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Biomedical subjects

R A Cowan

Publications and source records attributed to R A Cowan.

At least 19 recordsLinked to original sources
PubMed2002

ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin's disease.

PURPOSE: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks' duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months' treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility. PATIENTS AND METHODS: Two hundred eighty-two patients with previously untreated Hodgkin's disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment. RESULTS: Further accrual to the trial was halted at the planned third interim analysis in September 1996. After a median follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score <or= 2, nonbulky disease). CONCLUSION: Apart from possibly in the best-prognosis group, where results are equivalent, ChlVPP/EVA hybrid produces significantly better FFP, EFS, and OS than VAPEC-B in patients with previously untreated Hodgkin's disease.

Adolescent↗
PubMed2001

Prediction of scattered dose to the testes in abdominopelvic radiotherapy.

Radical abdominal radiotherapy in men runs the risk of impairing their fertility owing to scattered dose to the testes, outside of the treated volume. In patients for whom this is a concern it is important to be able to predict the dose to the testes before treatment in order to determine whether semen cryopreservation should be undertaken and testicular shielding performed during treatment. Measurements have been made on an anthropomorphic phantom to determine the magnitude of these doses for a four-field treatment consisting of an anterior-posterior parallel pair and a lateral parallel pair. A dataset is presented, which, together with a correction for patients size, allows an estimate of testicular dose to be made given only the photon energy, interfield distances and the distance from the testes to the nearest beam edge. Thermoluminescent dosimetry has been carried out in 17 patients to validate the use of the data tables. The results indicate that testicular doses may be estimated with a standard deviation corresponding to 1%-2% of the tumour dose, which is sufficient for the purpose of determining whether fertility is threatened by a planned treatment.

Adult↗
PubMed2001

Bone marrow toxicity in mice treated with indium-114m-labelled blood cells.

Clinical trials with autologous indium-114m-labelled lymphocytes have revealed significant anti-tumour effects in chronic lymphocytic leukaemia patients with highly resistant disease. Substitution of the lymphocyte vector with heat-damaged red blood cells (HDRBC) may make this treatment more universally applicable and reduce the dose-limiting myelosuppression encountered with labelled lymphocytes. Therefore, the bone marrow localization and toxicities of indium-labelled lymphocytes or HDRBC have been investigated in BDFI mice. At 24 hours approximately 4% and 1.2% of 114In(m) administered as labelled lymphocytes or HDRBC respectively was localized within the bone marrow and remained constant for 57 days thereafter. Toxicity towards bone marrow stem cells, measured as CFU-S, was equivalent for both cellular vectors. However, at clinically relevant activities, 114In(m) HDRBC were less toxic than labelled lymphocytes towards committed progenitors, assayed as in vitro-CFC and CFU-Meg. These data suggest that substitution of HDRBC for lymphocytes as the 114In(m) vector may be beneficial in reducing the myelosuppression associated with this technique.

Animals↗
PubMed2000

A doxorubicin-based regimen used in the treatment of elderly patients with high-grade non-Hodgkin's lymphoma.

A retrospective analysis was performed on 66 patients, aged 70 years or older, who received treatment with a weekly doxorubicin-containing regimen (VAPEC-B) for high grade non-Hodgkin's lymphoma (NHL). Two dosing schedules were employed. The choice of regimen was at the discretion of the treating clinician and reflected the performance status of the patient and the predicted tolerance to chemotherapy. Forty-nine patients received a half-dose schedule and 17 the full-dose schedule. Those receiving the half-dose regimen had a lower median performance status and received a lower dose intensity of chemotherapy (45% versus 83%). However, the outcomes of the two groups were similar: complete remission rate 41% versus 47%, and 5-year overall survival 36% versus 23%, for the half- and full-dose groups, respectively. A similar proportion of patients (51% versus 59%) completed each regimen, although there were more delays in treatment delivery experienced in those receiving the full dose. Half-dose VAPEC-B is an effective treatment option for elderly patients with high-grade NHL and has comparable efficacy with other published regimens. The use of such low-dose doxorubicin-containing regimens in elderly patients with high-grade NHL requires further investigation.

Aged↗
PubMed2000

Relationship of MRI and clinical staging to outcome in invasive bladder cancer treated by radiotherapy.

