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Biomedical subjects

A J Munro

Publications and source records attributed to A J Munro.

At least 37 records · Page 2Linked to original sources

The costs of hyperfractionation: an economic analysis incorporating consideration of waiting time for treatment.

Multiple fractions per day are being used increasingly in clinical radiotherapy. There are sound radiobiological reasons for this, but the approach uses more time on treatment machines than conventional radiotherapy. The effect of using hyperfractionated schedules for a small minority of radically treated patients has been assessed using a previously published model. The analysis shows that profitability is severely affected by pure hyperfractionation, and that a schedule with a 2-week gap could, by increasing the number of patients it would be possible to treat palliatively, actually increase profitability. Waiting times for treatment could increase, sometimes to clinically unacceptable levels, for patients in all categories.

Clinical Protocols↗

An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer.

Meta-analysis of the published results from 54 randomised controlled trials of adjuvant chemotherapy in head and neck cancer suggests that chemotherapy might increase absolute survival by 6.5% (95% confidence interval 3.1-9.9%). The odds ratio in favour of chemotherapy is 1.37 (95% confidence interval 1.24-1.5). Single-agent chemotherapy given synchronously with radiotherapy increased survival by 12.1% (95% confidence interval 5-19%). The benefit from neoadjuvant chemotherapy was less: a rate difference of 3.7% (95% confidence interval 0.9-6.5%). The results suggest that the investigation of optimal agents and scheduling for synchronous radiotherapy and chemotherapy might still be important in clinical trials in head and neck cancer.

Chemotherapy, Adjuvant↗

The influence of transurethral resection of prostate on prognosis of patients with adenocarcinoma of the prostate treated by radical radiotherapy.

Results of 999 patients with carcinoma of the prostate treated with radical radiotherapy were evaluated to assess the impact of pre-treatment transurethral resection of the prostate. (TURP). A total of 427 patients had a needle biopsy and 541 patients had a TURP. In 31 patients the diagnostic procedure could not be ascertained. In patients with stage T1/T2 disease (411) no adverse effect on prognosis was observed following TURP compared with needle biopsy. In patients with stage T3/T4 disease (534) a significantly higher distant relapse rate and cause-specific mortality were observed after TURP but overall survival was similar after TURP and needle biopsy. A significant correlation was observed between the probability of TURP and poorly differentiated cancers. Multivariate analysis which evaluated the influence of age, T stage, histologic differentiation and TURP did not demonstrate diagnostic TURP to be a significant independent prognostic variate for patients with prostate cancer managed by radical radiotherapy.

Adenocarcinoma↗

Waiting times for radiotherapy treatment: not all that mysterious and certainly preventable.

A computer program which deals specifically with the analysis and prediction of waiting times for radiotherapy has been written for a standard spreadsheet. The model has several components. The basic module calculates waiting times on the basis of any mismatch between the number of patients referred for treatment each week and the number of patients who can actually start treatment in that week. Monte Carlo simulations are used to estimate the 95% confidence intervals on projected waiting times. Another module calculates projected waiting times for three different categories of treatment, given user specified parameters, including financial data. The trade-offs between financial profit and waiting times for treatment are demonstrated. This shows quite explicitly the human consequences (in terms of delay in starting treatment) of decreasing, for fiscal reasons, resources allocated to certain categories of patients. The advantage of this type of analysis is that it clearly shows that waiting lists do not always arise through mismanagement of resources, they arise because resources are inadequate.

Appointments and Schedules↗

A randomized study of telephone contact following completion of radiotherapy.

The hypothesis tested was that routine contact by telephone might significantly improve the adequacy of support for patients during the potentially stressful period between completing radiotherapy and the first follow-up visit. The study was a randomized controlled trial in which 100 patients were allocated either to telephone contact (intervention arm) or usual care (control arm). Adequacy of support was assessed by a questionnaire administered at the first follow-up visit. There were no significant differences in the perceived adequacy of support between the two arms. Of the 72 patients who completed questionnaires, 76% of those in the intervention arm versus 61% in the control arm rated their support after radiotherapy as 'extremely adequate'. The 95% confidence interval (CI) for this 15% rate difference was -6- +36. Analysis by intention to treat showed a rate difference of only 4% (95% CI -17-(+)25) in favour of intervention. We conclude that, given the limited resources currently available, it is not possible to justify a policy of routine contact by telephone for all patients completing radiotherapy.

Adult↗

Publishing the findings of clinical research.

