PubMed Health⌕ Search

Biomedical subjects

K Schulze

Publications and source records attributed to K Schulze.

At least 19 recordsLinked to original sources
PubMed2006

Enhanced protection against Streptococcus pyogenes infection by intranasal vaccination with a dual antigen component M protein/SfbI lipid core peptide vaccine formulation.

We investigated the efficacy of a synthetic Streptococcus pyogenes vaccine targeting two virulence factors using the Lipid Core Peptide (LCP) delivery system. BALB/c mice were immunised intranasally with LCPs containing peptides encompassing T-cell and B-cell epitopes of the conserved C-repeat region of the M protein (J8) or the fibronectin-binding repeats region (FNBR) of SfbI, or a combination formulation containing peptides representing both antigens. LCPs were co-administered with the TLR2/6 agonist MALP-2 as mucosal adjuvant. Humoral and cellular immune responses stimulated at systemic and mucosal levels were strongest in mice immunised with the dual antigen formulation. Mice were completely protected following a respiratory challenge with a lethal dose of a heterologous S. pyogenes strain, whereas there was 70% and 90% survival in mice immunised with LCP-J8 and LCP-FNBR, respectively. This is the first report demonstrating the elicitation of better protective immunity by a dual antigen component S. pyogenes vaccine.

Adhesins, Bacterial↗
PubMed2006

A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer.

BACKGROUND: Superiority of irinotecan/cisplatin over etoposide/cisplatin was suggested in small-cell lung cancer (SCLC). This trial investigated irinotecan/carboplatin (IP) versus etoposide/carboplatin (EP). PATIENTS AND METHODS: The interim analysis at the phase II/phase III transition point of the multicenter trial is reported. Extensive disease SCLC patients were randomized to receive carboplatin AUC 5 mg x min/ml either in combination with 50 mg/m2 of irinotecan on days 1, 8 and 15 (IP) or with etoposide 140 mg/m2 days 1-3 (EP). The primary end point was response rate and the secondary end points were toxicity and progression-free survival. RESULTS: Seventy patients were randomized. Significant differences in grade 3 and 4 thrombopenia (17% IP versus 48% EP, P = 0.01) and neutropenia (26% IP versus 51% PE, P < 0.01) were found. Grade 3 and 4 diarrhea was more frequent with IP (18%) than with EP (6%) (P = 0.133). Response rates were 67% and 59% (P = 0.24) in the IP versus EP arm, respectively. Median progression-free survival (PFS) was 9 months (95% CI 7.1-10.9) in the IP arm and 6 months (95% CI 4.1-7.9) in the EP arm (P = 0.03). CONCLUSIONS: IP is active, less toxic and appears to improve PFS. Based on the phase II results the trial has been extended to phase III to assess the impact on overall survival.

Adult↗
PubMed2006

Imaging and modelling of digestion in the stomach and the duodenum.

Gastroduodenal physiology is traditionally understood in terms of motor-secretory functions and their electrical, neural and hormonal controls. In contrast, the fluid-mechanical functions that retain and disperse particles, expose substrate to enzymes, or replenish the epithelial boundary with nutrients are little studied. Current ultrasound and magnetic resonance imaging allows to visualize processes critical to digestion like mixing, dilution, swelling, dispersion and elution. Methodological advances in fluid mechanics allow to numerically analyse the forces promoting digestion. Pressure and flow fields, the shear stresses dispersing particles or the effectiveness of bolus mixing can be computed using information on boundary movements and on the luminal contents. These technological advances promise many additional insights into the mechanical processes that promote digestion and absorption.

Animals↗
PubMed2005

Obstetric complications in patients with schizophrenia and their unaffected siblings.

OBJECTIVE: We sought to explore whether obstetric complications (OCs) are more likely to occur in the presence of familial/genetic susceptibility for schizophrenia or whether they themselves represent an independent environmental risk factor for schizophrenia. METHODS: The presence of OCs was assessed through maternal interview on 216 subjects, comprising 36 patients with schizophrenia from multiply affected families, 38 of their unaffected siblings, 31 schizophrenic patients with no family history of psychosis, 51 of their unaffected siblings and 60 normal comparison subjects. We examined the familiality of OCs and whether OCs were commoner in the patient and sibling groups than in the control group. RESULTS: OCs tended to cluster within families, especially in multiply affected families. Patients with schizophrenia, especially those from multiply affected families, had a significantly higher rate of OCs compared to normal comparison subjects, but there was no evidence for an elevated rate of OCs in unaffected siblings. CONCLUSION: Our data provides little evidence for a link between OCs and genetic susceptibility to schizophrenia. If high rates of OCs are related to schizophrenia genes, this relationship is weak and will only be detected by very large sample sizes.

