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Clinical phase-I study of Na2B12H11SH (BSH) in patients with malignant glioma as precondition for boron neutron capture therapy (BNCT).

PURPOSE: Within the European collaboration on boron neutron capture therapy (BNCT), a clinical Phase I study is being carried out to establish BNCT as an alternative treatment modality for malignant glioma (WHO III/IV). Data about the pharmacokinetics, biodistribution and toxicity of the boron compound Na2B12H11SH (BSH) are of great importance to avoid radiation damage of healthy tissue and to deliver a sufficient radiation dose. METHODS AND MATERIALS: Twenty four patients suffering from a glioblastoma multiforme entered the study to date, infused with a maximum concentration of up to 50 mg BSH/kg. Boron concentration measurements in tissues, urine, and blood were carried out, using inductively coupled plasma-atomic spectroscopy (ICP-AES) and quantitative neutron capture radiography (QNCR). A cross-calibration of these boron determination techniques was carried out. RESULTS: In tumor tissue, confirmed by histopathology of small biopsies, we found a consistently high but heterogeneous boron uptake. Necrotic parts contain much lower amounts of boron; normal brain tissue has shown no significant uptake. In skin, bone, muscle, and dura mater only small amounts of boron were found. In blood samples, we found biphasic kinetics, but with variations of the half-lives from patient to patient. The compound is mainly excreted through the urine, but an additional entero-hepatic pathway can be demonstrated. Systematic investigations revealed no toxic side effect of the intravenously administered BSH. Comparable data were obtained by using ICP-AES and QNCR for boron concentration measurements. CONCLUSION: Taking into account the radiobiological considerations of the neutron beam source, we found promising facts that BNCT could be a useful irradiation method for highly malignant brain tumors. Favorable amounts of the boron compound BSH were found in tumor tissue, whereas healthy brain tissue has shown no significant uptake.

Aged↗

Do negative or positive emotions differentially impact mortality after adult stem cell transplant?

Multiple diverse biomedical variables have been shown to affect outcome after hematopoietic stem cell transplantation (HSCT). Whether psychosocial variables should be added to the list is controversial. Some empirical reports have fueled skepticism about the relationship between behavioral variables and HSCT survival. Most of these reports have methodological shortcomings. Their samples were small in size and included heterogeneous patient populations with different malignant disease and disease stages. Most data analyses did not control adequately for biomedical factors using multivariate analyses. The pre-transplant evaluations differed from study to study, making cross-study generalizations difficult. Nevertheless, a few recently published studies challenge this skepticism, and provide evidence for deleterious effects of depressive symptomatology on HSCT outcome. This mini review integrates the new data with previously reviewed data, focusing on the differential impact of negative and positive emotional profiles on survival. Pre-transplant negative emotional profiles are associated with worse survival in the long term, whereas pre-transplant optimism about transplant appears to affect survival in the short term. These data have practical implications for transplant teams. Pre-transplant psychological evaluation should assess for specific adverse behavioral risk factors, particularly higher levels of depression and lower levels of optimistic expectations about transplant. Transplant centers should develop collaborative studies to further test the effects of these adverse behavioral risk factors, and run multicenter hypothesis-driven clinical trials of psychological intervention protocols. Such studies should aim to better define pragmatics of assessment and intervention (timing, assessment tools, personnel), and evaluate their contribution to improving outcome after transplant.

Adult↗

Repeat donor HLA-DR mismatches in renal transplantation: is the increased failure rate caused by noncytotoxic HLA-DR alloantibodies?

