[Secondary surgery of breast reconstructions by breast implant. Assessment of patient satisfaction based on surgical technique implant conservation vs. autologous conversion]. / Chirurgie secondaire des reconstructions mammaires par prothèses. Évaluation de la satisfaction des patientes selon la technique chirurgicale : conservation d'implant vs conversion autologue.

INTRODUCTION: Breast reconstruction with implants has long-term disadvantages and is leading an increasing number of patients to request secondary corrective surgery. Two surgical strategies are possible: implant replacement (associated with capsulectomy/capsulotomy and/or lipofilling procedures) and implant removal associated with the provision of autologous tissue (flap and/or lipofilling). METHOD: Between 2010 and 2018, 54 patients underwent secondary surgery for correction of a first implant breast reconstruction. The reasons for dissatisfaction with the initial reconstruction, the procedures performed, and postoperative complications were analysed. Patient well-being and satisfaction were evaluated using the BREAST-Q questionnaire. RESULTS: Thirty-four patients benefited from a prosthesis change and 20 patients benefited from a permanent removal of their prosthesis combined with the addition of autologous tissue. The presence of a periprosthetic shell, pain, fixed appearance of the breast and breast asymmetry were the most frequent reasons for dissatisfaction. With a mean follow-up of 2.6 years, autologous conversion patients were generally more satisfied with the appearance of their breasts than patients who retained a breast implant (P<0.0001). CONCLUSION: In cases of poor esthetic or functional outcomes of implant-based breast reconstruction, removal of the prosthesis in combination with autologous reconstruction provides better results in terms of well-being and satisfaction than implant replacement.

Mucin gel formed by tumorigenic squamous lung carcinoma cells has Le(a)-X oligosaccharides and excludes antibodies from underlying cells.

Cells of cloned lines of human squamous lung carcinomas elaborate large glycoproteins that are associated with their tumorigenic potential. Two groups of clones (called Le(a)-X-positive and Le(a)-X-negative) were studied that either do or do not express the Le(a)-X oligosaccharide associated with large glycoproteins and mucins secreted by these clones. Le(a)-X-positive cells elaborate a mucin gel complex associated with their apical surfaces, which appears as a mosaic of extracellular plates. Clones of this type are tumorigenic in nude rodents when injected s.c. or when introduced into the lungs via intrabronchial aerosol. By contrast, the Le(a)-X-negative clones do not form extracellular plates and are not tumorigenic in the lungs or subcutaneously. We demonstrate that the extracellular plates of Le(a)-X-positive cells exclude antibodies from interacting with the underlying squamous lung carcinoma cells and may therefore exert an immunoprotective effect. In support of this possibility it was found that: (a) There is a substantial inflammatory cell infiltrate associated with regressing nodules of Le(a)-X-negative cells in nude rodent lung and subcutaneous nodules, while there is no observable infiltration associated with progressing Le(a)-X-positive tumors. (b) In the brain (an immunoprivileged site) tumors develop and progress when either Le(a)-X-negative or -positive cells are introduced.

Irradiated nude rat model for orthotopic human lung cancers.

The development of improved animal models for biological and preclinical studies of human lung cancer is important because lung cancer is the leading cause of cancer death in the United States. To determine whether the Rowett nude rat could serve as an orthotopic (organ-specific) model of this disease, nude rats (CR: NIH-RNU), with and without 500 rads of prior gamma-irradiation, were implanted intrabronchially with 10(7) cultured cells from 3 human lung cancer lines. Without irradiation, the NCI-H460 large-cell undifferentiated carcinoma had a 54% take-rate, whereas the NCI-H125 adenosquamous carcinoma and A549 adenocarcinoma had take-rates of 7 and 33%, respectively; irradiation increased the respective take-rates to 100, 83, and 90%. In irradiated rats, tumor age versus weight measurements showed progressive growth for all three tumors, with growth rates in the order: NCI-H460 greater than A549 greater than NCI-H125, requiring approximately 3, 5, and 9 weeks, respectively, for average tumor sizes to exceed 500 mg. The small-cell carcinoma cell line NCI-H345 was implanted only into irradiated rats and resulted in more slowly growing tumors. Histopathological study showed all model tumor types to have histological characteristics consistent with the clinical tumors from which the cell lines were derived. Each tumor type had a different growth pattern, with some of the the A549- and NCI-H125-derived tumors metastasizing to contralateral lung and/or regional lymph nodes. There was no evidence for immunological rejection in irradiated, tumor-bearing rats. Nonirradiated, implanted rats without gross tumor exhibited peribronchiolar mononuclear cell infiltration with or without fibrosis, suggesting prior immunological rejection. The successful orthotopic growth of these 4 human lung cancer cell lines in irradiated nude rats suggests that this model could be useful for biological and preclinical studies of human lung cancer, both in intact rats and via ex vivo perfusion of their tumor-bearing lungs.

