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A Barrett

Publications and source records attributed to A Barrett.

At least 37 records · Page 2Linked to original sources
PubMed1998

The linear-quadratic transformation of dose-volume histograms in fractionated radiotherapy.

BACKGROUND AND PURPOSE: Dose-volume histograms (DVHs) are often used in radiotherapy to provide representations of treatment dose distributions. DVHs are computed from physical dose and do not include radiobiological factors; therefore, the same DVH will be computed for a treatment plan whatever fractionation regimen is used. However, dose heterogeneity resulting from variation of daily treatment dose within the volume will have biological effects due to spatial heterogeneity of fraction size as well as total dose. The purpose of the paper is to present a radiobiological (LQ) transformation of the physical dose distribution which incorporates fraction size effects and may be better suited to the prediction of biological effects. METHODS: An analytic formula is derived for the linear-quadratic transformation of a normal distribution of dose to give the corresponding distribution of biologically equivalent dose given as 2 Gy fractions. This allows LQ-transformed DVHs to be computed from physical DVHs. The resultant LQ-DVH depends on the assumed value of the relevant alpha/beta ratio. It is a modified dose distribution (corrected for spatial heterogeneity of fraction size) but does not incorporate time factors or volume effects. RESULTS: The analysis shows that the LQ-transformed distribution is always broader than the distribution of physical dose. Radiobiological 'hot spots' and 'cold spots' are further from the mean than physical distributions would indicate. The difference between conventional DVHs and LQ-transformed DVHs is dependent on the fractionation regimen used. LQ-DVHs for a single dose distribution (treatment plan) can be computed for different fractionation regimens with some simplifying assumptions (e.g. no time-factor-dependence of late effects). Regimens calculated to be radiobiologically equivalent at a single point nevertheless result in non-equivalent LQ-DVHs when spatial variation of daily treatment dose is included. The difference is especially important for tumour sites (such as breast and head and neck) for which considerable dose heterogeneity may occur and for which different treatment regimens are in use. CONCLUSIONS: LQ-DVHs should be computed in parallel with conventional DVHs and used in the evaluation of treatment plans and fractionation regimens and in the analysis of high-dose side-effects in patients.

Brachytherapy↗
PubMed1998

Modelling the enhancement of fractionated radiotherapy by gene transfer to sensitize tumour cells to radiation.

BACKGROUND AND PURPOSE: Several strategies now exist for the use of gene transfer methodologies to sensitize tumour cells to radiation. These include the transfection of genes synthesizing cytokines, p53 gene replacement and methods based on the use of HSV-tk and gancyclovir. Very recently, the sequencing of radioprotector or repair genes, such as ATM, Ku80 and XRCC2, has made it possible to consider the design of gene transfer strategies resulting in protector gene knock-out. Selectivity of transfected gene expression might be achieved by use of tissue-specific promoters or by the trophism of viral vectors. The purpose of this study was to evaluate the probable efficacy of such strategies. METHODS: We have modelled gene transfer-mediated radiosensitization of tumour cells during radiotherapy, focusing on anti-protector gene strategies, to explore the role of transfection frequency, sensitizing efficacy, transfection stability, untransfectable subpopulations, the timing of gene therapy and the treatment schedule structure. RESULTS: We predict a substantial therapeutic benefit of gene transfer treatment (with at least weekly transfection) which modifies cellular radiosensitivity by a factor of 1.5 or more, despite modest efficiency of cellular transfection (e.g. 50%), transient retention of the transfected gene (e.g. 2-day half-life) and the existence of a small minority (e.g. 1%) of untransfectable cells. CONCLUSIONS: The analysis shows repeated administration of gene transfer treatment to be obligatory and implies that the existence of untransfectable minority subpopulations (i.e. cells inaccessible to the vector) will be the major limiting factor in therapy. Experimental work is needed to confirm these predictions before clinical studies begin.

Gene Expression Regulation↗
PubMed1998

Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology: MMT84.