Adolescent↗
PubMed2005

Entorhinal cortex entrains epileptiform activity in CA1 in pilocarpine-treated rats.

Layer III neurons of the medial entorhinal cortex (mEC) project to CA1 via the temporoammonic pathway and exert a powerful feed-forward inhibition of CA1 pyramidal neurons. The present study evaluates the hypothesis that disrupted inhibition of CA1 pyramidal neurons causes an eased propagation of entorhinal seizures to the hippocampus via the temporoammonic pathway. Using a method to induce a confined epileptic focus in brain slices, we investigated the spread of epileptiform activity from the disinhibited mEC to CA1 in control and pilocarpine-treated rats that had displayed status epilepticus and spontaneous recurrent seizures. In pilocarpine-treated rats, the mEC showed a moderate layer III cell loss and an enhanced susceptibility to epileptiform discharges compared to control animals. Entorhinal discharges propagated to CA1 in pilocarpine-treated rats but not in controls. Disconnecting CA3 from CA1 did not affect the spread of epileptiform activity to CA1 excluding its propagation via the trisynaptic hippocampal loop. Mimicking the invasion of epileptiform discharges by repetitive stimulation of the temporoammonic pathway caused a facilitation of field potentials in CA1 that were contaminated by population spikes and afterdischarges in pilocarpine-treated but not control rats. Single cell recordings of CA1 pyramidal neurons revealed a dramatic loss of feed-forward inhibition and the occurrence of strong postsynaptic excitatory potentials in pilocarpine-treated rats. Excitatory responses in CA1 were characterized by multiple NMDA receptor-mediated afterdischarges and a strong paired-pulse facilitation in response to activation of the temporoammonic pathway. Our results suggest that, irrespective of the enhanced seizure-susceptibility of the mEC in epileptic rats, the loss of feed-forward inhibition and the enhanced NMDA receptor-mediated excitability CA1 pyramidal cells ease the spread of epileptiform activity from the mEC to CA1 via the temporoammonic pathway bypassing the classical trisynaptic hippocampal loop.

Animals↗
PubMed2004

A study of hippocampal shape anomaly in schizophrenia and in families multiply affected by schizophrenia or bipolar disorder.

Hippocampal shape anomaly (HSA), characterised by a rounded hippocampus, has been documented in congenital malformations and epileptic patients. Subtle structural hippocampal abnormalities have been demonstrated in patients with schizophrenia. We tested the hypothesis that HSA is more frequent in schizophrenia, particularly in patients from families multiply affected by schizophrenia, and that HSA is transmitted within these families. We also aimed to define the anatomical features of the hippocampus and other cerebral structures in the HSA spectrum and to determine the prevalence of HSA in a control group. We reviewed the magnetic resonance imaging of a large number of subjects with schizophrenia and bipolar disorder, many of who came from multiply affected families, relatives of the affected probands, and controls. Quantitative measures of hippocampal shape and position and other qualitative anatomical measures were performed (including depth of dominant sulcus cortical cap, angle of dominant sulcus and hippocampal fissure, bulk of collateral white matter, prominence of temporal horn lateral recess and blurring of internal hippocampal architecture) on subjects with HSA. A spectrum of mild, moderate and severe HSA was defined. The prevalence of HSA was, 7.8% for the controls (n=218), 9.3% for all schizophrenic subjects (n=151) and 12.3% for familial schizophrenic subjects (n=57). There was a greater prevalence of moderate or severe forms of HSA in familial schizophrenics than controls. However, there was no increase in the prevalence of HSA in the unaffected first-degree relatives of schizophrenic patients or in patients with familial bipolar disorder. HSA was rarely transmitted in families. HSA was frequently associated with a deep, vertical collateral/occipito-temporal sulcus and a steep hippocampal fissure. Our data raise the possibility that HSA is linked to disturbances of certain neurodevelopmental genes associated with schizophrenia. However, the lack of any increase in prevalence in the unaffected relatives of patients and the lack of clustering within individual pedigrees argues against this developmental anomaly being commonly associated with genetic predisposition to the illness.

Adult↗
PubMed2004

Phase I dose escalation study of carboplatin to a fixed dose of irinotecan as first-line treatment of small cell lung cancer.