Current regulations and practice may not prevent a sponsor of clinical research from delaying or preventing the dissemination of findings that do not support his or her commercial, professional, or managerial interests. Pharmaceutical trials are particularly subject to this concern, but the issue of non-publication has a wider significance. Patients participate in research on the understanding that it will be of public benefit. To be fair to these patients we must confirm that data will be analysed without bias and that findings will be regarded as being in the public domain and hence available to interested reviewers even if the results do not justify publication. Clinical investigators and ethics committees have the power and the duty to enforce this outcome.

Biomedical Research↗

Results of a policy of surveillance in stage I testicular seminoma.

PURPOSE: To determine what proportion of patients with Stage I testicular seminoma will be cured with orchidectomy alone. METHODS AND MATERIALS: From August 1984 to December 1991 148 patients with Stage I testicular seminoma were entered on a prospective study of surveillance following orchidectomy. The eligibility criteria included a normal chest X ray, lymphogram, computed tomography (CT) of the abdomen and pelvis, and normal post-orchidectomy tumor markers (AFP and BHCG). Patients were followed with a clinical assessment (markers, chest X ray and CT abdomen and pelvis) at 4 to 6 monthly intervals. RESULTS: With a median follow-up of 47 months (range 7-87 months), the actuarial relapse-free rate was 81% at 5 years. Twenty-three patients have relapsed with a median time to relapse of 15 months (range 2-61 months). Four patients (17%) relapsed at 4 or more years from diagnosis. Twenty-one of the 23 relapses occurred in the paraaortic lymph nodes, one patient relapsed in the mediastinum and ipsilateral inguinal nodes and one patient had an isolated ipsilateral inguinal node relapse. Nineteen patients were treated for relapse with external beam radiation therapy of which three developed a second relapse and were salvaged with chemotherapy. Four patients were treated for first relapse with chemotherapy and one developed a second relapse and died of disease. Age at diagnosis was the only prognostic factor for relapse, with patients age < or = 34 having an actuarial relapse-free rate at 5 years of 70% in contrast to a 91% relapse-free rate in those > 34 years of age. CONCLUSIONS: We recommend that surveillance in Stage I testicular seminoma should only be performed in a study setting until further data regarding the risk of late relapse and the efficacy of salvage chemotherapy is available.

Adult↗

Carcinoma of the prostate: results of radical radiotherapy (1970-1985).

PURPOSE: To determine the outcome and prognostic factors in patients with localized carcinoma of the prostate treated with external beam radiation therapy. METHODS AND MATERIALS: A retrospective review of 999 patients with histologically confirmed adenocarcinoma of the prostate treated radically with megavoltage irradiation at the Princess Margaret Hospital between 1970 and 1985. Prognostic factors were analyzed using recursive partitioning method. RESULTS: Overall survival at 5 and 10 years were 69.8% and 40.1% for the whole group. The cause-specific survival rates were 78.9% and 53.5%, respectively. The cause-specific survival rates were significantly different at 10 years by T stage, T1 being 79.0%, T2 66.0%, T3 55% and T4 22%. The overall clinical local control rates was 77% in the first 5 years following treatment. There was no statistically significant difference in the local control rates of T1 and T2 stage disease at 5 years, the combined rate being 88%. Significant differences were observed between other stages, being 76% for T3 and 55% for T4. At 10 years the control rate for T1 tumours was maintained for T1 stage disease (92%) but was significantly reduced for other stages, T2 75%, T3 67% and for T4 37%. In the whole group 33.5% of patients had distant metastases in the first 5 years. The distant relapse rates at 10 years were significantly different by T stage, being 20% for T1, 33% for T2, 55% for T3 and 87% for T4. Multivariate analysis demonstrated that only T stage and histological grade were independent prognostic covariates for cause-specific survival. Age was the only other independent variate in terms of overall survival. The late radiation related morbidity was 2.3% overall; 1.3% affecting rectum and recto-sigmoid and 1.0% arising in the bladder. CONCLUSION: In terms of survival the results of radiotherapy of intracapsular disease were excellent, but they were less satisfactory in patients with direct extracapsular extension. The assessment of local control was difficult and may have reflected more the lack of local disease progression rather than true local tumor control. The treatment was well tolerated and there were few serious late complications.

Adenocarcinoma↗

B-cell lymphoma presenting as a midfacial necrotizing lesion.