The second International Society of Paediatric Oncology (SIOP) study for rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; and (2) to reduce the late effects from therapy by restricting the indications for surgery and/or radiotherapy after good response to initial chemotherapy. A further aim was to investigate the role of high-dose chemotherapy in young patients with parameningeal primary tumours. 186 previously untreated eligible patients entered the study. Patients with completely resected primary tumour received three courses of IVA (ifosfamide, vincristine and actinomycin D). Patients with incompletely resected tumour received six to 10 courses of IVA according to stage. Patients achieving complete remission with chemotherapy alone did not usually receive radiotherapy or undergo extensive surgery, but patients remaining in partial remission received local therapy with surgery and/or radiotherapy. Only patients over 5 years of age with parameningeal disease and patients over 12 years with tumours at any site were given systematic irradiation. Complete remission was achieved in 91% (170/186) of all patients. With a median follow-up of 8 years, the 5-year overall survival was 68% (+/- 3% standard error of the mean (SEM) and the 5-year event-free survival 53% (+/- 4% SEM). These results show an improvement over previous SIOP study (RMS75) in which survival was 52% and event-free survival was 47%. Among the 54 patients who exhibited isolated local relapse, 35% (19/54) survived in further remission longer than 2 years after retreatment, including local therapy (surgery +/- radiotherapy). Analysis of the overall burden of therapy received by all surviving children (including primary treatment and treatment for relapse if required) showed that 24% (28/116) were treated by limited surgery followed by three courses of IVA, 29% (34/116) were treated by chemotherapy alone (after initial biopsy) and 13% (15/116) received chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensive local therapy defined as radical wide field radiotherapy or radical surgery or both. Compared with the results obtained in the previous SIOP study, treatment in MMT84 was based on response to initial chemotherapy and, despite an overall reduction of the use of local therapy, significantly improved survival for patients with non-metastatic disease. This trial, also for the first time, provides evidence that retreatment after local relapse can achieve long-term second remissions.

Adolescent↗
PubMed1998

Enhanced speed and sensitivity in the cultural diagnosis of pulmonary tuberculosis with a continuous automated mycobacterial liquid culture (CAMLiC) system.

A total of 2800 sputum samples referred for mycobacterial investigation was examined by both continuous automated mycobacterial liquid culture (CAMLiC) and conventional Loewenstein-Jensen culture (LJC). The CAMLiC system was more sensitive than LJC, detecting 188 (98.4%) of 191 of all mycobacteria found by one or both methods compared to 150-162 (78.5-84.8%) found by LJC (the range for LJC takes into account all potential 'missed positives' due to contamination). Figures for Mycobacterium tuberculosis complex (MTBC) organisms specifically were 133 (98.4%) of 135 for CAMLiC and 115-122 (85.2-90.4%) for LJC. Detectable growth of MTBC organisms in CAMLiC occurred at a mean of 13.4 days after inoculation (range 3-32; SD 6.49; mode 8 days); 65.4% of such isolates were detected within 14 days and 87.2% within 21 days. In 73 instances the MTBC status of the isolate was defined by gene probe on the day of growth detection. Sufficient biomass for valid gene probe assay was always present. The speed, sensitivity and labour-sparing technology (no manual intervention is necessary before identification or discard) of CAMLiC make it possible for many laboratories to approach the Centers for Disease and Prevention (CDC) standard for culture and identification in mycobacteriology without resort to direct DNA detection techniques and at a much lower cost.

Bacteriological Techniques↗
PubMed1997

Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART Steering Committee.

BACKGROUND: Human tumour cells can proliferate rapidly, and giving radiotherapy in many small fractions may reduce long-term normal-tissue morbidity. In response to these observations, we developed the CHART (continuous hyperfractionated accelerated radiotherapy) regimen, which uses thirty-six small fractions of 1.5 Gy given three times per day, to give 54 Gy in only 12 consecutive days. We report the long-term follow-up of a trial of CHART versus conventional radiotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS: 563 patients were entered by thirteen centres between April, 1990, and March, 1995. We included patients with NSCLC localised to the chest with a performance status of 0 or 1 in whom radical radiotherapy was chosen as the definitive management. Patients were randomly allocated in a 3:2 ratio to CHART or conventional radiotherapy. The latter was thirty fractions of 2 Gy to a total dose of 60 Gy in 6 weeks. RESULTS: The groups were well matched for possible prognostic factors. Overall there was a 24% reduction in the relative risk of death, which is equivalent to an absolute improvement in 2-year survival of 9% from 20% to 29% (p = 0.004, 95% CI 0.63-0.92). Subgroup analyses (predefined) suggest that the largest benefit occurred in patients with squamous cell carcinomas (82% of the cases), in whom there was a 34% reduction in the relative risk of death (an absolute improvement at 2 years of 14% from 19% to 33%). During the first 3 months, severe dysphagia occurred more often in the CHART group than in the group on conventional radiotherapy (19 vs 3%). Otherwise, there were no important differences in short-term or long-term morbidity. INTERPRETATION: CHART compared with conventional radiotherapy gave a significant improvement in survival of patients with NSCLC. Further improvement may be achieved with dose escalation in conformal radiotherapy, by the addition of cytotoxic chemotherapy, and by hypoxic cell radiosensitisation.