BACKGROUND: Superiority of irinotecan (CPT-11) plus cisplatin over etoposide plus cisplatin in small cell lung cancer (SCLC) has recently been demonstrated. This study determines dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of escalating doses of carboplatin to a fixed dose of irinotecan in Caucasians with small cell lung cancer. PATIENTS AND METHODS: Patients with extensive small cell lung cancer received 50 mg/m(2) irinotecan on day 1, 8, and 15. Dose escalation of carboplatin on day 1 started in dose level 1 at an AUC of 5 mg x min/ml and was escalated to AUC 6 in level 2. Cycles were repeated on day 29. Dose escalation was evaluated after 3 consecutive patients. If no grade IV neutropenia lasting for > or =7 days or thrombopenia or non-hematologic toxicity > or = grade III occurred, treatment was continued in the next dose level. RESULTS: 16 patients were treated. DLT was reached in dose level 2 with 2 grade IV neutropenias and 1 grade IV thrombopenia and diarrhea. Toxicity was further investigated at dose level 1 in a total of 10 patients, which revealed 2 grade III neutropenias and 1 grade III diarrhea. Of 15 evaluable patients, 10 had a partial response, 3 had disease stabilization and 2 progressed. CONCLUSION: Dose level 1 was found to be MTD, this dose is currently compared to the combination of etoposide plus carboplatin within a randomised phase II/III trial.

Aged↗
PubMed2004

Immune responses of a liposome/ISCOM vaccine adjuvant against streptococcal fibronectin binding protein 1 (Sfb1) in mice.

BACKGROUND & OBJECTIVES: The fibronectin binding protein Sfb1 of Streptococcus pyogenes is a well characterised antigen which induces protection against lethal challenge with group A streptococcus (GAS) when adjuvanted with cholera toxin B-subunit (CTB). As an alternative to CTB adjuvanted intranasal immunisations we investigated the immune responses generated in mice using Sfb1 incorporated in to the skin and mucosal adjuvant SAMA4. METHODS: Mice (BALB/c) were vaccinated intradermally with 100 microl of either SAMA4 (adjuvant only group) or SAMA4/Sfb1 and were boosted 7 days later. Mice vaccinated with CTB based vaccines were immunised by intranasal inoculation with a mixture containing 30 microg Sfb1 and 10 microg CTB on days 1, 3, 5 and 15. At 14 days after the last booster immunisation the immune response was characterised and mice were challenged with 10(8) CFU of S. pyogenes. RESULTS: Mice vaccinated with SAMA4/Sfb1 elicited a Sfb1-specific IgG response in the sera that was significantly higher than that seen in control mice and mice immunised with the adjuvant only (P<0.05). No significant differences were seen for specific IgA antibodies in the sera in all groups examined. Compared with non-immunised and adjuvant only immunised controls, mice immunised with the Sfb1/SAMA4 vaccine exhibited a significant increase (P<0.05) in the number of Sfb1 reactive spleen cells in lymphoproliferation assays which were three fold higher than those seen for mice vaccinated with the Sfb1/CTB vaccine. Mice vaccinated with CTB/Sfb1 had the highest level of protection (80%) as where mice vaccinated with SAMA4 and SAMA4/Sfb1 displayed no protection (20% and 40%). INTERPRETATION & CONCLUSION: These data suggest that the SAMA4 adjuvant used in this study fails to elicit protective immunity in BALB/c mice when used to adjuvant the known protective antigen Sfb1.

Adhesins, Bacterial↗
PubMed2003

Radiotherapy patterns of practice: T1N0 glottic cancer in Ontario, Canada.

