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P Hoskin

Publications and source records attributed to P Hoskin.

17 recordsLinked to original sources
PubMed2001

Mitoxantrone is superior to doxorubicin in a multiagent weekly regimen for patients older than 60 with high-grade lymphoma: results of a BNLI randomized trial of PAdriaCEBO versus PMitCEBO.

A prospective, multicenter, randomized trial was undertaken to compare the efficacy and toxicity of adriamycin with mitoxantrone within a 6-drug combination chemotherapy regimen for elderly patients (older than 60 years) with high-grade non-Hodgkin lymphoma (HGL) given for a minimum of 8 weeks. A total of 516 previously untreated patients aged older than 60 years were randomized to receive 1 of 2 anthracycline-containing regimens: adriamycin, 35 mg/m(2) intravenously (IV) on day 1 (n = 259), or mitoxantrone, 7 mg/m(2) IV on day 1 (n = 257); with prednisolone, 50 mg orally on days 1 to 14; cyclophosphamide, 300 mg/m(2) IV on day 1; etoposide, 150 mg/m(2) IV on day 1; vincristine, 1.4 mg/m(2) IV on day 8; and bleomycin, 10 mg/m(2) IV on day 8. Each 2-week cycle was administered for a minimum of 8 weeks in the absence of progression. Forty-three patients were ineligible for analysis. The overall and complete remission rates were 78% and 60% for patients receiving PMitCEBO and 69% and 52% for patients receiving PAdriaCEBO (P =.05, P =.12, respectively). Overall survival was significantly better with PMitCEBO than PAdriaCEBO (P =.0067). However, relapse-free survival was not significantly different (P =.16). At 4 years, 28% of PAdriaCEBO patients and 50% of PMitCEBO patients were alive (P =.0001). Ann Arbor stage III/IV, World Health Organization performance status 2-4, and elevated lactate dehydrogenase negatively influenced overall survival from diagnosis. In conclusion, the PMitCEBO 8-week combination chemotherapy regimen offers high response rates, durable remissions, and acceptable toxicity in elderly patients with HGL.

Aged↗
PubMed2001

A survey of radiotherapy quality control practice in the United Kingdom for the START trial.

BACKGROUND AND PURPOSE: This paper compares the quality control checks performed in departments in the United Kingdom with those recommended by the Institute of Physics and Engineering in Medicine (IPEM) in Report 81. METHOD: The data were gathered by the quality assurance team for the START trial, during visits to individual departments. Data are compared with the frequencies suggested in IPEM report 81. Where applicable, data are also analyzed with respect to machine manufacturer. RESULTS: All departments with linear accelerators check the output at least weekly for both photons and electrons, however 11% of departments do not perform a constancy check of the output on a daily basis. The majority of departments check flatness at gantry zero on a monthly basis. However 27% of departments never check at non-zero gantry angles. In 51% of departments no fluoroscopy checks are performed on simulators on a daily basis. CONCLUSION: The majority of departments are following the frequencies suggested in IPEM report 81 although there are a number of discrepancies particularly for simulators. Accelerator type needs to be considered when designing quality assurance checks. In many departments more time than is currently allocated is needed on equipment, particularly simulators, to complete all of the checks suggested in Report 81.

Breast Neoplasms↗
PubMed2001

The START trial-measurements in semi-anatomical breast and chest wall phantoms.

This paper describes dosimetry measurements performed prior to departments entering patients into the START Trial, a breast fractionation trial. Absolute and relative doses were measured in semi-anatomical breast and chest wall phantoms, as part of a quality assurance programme visit. Doses were measured using an ionization chamber and the resulting distributions were compared with those calculated by the department. The mean ratio of measured to calculated dose at the START reference point was found to be 0.981 for the breast phantom and 0.978 for the chest wall phantom. This average measured dose was significantly less than the prescribed dose (p < 0.001). Differences were found between 2D and 3D planning systems and for departments using cobalt 60 beams. A number of departments had deviations of greater than 4%, which was the tolerance applied for this trial. It is essential for dose measurements of this type to be performed for randomized clinical trials involving radiotherapy, particularly where dose fractionation regimes are being compared.

Algorithms↗
PubMed2000

The impact of FDG positron emission tomography imaging on the management of lymphomas.