INTRODUCTION: Data from the UCLA/UNOS and Collaborative Transplant Studies Registries indicate that mismatched HLA-DR alloantigens expressed on a former donor renal allograft should not be repeated because of significantly poorer long-term survival. METHODS: Retransplant candidates waiting for another renal allograft were screened for HLA class II alloantibodies (aAb) using direct complement-dependent cytotoxicity and several sensitive aAb binding assays. RESULTS: When screened by complement-dependent cytotoxicity, 46% of the patients were aAb negative. In contrast, using aAb binding assays, 90% of the patients had HLA-DR aAb specific for previous HLA-DR allograft mismatches. Most important, no directly cytotoxic HLA-DR antibody was detected in 9 of 27 patients. CONCLUSION: Our studies suggest that crossing the same HLA-DR mismatch in a subsequent transplant may result in poorer survival due to underlying donor-specific HLA-DR aAb. If confirmed in a retrospective study of retransplant patients, B cell donor cross-matches using antiglobulin complement-dependent cytotoxicity or flow cytometry would appear essential if this barrier were to be crossed.

Antibody Specificity↗

Decline in ICU adverse events, nosocomial infections and cost through a quality improvement initiative focusing on teamwork and culture change.

BACKGROUND: Nosocomial infections occur in approximately 10% of patients in intensive care units (ICUs). Several studies have shown that a quality improvement initiative can reduce nosocomial infections, mortality, and cost. CONTEXT: Our hospital is located in Northern Mississippi and has a 28 bed Medical-Surgical ICU unit with 95% occupancy. We joined the ICU collaborative with the IMPACT initiative of the Institute of Healthcare Improvement (IHI) in October 2002. A preliminary prospective before (fiscal year (FY) 2001-2) and after (FY 2003) hypothesis generating study was conducted of outcomes resulting from small tests of change in the management of ICU patients. KEY MEASURES FOR IMPROVEMENT: Nosocomial infection rates, adverse events per ICU day, average length of stay, and average cost per ICU episode. STRATEGY FOR CHANGE: Four changes were implemented: (1) physician led multidisciplinary rounds; (2) daily "flow" meeting to assess bed availability; (3) "bundles" (sets of evidence based best practices); and (4) culture changes with a focus on the team decision making process. EFFECTS OF CHANGE: Between baseline and re-measurement periods, nosocomial infection rates declined for ventilator associated pneumonia (from 7.5 to 3.2 per 1000 ventilator days, p = 0.04) and bloodstream infections (from 5.9 to 3.1 per 1000 line days, p = 0.03), with a downward trend in the rate of urinary tract infections (from 3.8 to 2.4 per 1000 catheter days, p = 0.17). There was a strong downward trend in the rates of adverse events in the ICU as well as the average length of stay per episode. From FY 2002 to FY 2003 the cost per ICU episode fell from $3406 to $2973. LESSONS LEARNED: A systematic approach through collaboration with IHI's IMPACT initiative may have contributed to significant improvements in care in the ICU setting. Multidisciplinary teams appeared to improve communication, and bundles provided consistency of evidence based practices. The flow meetings allowed for rapid prioritization of activity and a new decision making culture empowered team members. The impact of these changes needs to be assessed more widely using rigorous study designs.

Cooperative Behavior↗

State monopoly systems and alcohol prevention in developing countries: report on a collaborative international study.

In many countries, state alcohol monopoly systems have been adopted as a means of public control over alcohol availability. These countries include industrialized as well as developing countries. In this paper, an analysis is presented on the present state and potentials of state alcohol monopoly systems in preventing alcohol abuse. Special reference is given to the specificity of alcoholic beverages supply in developing countries and the potential contributions of existing state monopoly systems in developed countries to assist developing countries willing to adopt and implement preventive national alcohol policies.

Alcoholic Beverages↗

Empacho in four Latino groups: a study of intra- and inter-cultural variation in beliefs.

It is usually impossible to know if reported differences between cultures are due to cultural differences or due to a difference in the methods used to study the cultures. This paper describes a collaborative, multisite study using a shared methodology to study intra- and inter-cultural variation in beliefs. A series of standard interview schedules were used to study Latin American beliefs about empacho in Guatemala, Mexico, and in the United States (Mexican-Americans and Puerto Ricans). Results showed consistency in beliefs about empacho both within and between the four samples.

Adolescent↗

Lessons learned from cross-border medical response to the terrorist bombings in Tabba and Ras-el-Satan, Egypt, on 07 October 2004.