AIMS: To describe the variation in the delivery of radiation therapy to patients with T1N0 glottic cancer who were diagnosed in Ontario, Canada, between 1982 and 1995. MATERIALS AND METHODS: The patient population consisted of a random sample of 461 patients treated with curative intent from the nine cancer centres that administer radiation therapy in the province. Abstracted variables included prescribed dose (Gy) and fractionation (f), beam energy and arrangement, set-up, field size, beam modifiers, positioning and treatment interruptions. RESULTS: Thirteen prescribed dose-fractionation schemes (> or = four cases each) were identified, including 50.0-53.0 Gy/20 f (54.5%), 55.0-61.0 Gy/25 f (30.3%), and 60.0-66.0 Gy/30-33 f (7.7%). All regimens used one fraction per day, 5 days per week. An isocentric set-up was used (94.3%), with megavoltage (MV) beam energies of Cobalt-60 (87.9%), 6 MV (6.1%) and 4 MV (6.1%). A lateral parallel-opposed pair of beams was the predominant technique (76.4%) versus an anterior oblique pair (17.2%) or angle-down pair (caudally directed fields to achieve shoulder clearance, 5.7%). Wedging (96.3%) and bolus (11.8%) were used as beam-modifying devices. Predominant field-width dimensions were 5.0-6.0 cm (43.4%) and 6.5-7.0 cm (43.1%), and field length dimensions were 5.0-6.0 cm (49.5%) and 6.5-7.0 cm (35.0%). Head, neck or chin immobilisation was used in 86.9% of the cases, with 94.6% of these being custom-made. We found that radiotherapy practice was stable over time, except for a trend of increasing field size and increasing use of immobilisation. In contrast, we found practice variations among the province's cancer centres. On the basis of our findings, we defined a predominant technical practice consisting of Cobalt-60 (reflecting machine availability during the period of the study), an isocentric set-up, a lateral parallel-opposed pair technique with wedging, and supine-head neutral positioning with custom immobilisation. Forty-two per cent of the cases had one or more components of treatment that differed from this definition. CONCLUSIONS: Description of practice variation can provoke discussion about unrecognised differences in practice policies, perhaps identifying the need for better evidence, treatment guidelines, or both.

Canada↗
PubMed2003

The appropriate rate of breast conserving surgery: an evidence-based estimate.

PURPOSE: The objective of the present study was to estimate the proportion of incident cases of breast cancer that should receive breast conserving surgery (BCS), using an evidence-based approach. METHODS: An extensive search of the literature was undertaken to identify eligibility criteria for BCS. The eligibility criteria for BCS were combined with the information about case mix and patient preference to estimate the need for BCS. An epidemiological approach was then used to estimate the incidence of each eligibility criterion for BCS in a typical North American population of breast cancer patients. The effect of sampling error on the estimated appropriate rate of BCS was calculated, and the effect of systematic error using alternative sources of information, was estimated by sensitivity analysis. RESULTS: The analysis showed that 69.6% of breast cancer cases are eligible for BCS, and that 48.0 +/- 6.0% of breast cancer patients are both eligible for BCS and prefer it to mastectomy. Based on sensitivity analysis, the plausible range of the appropriate rate was 42.1% to 49.43%. The proportion of breast cancer cases in which BCS was appropriate was stage dependent; 63.0 +/- 11.5% in ductal carcinoma in-situ; 57.0 +/- 9.9% in stage I; 52.2 +/- 9.4% in stage II, and 27.2 +/- 5.2% in stage III. CONCLUSIONS: This model suggests that BCS is appropriate in 48% of all breast cancer patients. This information may be useful in auditing surgical practice, and may serve as a basis for planning of ancillary services, including radiotherapy.

Breast Neoplasms↗
PubMed2002

Asymmetric hemodynamic responses of the human auditory cortex to monaural and binaural stimulation.

Applying whole-head functional magnetic resonance imaging (fMRI) in 11 neurologically intact subjects, hemodynamic responses to mon- or binaurally presented auditory stimuli were measured. To expand on previous studies in this research area, we used tones and consonant-vowel (CV) syllables. In one group of subjects (n=6) the perceived loudness of the monaurally presented stimuli were adjusted so that they matched the loudness of the binaurally presented stimuli. In a second group (n=5) no loudness adjustment was performed, thus the monaural stimuli were perceived less loud ( approximately 10 dB) than the binaural stimuli. These extensions allowed us to test whether CV syllables and tones produce different contralaterality effects (stronger hemodynamic responses in the auditory cortex contralateral to the stimulated ear) and whether binaural stimulation results in stronger activations in the auditory areas than during both monaural stimulation conditions (binaural summation) independent of loudness influences. In summary, we obtained the following findings: (1) strong contralaterality effects during monaural acoustic stimulation in the posterior superior temporal gyrus (STG) comprising the planum temporale and the dorsal bank of the superior temporal sulcus to CV syllables and tones; (2) the hemodynamic responses to contralaterally presented stimuli (during the monaural conditions) were mostly stronger than those to binaurally presented CV syllables; (3) there was no interaction between stimulus type and the size of the contralaterality effect; (4) there was no indication of binaural summation, rather we found stronger hemodynamic responses to the sum of both monaural stimulations (right and left ear) than to binaural stimulation in all auditory areas; (5) there were generally stronger hemodynamic responses to CV syllables than to tones in the posterior STG, while the hemodynamic responses to tones were stronger in the anterior part of the STG (temporal pole); and finally (6) there was no general difference in terms of hemodynamic response in the auditory cortex between the two groups when receiving either loudness-matched or non-loudness-matched monaural stimulation. These findings are discussed in the context of the underlying neurophysiological mechanisms, the peculiarities of functional fMRI, and the direct access and callosal relay models of hemispheric lateralization.