Adult↗
PubMed1997

A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer.

BACKGROUND AND PURPOSE: Continuous, hyperfractionated, accelerated radiotherapy (CHART) has shown promise of improved tumour control and reduced late morbidity in pilot studies and has now been tested in a multicentre randomised controlled clinical trial. MATERIAL AND METHODS: Patients with squamous cell cancer in the main sites within the head and neck region with the general exception of early T1 N0 tumours were entered into the study by 11 centres. There was a 3:2 randomisation to either CHART, where a dose of 54 Gy was given in 36 fractions over 12 days, or to conventional therapy where 66 Gy was given in 33 fractions over 6.5 weeks. A total of 918 patients were included over a 5 year period from March 1990. RESULTS: ACUTE MORBIDITY: Acute radiation mucositis was more severe with CHART, occurred earlier but settled sooner and was in nearly all cases healed by 8 weeks in both arms. Skin reactions were less severe and settled more quickly in the CHART treated patients. TUMOUR CONTROL AND SURVIVAL: Life table analyses of loco-regional control, primary tumour control, nodal control, disease-free interval, freedom from metastasis and survival showed no evidence of differences between the two arms. In exploratory subgroup analyses there was evidence of a greater response to CHART in younger patients (P = 0.041) and poorly differentiated tumours appeared to fare better with conventional radiotherapy (P = 0.030). In the larynx there was evidence of a trend towards increasing benefit with more advanced T stage (P = 0.002). LATE TREATMENT RELATED MORBIDITY: Osteoradionecrosis occurred in 0.4% of patients after CHART and 1.4% of patients after conventional radiotherapy. The incidence of chondritis or cartilage necrosis was similar in both arms. Life table analysis showed evidence of reduced severity in a number of late morbidities in favour of CHART. These were most striking for skin telangiectasia, superficial and deep ulceration of the mucosa and laryngeal oedema. CONCLUSION: Similar local turnout control was achieved by CHART as compared with conventional radiotherapy despite the reduction in total dose from 66 to 54 Gy supporting the importance of repopulation as a cause of radiation failure. The effects seen in advanced laryngeal cancer and those related to histological differentiation need further study. Reduced late morbidity is a factor which together with patient preference should be considered in the decision as to the programme of radiotherapy to employ in the curative treatment of head and neck cancer.

Adult↗
PubMed1997

Does histology influence outcome in childhood Hodgkin's disease? Results from the United Kingdom Children's Cancer Study Group.

PURPOSE: Histology has been identified as an important prognostic factor in Hodgkin's disease (HD) in adults. Information regarding the impact of histology on outcome in childhood HD is scarce. This study determines the effect of histology on the overall survival (OS) or progression-free survival (PFS) in a national series of children treated in a standardized manner. PATIENTS AND METHODS: The results of treatment of 331 assessable patients, treated between January 1, 1982 and June 30, 1992, in the United Kingdom Children's Cancer Study Group (UKCCSG) Hodgkin's study I were reviewed to evaluate OS, PFS, and deaths according to stage and histology. Treatment was either involved-field radiation alone (stage IA) or chlorambucil, vinblastine, procarbazine, and prednisolone (ChlVPP) chemotherapy with or without mediastinal radiation. All were clinically staged at diagnosis. RESULTS: Nodular sclerosing (NS) HD was the most common histologic subtype (155 of 331 patients [47%]) and was uniformly distributed through all stages. Lymphocyte-depletion (LD) HD was extremely uncommon (< 1%). Mixed-cellularity (MC) HD had the highest relapse rate, but this was only significant (P < .05) in stage I patients who received local irradiation alone. There was no other statistically significant difference in OS and PFS between the various histologic subtypes. Multivariate analysis for PFS and OS confirmed that stage was the most important prognostic factor and that histology did not have an effect after stratification by stage. CONCLUSION: This study demonstrates that with effective multiagent chemotherapy, histologic subtype does not influence outcome. The high relapse rates in stage I MC subtype indicates that MC HD is biologically aggressive and systemic treatment with or without local irradiation may be indicated. The high relapse rate in stage IV patients appeared to be independent of histology.