A case of midfacial necrotizing lesion (midline nonhealing granuloma) is reported. Paraffin- and frozen-section immunocytochemistry suggested a tumor of B-cell lineage and was confirmed by Southern blot analysis that disclosed an immunoglobulin heavy chain gene rearrangement with no evidence of T-cell receptor genetic aberration. The tumor was of B-cell lineage despite the tumor site and the angiocentric pattern, which are typically seen with peripheral T cell lymphoma with this presentation.

Aged↗

Analysis of supradiaphragmatic clinical stage I and II Hodgkin's disease treated with radiation alone.

Patients with clinical Stage I and II Hodgkin's disease have been managed at the Princess Margaret Hospital for over 20 years, without the use of routine staging laparotomy. Our experience identified as adverse prognostic factors presence of a large mediastinal mass, B symptoms, and advanced age in presence of unfavorable histology (20). We had suggested previously that the use of extended field radiation therapy (XRT) was associated with a lower risk of relapse than involved field XRT or mantle XRT. There has been a trend over the past decade to select those patients with favorable prognostic factors for treatment with XRT alone and to use mantle plus upper abdominal XRT (extended field XRT) to treat them. A retrospective study of patients with clinical Stage I and II Hodgkin's disease treated at the Princess Margaret Hospital between 1978 and 1986 was conducted to determine the impact of patient selection and extended field radiation on outcome. The study involved 250 patients with supradiaphragmatic disease selected for treatment with radiation alone on the absence of adverse prognostic factors. Radiation techniques included involved field radiation in selected patients (those with upper neck involvement), mantle radiation in the earlier years, and mantle plus upper abdominal radiation in the later years of the study. Actuarial survival was 83.3% at 8 years; cause-specific survival was 90.1% and the relapse-free rate 71.6%. Local tumor control was 94.6%; only two patients had true infield failure. Multivariate analysis showed that significant prognostic factors included age, histology, and erythrocyte sedimentation rate. Extent of the radiation treatment volume was significant and influenced the risk of relapse, particularly out-of-field relapse, independently of other factors. A dose of 35 Gy was found to be sufficient for control of clinical disease. This study validated a previously developed model for the selection of clinically staged patients with Stage I and II Hodgkin's disease for treatment with radiation alone. Careful selection of these patients can yield excellent results without requiring that staging laparotomy be routinely performed or the use of systemic chemotherapy as the initial treatment.

Adolescent↗

Decision analysis in oncology: panacea or chimera?

A review of the literature on the use of decision analysis in clinical oncology shows that, although these techniques have been available for more than 25 years, they have not been widely applied: only 19 decision analyses of therapeutic management in clinical oncology were found. The main disadvantages concern the difficulty of accurately assessing probabilities and defining measures of outcome. Time-consuming analysis may produce results that are either equivocal or simply confirm the expectations of common sense. If the basic design fails to include all relevant factors then any conclusions will be of little value. The main advantages are that, by demanding that problems be explicitly stated and analysed in a logical fashion, deficiencies in current knowledge, belief and practice are identified. The usefulness of these techniques lies in formulating management guidelines, either for treatment or for follow-up. They have only a limited role in decision making for individual patients.

Decision Support Techniques↗

Kaposi's sarcoma in HIV infection treated with vincristine and bleomycin.

OBJECTIVE: To evaluate the efficacy and toxicity of vincristine and bleomycin when used in combination to treat patients with progressive Kaposi's sarcoma. DESIGN: A retrospective case notes review. SETTING: The departments of Immunology and Genito-Urinary Medicine, St Mary's Hospital, London, UK. PATIENTS: All patients presenting with progressive Kaposi's sarcoma and requiring chemotherapy between January 1987 and January 1990, who had received no previous systemic chemotherapy. INTERVENTIONS: Treatment with vincristine (2 mg) and bleomycin (30 mg, 18 h infusion), or vinblastine (2.5-5.0 mg) if peripheral neuropathy developed. Treatment with zidovudine and prophylaxis of opportunistic infections where indicated. OUTCOME MEASURES: Response, toxicity and survival. RESULTS: Overall, patients had a poor prognosis: 33 out of 46 (72%) had had a previous opportunistic infection, had a mean CD4 count of 144 x 10(6) (20 out of 46 tested) and a mean Karnofsky index of 75.4. They received a median of five cycles of therapy: a partial response was achieved in twenty-six patients (57%), disease progression was halted in a further 16 (35%), while disease progression continued in four (9%) despite therapy; there were no complete responders. Mean duration of response was 2 months (s.d., 1.26 months), survival was 8 months (s.d., 6.7 months) from start of therapy and 17 months (s.d., 8.9. months) from first AIDS diagnosis. On multivariate analysis the best predictor of mortality was the presence of previous opportunistic infection (P = 0.00653). Side-effects were minimal in comparison with other studies. The most common side-effect, in 13 cases (28%), was peripheral neuropathy, which may in part represent the prevalence of HIV neuropathy or remain as background. Haematological toxicity was uncommon. CONCLUSIONS: Treatment for HIV-related Kaposi's sarcoma in advanced HIV disease is becoming more necessary as disease profiles change. Conventional chemotherapy regimens for malignancy are not well tolerated in these patients and may not be indicated. This regimen is effective and has low toxicity in AIDS patients. Non-responders should be considered for more intensive regimens.