AIM: To compare MRI and clinical staging of invasive bladder cancer prospectively and identify additional prognostic features on MRI before radiotherapy. METHODS AND MATERIALS: 143 patients with a pathological diagnosis of transitional cell carcinoma underwent MRI (1.0 T) of the abdomen and pelvis before radical radiotherapy. Tumour size, site, degree of infiltration, presence of adenopathy and hydronephrosis were assessed and an appropriate radiological stage assigned. Following radiotherapy all patients received regular cystoscopic follow-up. Date of first relapse and date of death were recorded. RESULTS: The median follow-up was 2.8 years for survivors. Those patients upstaged from T2a clinically to T3b on MRI had a significantly worse outcome (P = 0.0078). In univariate analysis a number of MRI features were significantly associated with adverse outcome: tumour size, circumferential tumour extent, and presence of hydronephrosis (all P < 0.05). After adjustment for clinical T stage and histological grade, all these MRI features and the MRI T stage were found to confer additional prognostic information in predicting early disease relapse and death (P < 0.05). CONCLUSION: This study demonstrates that MRI before radiotherapy provides valuable additional prognostic information compared to clinical staging.

Aged↗
PubMed1999

Does salivary gland scintigraphy predict response to pilocarpine in patients with post-radiotherapy xerostomia?

This study was undertaken to determine whether standard salivary gland scintigraphy may be used for the objective assessment of salivary gland sialogogues, in particular oral pilocarpine, in the treatment of post-radiotherapy xerostomia. Nine patients, with xerostomia following radiotherapy to the head and neck region underwent salivary gland scintigraphy with technetium-99m pertechnetate (40 MBq) both before and following 1 month of oral pilocarpine (5 mg tds). For each scan, the percentage uptake in the first 14 min, the peak uptake, time to peak uptake and the percentage of activity excreted following lemon juice stimulation were calculated. The results were correlated with the subjective response as assessed by questionnaire and visual analogue scale. We found no correlation between subjective response and any of the four scan parameters analysed. We could not identify any parameter that predicted those patients who would respond to pilocarpine. In addition, only one parameter, the percentage of activity excreted following stimulation, correlated with previous dose of radiotherapy to the gland. In conclusion, in this study salivary gland scintigraphy did not appear to correlate with or predict response to oral pilocarpine. However, future studies might consider performing salivary gland scintigraphy prior to radiotherapy as well as at differing time points following the commencement of pilocarpine.

Administration, Oral↗
PubMed1999

The diagnostic value of positron emission tomography (PET) with radiolabelled fluorodeoxyglucose (18F-FDG) in head and neck cancer.

Positron emission tomography (PET) scanning has recently been introduced into clinical practice but its usefulness in the management of head and neck cancer is not well defined. The aim of this prospective preliminary study was to examine the clinical value of fluorodeoxyglucose (FDG)--PET in patients with head and neck cancer treated by radiotherapy with surgery in reserve by (i) relating quantitative uptake of isotope to tumour type and histological grade and (ii) comparing the imaging findings of PET and magnetic resonance imaging (MRI) in post-radiotherapy assessment of tumour response. Twenty-one patients had pre-treatment PET and MRI scans and these were repeated four and eight months after treatment if there was no clinical relapse. Pre-treatment uptake of FDG using tumour to cerebellar ratio parameters was significantly related to the histological grade of squamous cancer (p = 0.04) but not to tumour type. Discordance of post-treatment PET/MRI findings in one case indicates a possible role for PET in the early detection of tumour recurrence. Other potential uses of PET scanning in the management of head and neck cancer are discussed.

Adult↗
PubMed1998

Clinical variability of target volume description in conformal radiotherapy planning.