An electrophysiological study on the effects of tryptophan and cortisol on schizophrenic and other mentally ill patient groups and on normal subjects.

Direct current potentials measured on the scalp suprajacent to the midline prefrontal cortex appear to monitor the metabolic activity, via CO2 production, of this portion of the cerebrum. Changes in the frontal potential 90 min after oral administration of 2.0 g L-tryptophan and of 50 mg cortisol were studied in groups of subjects defined by age, sex, psychiatric diagnosis, and medication. Twelve normal males, 10 nonschizophrenic male psychiatric inpatients, and 6 normal females showed a significant decrease in their frontal voltages, most marked in the females, after tryptophan loading. A nonsignificant voltage increase was produced by subsequent administration of cortisol. Tryptophan-loading had an opposite, voltage-increasing effect, on the 30 schizophrenic subjects tested. This abnormal response was greatest in the male and postmenopausal schizophrenic subjects. Besides this sex effect, the abnormality increased with age up to a point, and was decreased by antipsychotic medication and cortisol. An explanation in terms of an abnormality in the relative hydroxylation of indoles in schizophrenic subjects is proposed.

Neurobehavioral effects of alcohol in AMPA receptor subunit (GluR1) deficient mice.

Of the ionotropic glutamatergic receptors, the NMDA receptor is clearly implicated in the acute and chronic effects of ethanol; however, the role of the AMPA receptor in mediating the effects of ethanol in vivo is as yet unclear. Using mice deficient in the AMPA receptor subunit GluR1 (GluR1-/- mice), we investigated whether the AMPA receptor had a significant role in mediating the effects of ethanol. GluR1-/- mice showed greater locomotor activity in a novel environment, but by the fifth day of repeated testing their activity was the same as that of wild-type mice. In contrast to their enhanced locomotor activity, on an accelerating rotarod GluR1-/- mice performed consistently worse than wild-types. With regard to the effects of ethanol on motor responses, GluR1-/- mice did not differ significantly from wild-type mice in ethanol's sedative or incoordinating effects. However, the GluR1-/- mice were insensitive to the hypothermic effects of a hypnotic dose of ethanol in contrast to wild-types; this effect was dissociable from the hypnotic effects of ethanol. Further, tolerance to ethanol developed equally for GluR1-/- mice versus wild-type mice. In terms of alcohol drinking behavior, compared to wild-types, GluR1-/- mice differed neither in the acquisition of voluntary ethanol consumption nor in stress-induced ethanol drinking, nor in the expression of an alcohol deprivation effect (ADE) which is used as a model of relapse-like drinking behavior. In summary, although the loss of a hypothermic effect of ethanol in GluR1-/- mice indicates a critical role for the AMPA receptors in this effect, the GluR1 subunit of the AMPA receptor does not seem to play a critical role in the etiology of alcohol dependence. However, changes observed in activity patterns may be related to the putative role of AMPA receptors in attention deficit hyperactivity disorder.

Cyclothiazide and AMPA receptor desensitization: analyses from studies of AMPA-induced release of [3H]-noradrenaline from hippocampal slices.