INTRODUCTION: Large-scale, terrorist attacks can happen in peripheral areas, which are located close to a country's borders and far from its main medical facilities and involve multi-national casualties and responders. The objective of this study was to analyze the terrorist suicide bombings that occurred on 07 October 2004, near the Israeli-Egyptian border, as representative of such a complex scenario. METHODS: Data from formal debriefings after the event were processed in order to learn about victim outcomes, resource utilization, critical events, and time course of the emergency response. RESULTS: A total of 185 injured survivors were repatriated: four were severely wounded, 13 were moderately injured, and 168 were mildly injured. Thirty-eight people died. A forward medical team landed at the border town's airport, which provided reinforcement in the field and in the local hospital. Israeli and Egyptian search and rescue teams collaborated at the destruction site. One-hundred sixty-eight injured patients arrived at the small border hospital that rapidly organized itself for the mass-casualty incident, operating as an evacuation "staging hospital". Twenty-three casualties secondarily were distributed to two major trauma centers in the south and the center of Israel, respectively, either by ambulance or by helicopter. CONCLUSION: Large-scale, terrorist attacks at a peripheral border zone can be handled by international collaboration, reinforcement of medical teams at the site itself and at the peripheral neighboring hospital, rapid rearrangement of an "evacuation hospital", and efficient transport to trauma centers by ambulances, helicopters, and other aircraft.

Blast Injuries↗

Development of a highly sensitive search strategy for the retrieval of reports of controlled trials using PubMed.

OBJECTIVE: To develop, through revision of the Cochrane Collaboration search strategy for OVID-MEDLINE, a highly sensitive search strategy to retrieve reports of controlled trials using PubMed. METHODS: The original highly sensitive Cochrane strategy was revised to take into account additional Medical Subject Headings (MeSH) and other terminology as well as the current unique features of PubMed. We compared the retrieval of the revised strategy with that of the original Cochrane strategy before and after translation of the strategies into PubMed format. Finally, we used a gold standard database of reports of controlled trials identified by electronic and hand search of selected journals to test the revised strategy in PubMed format. RESULTS: The revised strategy included a search statement modified for increased precision, and added 'Cross-over Studies' as a MeSH term and the term 'latin square' as a text word. Compared to the original Cochrane strategy, the revised strategy identified 53 additional reports of controlled trials accessing MEDLINE through OVID. When the revised strategy and original Cochrane strategy were translated into PubMed format, the revised strategy retrieved 90 reports of controlled trials not identified by the original strategy. Finally, the revised strategy in PubMed format retrieved all of the reports of controlled trials in the gold standard database. Ninety-eight per cent of the gold standard reports of controlled trials were retrieved by Phase 1 of the optimal PubMed search strategy. CONCLUSIONS: Failure to identify all relevant trials for systematic review could result in bias. We developed a highly sensitive search strategy for the retrieval of reports of controlled trials for use with PubMed that retrieves more relevant citations (greater sensitivity) and fewer non-relevant citations (greater precision) than the original Cochrane search strategy.

Bias↗

Influence of PMMA shielding on DNA fragmentation induced in human fibroblasts by iron and titanium ions.

In the framework of a collaborative project on the influence of the shielding on the biological effectiveness of space radiation, we studied DNA fragmentation induced by 1 GeV/nucleon iron ions and titanium ions with and without a 197-mm-thick polymethylmethacrylate (PMMA) shield in AG1522 human fibroblasts. Pulsed- and constant-field gel electrophoresis were used to analyze DNA fragmentation in the size range 1-5700 kbp. The results show that, mainly owing to a higher production of small fragments (1-23 kbp), titanium ions are more effective than iron ions at inducing DNA double-strand breaks (DSBs), their RBE being 2.4 and 1.5, respectively. The insertion of a PMMA shield decreases DNA breakage, with shielding protection factors (ratio of the unshielded/shielded cross sections for DSB production) of about 1.6 for iron ions and 2.1 for titanium ions. However, the DSB yield (no. of DSBs per unit mass per unit dose) is almost unaffected by the presence of the shield, and the relative contributions of the fragments in the different size ranges are almost the same with or without shielding. This indicates that, under our conditions, the effect of shielding is mainly to reduce the dose per unit incident fluence, leaving radiation quality practically unaffected.

