[Multiple sclerosis management system 3D. Moving from documentation towards management of patients]. / Multiple-Sklerose-Dokumentationssystem 3D. Von der Dokumentation zum Patientenmanagement.

BACKGROUND: The increasing therapeutic options for relapsing-remitting multiple sclerosis require a specific treatment and risk management to recognize the individual response as well as potential side effects. To switch from pure MS documentation to MS management by implementing a new multiple sclerosis management and documentation tool may be of importance. METHOD: This article presents the novel computer-based patient management system "multiple sclerosis management system 3D" (MSDS 3D). RESULTS: MSDS 3D allows documentation and visualization of visit schedules and mandatory examinations via defined study modules by integration of data input from patients, attending physicians and MS nurses. It provides forms for the documentation of patient visits as well as clinical and diagnostic findings. Information is collected via interactive touch screens. A specific module which is part of MSDS 3D's current version allows the monthly monitoring of patients under treatment with natalizumab. A checklist covering clinical signs of progressive multifocal leukoencephalopathy (PML) and a detailed questionnaire about the handling of natalizumab in practice have additionally been added. DISCUSSION: The MS patient management system MSDS 3D has successfully been implemented and is currently being evaluated in a multi-centre setting. Advanced assessment of patient data may allow improvements in clinical practice and research work. The addition of a checklist and a questionnaire into the natalizumab module may support the recognition of PML during its early, treatable course.

Rapidly progressive course of very late onset multiple sclerosis presenting with Parkinsonism: case report.

Multiple sclerosis mainly affects young adolescents, making late-onset multiple sclerosis a rarity and diagnostic challenge, particularly for cases after age 80 years. We present an 82-year-old patient with multiple sclerosis with very late onset. As well as spastic paraplegia, additional Parkinsonism secondary to demyelination in the basal ganglia was observed in this case. In most publications, spinal cord lesions were more common in late-onset multiple sclerosis which, in contrast, could not be found in our case. Despite different treatment strategies, rapid clinical deterioration and death after about 2 years of disease course occurred. Further discrimination in late-onset multiple sclerosis (50-70 years) and multiple sclerosis with very late onset (above 70 years) might be considered. Future trials to elucidate potential benefit of immunosuppressive (and neuroprotective) therapies in these age groups are mandatory.

Desmin/vimentin intermediate filaments are dispensable for many aspects of myogenesis.

An expression vector was prepared containing a cDNA coding for a truncated version of the intermediate filament (IF) protein desmin. The encoded truncated desmin protein lacks a portion of the highly conserved alpha-helical rod region as well as the entire nonhelical carboxy-terminal domain. When transiently expressed in primary fibroblasts, or in differentiating postmitotic myoblasts and multinucleated myotubes, the truncated protein induces the complete dismantling of the preexisting vimentin or desmin/vimentin IF networks, respectively. Instead, in both cell types vimentin and desmin are packaged into hybrid spheroid bodies scattered throughout the cytoplasm. Despite the complete lack of intact IFs, myoblasts and myotubes expressing truncated desmin assemble and laterally align normal striated myofibrils and contract spontaneously in a manner indistinguishable from that of control myogenic cells. In older cultures the spheroid bodies shift from a longitudinal to a predominantly transverse orientation and loosely align along the I-Z-I-regions of striated myofibrils (Bennett, G.S., S. Fellini, Y. Toyama, and H. Holtzer. 1979. J. Cell Biol. 82:577-584), analogous to the translocation of intact desmin/vimentin IFs in control muscle. These results suggest the need for a critical reexamination of currently held concepts regarding the functions of desmin IFs during myogenesis.

The vinculin/sarcomeric-alpha-actinin/alpha-actin nexus in cultured cardiac myocytes.