1. Responses in brain produced by the activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subtype of ionotropic receptor for L-glutamate are often rapidly desensitizing. AMPA-induced desensitization and its characteristics, and the potentiating effect of cyclothiazide were investigated in vitro by analysing AMPA-induced release of [3H]-noradrenaline from prisms of rat hippocampus. 2. AMPA (1-1000 microM) stimulated the release of [3H]-noradrenaline in a concentration-dependent manner that was both calcium-dependent and tetrodotoxin-sensitive, and attenuated by the AMPA-selective antagonists, NBQX (1 and 10 microM), LY 293558 (1 and 10 microM) and GYKI 52466 (10 and 30 microM). 3. By use of an experimental procedure with consecutive applications of AMPA (100 microM, 28 min apart), the second response was reduced, indicative of receptor desensitization, and was reversed by cyclothiazide in a concentration-dependent manner (1-300 microM). The concentration-response curve for AMPA-induced release of [3H]-noradrenaline was shifted leftwards, but the reversal by cyclothiazide of the desensitized response was partial and failed to reach the maximal response of the first stimulus. 4. Observations made with various schedules of cyclothiazide application indicated that the initial AMPA-evoked response was already partially desensitized (150% potentiation by 100 microM cyclothiazide) and that the desensitization was not likely to be due to a time-dependent diminution and was longlasting (second application of cyclothiazide was ineffective). 5. Co-application of a number of drugs with actions on second messenger systems, in association with the second AMPA stimulus, revealed significant potentiation of the AMPA-induced release of [3H]-noradrenaline: forskolin (10 microM, +78%), Rp-cAMPS (100 microM, +65%), Ro 31-8220 (10 microM, +163%) and thapsigargin (100 pM, + 161%). 6. The AMPA receptor-mediated response regulating the release of [3H]-noradrenaline from rat hippocampal slices was desensitized and cyclothiazide acted to reverse partially the desensitization in a concentration-dependent manner. Since the time-course of desensitization was longer lasting than that noted in previous electrophysiological studies, multiple events may be involved in the down-regulation of AMPA receptor activity including receptor phosphorylation and depletion of intracellular Ca2+ stores.

Malignant fibrous histiocytoma of the heart presenting as unilateral pulmonary thromboembolism and infarct.

A malignant fibrous histiocytoma of the heart located at the pulmonic valve and thrombotic occlusion of branches of the left pulmonary artery with pulmonary infarct were found at autopsy in a 77-year-old man. The thrombi contained malignant cells. The patient had undergone left upper lobectomy four years earlier for thromboembolism with infarct, and review of the slides from that procedure revealed similar malignant cells within thrombi. This case is remarkable for the slow growth of the neoplasm and the prolonged survival of the patient, without specific therapy.

A Markov model of the natural history of prostate cancer.

The objective of this study was to lay a foundation for future cost-benefit analyses evaluating the public health impact of treatment and screening protocols for prostate cancer. Specifically we wanted to define the relative impact on cancer-specific mortality rates of the individual epidemiological components: pathological incidences by age groups, cancer progression rates, and the effect of competing causes of death, assuming expectant management (i.e. no definitive treatment). A biological model of prostate cancer incidence and progression was converted into a standard Markov tree where competing causes of death could occur. Weighted averages of progression rates were obtained from clinical studies. Separate cohorts of 30 year old black and white men were followed for 50 years. The model yielded cancer-specific mortality rates, overall mortality rates, and pathologic prevalences for both white and black males, consistent with the literature. Sensitivity analyses showed that of all the parameters studied, the pathological incidence of cancer in men under 50 years of age had the greatest impact on the cancer-specific mortality rates. Also important was the annual probability of progression of A1 lesions. However the other parameters including pathological incidence in older males, and progression from locally-extensive to metastatic lesions had much smaller effects. In summary, this model correlates the clinical literature with the epidemiology of prostate cancer and can be used for further decision analyses. We recommend that future research be done to more precisely quantify the pathological incidence of prostate cancer in men under 50-60 years of age. More certainty is also needed before generalizing the results of relatively small A1 series to millions of men, since A1 progression rates critically affect the eventual cancer-specific mortality. Enough uncertainty remains at this point however, that we cannot advocate widespread screening for prostate cancer until its merit be demonstrated either by the definitive long term study, or by examination of costs and quality-of-life-adjusted benefits.

The Kallmann's syndrome variant (KSV) model of the schizophrenias.

The KSV model of the schizophrenias proposes that up to 70% of schizophrenics have a pathogenic allele, or abnormal expression, of the KALIG-1 gene which is located at Xp22.3. This gene encodes a nerve-cell adhesion molecule (N-CAM) like protein, and is deleted in 66% of patients with Kallmann's syndrome, anosmia with secondary hypogonadism. Although superficially distinct, the schizophrenias and Kallmann's syndrome show numerous parallel trait defects which occur with a similar sex distribution. These defects are usually more profound in Kallmann's syndrome. Occasionally, Kallmann's patients exhibit additional defects, such as ichthyosis, which are due to the further deletion or translocation of adjacent genes. Since schizophrenics exhibit virtually all known trait defects in Kallmann's except these, it suggests that the aberrant genes are defective, but not deleted in schizophrenia. It also appears that compensatory mechanisms, involving serine proteases, are active in schizophrenia, which largely preserve fertility, but at the expense of an increased vulnerability to develop a psychosis by an episodic disruption of the blood-CSF barrier. Consequently, schizophrenia is rare in Kallmann's patients, while most schizophrenics are capable of reproduction.

