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A Barrett

Publications and source records attributed to A Barrett.

At least 55 records · Page 3Linked to original sources
PubMed1996

Information for patients with cancer. Does personalization make a difference? Pilot study results and randomised trial in progress.

Although there are a number of groups working on the provision of personalized patient information there has been little evaluation. We have developed and piloted a method of giving patients on-line access to their own medical records with associated explanations. We are comparing, in a randomised trial, personalized with general computer based information for patients undergoing radiotherapy for cancer. We present results from the pilot study and the evaluation methods to be employed.

Adult↗
PubMed1995

Optimum combination of targeted 131I and total body irradiation for treatment of disseminated cancer.

PURPOSE: Radiobiological modeling was used to explore optimum combination strategies for treatment of disseminated malignancies of differing radiosensitivity and differing patterns of metastatic spread. The purpose of the study was to derive robust conclusions about the design of combination strategies that incorporate a targeting component. Preliminary clinical experience of a neuroblastoma treatment strategy, which is based upon general principles obtained from modelling, is briefly described. METHODS AND MATERIALS: The radiobiological analysis was based on an extended (dose-rate dependent) formulation of the linear quadratic model. Radiation dose and dose rate for targeted irradiation of tumors of differing size was in part based on microdosimetric considerations. The analysis was applied to several tumor types with postulated differences in the pattern of metastatic spread, represented by the steepness of the slope of the relationship between numbers of tumors present and tumor diameter. The clinical pilot study entailed the treatment of five children with advanced neuroblastoma using a combination of 131I metaiodobenzylguanidine (mIBG) and total body irradiation followed by bone marrow rescue. RESULTS: The theoretical analysis shows that both intrinsic radiosensitivity and pattern of metastatic spread can influence the composition of the ideal optimum combination strategy. High intrinsic radiosensitivity generally favors a high proportion of targeting component in the combination treatment, while a strong tendency to micrometastatic spread favors a major contribution by total body irradiation. The neuroblastoma patients were treated using a combination regimen with an initially low targeting component (2 Gy whole body dose from targeting component plus 12 Gy from total body irradiation). The treatment was tolerable and resulted in remissions in excess of 9 months in each of these advanced neuroblastoma patients. CONCLUSIONS: Radiobiological analysis, which incorporates simple models of metastatic spread, emphasizes the importance of the total body irradiation component in a targeting/total body irradiation combination strategy. However, the analysis favors a larger targeting component than is used in clinical practice at present. A cautious escalation of the 131I mIBG component in the combination treatment of advanced neuroblastoma appears justified.

Child↗
PubMed1995

Multi-modality megatherapy with [131I]meta-iodobenzylguanidine, high dose melphalan and total body irradiation with bone marrow rescue: feasibility study of a new strategy for advanced neuroblastoma.

New therapeutic approaches are needed for advanced neuroblastoma as few patients are currently curable. We describe an innovative strategy combining [131I]meta-iodobenzylguanidine ([131I]mIBG) therapy with high dose chemotherapy and total body irradiation. The aim of combining these treatments is to overcome the specific limitations of each when used alone to maximise killing of neuroblastoma cells. Five children received combined therapy with [131I]mIBG followed by high dose melphalan and fractionated total body irradiation. Autologous bone marrow transplantation was undertaken in 3 patients and allogeneic in 2 patients. One patient received additional localised radiotherapy to residual bulk disease. One patient is alive without relapse 32 months after treatment. 4 patients relapsed after remissions of 9, 10, 14 and 21 months. These results indicate that this combined modality approach is feasible and safe, but further evaluation is necessary to establish whether it has advantages over conventional megatherapy using melphalan alone.

3-Iodobenzylguanidine↗
PubMed1995

Peer consultation: a look at process.

After attending graduate nursing school, and being exposed to the concepts of peer supervision and consultation, six women formed a peer consultation group. A peer consultation group, simply stated, is a professional support group. In this article, evolution of the group process is described from personal experience and personal perspectives. The aim is to inspire other CNSs and nursing personnel involved in advanced practice to consider involvement in such a group to enhance their own professional growth and well-being. Although the format, group size, individual composition, and beneficial aspects of the group have varied throughout the 5-year tenure, group members unanimously agree that such a forum has been invaluable for their professional growth and development.