PURPOSE: The pivotal step in radiation planning is delineation of the target volume and production of a treatment plan to encompass this. This study assesses the variation of physicians in creation of these volumes. METHODS AND MATERIALS: Three radiologists and eight radiation oncologists outlined the gross tumour volume (GTV) on the planning CT scans of four cases with T3 bladder cancer. In addition, the radiation oncologists (RO) created a planning target volume according to a set protocol for all cases. Volumes were produced and comparison of these volumes and the position of the isocenters were analysed. In addition, the margins allowed were measured and compared. RESULTS: There was a maximum variation ratio (largest to smallest volume outlined) of the GTV in the four cases of 1.74 among radiologists and 3.74 among oncologists. There was a significant difference (p = 0.01) in mean GTV between RO and the radiologists. The mean GTV of the RO exceeded the radiologists by a factor of 1.29 with a mean difference of 13.4 cm3. The variation ratio in PTV among oncologists ranged from 1.25 to 3.33. There was no significant difference in mean PTV values between the two groups of ROs divided by specialization in uro-oncology. The mean variation in location of the isocenter from the centroid of the radiologists' volume in the four cases was from 2.6 to 5.7 mm. There was, however, a wide range of values from 1.4 mm to 24.1 mm. Median margin per case ranged from 14.7 to 18.7 mm. Minimum margins allowed in each case varied from minus 7 mm to 9 mm. CONCLUSION: This study demonstrates significant interphysician variability in producing target volumes and radiation plans for conformal radiotherapy. The scale of this difference is clearly of significance, with up to 3-fold variation in volumes delineated by clinicians. The factors leading to these differences will be further addressed. The existence of such variability, however, clearly needs to be accepted as a factor in the overall uncertainty analysis in conformal radiotherapy planning.

Humans↗
PubMed1998

The role of radiotherapy in the treatment of localised intermediate and high grade non-Hodgkin's lymphoma in elderly patients.

BACKGROUND AND PURPOSE: The treatment of elderly patients with high or intermediate grade non-Hodgkin's lymphoma (NHL) remains difficult and controversial. In order to audit our own practice, 270 elderly patients treated between 1988 and 1993 with this diagnosis were retrospectively reviewed. MATERIAL AND METHODS: 81 patients unfit for chemotherapy received fractionated radiotherapy for apparently localised stage I or II disease. The median age of the patients was 78 years (range 70-87 years). Forty stage I and 17 stage II patients had extra-nodal sites of disease. The radiation field included the primary site plus immediate adjacent nodes. RESULTS: After a median follow-up of 3.9 years the 5-year overall and disease-free survival rates were 33% and 31%, respectively. Age (hazard ratio (HR) 1.22, P = 0.03), stage (HR 5.50, P = 0.02) and lactate dehydrogenase level (HR 1.003, P = 0.004) were identified as independent risk factors for relapse. CONCLUSION: These factors can define a group in which radiotherapy can produce acceptable survival rates (age < or = 80 years, stage I and lactate dehydrogenase < or = 500). This group represented 34% of those patients where all these variables were recorded and had 5-year disease-free and overall survival rates of 56% and 62%, respectively.

Age Factors↗
PubMed1997

Bladder movement during radiation therapy for bladder cancer: implications for treatment planning.

PURPOSE: To describe and quantify bladder movement during radical radiation therapy (RT). To attempt to identify factors that predict for excessive alterations in bladder position. To use the above information to assist in defining the "adequate" planning target volume margin. METHODS AND MATERIALS: Thirty patients with bladder cancer suitable for radical courses of RT were followed prospectively. Patients had an initial planning computerized tomography (CT) scan of the pelvis and three subsequent scans performed weekly during the treatment period. The following measurements were made on each scan in the midbladder slice: maximum anteroposterior (AP) and lateral bladder dimensions, AP rectal diameter, and the distance (margin) between the bladder walls (anterior, posterior, right, and left lateral) and the 95% isodose line. Various patient and tumor data, including bladder and bowel symptoms, were recorded to attempt correlation with bladder movement. RESULTS: Bladder size: the median bladder size (area) over all scans in all patients was 36.9 cm2 (range: 16.2 to 80.9 cm2). The change in bladder area across each sequence varied from 3.3 to 29.1 cm2 (7-55% change in area between scans). Patients with bladders of larger than the median size on the planning scan (despite emptying) were more likely to have alteration in size than those with small bladders, and this change was in the direction of contraction (p = 0.01). Bladder displacement: bladder wall movement of > 1.5 cm was defined as "significant." Eighteen of 30 patients (60%) demonstrated "significant" movement of at least one bladder wall relative to the original isodose plot. Movement resulting in margin reduction occurred in 10 patients (33%). Two patients required treatment replanning due to consistently altered bladder position. There was no pattern to displacement through RT, and all walls were at approximately equal risk of movement. Factors influencing bladder movement: posterior bladder wall movement appeared to relate to "marked" (>2 cm) rectal diameter change. There was a trend for patients with larger amounts of residual bladder tumor (greater than the median) to exhibit more bladder movement; 11 of 14 "moved" compared with 7 of 16 patients with less residual tumor. Other clinical factors including age, sex, body size, acute RT reaction, and tumor stage did not appear to relate to bladder movement. CONCLUSION: Bladder movement during RT is clinically relevant and is random with respect to both time and direction. We recommend, at least with respect to tumor-bearing regions of the bladder, that no less than a 2.0 cm margin should be allowed.