Experiments are described supporting the proposition that the assembly of stress fibers in non-muscle cells and the assembly of myofibrils in cardiac cells share conserved mechanisms. Double staining with a battery of labeled antibodies against membrane-associated proteins, myofibrillar proteins, and stress fiber proteins reveals the following: (a) dissociated, cultured cardiac myocytes reconstitute intercalated discs consisting of adherens junctions (AJs) and desmosomes at sites of cell-cell contact and sub-sarcolemmal adhesion plaques (SAPs) at sites of cell-substrate contact; (b) each AJ or SAP associates proximally with a striated myofibril, and conversely every striated myofibril is capped at either end by an AJ or a SAP; (C) the invariant association between a given myofibril and its SAP is especially prominent at the earliest stages of myofibrillogenesis; nascent myofibrils are capped by oppositely oriented SAPs; (d) the insertion of nascent myofibrils into AJs or into SAPs invariably involves vinculin, alpha-actin, and sarcomeric alpha-actinin (s-alpha-actinin); (e) AJs are positive for A-CAM but negative for talin and integrin; SAPs lack A-CAM but are positive for talin and integrin; (f) in cardiac cells all alpha-actinin-containing structures invariably are positive for the sarcomeric isoform, alpha-actin and related sarcomeric proteins; they lack non-s-alpha-actinin, gamma-actin, and caldesmon; (g) in fibroblasts all alpha-actinin-containing structures are positive for the non-sarcomeric isoform, gamma-actin, and related non-sarcomeric proteins, including caldesmon; and (h) myocytes differ from all other types of adherent cultured cells in that they do not assemble authentic stress fibers; instead they assemble stress fiber-like structures of linearly aligned I-Z-I-like complexes consisting exclusively of sarcomeric proteins.

Polygons and adhesion plaques and the disassembly and assembly of myofibrils in cardiac myocytes.

Successive stages in the disassembly of myofibrils and the subsequent assembly of new myofibrils have been studied in cultures of dissociated chick cardiac myocytes. The myofibrils in trypsinized and dispersed myocytes are sequentially disassembled during the first 3 d of culture. They split longitudinally and then assemble into transitory polygons. Multiples of single sarcomeres, the cardiac polygons, are analogous to the transitory polygonal configurations assumed by stress fibers in spreading fibroblasts. They differ from their counterparts in fibroblasts in that they consist of muscle alpha-actinin vertices and muscle myosin heavy chain struts, rather than of the nonmuscle contractile protein isoforms of stress fiber polygons. EM sections reveal the vertices and struts in cardiac polygons to be typical Z and A bands. Most cardiac polygons are eliminated by day 5 of culture. Concurrent with the disassembly and elimination of the original myofibrils new myofibrils are rapidly assembled elsewhere in the same myocyte. Without exception both distal tips of each nascent myofibril terminate in adhesion plaques. The morphology and composition of the adhesion plaques capping each end of each myofibril are similar to those of the termini of stress fibers in fibroblasts. However, whereas the adhesion complexes involving stress fibers in fibroblasts consist of vinculin/nonmuscle alpha-actinin/beta- and gamma-actins, the analogous structures in myocytes involving myofibrils consist of vinculin/muscle alpha-actinin/alpha-actin. The addition of 1.7-2.0 microns sarcomeres to the distal tips of an elongating myofibril, irrespective of whether the myofibril consists of 1, 10, or several hundred tandem sarcomeres, occurs while the myofibril appears to remain linked to its respective adhesion plaques. The adhesion plaques in vitro are the equivalent of the in vivo intercalated discs, both in terms of their molecular composition and with respect to their functioning as initiating sites for the assembly of new sarcomeres. How 1.7-2.0 microns nascent sarcomeres can be added distally during elongation while the tips of the myofibrils remain inserted into submembranous adhesion plaques is unknown.

Differential distribution of subsets of myofibrillar proteins in cardiac nonstriated and striated myofibrils.