Cholecystokinin-GABA interactions in rodent cortex: analyses of cholecystokinin effects on K(+)- and L-glutamate-induced release of [3H]GABA from rat cortical slices and cultured mouse cortical neurones.

Neurones of the cerebral cortex immunoreactive for the neuropeptide, cholecystokinin (CCK), also invariably contain GABA. Hence CCK is believed to modulate some aspect of GABAergic synaptic activity. The present study therefore investigated the effects of CCK on basal, K(+)- and L-glutamate-induced release of [3H]GABA from slices of rat neocortex and cultured murine neocortical neurones. Rat neocortical prisms loaded with [3H]GABA (10 nM) were superfused with Krebs-Henseleit buffer and stimulated twice (S1 and S2, 2 min) with K+ (30 mM). Release associated with each stimulus was measured and expressed relative to basal release (R1 and R2). The effects of non-selective and CCKB selective agonists, CCK-8S and CCK-4, respectively, on basal and K(+)-induced release of [3H]GABA were subsequently assessed by alternately including the peptides in S2 and comparing R2/R1 and S2/S1 ratios to control experiments. Contrary to previous findings, CCK-8S (30 nM-1 microM) and CCK-4 (0.3 nM-1 microM) failed to influence basal or K(+)-induced release. In similar experiments, murine cortical neurones superfused with HEPES balanced salt buffer, released exogenous [3H]GABA upon stimulation (1 min) with either K+ (55 mM) or L-glutamate (30 microM). However, CCK-8S, CCK-4 (both 300 nM-1 microM) and the CCKB selective antagonist, L365,260 (1 microM), failed to influence basal, K(+)- or L-glutamate-induced release of [3H]GABA from these neurones when included in S2. These data therefore do not support the postulate that CCK acting via CCKA or CCKB receptors modulates release of GABA under the present experimental conditions. GABA-CCK interactions were not specifically studied because only L-glutamate (30 microM) significantly elevated release of CCK-like immunoreactivity (115% above basal) in murine cortical neurones: basal release of CCK was estimated to be 7 and 11 pM from neurones and slices, respectively. Further studies employing more rigorous stimulation and perhaps examining endogenous GABA release are necessary to fully investigate the co-release of CCK and GABA.

Preoperative predictors of cost in Medicare-age patients undergoing coronary artery bypass grafting.

BACKGROUND: Identification of preoperative factors that contribute to the cost of coronary artery bypass grafting could aid in predicting the procedure's expense. In this study, 30 sociodemographic and clinical preoperative factors were examined with "survival analysis" techniques to determine characteristics related to total hospital cost. METHODS: Characteristics of all patients age 65 or older undergoing isolated coronary artery bypass grafting from July 1993 to April 1995 (n = 757) were recorded. Software was developed within the hospital's Transitions Systems, Inc, database to calculate the outcome variable of total cost. Nonparametric methods were used for the univariate analysis of the data, and the Cox proportional hazards model was used for the multivariable analysis, censoring 25 patients who died in the hospital. RESULTS: Median hospital cost from the day of the operation until discharge was $15,198. Median length of stay after the operation was 6 days. Multivariable analysis revealed that age, preoperative renal failure, history of cerebrovascular accident, low ejection fraction, and surgical urgency were independent predictors of total cost. CONCLUSIONS: This study, using an accurate representation of true hospital cost and a modeling technique that accounts for the confounding effect of in-hospital death on cost, provides a template for analysis of cost in other patient groups.

Pharmaceutical cost growth under capitation: a case study.

Rising drug spending has generated concern among purchasers and policymakers. This paper compares drug cost growth in a capitated system with that in managed care systems that generally did not place physicians directly at risk for drug spending. We focus on cost growth because a substantial body of literature indicates that managed care interventions that reduce the level of costs may not influence the rate of cost growth. Drug cost growth under capitation initially was below that of other systems but still above targeted rates. Over time the capitation rates rose, the amount of risk transferred to physicians declined, and spending growth accelerated.

Distribution of opioid peptide gene expression in the limbic system of Fawn-Hooded (alcohol-preferring) and Wistar-Kyoto (alcohol-non-preferring) rats.