The role of 2-(F-18)-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging in the management of patients with lymphoma has been evaluated. 29 patients (12 Hodgkin's disease, 17 non-Hodgkin's lymphoma (NHL)) who underwent FDG-PET imaging during their lymphoma treatment programme were reviewed retrospectively. Correlation between FDG-PET and CT was evaluated, together with the impact upon clinical management of the findings on FDG-PET imaging. FDG-PET added extra information to the findings on clinical examination and CT in 12 patients (41%). This was seen both in patients with negative and positive CT scan. Two false positive FDG-PET scans were seen, reflecting FDG uptake in extranodal sites. Information from FDG-PET imaging resulted in a change in clinical management in 10 patients (34%); in two, initial management was altered, and in eight consolidation therapy after completion of initial chemotherapy was influenced. These changes in clinical management occurred in six patients with high grade NHL, two with low grade NHL and two with Hodgkin's disease. No specific subgroup was identified in whom FDG-PET was particularly discriminant.

Adolescent↗
PubMed2000

A pilot study to assess the feasibility of prior scalp cooling with palliative whole brain radiotherapy.

The objective of this work was to perform a feasibility study on the use of scalp cooling during palliative whole brain radiotherapy. Seven patients (1 male, 6 female) with good performance status underwent scalp cooling prior to and during radiotherapy for cerebral metastases. Five patients were prescribed 12 Gy in two fractions and two patients were prescribed 20 Gy in five fractions. Phantom thermoluminescent dosemeter (TLD) studies to assess the build-up effect from the scalp cap were performed. Seven out of eight patients that were offered scalp cooling completed treatment uneventfully. One patient reported discomfort on application of the scalp cap and continued treatment without scalp cooling. No patients reported other adverse effects from use of the cap during treatment or at follow-up. TLD studies demonstrated a 55-80% increase in dose to the scalp after application of the scalp cap. All patients experienced hair loss. Scalp cooling caps are well tolerated through a course of palliative whole brain radiotherapy. The scalp dose is significantly increased owing to a bolus effect from the scalp cap.

Adult↗
PubMed2000

Breast radiotherapy phantom design for the START trial. START trial management group.

The design of phantoms for use in radiotherapy involves a number of complex issues. This paper describes breast and chest wall phantoms that have been designed and constructed for the START trial. Four phantoms have been manufactured, including two two-dimensional phantoms used on the first round of audit visits to assess the ability of departments to plan with the required accuracy. Two further phantoms have been constructed and will be used in the second round of audit visits; one is a water-filled three-dimensional phantom for investigating off-axis dosimetry, the other is to be used to assess dose in the junction region between the tangential fields and the supraclavicular fossa field. The manufacturing and design process for each of the phantoms is discussed.

Breast Neoplasms↗
PubMed1999

A feasibility study of continuous hyperfractionated accelerated radiotherapy (CHART) and brachytherapy in patients with early oral or oropharyngeal carcinomas.

Overall time is important in the curative treatment of head and neck cancer (Dische, S., Saunders, M.I., Barrett, A., Harvey, A., Gibson, D., Parmar, M., 1997, Radiother. Oncol., 44:123-136). Results are presented on outcome and morbidity in ten patients with head and neck cancer treated with external beam irradiation (CHART protocol) and interstitial implantation, completing treatment in 12 days. Local control and overall survival at 5 years was 67%. Acute and late morbidity was acceptable giving scope for dose escalation.

Adult↗
PubMed1999

High-dose BEAM chemotherapy with autologous haemopoietic stem cell transplantation for Hodgkin's disease is unlikely to be associated with a major increased risk of secondary MDS/AML.

Hodgkin's disease is curable in the majority of patients, although a proportion of patients are resistant to or relapse after initial therapy. High-dose therapy with autologous stem cell support has become the standard salvage therapy for patients failing chemotherapy, but there have been reports of a high incidence of myelodysplasia/acute myeloid leukaemia (MDS/AML) following such treatment. Patients who receive such therapy form a selected group, however, who have already been subjected to other leukaemogenic factors, such as treatment with alkylating agents. In order to ascertain the true risk of MDS/AML, comparison must be made with other patients subjected to the same risks but not undergoing transplantation. We report a retrospective comparative study of 4576 patients with Hodgkin's disease from the BNLI and UCLH Hodgkin's databases, which includes 595 patients who have received a transplant. Statistical analysis including Cox's proportional hazards multivariate regression model with time-dependent covariates was employed. This analysis reveals that the risk of developing MDS/AML was dominated by three factors, namely quantity of prior therapy (relative risk [RR] 2.01, 95% confidence intervals [CI] 1.49-2.71, for each treatment block, P < 0.0001) and whether the patient had been exposed to MOPP (RR 3.61, 95% CI 1.64-7.95, P = 0.0009) or lomustine chemotherapy (RR 4.53, 95% CI 1.96-10.44, P = 0.001). Following adjustment for these factors in the multivariate model the relative risk associated with transplantation was 1.83 (95% CI 0.66-5.11, P = 0.25). This study provides no evidence of a significantly increased risk of MDS/AML associated with BEAM therapy and autologous transplantation in Hodgkin's disease. Concern over MDS/AML should not mitigate against the timely use of this treatment modality.