Consultants↗
PubMed1995

Dosimetric considerations in 131I-MIBG therapy for neuroblastoma in children.

Dosimetric calculations have been made for organ doses in patients receiving 131I-MIBG therapy as treatment for neuroblastoma. As well as whole body and liver dose, consideration has been given to dosimetry of organs (lung, urinary bladder) whose tolerance may become treatment limiting when 131I-MIBG is given as part of combined modality therapy. Data from both adults and children receiving radiolabelled MIBG for diagnostic or therapeutic purposes have been compared in constructing dosimetry models for children. A recently published urodynamic model has been used in the estimation of radiation dose to the bladder. The results show that liver and lung may receive doses greater than the average total body dose (0.58 mGy MBq-1 and 0.35 mGy MBq-1, respectively, as compared with 0.25 mGy MBq-1 to the whole body). The organ dose estimates do not differ greatly from previous analyses except in the case of the bladder for which the new modelling studies have resulted in lower dose estimates (0.76 mGy MBq-1 administered, for dose to bladder surface from bladder contents) than in some published series. This may result from differing assumptions regarding parameters such as bladder content and urine flow rate, an enhanced fluid intake being assumed in the present bladder dose estimates. Average doses to the bladder wall from the contents were estimated to be 7.4-11.3% of the surface doses. The urodynamic modelling analysis shows that the bladder could receive a much greater dose (by an order of magnitude) in patients who were inadequately hydrated or had impaired renal function.

3-Iodobenzylguanidine↗
PubMed1994

Combination chemotherapy for primitive neuroectodermal and other malignant brain tumours.

The toxicity and efficacy of a chemotherapy schedule comprising vincristine and cyclophosphamide, alternating with carboplatin and etoposide, has been assessed in a group of 15 patients with medulloblastoma, supratentorial primitive neuroectodermal tumours (PNET) or other malignant brain tumours. The patients comprised four adults and 11 children. Chemotherapy was given for palliation of recurrent disease (six patients), as an adjuvant to radiotherapy and surgery in five poor prognosis patients, or to delay the need for radiotherapy in four children aged 2 years or less. The treatment was generally well tolerated, with the principal toxicity being myelo-suppression. Among the ten assessable patients, there were six complete responders and one partial, an overall response rate of 70%. Three patients had progressive disease. Responses, although associated with good symptomatic improvement, were short lived, with two patients relapsing while still receiving chemotherapy. Three of four very young children relapsed within 7 months of completing chemotherapy and then received radiotherapy. It is concluded that this schedule merits further evaluation and comparison with more protracted and toxic schedules.

Adolescent↗
PubMed1994

Prediction of accumulation of 131I-labelled meta-iodobenzylguanidine in neuroblastoma cell lines by means of reverse transcription and polymerase chain reaction.

Radiolabelled meta-iodobenzylguanidine (mIBG) currently provides one of the most promising options for targeted radiotherapy of neuroblastoma. No means currently exists for prediction of mIBG uptake in tumour cells of individual patients other than semiquantitative inferences from diagnostic scanning which depend on the continued existence of a macroscopic tumour mass. A biological rapid assay which could be applied at initial biopsy would be invaluable in selecting patients for therapeutic strategies which incorporate radiolabelled mIBG. We have assessed the expression of the noradrenaline transporter gene in six human neuroblastoma cell lines and in three non-neural crest-derived cell lines using reverse transcription followed by the polymerase chain reaction. Transcription of this gene was observed in five out of six neuroblastoma cell lines but in none of the control cells. A highly significant correlation was established (P < 0.01) between gene expression and active cellular accumulation of mIBG. It is suggested that semiquantitative evaluation of noradrenaline transporter gene transcripts may be predictive of mIBG uptake by tumours in vivo.