Preprodynorphin and preproenkephalin mRNA expression was examined in the CNS of two rat strains, the alcohol-preferring Fawn-Hooded (FH) and the alcohol-non-preferring Wistar-Kyoto (WKY), using in situ hybridisation histochemistry. Relative to the WKY, the FH showed significantly lower levels of preproenkephalin mRNA in the striatum and nucleus accumbens (-24% and -17% respectively), but a higher level of preprodynorphin mRNA in the hippocampus (+33%). The depressed level of preproenkephalin mRNA in the nucleus accumbens may be implicated in alcohol-seeking behaviour.

The role of opioid-dopamine interactions in the induction and maintenance of ethanol consumption.

1. Alcohol is one of the most widely used recreational drugs, but also one of the most widely abused, causing vast economic, social and personal damage. 2. Several animal models are available to study the reinforcing mechanisms that are the basis of the abuse liability of ethanol. Innate differences in opioid or dopamine neurotransmission may enhance the abuse liability of ethanol, as indicated by animal and human studies. 3. Opioid antagonists have been shown to be effective, both experimentally and clinically, in decreasing ethanol consumption, presumably since ethanol induces the release of endogenous opioid peptides in vivo. However, ethanol may also stimulate the formation of opiate-like compounds, which could interact with opioid (or dopamine) receptors. Ethanol may cause changes in neurotransmission mediated via opioid receptors that determines whether alcohol abuse is more or less likely. 4. Ethanol appears to facilitate dopamine release by increasing opioidergic activity, disinhibiting dopaminergic neurons (by inhibition of GABAergic neurotransmission) via mu-opioid receptors in the ventral tegmental area (VTA) and delta-opioid receptors in the nucleus accumbens (NAcc). The effects of ethanol would be antagonised by presynaptic kappa-opioid receptors present on dopaminergic terminals in the NAcc. 5. Mesolimbic dopamine release induced by ethanol consumption seems to indicate ethanol-related stimuli are important, focussing attention on and enabling learning of the stimuli. However, studies indicate that there are redundant pathways, and neural pathways 'downstream' of the mesolimbic dopamine system, which also enable the reinforcing properties of ethanol to be mediated.

The danger of applying group-level utilities in decision analyses of the treatment of localized prostate cancer in individual patients.

The optimal management strategy for men who have localized prostate cancer remains controversial. This study examines the extent to which suggested treatment based on the perspective of a group or society agrees with that derived from individual patients' preferences. A previously published decision analysis for localized prostate cancer was used to suggest the treatment that maximized quality-adjusted life expectancy. Two treatment recommendations were obtained for each patient: the first (group-level) was derived using the mean utilities of the cohort; the second (individual-level) used his own set of utilities. Group-level utilities misrepresented 25-48% of individuals' preferences depending on the grade of tumor modeled. The best kappa measure achieved between group and individual preferences was 0.11. The average quality-adjusted life years lost due to misrepresentation of preference was as high as 1.7 quality-adjusted life years. Use of aggregated utilities in a group-level decision analysis can ignore the substantial variability at the individual level. Caution is needed when applying a group-level recommendation to the treatment of localized prostate cancer in an individual patient.

Hypometabolism in olfactory cortical projection areas of male patients with schizophrenia: an initial positron emission tomography study.

Several studies have reported olfactory deficits in schizophrenic patients. This study examines local cerebral metabolic rate within two cortical areas in eight normal men and eight schizophrenic men. A significantly greater degree of hypometabolism was observed in the schizophrenic men in the cortical area of the nondominant hemisphere that receives direct uncrossed olfactory projections.

Effects of acute ethanol on GABA release and GABA(A) receptor density in the rat mesolimbic system.

The present study has addressed whether acute ethanol administration mediates changes in GABA release and GABA(A) receptor density in the rat mesolimbic system. In vivo microdialysis was performed in the ventral pallidum and between the ventral tegmental area and substantia nigra of conscious ethanol-naive rats. Extracellular levels of endogenous GABA were stable in both brain regions and not significantly affected following administration of 5 ml of 20% ethanol by gavage, despite clear overt behavioral signs of intoxication. Two hours following ethanol administration, animals were decapitated and the brains processed for autoradiography. Adjacent tissue sections were incubated with [3H]SR95531 or [3H]muscimol and the resulting autoradiograms quantified. Binding of both radioligands was significantly reduced in the striatum of rats treated with ethanol compared to vehicle (15 +/- 2% for [3H]SR95531 and 33 +/- 6% for [3H]muscimol). In contrast, ethanol had no effect on [3H]SR95531 binding in hippocampus, while that of [3H]muscimol was increased by 100 +/- 30%. Ethanol had no effect on the binding of either radioligand in all other areas examined. Therefore, while acute ethanol had no effect on the release of GABA in either the ventral pallidum or ventral tegmental area, changes in the binding density of GABA(A) ligands were observed in selected brain regions.