Acute Disease↗
PubMed1999

A pilot study of continuous, hyperfractionated, accelerated radiotherapy in rectal adenocarcinoma.

This pilot study investigated the feasibility, toxicity and effect of continuous, hyperfractionated, accelerated radiotherapy (CHART) in 19 patients with adenocarcinoma of the rectum who were treated at Mount Vernon Hospital between April 1992 and April 1994. A total dose of 54 Gy was given in 36 fractions over 12 consecutive days; three fractions of 1.5 Gy were employed each day with an interfraction interval of 6 hours. Of these 19 patients, 13 had local pelvic recurrence from rectal carcinoma, four had a primary rectal carcinoma (which was unsuitable for abdominoperineal resection because of patient frailty), and two had large, fixed, unresectable tumours and were given radiotherapy preoperatively to a lower dose of 42 Gy in 28 fractions over 10 days to facilitate surgery. However, none of the 19 patients subsequently underwent surgical resection. Treatment compliance with radiotherapy was 95%. Acute bowel toxicity was assessed by means of a daily bowel chart for 6 weeks and then at 8, 12 and 26 weeks after the completion of radiotherapy. Patients were subsequently scored using the World Health Organization (WHO) grading system. No toxic deaths were observed in this study. There were five grade 3 and one grade 4 toxicities (WHO scale) observed in six patients. There has been minimal acute bladder toxicity in two patients and skin reactions have been surprisingly minimal in all but three patients. Small bowel obstruction and late bowel damage, possibly attributable to radiotherapy, occurred in three patients. Complete pain relief was achieved in recurrent rectal cancer in 100% of patients, at a median of 15 days since commencing radiotherapy (range 7-63 days), and has been maintained for mean and median durations of 19 and 18 months respectively (range 1.5-45 months). Five patients have had a recurrence of pain at 3, 4, 8, 9 and 18 months respectively. All four patients with primary rectal adenocarcinoma achieved a complete response, which has been sustained for 4 months (until death), 54 and 57 months, although one patient relapsed locally at 8 months. In summary, CHART appears to be a feasible treatment for pelvic tumours with regard to toxicity. Patients with pain from a locoregional recurrence achieved rapid complete pain relief, which was sustained for many months.

Adenocarcinoma↗
PubMed1999

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Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Is a man's facial appearance predictive of how he will die?

The ability of a range of health professionals including an oncologist, a haematologist, a cardiologist, a general practitioner and a counsellor to predict the cause of death from facial appearance has been evaluated. Each participant was asked to predict the cause of death from facial photographs of 200 caucasian male doctors whose cause of death was known to be due to either arterial disease or neoplasia. Statistically significant concordance was found between the oncologist and both the GP and the counsellor in their predictions of cause of death, although the individual accuracy was no greater than would be expected by chance. This suggests that common judgments based on facial appearances may be shared among certain health professionals.

Adult↗
PubMed1998

Effects of impaired renal function on the pharmacokinetics of raltitrexed (Tomudex ZD1694).

This open-label, non-randomized, parallel-group trial investigated the pharmacokinetics of raltitrexed (Tomudex, formerly ZD1694) after a single intravenous dose of 3.0 mg m(-2), comparing eight cancer patients with mild to moderate renal impairment (creatinine clearance 25-65 ml min(-1)) with eight cancer patients with normal renal function (creatinine clearance >65 ml min(-1)). The primary end points were area under the plasma raltitrexed concentration-time curve from the start of the infusion to the last determined concentration (AUC(0-tldc)) and AUC to infinity (AUC(0-infinity)); secondary end points were peak concentrations of raltitrexed (Cmax) and elimination half-life (t(1/2gamma)). The groups were compared statistically using analysis of covariance. The AUCs were greater for patients with renal impairment than for patients with normal renal function (2452.2 compared with 1247.3 ng h ml(-1) for AUC(0-tldc) (ratio 1.97; 95% CI 1.36-2.84); 2961.5 compared with 1457.0 ng h ml(-1) for AUC(0-infinity) (ratio 2.03; 1.25-3.29). These differences were statistically significant (P = 0.002 and P = 0.008 for AUC(0-tldc) and AUC(0-infinity) respectively. Terminal half-life was longer for the renally impaired patients (271.2 compared with 143.3; P = 0.030). There was no significant statistical difference between the groups for Cmax (652.9 compared with 564.7 ng ml(-1) for patients with impaired and normal renal function respectively: ratio 1.16; 0.91-1.46; P = 0.204). There was a clear relationship between raltitrexed clearance and creatinine clearance. Adverse events, severe (WHO grade 3 or 4) toxicity and hospitalization due to adverse events were more frequent in the group with renal impairment. Therefore, a reduction in raltitrexed dose and increased interval between doses is recommended for patients with mild to moderate renal impairment.