3-Iodobenzylguanidine↗
PubMed1994

Image analysis derived ploidy and proliferation indices in soft tissue sarcomas: comparison with clinical outcome.

AIMS: To compare prognostic information obtained by image analysis cytometry of paraffin wax embedded soft tissue sarcomas with conventional assessment. METHODS: A CAS 200 image analyser was used to determine DNA content of Feulgen stained cytology preparations and tissue sections and to quantify immunostaining by Ki67 and PC10 antibodies. A mitotic count in 50 high power fields was undertaken and histological grade assigned by the Trojani system. Clinical details including follow up and outcome were obtained by case note review. The Kruskal-Wallis one way analysis test, Spearman rho significance test, Kaplan-Meier method, and log-rank test were applied in statistical analysis. RESULTS: Ploidy status, DNA index, 2.5c exceeding rate, 5c exceeding rate, mitotic count and Trojani grade all correlated significantly with clinical outcome. The relation between Ki67 index and outcome did not reach significance. The PC10 index and outcome were not related. Only 2.5c exceeding rate, 5c exceeding rate, and mitotic count correlated significantly with Trojani grade. CONCLUSIONS: DNA content determination of soft tissue sarcomas by image analysis provides quantifiable information of benefit in prediction of outcome. Larger series are required to determine the independent value of ploidy. In this study quantification of anti-Ki67 and anti-PC10 immunostaining was not of prognostic benefit) by contrast with mitotic count and Trojani grade.

Cell Division↗
PubMed1993

Radiobiological modeling of combined targeted 131I therapy and total body irradiation for treatment of disseminated tumors of differing radiosensitivity.

PURPOSE: A model is presented for calculating combinations of targeted 131I and total body irradiation, followed by bone marrow rescue, in the treatment of tumors of different radiosensitivity. The model is used to evaluate the role of the total body irradiation component in the optimal combination regime as a function of the radiosensitivity of the tumor cells. METHODS AND MATERIALS: A microdosimetric model was used to calculate absorbed dose in small tumors and micrometastases when uniformly targeted by the radionuclide 131I. Cell kill was calculated from absorbed dose using an extended version of the linear quadratic model. The addition of varying total doses of total body irradiation, assuming 2 Gy fractions, was also calculated using the linear quadratic model. The net cell kill from combined modality (targeted 131I and total body irradiation) was computed for varying proportions of the two components, for a range of tumor sizes, restricting the total radiation dose to within tolerance for a full-course TBI regime (approximately 14 Gy total) in all cases. The calculations were repeated for a range of presumed tumor uptakes of the targeting agent and for a range of tumor radiosensitivities, typical of those reported for tumor cells of differing type in culture. Optimal regimes were identified as those predicted to yield a high probable tumor cure rate (evaluated using a Poisson statistical model) for all tumor sizes. RESULTS: The analysis supports earlier model studies which predicted that systemic combination treatment with targeted 131I and total body irradiation would be superior to either component used alone. The intrinsic tumor radiosensitivity is found to be a factor which influences the optimal combination of the 131I and external beam total body irradiation components. The total body irradiation component is greater in optimal regimes treating radio-resistant than radiosensitive tumors. However, an obligatory total body irradiation component is also predicted for more radiosensitive tumors; the analysis suggests that the total body irradiation component should in no circumstances be less than 2 x 2 Gy, whilst practical arguments exist in favor of higher doses. CONCLUSION: Total body irradiation is an obligatory component for effective systemic treatment of disseminated malignant tumors to which 131I can be selectively targeted. Clinical studies applying this strategy to the treatment of neuroblastoma by 131I targeted by meta-iodo-benguanidine (mIBG), total body irradiation and bone marrow rescue are now in progress.

Dose-Response Relationship, Radiation↗
PubMed1993

Multifocal synchronous osteosarcoma: the Scottish Bone Tumour Registry experience.