Cells, Cultured↗

Pressurised metered-dose inhalers versus all other hand-held inhalers devices to deliver bronchodilators for chronic obstructive pulmonary disease.

BACKGROUND: Bronchodilator therapy for COPD may be delivered by a number of different inhaler devices. OBJECTIVES: To determine the efficacy of pressurised metered dose inhalers (pMDI) compared to any other handheld inhaler device for the delivery of bronchodilators in non-acute COPD. SEARCH STRATEGY: The Cochrane Collaboration, Asthma and Wheeze Randomised Controlled Clinical Trials register was searched for studies. The UK pharmaceutical companies who manufacture inhaled COPD medication were also contacted. SELECTION CRITERIA: Two reviewers independently reviewed the results of computerised search and any potentially relevant articles were obtained in full. DATA COLLECTION AND ANALYSIS: One reviewer extracted details of each trial and a second reviewer checked all extracted data. Dichotomous outcomes such as exacerbation rate were assessed using relative risk, with 95% confidence interval (CI). MAIN RESULTS: Fourteen studies appeared potentially relevant but only three studies (61 patients) met the entry criteria. Two studies compared a dry powder device (Turbuhaler or Rotahaler) with a pMDI for beta2-agonist delivery, and one (36 patients cross-over design) the Respimat (soft mist device for ipratropium) vs a pMDI. For the Turbuhaler and Rotahaler, none of the reported outcome measures were significantly different. The Rotahaler study used a high and low dose of medication with or without large volume spacer. The study using the Respimat showed significant increases in FEV1 when compared to a pMDI (difference in change from base line 70 ml, 95% CI 10, 130 ml). The effect on change in FVC was of similar size. There were no differences between these two devices for any other reported outcomes. Although none of the included studies required prior patient ability to use any of the inhalers (and no study mentioned device training), it was assumed that all patients randomised into the study would have undergone training in use of the study inhalers and were capable of using those devices. REVIEWER'S CONCLUSIONS: In patients with stable COPD, pMDI produced similar outcomes to a dry powder device for delivering beta2-agonists, but the very small number of studies and included patients does not permit firm conclusions to be drawn. The soft mist device for ipratropium was more effective than a pMDI, but the data come from one small study. There need to be further well designed randomised controlled trials to define the role of inhaler devices using bronchodilators in stable COPD.

Adrenergic Agonists↗

[Influenza surveillance in Switzerland].

The Swiss Sentinel Network (SSN) has monitored influenza activity in Switzerland since 1986. Between 2600 and 6600 cases of influenza-like-illness (ILI) are reported each influenza season by the 150-200 general practitioners, internists and paediatricians who voluntarily participate in the SSN. Based on these figures, there are an estimated 100,000 to 230,000 cases of ILI in Switzerland each year during the main influenza-season (10 week-peak-periods). Among patients over 60 years, 13% to 20% developed pneumonia and 1.3% to 2.7% had to be hospitalised. This represents an estimated 1800 hospitalisations caused by influenza for the country as a whole each year. Based on data from the Swiss Medical Statistic VESKA (H+), there are an estimated 1600 hospitalisations per year, confirming the estimation of the SSN. Collaboration with the Swiss National Center for influenza allows identifications of circulating influenza-strains and the determination of eventual deviations from the vaccine strains. The SSN has been a valuable surveillance tool during the last ten years and has provided useful data on the extent and importance of influenza in Switzerland. It therefore makes an important contribution to the elaboration of targeted and appropriate prevention measures against influenza.

Adolescent↗

Challenges and opportunities in the care of international patients: clinical and health services issues for academic medical centers.