Cultured cardiac myocytes were stained with antibodies to sarcomeric alpha-actinin, troponin-I, alpha-actin, myosin heavy chain (MHC), titin, myomesin, C-protein, and vinculin. Attention was focused on the distribution of these proteins with respect to nonstriated myofibrils (NSMFs) and striated myofibrils (SMFs). In NSMFs, alpha-actinin is found as longitudinally aligned, irregular approximately 0.3-microns aggregates. Such aggregates are associated with alpha-actin, troponin-I, and titin. These I-Z-I-like complexes are also found as ectopic patches outside the domain of myofibrils in close apposition to the ventral surface of the cell. MHC is found outside of SMFs in the form of discrete fibrils. The temporal-spatial distribution and accumulation of the MHC-fibrils with respect to the I-Z-I-like complexes varies greatly along the length of the NSMFs. There are numerous instances of I-Z-I-like complexes without associated MHC-fibrils, and also cases of MHC-fibrils located many microns from I-Z-I-like complexes. The transition between the terminal approximately 1.7-microns sarcomere of any given SMF and its distal NSMF-tip is abrupt and is marked by a characteristic narrow alpha-actinin Z-band and vinculin positive adhesion plaque. A titin antibody T20, which localizes to an epitope at the Z-band in SMFs, precisely costains the 0.3-microns alpha-actinin aggregates in ectopic patches and NSMFs. Another titin antibody T1, which in SMFs localizes to an epitope at the A-I junction, typically does not stain ectopic patches and NSMFs. Where detectable, the T1-positive material is adjacent to rather than part of the 0.3-microns alpha-actinin aggregates. Myomesin and C-protein are found only in their characteristic sarcomeric locations (even in just perceptible SMFs). These A-band-associated proteins appear to be absent in ectopic patches and NSMFs.

Localized prostate cancer treated by external-beam radiotherapy alone: serum prostate-specific antigen--driven outcome analysis.

PURPOSE: To determine the 5-year rate of survival with no evidence of disease (NED) using strict biochemical criteria in men with prostate cancer treated by external-beam radiotherapy alone and to examine possible clinical and treatment factors that predict the likelihood of NED survival. MATERIALS AND METHODS: Five hundred men with clinically localized prostate cancer consecutively treated with external-beam radiotherapy alone with no prior, concomitant, or adjuvant endocrine therapy were identified. All patients had serial serum prostate-specific antigen (PSA) values determined after treatment and 451 patients had pretreatment PSA values determined. The median follow-up duration is 20 months (range, 2 to 72; mean, 36). RESULTS: The 5-year rate of overall survival in this group of patients was 80%. The 5-year rate of survival without clinical evidence of disease (cNED) was 72%. The 5-year rate of survival without evidence of clinical, radiographic, or biochemical relapse (bNED) was 51%. Multivariate analysis demonstrated that a pretreatment serum PSA level < or = 15 ng/mL was the most important predictor of bNED survival (P < .0001). Patients with early-stage (T1, T2a/b) tumors and a pretreatment serum PSA less than 15 ng/mL had a 3-year rate of bNED survival of 86%. The rate of bNED survival for patients with a pretreatment PSA level greater than 15 ng/mL was 38% at 3 years. CONCLUSION: Pretreatment serum PSA level is the most important predictor of treatment outcome in this group of patients treated with definitive radiotherapy alone. External-beam radiation alone can produce acceptable early rates of bNED survival in patients with clinically organ-confined tumors and a pretreatment PSA level < or = 15 ng/mL. To produce acceptable results in those patients with pretreatment PSA levels more than 15 ng/mL, effective adjuvant treatments in addition to aggressive local treatments are necessary.

Patterns-of-failure analysis of patients with high pretreatment prostate-specific antigen levels treated by radiation therapy: the need for improved systemic and locoregional treatment.