Acquired Immunodeficiency Syndrome↗

An assessment of combined tumour markers in patients with seminoma: placental alkaline phosphatase (PLAP), lactate dehydrogenase (LD) and beta human chorionic gonadotrophin (beta HCG).

We have assessed the tumour markers placental alkaline phosphatase (PLAP), lactate dehydrogenase (LD), and human chorionic gonadotrophin (beta HCG) using 2,000 serum samples from 286 patients with seminoma. The ROC curves show that no one marker performs adequately for the detection of disease either at initial staging or during follow-up. We used a Markov model heuristically to devise strategies, in which marker results were assessed in combination, which might be useful in clinical practice. We found that the best strategy was to consider a test result abnormal only if either the beta HCG was greater than 6 Ul-1 or the LD was greater than 400 U l-1 and the PLAP level was greater than 60 U l-1. This will detect about 50% of patients with disease and the false-positive rate is 2%. In practical terms this means that PLAP need only be estimated in patients whose beta HCG is less than 6 IU l-1 and whose LD is greater than 400 U l-1.

Alkaline Phosphatase↗

Bone metastases: pathophysiology and management policy.

The pathophysiology and options for management of bone metastases as well as criteria for determining response to therapy are reviewed. Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. In the majority of patients, the primary tumor is in the breast, prostate, or lungs. Although almost all patients will die of their disease, a proportion of the patients will survive for several years. Treatment is primarily palliative: the intention is to relieve pain, prevent fractures, maintain activity and mobility, and, if possible, to prolong survival. Therapeutic options include local treatment with radiotherapy and/or surgery, and systemic treatment using chemotherapy, endocrine therapy, radioisotopes, agents such as diphosphonates, which inhibit resorption of bone, as well as analgesic and antiinflammatory drugs. The mechanisms by which pain is relieved by several of these therapies remain unclear but actions beyond a simple tumoricidal effect appear to be important. There have been few randomized trials comparing the therapeutic options, and the criteria for assessing response to therapy have, in general, been poorly defined. There is a need for rigorous clinical investigations that assess the efficacy of the various therapeutic possibilities by using well-defined and validated criteria of response.

Bone Neoplasms↗

Is placental alkaline phosphatase (PLAP) a useful marker for seminoma?

The usefulness of placental alkaline phosphatase (PLAP) as a tumour marker was assessed in 1578 serum samples from 236 patients with seminoma. Smoking habits were known for all but 7 patients (22 samples). Smoking was associated with significantly higher mean levels of PLAP in disease-free patients (28.8 [S.E. 2.1] U/l vs. 15.9 [1.3] U/l in non-smokers). Mean PLAP levels were higher in patients with active disease (78.6 [23.5] U/l in non-smokers and 47.2 [18.5] U/l in smokers). The median values showed a similar trend. However, there was considerable overlap between the various groups and differences between mean and median values indicated that PLAP values were distributed asymmetrically. The predictive value of PLAP as a tumour marker was consequently much less than superficial inspection of these values might suggest. In 97 patients on surveillance, only 2 out of 11 patients who relapsed had elevated PLAP at the time of clinically detectable relapse. With the upper limit of normal PLAP quoted by our laboratory (35 U/l), specificity and sensitivity were, respectively, 88% and 45% (all patients) and 96% and 47% (non-smokers). The sensitivity and specificity of PLAP were assessed in more detail for a series of threshold values (normal vs. abnormal) with a graphical method. Only in non-smokers did PLAP seem useful and even in this group the positive predictive value of an "abnormal" test may be low; less than 50% in clinically relevant circumstances. Serum PLAP assay cannot usefully stand alone as a marker for seminoma and its routine estimation contributes little to follow-up.

Adult↗