International visitors who travel to the United States for the express purpose of receiving medical care constitute a small, but unique and important, subset of patients in this country. These visitors have traditionally sought care at what are widely regarded as the premier U.S. academic medical centers. Their care may prove challenging due to logistical, medical, language, and cross-cultural issues, and has the potential to distract from the educational and research missions of these medical centers. The author reflects on how one academic medical center, the Johns Hopkins Medical Institutions, has experienced and responded to these challenges. Specific issues include scheduling and evaluation challenges, language and cultural differences, and arranging continuity care. The author concludes that when an institution invests the resources necessary to address these issues, and enlists physicians stimulated by this challenging group of patients, the arrangement is mutually beneficial to the international patients and the institution. Scholarly evaluation of this phenomenon has been virtually nonexistent, due to both the unique niche occupied by these programs and institutional competition for this group of patients. However, collaborative evaluation of international patient programs will provide the opportunity to assess similarities, differences, and effectiveness, benefiting both those providing and those receiving care by improving the appropriateness and quality of care.

Academic Medical Centers↗

Psychological distress among informal supporters of frail older people at home and in institutions. The Resource Implications Study Group of the MRC Cognitive Function and Ageing Study.

OBJECTIVE: Investigate presence of psychiatric morbidity in informal carers using 30-item General Health Questionnaire (GHQ) and examine which factors best predict psychiatric morbidity. DESIGN: Two-year longitudinal, panel survey of informal supporters of frail elderly subjects, using semi-structured interview schedules. Subjects were those defined as frail after screening stratified random sample of people aged 65 or over. SETTING: Informal supporters of frail elderly subjects residing in private households or residential or nursing homes in four UK districts. RESPONDENTS: 623 informal supporters of subjects living at home, 129 regular visitors of those in long-term care. MEASURE: 30-item GHQ (cross-sectional analysis). RESULTS: Stepwise multiple regression indicated main predictors of high GHQ scores in key supporters were: subjects had at least three problems of behaviour (b = 1.56, 95% CI 1.25-1.94); supporters had to alter working hours (b = 1.70, 95% CI 1.15-2.51); supporters were female (b =1.26, 95% CI 1.06-1.50). The following variables predicted low GHQ scores: supporters able to leave subject all day (b = 0.71, 95% CI 0.64-0.80); subjects never wandered (b = 0.78, 95% CI 0.62-0.99); supporters were 'other relatives' or friends of subject (b = 0.74, 95% CI 0.59-0.91). For visitors, spouses were most likely to have high GHQ scores (b = 2.46, 95% CI 1.32-4.57). CONCLUSIONS: Results suggest the need for greater collaboration between formal and informal care. Little work has been carried out to ascertain which interventions are most effective in alleviating carer stress: a series of randomized controlled trials to determine long-term effectiveness of various interventions for different groups of carers is required.

Adult↗

Collaborative study on rat sperm motion analysis using CellSoft Series 4000 semen analyzer.

A collaborative study was conducted to determine useful and sensitive rat sperm motion parameters in a CellSoft Series 4000 semen analyzer to detect the effects of compounds on sperm motion. The effects on the sperm motion parameters were investigated using alpha-chlorohydrin, boric acid, ethinylestradiol, ethyl methanesulfonate, nitrazepam, nitrobenzene, ornidazole, sulfasalazine or valproic acid which are well known to induce reproductive or testicular toxicities. All compounds used in this study decreased percentage of motile sperm (% motile). Curvilinear velocity (VCL), maximum and mean amplitude of lateral head displacement (ALH max and ALH mean) were decreased by treatment with all compounds except for valproic acid. Treatment with alpha-chlorohydrin, ornidazole or sulfasalazine under mid-dosage regimens decreased only these parameters. Beat cross frequency (BCF) was increased by treatment with sulfasalazine. There were some treatments which caused either decreased or increased changes irrespective of dosage regimen in linearity, average radius, percentage of circular-swimming sperm out of motile sperm (circular/motile) and percentage of circular-swimming sperm out of all sperm (circular/all). Based on these results, we concluded that % motile, VCL, ALH max and ALH mean are considered useful and sensitive parameters for evaluating the effects of compounds on sperm motion. A parameter of BCF can be useful to detect the effects of specific compounds on sperm motion. Linearity, average radius, circular/motile and circular/all are not considered useful or sensitive indicators to detect the effects of compounds on sperm motion.