PURPOSE: The patterns of failure (local and/or regional v metastatic) have been determined for patients with prostate cancer and pretreatment prostate-specific antigen (PSA) levels > or = 20 ng/mL treated with radiation alone with the purpose to design appropriate multimodal treatments. MATERIALS AND METHODS: One hundred twenty patients with pretreatment PSA levels > or = 20 ng/mL were treated with external-beam radiation alone between February 1988 and October 1993. They were arbitrarily divided by PSA levels, 20 to 29.9 ng/mL, 30 to 49.9 ng/mL, and > or = 50 ng/mL, and analyzed in terms of freedom from any failure (no evidence of biochemical disease [bNED], and PSA level < 1.5 ngm/mL and not increasing), as well as freedom from imaging evidence of distant metastasis (fdm). RESULTS: There was no significant difference in short-term outcome by pretreatment PSA level, and thus all patients were pooled for analysis. At 4 years, 81% were fdm and 28% were free of any failure. This suggests that approximately 50% have recurred with local and/or regional disease or undetectable metastatic disease. Multivariate analysis indicated that low palpation stage and higher center of prostate dose were associated with better bNED survival. Multivariate analysis indicated that increasing stage and younger age are significantly associated with increasing distant metastasis. CONCLUSION: Patients with pretreatment PSA levels > or = 20 ng/mL are not optimally treated by irradiation alone. The pattern of failure suggests improvement may come from systemic treatment of metastatic disease and high-dose radiation to improve locoregional disease. To evaluate this, we have begun a multimodal trial of chemohormonal therapy followed by extended-field irradiation.

Cannabinoid CB1 receptor-mediated inhibition of noradrenaline release in guinea-pig vessels, but not in rat and mouse aorta.

Cannabinoids exert complex effects on blood pressure related to their interference with cardiovascular centres in the central nervous system and to their direct influence on vascular muscle, vascular endothelium and heart. In view of the relative lack of information on the occurrence of CB1 receptors on the vascular postganglionic sympathetic nerve fibres, the aim of the present study was to examine whether cannabinoid receptor ligands affect the electrically evoked tritium overflow in superfused vessels (tissue pieces) from the guinea-pig, the rat and the mouse preincubated with 3H-noradrenaline. The cannabinoid receptor agonist WIN 55,212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]-pyrrolo[1,2,3-de]1,4-benzoxazinyl](1-naphthalenyl) methanone) inhibited the evoked tritium overflow in the guinea-pig aorta, but not in that of the rat or mouse. The concentration-response curve of WIN 55,212-2 was shifted to the right by the CB1 receptor antagonist rimonabant, yielding an apparent pA2 value of 7.9. The most pronounced (near-maximum) inhibition obtained at the highest WIN 55,212-2 concentration applied (3.2 microM) amounted to 40%. WIN 55,212-2 also inhibited the evoked overflow in guinea-pig pulmonary artery, basilar artery and portal vein, again in a manner sensitive to antagonism by rimonabant. The latter did not affect the evoked overflow by itself in the four vessels, but did increase the electrically evoked tritium overflow from superfused guinea-pig hippocampal slices preincubated with 3H-choline and from superfused guinea-pig retina discs preincubated with 3H-noradrenaline (labelling dopaminergic cells in this tissue). The inhibitory effect of 3.2 microM WIN 55,212-2 on the evoked overflow from the guinea-pig aorta was comparable in size to that obtained with agonists at the histamine H3, kappa opioid (KOP) and ORL1 (NOP) receptor (1 or 10 microM, producing the respective near-maximum effects) whereas prostaglandin E2 1 microM caused a higher near-maximum inhibition of 70%. Prostaglandin E2 also induced an inhibition by 65 and 80% in the rat and mouse aorta respectively, indicating that the present conditions are basically suitable for detecting presynaptic receptor-mediated inhibition of noradrenaline release. The results show that the postganglionic sympathetic nerve fibres in the guinea-pig aorta, but not in the rat or mouse aorta, are endowed with presynaptic inhibitory cannabinoid CB1 receptors; such receptors also occur in guinea-pig pulmonary artery, basilar artery and portal vein. These CB1 receptors are not subject to an endogenous tone and the extent of inhibition obtainable via these receptors is within the same range as that of several other presynaptic heteroreceptors, but markedly lower than that obtainable via receptors for prostaglandin E2.

The controversies and pitfalls in modeling normal tissue radiation injury/damage.

Highly conformal fields have become achievable in routine clinical practice. The optimal shape of the resultant dose distributions depends on information that is not currently available. This missing information is the dose-volume response of the normal tissues at risk. These functions are now the subject of aggressive research. The research involves collecting the dose-response data, modeling the dose-response function, and fitting the models to the data. The controversies addressed here influence the selection of the biomathematical model that one might use to describe such a function. The form that the dose-volume response function takes depends on the nature of the volume effect. The nature of the volume effect for a given radiation response is the subject of considerable debate. Related to this debate, this report addresses the existence of the volume effect, the existence of a threshold volume, and the existence of functional subunits. The pitfalls relate to the problems in accurate determination and application of the dose-response functions.

