Assuming a log-normal distribution of errors in the clinically measured volumes, the model produced, for each tumour separately, in vivo estimates of proportional cell kill, initial resistance and tumour doubling times during therapy. After 4 weeks' treatment, these data could then be used to predict subsequent tumour volumes with good accuracy. In addition, for the 13 tumours that became operable after the neoadjuvant chemotherapy, there was a significant association between the final volume as predicted by the model and the final pathological volume (P < 0.05). This approach could be usefully employed to determine those tumours that are primarily resistant to the treatment regimen, permitting changes of therapy to more effective drugs at a time when the tumour is clinically responding but destined to progress.

Antineoplastic Agents↗

PubMed1996

Serum progesterone and prognosis in operable breast cancer.

Several studies have now shown that women with operable breast cancer undergoing tumour excision during the luteal phase of the menstrual cycle have a better prognosis than those having surgery during the follicular phase. As part of a prospective study of prognostic factors in breast cancer, blood was taken at the time of surgery. Between 1975 and 1992 this was available from 289 premenopausal women within 3 days of tumour excision. All were treated by either modified radical mastectomy or breast conservation including axillary clearance and the date of last menstrual period (LMP) was known in 239 (80%) cases. Blood samples were assayed for both oestradiol (E2) and progesterone (P). Because of the wide inter-individual variation in E2 levels there was no clear relationship between E2 and LMP. However, using a running mean smoothing technique the expected cyclical variation could be discerned. There was no significant association between E2 and survival. Smoothing of the P data yielded a pattern similar to the normal hormone profile. Those cases with a progesterone level of 4 ng ml-1 or more had a significantly better survival than those with a level < 4 ng ml-1. This was especially clear in node-positive patients (P < 0.01). The possibility of misclassification of menstrual cycle status, because of misreported LMP, has been minimised by applying an independent hormonal measurement (P) of cycle activity. This parameter will also identify women who may be undergoing anovular cycles. Thus this study has confirmed that a raised level of progesterone at the time of tumour excision is associated with an improvement in prognosis for women with operable breast cancer.

Breast Neoplasms↗

PubMed1996

A randomised comparison of a third-generation regimen (PACEBOM) with a standard regimen (CHOP) in patients with histologically aggressive non-Hodgkin's lymphoma: a British National Lymphoma Investigation report.

A combination of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) has been a standard therapy for histologically aggressive non-Hodgkin's lymphomas for over 20 years, but several newer regimens, referred to as second or third generation, have been reported to give improved results in single-centre studies. Positive evidence from randomised trials has been lacking, and the British National Lymphoma Investigation therefore commenced a randomised comparison of CHOP vs a third-generation regimen, PACEBOM, in November 1987. A total of 459 eligible patients were entered into the trial: 226 in the CHOP arm and 233 in the PACEBOM arm. Overall, there was no significant difference in outcome between the two arms of the trial. In patients with stage IV disease there was an apparent improvement in survival for those treated with PACEBOM, but considerable caution must be exercised with such subgroup analysis.

Aged↗

PubMed1995

Ductal carcinoma in situ: assessment of necrosis and nuclear morphology and their association with biological markers.

One hundred and five cases of pure ductal carcinoma in situ (DCIS) seen in the Guy's Hospital breast unit between 1975 and 1991 were reviewed. The presence and extent of necrosis and the degree of cytonuclear differentiation were assessed and the expression of p53 protein, cerbB2 protein, progesterone receptor, and a proliferation antigen KiS1, all factors reported to be of prognostic significance in invasive ductal carcinoma, was evaluated using immunohistochemical methods. A strong correlation was seen between the presence and extent of necrosis and the degree of cytonuclear differentiation and between both these morphological criteria and the biological markers as well as between the individual markers. The presence of extensive necrosis was associated with lack of cytonuclear differentiation and both were associated with a high proliferation rate, the presence of cerbB2 and p53 protein, and the absence of progesterone receptors. In cases with little or no necrosis, there was good nuclear differentiation and a strong correlation with the presence of progesterone receptor, absence of cerbB2 and p53 protein, and a low rate of proliferation.

Biomarkers, Tumor↗

PubMed1995

Bilateral penetrating keratoplasty for keratoconus.

PURPOSE: To determine the effect of bilateral surgery on the rejection-free survival of penetrating keratoplasties (PK) performed for keratoconus. METHODS: The records of 587 patients with a PK for keratoconus who attended a single center over a 7-year period were reviewed. Details on 400 patients were sufficiently complete to permit a multivariate analysis of the factors suspected to influence graft survival. In 165 of these patients with bilateral grafts, the effect of a contralateral PK on graft survival was evaluated using actuarial methods. RESULTS: In first grafts for all patients, there was an increased rate of graft rejection with a host trephine greater than 7.50 mm in diameter and in patients with severe allergic eye disease (P < 0.01). In patients who had bilateral grafts, a graft to the contralateral eye increased the risk of rejection in the first eye to be grafted, and although this effect reduced with time, it was still present after an interval of up to 6 years between surgeries. A rejection episode in the first eye to be grafted increased the risk of rejection in the second eye (P < 0.001), but overall the second eye had a significantly lower risk of rejection when compared with either the first grafted eye or unilaterally grafted eyes (P < 0.001). The risk to the second grafted eye further reduced as the interval between the surgeries increased. CONCLUSIONS: In keratoconus, the diameter of the host trephine, severe allergic eye disease, and a graft surgery to the contralateral eye determine the risk of rejection in the index eye. The reasons the second grafted eye of patients receiving bilateral PKs appears to have an enhanced rejection-free survival are discussed.

Cornea↗