Animals↗

Ocular component data in schoolchildren as a function of age and gender.

PURPOSE: To describe the refractive error and ocular components of a large group of school-aged children as a function of age and gender. METHODS: In this report, we describe the refractive error and ocular components of 2583 school-aged children (49.3% girls, overall mean [+/-SD] age 10.0 +/- 2.3). Measurement methods included cycloplegic autorefraction, autokeratometry, videophakometry, and A-scan ultrasonography. For statistical comparisons across gender and age, a critical point of alpha = 0.005 was used to assess significance because of the large sample size and the large number of comparisons made. RESULTS: Of these 2583 children, 10.1% were myopic (-0.75 D or more myopia in both meridians), and 8.6% were hyperopic (+1.25 D or more hyperopia in both meridians). As would be expected, there was a significant effect of age on refractive error (spherical equivalent, p < 0.0001), toward less hyperopia/more myopia. There was no significant difference in the average refractive error between girls and boys (p = 0.0192). Girls had steeper corneas than boys (0.74 D steeper in the vertical meridian and 0.63 D steeper in the horizontal meridian, p < 0.0001). There were no significant differences in corneal power with age (p = 0.16). Both older age and male gender were significantly associated with deeper anterior chambers (p < 0.0001 for both). The crystalline lens showed significant thinning with age (p < 0.0001), however, there was no significant difference in the lens thickness between girls and boys (p = 0.66). Both Gullstrand lens power and calculated lens power showed significant effects of age and gender (p < 0.0001 for both). Girls, on average, had Gullstrand lens powers that were 0.28 D steeper and calculated lens powers that were 0.80 D more powerful than boys. Axial length also showed significant effects of age and gender (p < 0.0001 for both). Girls' eyes were, on average, 0.32 mm shorter than those of boys. CONCLUSIONS: These cross-sectional data show a general pattern of ocular growth, no change in corneal power, and crystalline lens thinning and flattening between the ages of 6 and 14 years. Girls tended to have steeper corneas, stronger crystalline lenses, and shorter eyes compared with boys.

Adolescent↗

Difficulties encountered by nurses in the care of terminally ill cancer patients in general hospitals in Japan.

The aim of this study was to investigate the difficulties encountered by nurses who have cared for terminally ill cancer patients at general hospitals. To collect data, a survey by questionnaire was self-administered. The respondents were 375 nurses and the response rate was 70.2%. Factor analysis was conducted on 80 items related to the difficulties encountered by nurses who have cared for terminally ill cancer patients to allow reasonable item reduction and to explore better domains. Two items were excluded and the results revealed eight underlying domains: 'Communication with patients and families', 'Knowledge and skill of nurses', 'Treatment and informed consent (IC)', 'Personal issues', 'Collaboration as a team including patients and families', 'Environment and system', 'Collaboration among nurses', and 'Near-death issues'. Cronbach's alpha coefficients for each domain ranged from 0.77 to 0.93. The results showed that nurses working at general hospitals have experienced a high degree of difficulty overall while caring for the dying, particularly with communication with patients and families. It was concluded that this study was useful in determining the specific areas where nursing education and research should be focused.

Adult↗

[Network of research units and primary health care].