We report 3 cases of multifocal synchronous osteosarcoma constituting 1% of osteosarcoma cases in the Scottish Bone Tumour Registry over 30 years. All were children and had a median age of 10 years. They all presented with multiple bony lesions in the absence of demonstrable pulmonary metastases. Treatment was with palliative radiotherapy in two and combination chemotherapy and radiotherapy in the most recent case. Survival was poor in all cases, with a median of 7 months. A proposal is made for genetic studies in future cases to help elucidate the origin of these tumours. The multicentric and metastatic hypotheses are discussed.

Adolescent↗
PubMed1993

Kinetic considerations in the choice of treatment schedules for neuraxis radiotherapy.

Neuraxis radiotherapy of radiosensitive tumours such as medulloblastoma is usually carried out using conventionally sized fractions and a shrinking field technique. Plowman and Doughty (Br. J. Radiol., 64 (1991) 603-607) have proposed a partial transmission block (PTB) technique which entails the use of small daily doses over a conventional time period. Radiobiological analysis suggests that, although the PTB technique may be adequate for slowly growing tumours, therapeutic efficacy is likely to be compromised where the tumour doubling time is short. Accelerated hyperfractionation (twice daily fractions) provides a possible alternative to both conventional scheduling and the PTB technique. Direct measurement of the kinetics of tumour cells in CSF, where possible, may provide useful guidance in the choice of regimes.

Cell Survival↗
PubMed1992

An audit of travel and waiting times for outpatient radiotherapy.

The object of this study was to assess the non-medical factors which detract from the quality of outpatient receiving service to a population of 2.7 million in a wide geographical area. We conducted a survey by patient questionnaire of all outpatients receiving radiotherapy in the West of Scotland on a single day in 1990. A total of 216 outpatients attended for radiotherapy with a 92% response rate to the questionnaire being achieved. Median values (and ranges) were: age 58 (4-85) years, number of daily treatments 20 (4-33), distance travelled in one direction 10 (1-60) miles, travelling time 45 (5-130) minutes, waiting time in the unit for treatment 60 (0-200) minutes, and a time away from home of 2 hours 50 minutes (35 minutes-7 hours). Sixteen per cent of patients had a relative who lost time from work by transporting the patient and only 12 of 60 patients who were away from home over a meal time were offered a hospital meal. Sixteen per cent of patients came by ambulance and 73% by motor car. Of 146 travelling by car 27% used a charity service and 20% a volunteer driver ambulance service car. It is concluded that long travelling distances, travelling times and treatment waiting times for many patients require revision of transport provision, a strict appointment system, more treatment machines and hostel accommodation.

Adolescent↗
PubMed1992

Training for clinical oncology: experience in Glasgow 1987-1992.

This paper describes how a joint core training course in clinical oncology was set up at the Beatson Oncology Centre in Glasgow. The course extends over a period of two years and modules are taught in cancer basic sciences, physics and surgical oncology, pathology and natural history of malignant disease, and statistics. The structure and content of the course are described, together with an analysis of the problems encountered. There is an assessment of effectiveness. Proposals are made for a scheme for joint accreditation in oncology.

Cancer Care Facilities↗
PubMed1992

131I-meta-iodobenzylguanidine therapy in neuroblastoma spheroids of different sizes.

Mathematical models have predicted that targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (mIBG) is less likely to cure small rather than large micrometastases if 131I is the conjugated radionuclide. This study uses multicellular tumour spheroids as an in vitro model to test the hypothesis that smaller tumours of sub-millimetre dimensions are relatively resistant to 131I-mIBG. Spheroids of the human neuroblastoma cell line SK-N-BE(2c), either 250 microns or 400 microns diameter, were incubated with 131I-mIBG at concentrations of up to 6.0 MBq ml-1. Using both regrowth delay and spheroid 'cure' as endpoints, the greater vulnerability of larger spheroids was confirmed. From this in vitro result we conclude that when used in vivo 131I-mIBG may spare smaller micrometastases. Therefore, either a radionuclide such as 211At which emits a shorter path length radiation should be conjugated to mIBG, or targeted radiotherapy should be combined with a treatment such as total body irradiation, the efficacy of which is not reduced in smaller tumours.

3-Iodobenzylguanidine↗