Adult↗
PubMed1996

Nicotinamide pharmacokinetics in humans: effect of gastric acid inhibition, comparison of rectal vs oral administration and the use of saliva for drug monitoring.

The effect of inhibiting gastric acid secretion on nicotinamide pharmacokinetics was studied in five volunteers with the intent of reducing the large variations observed previously in the time to and magnitude of peak plasma concentrations. Plasma levels were determined using a standard high-performance liquid chromatography (HPLC) method after an oral dose of 3 g of nicotinamide either alone or preceded by pretreatment with omeprazole. Suppression of gastric acid production had no significant effect on the rate of uptake or on the peak levels achieved. To bypass gastric acidity, the rectal route was also assessed using a suppository in four volunteers and one patient undergoing radiotherapy. Absorption was slow and variable and much lower plasma levels were observed than after oral dosing. Thus, no improvement in the pharmacokinetics of nicotinamide was observed using either of these two approaches. Parallel estimations were made using a novel and non-invasive method for monitoring nicotinamide pharmacokinetics in saliva. A large and variable fraction of the total amount of nicotinamide-related material in saliva was found to be nicotinic acid, a metabolite not normally found in human plasma. This conversion was inhibited by the use of a chlorhexidine mouthwash, indicating that the oral flora was responsible for its production. The time to peak levels of nicotinamide or of nicotinamide plus nicotinic acid in saliva correlated well with that in plasma. However, peak concentrations for nicotinamide alone were significantly lower than in plasma, and very variable, whereas for nicotinamide plus nicotinic acid saliva levels were 20-30% higher, but more consistent. Although there are some practical difficulties in quantitatively handling saliva, the method is very useful for monitoring nicotinamide pharmacokinetics and for assessment of compliance with nicotinamide treatment.

Absorption↗
PubMed1994

The significance of MALT histology in thyroid lymphoma: a review of patients from the BNLI and Royal Marsden Hospital.

Data from a series of 45 patients with Stage I and II non-Hodgkin's lymphoma (NHL) of the thyroid gland were analysed retrospectively to determine the incidence and prognostic significance of histopathological features of tumour origin from mucosa associated lymphoid tissue (MALT). The overall 5- and 10-year cause specific survival from NHL for the series was 79%. Evidence of tumour origin from MALT was the only significant prognostic factor for overall survival identified by multivariate analysis of the series (P < 0.01). A total of 31 (69%) tumours showed such evidence, the cause specific patient survival from NHL at 5 and 10 years being 90% compared with only 55% at 5 years for the 14 patients without such evidence. For patients given initial treatment with radiotherapy alone, those with evidence of tumour origin from MALT had a relatively low relapse rate and a relatively high success rate from salvage therapy, compared with a relatively high relapse rate and negligible success from salvage therapy in those without evidence of such tumour origin.

Adolescent↗
PubMed1986

Prognostic factors in stage I non-seminomatous germ-cell testicular tumors managed by orchiectomy and surveillance: implications for adjuvant chemotherapy.

Between February 1979 and March 1985, 126 patients with clinical stage I non-seminomatous germ-cell testicular tumors were entered into a surveillance study after orchiectomy. Of this group, 36 (28%) have relapsed. The prognostic significance of 13 clinical, histopathologic, and biochemical factors has been analyzed. Vascular invasion and lymphatic invasion (LI) within the primary tumor, histology, and involvement of the epididymis and rete testis were significantly associated with an increased risk of relapse. However, multiple regression analysis showed that only histology and LI were significant, independent prognostic factors. These findings provide the basis for the consideration of adjuvant chemotherapy for patients with apparent clinical stage I testicular non-seminoma who are at high risk of harboring occult metastases.

Adult↗