Aged↗
PubMed1996

A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures.

Although vitamin D supplementation in the frail elderly improves calcium absorption, suppresses parathyroid hormone, decreases bone loss and reduces the risk of fractures, such treatment may be ineffective in patients with vertebral osteoporosis, because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel. We have therefore performed a randomized, single masked study comparing the effects of alfacalcidol treatment (0.25 micrograms twice daily) and vitamin D2 supplementation (500-1000 units daily) on calcium absorption and bone turnover in 46 elderly women (median age 69 years, range 64-79 years) with radiological evidence of vertebral fractures. Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D2 (p < 0.001), but was unchanged in the group receiving alfacalcidol. Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period. Fractional 45Ca absorption increased after 3 months of treatment with alfacalcidol (p < 0.05), but was unchanged with vitamin D2. There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol (p < 0.05) which was not seen in the group receiving vitamin D2. Our study shows that vitamin D2 supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis. By increasing calcium absorption in such patients, alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis.

Absorption↗
PubMed1995

Are elderly Asians in Britain at a high risk of vitamin D deficiency and osteomalacia?

Many studies have shown the indigenous elderly population and Asian immigrants to be groups at particular risk of vitamin D deficiency and osteomalacia, but there are no data on the risks in elderly Asians. In this community-based study a group of elderly Asians was compared with control groups of elderly and young whites and young Asians. Levels of 25-hydroxyvitamin D3 (25-OHD3) were significantly lower (p < 0.0001) in elderly Asians (21/37) and young Asians (7/17) compared with white controls. The difference in parathyroid hormone (PTH) between Asians and whites was also significant (p < 0.0007) as was that between young and old (p < 0.0002). Abnormal PTH and 25-OHD3 (high PTH and low 25-OHD3), indicative of a high risk of osteomalacia, occurred in 22% of elderly Asians compared with 6% of elderly whites. The calcium, phosphate and alkaline phosphatase were normal in all individuals. Among the Asians, vegetarianism was not related to lower 25-OHD3 levels. Symptoms suggestive of osteomalacia were more common (p < 0.05) in elderly Asians than in their white counterparts. This first study of 25-OHD3 levels in community-resident elderly Asians suggests that more than half were low, placing them at a significantly higher risk of osteomalacia.

Adult↗
PubMed1994

Artificial ultraviolet whole-body radiation does not modify serum lipoprotein, plasma fibrinogen, plasminogen or antithrombin III concentrations in post-myocardial infarction patients.

The relationship of ischaemic heart disease (IHD) to seasonal and latitude variation has prompted speculation that exposure to the ultraviolet component of solar radiation may reduce IHD risk. This hypothesis was partially tested by exposing 14 post-myocardial infarction patients to a 6 week course of artificial whole-body ultraviolet radiation (UVR). Serum lipoprotein and plasma coagulation factor concentrations were measured before and after the course of UVR. Results were compared with similar measurements from a placebo-controlled group of 13 post-myocardial patients. Despite a more than two-fold rise in mean serum 25-OHD, serum lipoprotein and plasma fibrinogen, antithrombin III and plasminogen concentrations did not change significantly in the UVR group. Significant but minor change in prothrombin time and thrombin time in the placebo group appear unlikely to be of biological significance. Seasonal and latitude variation in these IHD risk factors appear unrelated to corresponding variation in solar UVR exposure.

Antithrombin III↗