OBJECTIVES: To find the connections between Primary Health Care (PHC) and Research Units (RU) and the participation of PHC professionals in Research Committees (RC) and Clinical Research Ethical Committees (CREC). To evaluate RUs' PHC-related research activities, analyse the RUs and how much they are used by PHC. DESCRIPTION: A descriptive, crossover study, with data collected by means of a mailed questionnaire. SETTING: The 110 units which were part of the RU network by the end of 1993. PARTICIPANTS: Representatives of RUs. INTERVENTIONS: In May 1994 a self-filled questionnaire containing 29 items was sent out to RUs. During October/November 1994 non-repliers were recontacted. MEASUREMENTS AND MAIN RESULTS: 80 RUs replied. 30 RUs were connected with PHC; 14 were totally dependent on PHC; and 16 were partially linked to PHC. A minority of PHC professionals took part in RCs, except in the cases of those totally dependent on PHC. Participation in the CRECs was unusual. RUs had little connection with Family & Community Medicine teaching units, although this figure was higher for RUs connected to PHC. 86.2% of RUs were open to PHC professionals, although involvement was generally low. 71.4% of RUs stated they had carried out some project of their own related to PHC; and 77.6% had collaborated in at least one PHC project. CONCLUSIONS: PHC has paid little attention to the creation of RUs and has participated little in RCs and CRECs. Teaching units should tighten their relationship with RUs, which do an important amount of PHC research. PHC researchers offered a wide range of services, which were little-used. Teaching units should publicise their existence more and extend their times of availability.

Cross-Sectional Studies↗

Intensity-modulated radiotherapy: current status and issues of interest.

PURPOSE: To develop and disseminate a report aimed primarily at practicing radiation oncology physicians and medical physicists that describes the current state-of-the-art of intensity-modulated radiotherapy (IMRT). Those areas needing further research and development are identified by category and recommendations are given, which should also be of interest to IMRT equipment manufacturers and research funding agencies. METHODS AND MATERIALS: The National Cancer Institute formed a Collaborative Working Group of experts in IMRT to develop consensus guidelines and recommendations for implementation of IMRT and for further research through a critical analysis of the published data supplemented by clinical experience. A glossary of the words and phrases currently used in IMRT is given in the. Recommendations for new terminology are given where clarification is needed. RESULTS: IMRT, an advanced form of external beam irradiation, is a type of three-dimensional conformal radiotherapy (3D-CRT). It represents one of the most important technical advances in RT since the advent of the medical linear accelerator. 3D-CRT/IMRT is not just an add-on to the current radiation oncology process; it represents a radical change in practice, particularly for the radiation oncologist. For example, 3D-CRT/IMRT requires the use of 3D treatment planning capabilities, such as defining target volumes and organs at risk in three dimensions by drawing contours on cross-sectional images (i.e., CT, MRI) on a slice-by-slice basis as opposed to drawing beam portals on a simulator radiograph. In addition, IMRT requires that the physician clearly and quantitatively define the treatment objectives. Currently, most IMRT approaches will increase the time and effort required by physicians, medical physicists, dosimetrists, and radiation therapists, because IMRT planning and delivery systems are not yet robust enough to provide totally automated solutions for all disease sites. Considerable research is needed to model the clinical outcomes to allow truly automated solutions. Current IMRT delivery systems are essentially first-generation systems, and no single method stands out as the ultimate technique. The instrumentation and methods used for IMRT quality assurance procedures and testing are not yet well established. In addition, many fundamental questions regarding IMRT are still unanswered. For example, the radiobiologic consequences of altered time-dose fractionation are not completely understood. Also, because there may be a much greater ability to trade off dose heterogeneity in the target vs. avoidance of normal critical structures with IMRT compared with traditional RT techniques, conventional radiation oncology planning principles are challenged. All in all, this new process of planning and treatment delivery has significant potential for improving the therapeutic ratio and reducing toxicity. Also, although inefficient currently, it is expected that IMRT, when fully developed, will improve the overall efficiency with which external beam RT can be planned and delivered, and thus will potentially lower costs. CONCLUSION: Recommendations in the areas pertinent to IMRT, including dose-calculation algorithms, acceptance testing, commissioning and quality assurance, facility planning and radiation safety, and target volume and dose specification, are presented. Several of the areas in which future research and development are needed are also indicated. These broad recommendations are intended to be both technical and advisory in nature, but the ultimate responsibility for clinical decisions pertaining to the implementation and use of IMRT rests with the radiation oncologist and radiation oncology physicist. This is an evolving field, and modifications of these recommendations are expected as new technology and data become available.

Algorithms↗