Strategies for treating possible tumor extension: some theoretical considerations.

When there is a small possibility of cancer having extended to a region some distance from the main bulk of disease, it may be unclear whether to include that region in the target volume and, if so, what dose should be delivered to it. We have constructed a theoretical model that includes dose and volume relationships for both diseased and normal tissue. With this model one can calculate the change in tumor control probability (TCP) when varying doses are delivered to the regions of known and suspected disease. Values of TCP as a function of dose to the region of suspected disease have been calculated for a wide range of the variables on which the model depends. We conclude that the strategy of treating the region of suspected disease to about 70% of the dose delivered to the region of known disease is almost always better than not treating it at all, or treating both regions to a uniform but reduced dose designed to keep the probability of complication the same. The gain in TCP could be from 5 to 15% for situations of clinical interest.

A radiation overdose incident: initial data.

PURPOSE: To estimate tolerance limits for irradiated human tissues by evaluating reactions observed in 426 patients who had received significant overdoses from an improperly calibrated cobalt unit. METHODS AND MATERIALS: A data file was designed to store essential technical and dosimetric information sufficient to analyze the response, estimate complication rates, and derive dose-response functions, using hierarchical region, system, and organ coding protocols. RESULTS: A total of 795 discrete target tissues had been irradiated in 426 evaluable subjects studied. In 183 patients who survived beyond 1 year, there were 62 (34%) with immediate severe complications in 386 irradiated sites including brain, spinal cord, skin, oropharyngeal mucosa, colon, and rectum. CONCLUSION: This unique data set includes responses to high doses and unusual fractionation beyond the range of conventional clinical experience. It provides a resource for estimating human tissue tolerance limits, for testing clinically relevant radiobiological models and for developing new optimization algorithms.

Normal tissue reactions and complications following high-energy neutron beam therapy. II: Complication rates adjusted for censoring.

A dose response analysis was performed on patients at risk for significant radiation injuries following neutron radiotherapy. Complication rates were calculated at various dose intervals using a maximum likelihood method that is formally equivalent to the product limit estimator of survival. The variance of each complication rate was used to weight a logistic regression on log dose. The treatment sites that were analyzed were head and neck, pelvis, thorax, and pancreas. Except for osteomyelitis of the mandible, complications of all types were considered collectively at each site and dose increment since there were too few complications to determine dose response functions for individual types of injuries. The head and neck was observed to be the site with the highest tolerance to radiation whereas the thorax was the most sensitive site.

Factors influencing incidence of acute grade 2 morbidity in conformal and standard radiation treatment of prostate cancer.

PURPOSE: The fundament hypothesis of conformal radiation therapy is that tumor control can be increased by using conformal treatment techniques that allow a higher tumor dose while maintaining an acceptable level of complications. To test this hypothesis, it is necessary first to estimate the incidence of morbidity for both standard and conformal fields. In this study, we examine factors that influence the incidence of acute grade 2 morbidity in patients treated with conformal and standard radiation treatment for prostate cancer. METHODS AND MATERIALS: Two hundred and forty-seven consecutive patients treated with conformal technique are combined with and compared to 162 consecutive patients treated with standard techniques. The conformal technique includes special immobilization by a cast, careful identification of the target volume in three dimensions, localization of the inferior border of the prostate using the retrograde urethrogram, and individually shaped portals that conform to the Planning Target Volume (PTV). Univariate analysis compares differences in the incidence of RTOG-EORTC grade two acute morbidity by technique, T stage, age, irradiated volume, and dose. Multivariate logistic regression includes these same variables. RESULTS: In nearly all categories, the conformal treatment group experienced significantly fewer acute grade 2 complications than the standard treatment group. Only volume (prostate +/- whole pelvis) and technique (conformal vs. standard) were significantly related to incidence of morbidity on multivariate analysis. When dose is treated as a continuous variable (rather than being dichotomized into two levels), a trend is observed on multivariate analysis, but it does not reach significant levels. The incidence of acute grade 2 morbidity in patients 65 years or older is significantly reduced by use of the conformal technique. CONCLUSION: The conformal technique is associated with fewer grade 2 acute toxicities for all patients. This conclusion is valid irrespective of selection criteria except in a few cases. Older age is associated with increased toxicity only with the standard technique and not then at a statistically significant level. Elderly patients should not be excluded from external beam radiation because of increased morbidity especially if conformal treatment is available. Volume is not significantly related to morbidity in patients with standard treatment, but it is for conformal treatment. Furthermore, it remains significant in a multivariate analysis that also shows the advantage of conformal treatment. Grade 2 acute toxicities are more volume dependent than dose dependent.