Acoustic Stimulation↗
PubMed2002

Appearance of peristaltic reflex in isolated guinea pig ileum in response to boluses of air, water, oil, and cellulose.

Distension of an isolated preparation of guinea pig ileum triggers the peristaltic reflex, a characteristic movement of the intestinal walls which generates luminal pressures and clearance of luminal contents. To determine how the reflex responds to properties of luminal contents, we compared the responses triggered by boluses of air, oil, and cellulose to boluses of Krebs' solution. We found that oil and cellulose increased pressures and contraction length and decreased outflow. Cellulose, but not oil, slowed the velocity with which the contraction propagated and increased the delay with which the end point (upstream edge) of the contraction started to propagate after the lead point (downstream edge). Air tended to produce short contraction segments and high velocity. We conclude that bolus properties such as viscosity determine the response that isolated intestinal segments generate to distension. Response patterns are reflected in contraction length, propagation velocity, and other visual parameters that define wall movements.

Air↗
PubMed2002

Voluntary self-administration of both morphine and cocaine by rats.

Voluntary self-administration of cocaine and/or morphine was studied in rats. Male rats were offered water bottles or bottles containing either cocaine or morphine, both cocaine and morphine (combination) or cocaine and morphine as a mixture. Alternating the three drug-containing bottles had no effect on drug choice. When offered alone, rats consumed about 12 +/- 8 mg/kg/day of cocaine or 0.3 +/- 0.3 mg/kg/day of morphine. When both drugs were offered in combination, they consumed a higher amount of cocaine (22 +/- 7), but the same amount of morphine (0.4 +/- 0.3). Availability of cocaine/morphine mixture kept morphine consumption constant (0.3 +/- 0.1), but markedly decreased cocaine intake (0.3 +/- 0.2). Addition of saccharin to the drug solutions only slightly increased consumption of both drugs, whereas saccharin added as a competitor or distracter to the drug solution reduced cocaine but not morphine self-administration. Animals showed wide interindividual variations but surprisingly small intraindividual variations in self-administration of cocaine or morphine under all conditions. No correlation between cocaine and morphine intake was apparent in the combination situation. Forcing animals first with cocaine had no effect on subsequent intake of cocaine or morphine presented in combination. However, forcing animals first with morphine subsequently increased morphine and reduced cocaine intake. In conclusion, morphine intake was the same if offered alone, in combination or as a mixture, whereas cocaine intake increased during a combination but decreased in the mixture situation. Cocaine pre-exposure had no effect on subsequent voluntary morphine or cocaine choice, whereas morphine pre-exposure increased subsequent voluntary morphine but decreased cocaine intake. These results suggest the possibility of two reward centers, one for each drug, the morphine center exerting a dominant influence over the cocaine center.

Administration, Oral↗
PubMed2001

A population-based study of glioblastoma multiforme.

PURPOSE: To describe (1) the use of surgery and radiotherapy (RT) in the treatment of patients with glioblastoma (GBM) in Ontario, (2) survival, and (3) proportion of survival time spent in the hospital after diagnosis. METHODS AND MATERIALS: We performed a population-based cohort study of all Ontario Cancer Registry (OCR) cases of GBM diagnosed between 1982 and 1994. We linked OCR records, hospital files containing surgical procedure codes from the Canadian Institute for Health Information, and province-wide RT records. We studied the odds of treatment using multivariate logistic regression. We expressed the time spent in the hospital as the mean number of days per case, and as a proportion of the interval between diagnosis and death, or 24 months following diagnosis, whichever came first. We used the life-table method and Cox proportional hazards regression to describe survival. RESULTS: The proportion of patients with GBM undergoing any surgery directed at the tumor varied with age (p < 0.0001) and region of residence (p < 0.0001). The proportion undergoing RT varied with age (p < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.01). RT dose > or = 53.5 Gy varied with age (p < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.0002). Median survival was 11 months among patients receiving RT and 3 months among those not receiving RT. The percentage of survival time spent in the hospital was similar among those who received from 49.5 to < 53.5 Gy, compared to > or = 53.5 Gy. Overall survival and the adjusted relative risk of death varied with age and region of residence. CONCLUSION: We observed practice variation in the treatment of patients with GBM according to age, region of residence, and year of diagnosis. Survival did not increase during the study period. The variation in RT dose between those receiving from 49.5 to < 53.5 Gy compared to > or =53.5 Gy was not paralleled by variation in survival between regions where one or the other of the dose ranges predominated, nor was variation in dose ranges among the regions paralleled by variation in the proportion of survival time spent in the hospital.