Lung tolerance to hyperthermia by in vivo perfusion.

In vivo isolated lung perfusion is a novel technique for targeting anticancer therapy to the lung while avoiding systemic toxicity as normal lung toxicity from the antitumour therapy becomes the limiting factor. This study was performed to investigate the effects of hyperthermia on lung function in an intact animal model in which both acute and subacute toxicity could be monitored. Dogs underwent in vivo isolated lung perfusion. A control group was perfused to a lung temperature of 37 degrees C (group 1) and two other groups were treated in an identical manner except that the perfusion temperature was 43 degrees-44.8 degrees C in group 2 and greater than 45 degrees C in group 3. An assessment of lung injury was performed pre-perfusion, immediately post-perfusion and 2 weeks post-perfusion by measurement of extravascular lung water (Qev), serotonin uptake and wet weight to dry weight ratio. Our findings showed that the lung was tolerant to hyperthermia up to about 44 degrees C for 1 h. Analysis of 4 animals who survived perfusion above 3/44.0 degrees C showed a highly significant decrease in serotonin uptake between pre- and post-perfusion values (82.4 +/- 1.2 vs 40.4 +/- 3.9, P less than 0.02); at 2 weeks serotonin uptake had returned to normal in all 3 dogs. Fulminating pulmonary oedema developed at temperatures over 45 degrees C. Serotonin uptake may be a sensitive predictor of thermal lung injury.

Thoracic empyema: causes, diagnosis, and treatment.

Thoracic empyema is a disease that has been recognized for centuries. The principles of management as stated by Hippocrates remain more or less unchanged. Diagnosis can be masked by the underlying cause, preemptive antibiotic treatment, or the now frequently associated debilitating diseases. With no other specific investigation, the main diagnostic test remains diagnostic thoracentesis. When an empyema is encountered, the objectives are to save life; eliminate the empyema, its complications, and chronicity; return pulmonary mechanics to normal; and reduce the duration of the hospital stay. The introduction of antibiotics has dramatically influenced the spectrum of the disease now encountered. If the original infection is adequately treated, empyema rarely occurs. Penicillin has removed the major cause of empyema, and further developments in antibiotics now mean that the majority of empyemas occur when patients are disabled by other disease processes or malnutrition, or where there remains a delay in medical attention. These patients are often less able to withstand the prolongation of the infective processes that is sometimes encountered with the staged approach to treatment. Developments in operative and postoperative care have meant that these patients can best be treated by more aggressive and definitive surgical management.

Consideration of the likely benefit from implementation of prostate image-guided radiotherapy using current margin sizes: a radiobiological analysis.

OBJECTIVE: To estimate the benefit of introduction of image-guided radiotherapy (IGRT) to prostate radiotherapy practice with current clinical target volume-planning target volume (PTV) margins of 5-10 mm. METHODS: Systematic error data collected from 50 patients were used together with a random error of σ=3.0 mm to model non-IGRT treatment. IGRT was modelled with residual errors of Σ=σ=1.5 mm. Population tumour control probability (TCP(pop)) was calculated for two three-dimensional conformal radiotherapy techniques: two-phase and concomitant boost. Treatment volumes and dose prescriptions were ostensibly the same. The relative field sizes of the treatment techniques, distribution of systematic errors and correlations between movement axes were examined. RESULTS: The differences in TCP(pop) between the IGRT and non-IGRT regimes were 0.3% for the two-phase and 1.5% for the concomitant boost techniques. A 2-phase plan, in each phase of which the 95% isodose conformed to its respective PTV, required fields that were 3.5 mm larger than those required for the concomitant boost plan. Despite the larger field sizes, the TCP (without IGRT) in the two-phase plan was only 1.7% higher than the TCP in the concomitant boost plan. The deviation of craniocaudal systematic errors (p=0.02) from a normal distribution, and the correlation of translations in the craniocaudal and anteroposterior directions (p<0.0001) were statistically significant. CONCLUSIONS: The expected population benefit of IGRT for the modelled situation was too small to be detected by a clinical trial of reasonable size, although there was a significant benefit to individual patients. For IGRT to have an observable population benefit, the trial would need to use smaller margins than those used in this study. Concomitant treatment techniques permit smaller fields and tighter conformality than two phases planned separately.