Analysis of the histopathology of radiation myelopathy.

An analysis of published histopathology reports of patients with radiation myelopathy was performed. Radiation lesions in the spinal cord were classified as primarily white matter parenchymal lesions (type 1), primarily vascular lesions (type 2), or a combination of vascular and white matter lesions (type 3). The presence or absence of a mononuclear inflammatory reaction was also noted. Type 1 and type 3 lesions had comparable latent periods, both significantly shorter than those observed for type 2 lesions. The anatomical level of the irradiation did not appear to influence the type of lesion. Inflammatory reaction was observed with greater frequency in type 3 lesions. For all types of lesions, the average latent periods in patients with inflammatory reactions were shorter than in those without inflammation. In the cases in which disease status was evaluated, 70% of the patients were free of disease or had no evidence of recurrence at autopsy.

Survival in radiation myelopathy.

Survival in radiation myelopathy has been the subject of analysis. Factors affecting survival are the level of the lesion, the age of the patient, and the latent period of the injury. The influence of age and level of the lesion is compared with the effects of these same parameters in traumatic myelopathy. Patients with cervical cord lesions have more rapid morbidity in both radiation and traumatic myelopathy. For thoracic but not cervical lesions, younger patients have a greater survival expectation than older patients. Patients with shorter latent periods have a more rapid mortality in cervical radiation myelopathy, but no demonstrable effect is seen in thoracic radiation myelopathy.

Postoperative radiation therapy for surgically staged endometrial cancer: impact of time factors (overall treatment time and surgery-to-radiation interval) on outcome.

PURPOSE: To evaluate the impact of prolonged overall radiation treatment (RT) time and surgery-to-radiation interval on local control (LC) and disease-specific survival (DSS) of surgically staged endometrial cancer patients in relation to known prognostic factors. METHODS AND MATERIALS: Between 1971 and 1993, 195 endometrial cancer patients received postoperative RT at the Fox Chase Cancer Center. All patients underwent total abdominal hysterectomy (TAH), with 38% also having lymph node sampling. All patients received whole pelvic external beam RT to a median dose of 45 Gy (range 40 to 60 Gy). Sixty-nine percent received a vaginal cuff boost with either low dose rate or high dose rate brachytherapy. Tumor and treatment factors were analyzed for impact on LC and DSS. Median follow-up was 47 months (range: 6 to 187 months). RESULTS: The overall actuarial 5-year LC rate was 85%. In multivariate analysis, tumor grade, pathologic stage, external radiation dose, and surgical lymph node evaluation were independent prognostic variables for improved LC. Surgery-to-radiation interval of greater than 6 weeks was a marginally significant factor for decreased LC (p = 0.06). Overall RT time and external beam treatment time did not appear to impact LC rates. The overall actuarial 5-year DSS rate was 86%. In multivariate analysis, depth of myometrial invasion, tumor grade, and pathologic stage were independent prognostic variables for DSS. In addition, a surgery-to-radiation interval of greater than 6 weeks was significantly associated with decreased DSS (p < 0.005). CONCLUSIONS: Surgery-to-radiation interval of greater than 6 weeks is a significant independent prognostic variable for decreased DSS and a marginally significant variable for decreased LC in patients irradiated postoperatively for endometrial cancer. Other time factors (overall RT time and external beam treatment time) did not appear to impact outcome. Based on this analysis, postoperative radiation therapy for endometrial cancer should be initiated within 6 weeks following surgery.