Adult↗
PubMed2001

Plasticity of rat central inhibitory synapses through GABA metabolism.

1. The production of the central inhibitory transmitter GABA (gamma-aminobutyric acid) varies in response to different patterns of activity. It therefore seems possible that GABA metabolism can determine inhibitory synaptic strength and that presynaptic GABA content is a regulated parameter for synaptic plasticity. 2. We altered presynaptic GABA metabolism in cultured rat hippocampal slices using pharmacological tools. Degradation of GABA by GABA-transaminase (GABA-T) was blocked by gamma-vinyl-GABA (GVG) and synthesis of GABA through glutamate decarboxylase (GAD) was suppressed with 3-mercaptopropionic acid (MPA). We measured miniature GABAergic postsynaptic currents (mIPSCs) in CA3 pyramidal cells using the whole-cell patch clamp technique. 3. Elevated intra-synaptic GABA levels after block of GABA-T resulted in increased mIPSC amplitude and frequency. In addition, tonic GABAergic background noise was enhanced by GVG. Electron micrographs from inhibitory synapses identified by immunogold staining for GABA confirmed the enhanced GABA content but revealed no further morphological alterations. 4. The suppression of GABA synthesis by MPA had opposite functional consequences: mIPSC amplitude and frequency decreased and current noise was reduced compared with control. However, we were unable to demonstrate the decreased GABA content in biochemical analyses of whole slices or in electron micrographs. 5. We conclude that the transmitter content of GABAergic vesicles is variable and that postsynaptic receptors are usually not saturated, leaving room for up-regulation of inhibitory synaptic strength. Our data reveal a new mechanism of plasticity at central inhibitory synapses and provide a rationale for the activity-dependent regulation of GABA synthesis in mammals.

3-Mercaptopropionic Acid↗
PubMed2001

Uniting Bose-Einstein condensates in optical resonators.

The relative phase of two initially independent Bose-Einstein condensates can be laser cooled to unite the two condensates by putting them into a ring cavity and coupling them with an internal Josephson junction. First, we show that this phase cooling process already appears within a semiclassical model. We calculate the stationary states, find regions of bistable behavior, and suggest a Ramsey-type experiment to measure the buildup of phase coherence between the condensates. We also study quantum effects and imperfections of the system.

Journal Article↗
PubMed2001

Estimating the need for radiotherapy for lung cancer: an evidence-based, epidemiologic approach.

BACKGROUND AND OBJECTIVES: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to use an evidence-based approach to estimate the proportion of incident cases of lung cancer that will require RT at any point in the evolution of the illness. METHODS: A systematic review of the literature was undertaken to identify indications for RT for lung cancer, and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of lung cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error, was estimated by sensitivity analysis. RESULTS: It was shown that 53.6% +/- 3.3% of small-cell lung cancer (SCLC) cases develop one or more indications for RT at some point in the course of the illness, 45.4% +/- 4.3% in their initial treatment, and 8.2% +/- 1.5% later for recurrence of progression. Overall, 64.3% +/- 4.7% of non-small-cell lung cancer (NSCLC) cases require RT, 45.9% +/- 4.3% in their initial treatment, and 18.3% +/- 1.8% later in the course of the illness. The proportion of NSCLC cases that ever require RT is stage dependent; 41.0% +/- 5.5% in Stage I; 54.5% +/- 6.5% in Stage II; 83.5% +/- 10.6% in Stage III; and 65.7% +/- 7.6% in Stage IV. In total, 61.0% +/- 3.9% of all patients with lung cancer will develop one or more indications for RT at some point in the illness, 44.6% +/- 3.6% in their initial treatment, and 16.5% +/- 1.5% later for recurrence or progression. CONCLUSION: This method provides a rational starting point for the long-term planning of radiation services, and for the audit of access to RT at the population level. We now plan to extend this study to the other major cancer sites to enable us to estimate the appropriate RT treatment rate for the cancer population as a whole.

Algorithms↗