Actuarial Analysis↗
PubMed1996

Did the decline continue? Comparing the labor-market quality of United States immigrants from the late 1970s and late 1980s.

"The issue addressed in this paper is whether or not the decline in immigrant labor-market quality in the U.S. observed in the late 1960s and 1970s continued in the 1980s." The data are from the Immigration and Naturalization Service and are provided for the years 1979-1980 and 1989-1990. "Given the rise in earnings inequality that has occurred in the United States over the 1980s, the returns to immigration for the more highly skilled will have increased relative to the low skilled, ceteris paribus. For this reason, it is possible that the skill decline of immigrants may have halted in the 1980s as immigrants of differing skill levels respond to the altered circumstances they would face in the United States. The empirical results show that the skill decline did indeed halt...."

Americas↗
PubMed1996

WR-1065, the active metabolite of amifostine (Ethyol), does not inhibit the cytotoxic effects of a broad range of standard anticancer drugs against human ovarian and breast cancer cells.

Amifostine (WR-2721, Ethyol), a phosphorylated thiol, demonstrates the unique ability to protect normal but not tumour tissue from cytotoxic damage induced by radiation therapy and chemotherapy. This study tested the effect of amifostine's active metabolite, the free thiol, WR-1065, on the cytotoxicity of standard anticancer drugs against human A2780 ovarian and MCF7 breast cancer cell lines in vitro, using the well-characterised sulphorhodamine B assay. 50% inhibitory concentration (IC50) values were determined for each of 16 different anticancer drugs in the presence and absence of the highest nontoxic dose of WR-1065 from concentration-response curves constructed in triplicate and based on 18 replicate cell culture plates for each tested drug concentration. Pretreatment with WR-1065 had no statistically significant effect on the IC50 value of any of the 16 drugs tested against either the A2780 or MCF7 human tumour cells. These data expand upon previous reports showing that amifostine does not protect tumours from the cytotoxic effects of anticancer agents. The ability of amifostine to protect against dose-limiting toxicity to a variety of normal tissues without protection of tumour should enhance the efficacy ratio of a wide range of standard anticancer drugs.

Antineoplastic Agents↗
PubMed1996

Randomised multicentre trials of CHART vs conventional radiotherapy in head and neck and non-small-cell lung cancer: an interim report. CHART Steering Committee.

While radiotherapy is proceeding, tumour cells may proliferate. The use of small individual doses reduces late morbidity. Continuous hyperfractionated accelerated radiation therapy (CHART), which reduces overall treatment from 6-7 weeks to 12 days and gives 36 small fractions, has now been tested in multicentre randomised controlled clinical trials. The trial in non-small-cell lung cancer included 563 patients and showed improvement in survival; 30% of the CHART patients were alive at 2 years compared with 20% in the control group (P = 0.006). In the 918 head and neck cases, there was only a small, non-significant improvement in the disease-free interval. In this interim analysis there was a trend for those with more advanced disease (T3 and T4) to show advantage; this will be subject to further analysis when the data are more mature. The early mucosal reactions appeared sooner and were more troublesome with CHART, however they quickly settled; so far no difference in long-term morbidity has emerged. These results support the hypothesis that tumour cell repopulation can occur during a conventional course of radiotherapy and be a cause of treatment failure.

Adult↗
PubMed1996

Sclerosing epithelioid fibrosarcoma.

A case of sclerosing epithelioid fibrosarcoma arising in the thigh of a 40-year-old man is reported. This recently described sarcoma has a distinctive histological appearance which may cause confusion with a variety of other sarcomas with an epithelioid pattern, and indeed with benign soft tissue tumours showing hyalinization. Despite its bland cytology, sclerosing epithelioid fibrosarcoma is capable of metastases, often several years after surgical removal. The patient described here developed lung metastases five years after excision and remains alive a further three years later. The differential diagnosis and possible histogenesis are discussed.

Adult↗
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↗