A heuristic approach to edge detection in on-line portal imaging.

PURPOSE: Portal field edge detection is an essential component of several postprocessing techniques used in on-line portal imaging, including field shape verification, selective contrast enhancement, and treatment setup error detection. Currently edge detection of successive fractions in a multifraction portal image series involves the repetitive application of the same algorithm. As the number of changes in the field is small compared to the total number of fractions, standard edge detection algorithms essentially recalculate the same field shape numerous times. A heuristic approach to portal edge detection has been developed that takes advantage of the relatively few changes in the portal field shape throughout a fractionation series. METHODS AND MATERIALS: The routine applies a standard edge detection routine to calculate an initial field edge and saves the edge information. Subsequent fractions are processed by applying an edge detection operator over a small region about each point of the previously defined contour, to determine any shifts in the field shape in the new image. Failure of this edge check indicates that a significant change in the field edge has occurred, and the original edge detection routine is applied to the image. Otherwise the modified edge contour is used to define the new edge. RESULTS: Two hundred and eighty-one portal images collected from an electronic portal imaging device were processed by the edge detection routine. The algorithm accurately calculated each portal field edge, as well as reducing processing time in subsequent fractions of an individual portal field by a factor of up to 14. CONCLUSIONS: The heuristic edge detection routine is an accurate and fast method for calculating portal field edges and determining field edge setup errors.

The latent period in clinical radiation myelopathy.

Seventy-seven papers containing data on more than 300 cases of radiation myelopathy have been analyzed. The data suggest that the latent periods are similar in the cervical and thoracic levels of the spinal cord and are bimodally distributed. Myelopathy of lumbar cord apparently has a shorter latent period. As in controlled animal experiments, the latent period decreases with increasing dose. Furthermore, the variation in latent periods also decreases with dose. It is also seen that retreated patients and pediatric or adolescent patients have greatly reduced latent periods. The implications of these findings as they compare with the animal data are discussed.

An evaluation of setup uncertainties for patients treated to pelvic sites.

PURPOSE: Successful delivery of conformal fields requires stringent immobilization and treatment verification, as well as knowledge of the setup reproducibility. The purpose of this study was to compare the three-dimensional distribution of setup variations for patients treated to pelvic sites with electronic portal imaging devices (EPID) and portal film. METHODS AND MATERIALS: Nine patients with genitourinary and gynecological cancers immobilized with custom casts and treated with a four-field whole-pelvis technique were imaged daily using an EPID and filmed once every five to seven treatments. The three-dimensional translational and rotational setup errors were determined using a technique that relies on anatomical landmarks identified on simulation and treatment images. The distributions of the translational and rotational variations in each dimension as well as the total displacement of the treatment isocenter from the simulation isocenter were determined. RESULTS: Grouped analysis of all patients revealed average unidirectional translational deviations of less than 2 mm and a standard deviation of 5.3 mm. The average total undirected distance between the treatment and simulated isocenters was 8.3 mm with a standard deviation of 5 mm. Individual patient analysis revealed eight of nine patients had statistically significant nonzero mean translational variations (p < 0.05). Translational variations measured with film were an average of 1.4 mm less than those measured with EPID, but this difference was not statistically significant. CONCLUSION: Translational variations measured in this study are in general agreement with previous studies. The use of the EPID in this study was less intrusive and may have resulted in less additional attention being given each imaging setup. This may explain the slightly larger average translational variations observed with EPID vs. film, and suggests that the use of EPIDs is a superior method for assessing the true extent of setup displacements. Although no statistically significant translational variations for the patient group overall were observed, 90% of patients had significant translational variations in at least one direction when analyzed separately. The margin to be added to the clinical target volume (CTV) to account for setup uncertainties will depend on whether it is possible to identify patients with significant translational variations, and to eliminate these displacements from routine treatments. The choice to eliminate these variations and to use a smaller CTV margin will have to be accompanied by stringent frequent position verification methods and repositioning.