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Conformal static field radiation therapy treatment of early prostate cancer versus non-conformal techniques: a reduction in acute morbidity.

Patients with early prostate cancer have been definitively treated using our previously described technique of CT-based 3D treatment planning and beam's eye view techniques with patients immobilized in alpha cradle casts. An average of 14% bladder (range 6-31%) and 14% rectal (range 7-25%) volume receiving a given dose was eliminated using four conformally blocked fields, with a 1.5 cm margin around the prostate contour, when compared to stage matched controls. Treatment-related acute morbidity was compared for 26 patients treated by the conformal techniques (CG) since April 1989 and 20 consecutive patients treated immediately prior to the conformal techniques with prostate only fields from May 1985-March 1989 (NCG). Acute urinary symptoms (frequency, dysuria, hematuria) or acute rectal symptoms (diarrhea, tenesmus, blood) occurred in 77% (20/26) of the CG versus 80% (16/20) of the NCG patients. Only 31% (8/26) of the CG versus 60% (12/20) of the NCG patients (p < .05) experienced symptoms to a degree which prompted physician intervention (medication and/or interruption of treatment). Two of 26 CG patients (8%) required medication for both bladder and rectal symptoms compared to 5/20 (25%) NCG patients (p = .09). Symptoms persisted for an average of 2.5 weeks versus 3.5 weeks in the CG and NCG groups, respectively. Persistent symptoms at or beyond the 1 month follow-up were present in 3/26 (11%) CG patients (average duration 1.5 months) and were present in 4/20 (20%) of the NCG patients (average duration 2.5 months). Thus, although the percentage of patients who experience acute irritation of the bladder and/or rectum is similar in the two groups, it appears that the percentage requiring medication and/or interruption of treatment is significantly less when 3D treatment planning, rigid immobilization, and conformal blocks are used. The amount of bladder and rectal tissue that is eliminated by our conformal technique is important as shown clinically by the lesser severity and shorter duration of acute symptomatology.

Aged↗

Intermediate endpoint biomarkers for chemoprevention.

The understanding of intermediate endpoint biomarker expression in relation to the sequential events in bladder tumorigenesis establishes a useful approach for evaluating chemopreventive agents. Biomarkers may be genotypic or phenotypic and function as biomarkers of susceptibility, exposure, effect, or disease. This paper reviews several years of research on biomarkers and their use in monitoring chemoprevention therapy. In initial animal experiments, mice were dosed with N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) while co-administering N-(4-hydroxyphenyl)retinamide (4-HPR). 4-HPR did not statistically reduce tumor incidence, but did affect tumor differentiation and, consequently, nuclear size and DNA ploidy. These results suggest that nuclear size and ploidy may function as intermediate endpoint biomarkers of effect for oncogenesis and that epigenetic as well as genetic mechanisms may be primary in the oncogenic process. Early biomarkers of effect which occur prior to genetic effects or chromosome aberration may portend a higher probability of being modulated by differentiating agents such as retinoids. In vitro studies demonstrated that RPMI-7666 cells cultured with a phorbol ester tumor promoter (12-O-tetradecanoyl-phorbol-13-acetate) could be redifferentiated with 13-cis-retinoic acid and dimethyl sulfoxide (DMSO). F-actin, a cytoskeletal biomarker with a presumed function in the epigenetic mechanisms of carcinogenesis, could also be normalized in HL-60 cells treated with 4-HPR or DMSO. A clinical evaluation of F-actin in patients with varying degrees of risk confirmed the value of F-actin as a differentiating biomarker useful for bladder cancer risk assessment. The clarification of when the phenotypic changes of F-actin occur in the oncogenic process was achieved when a variety of biochemical changes were mapped in the patients with bladder cancer. These studies confirmed that G-actin, a reciprocal form of F-actin, is increased relatively early in bladder cancer oncogenesis when multiple biomarkers are quantitated in the field, adjacent area, and the tumor. Comparison of each individual biomarker's expression from field, adjacent to tumor, and tumor, and subsequent cluster analysis of these biomarkers, indicated that the possible sequence of phenotypic expression of biomarkers in bladder cancer oncogenesis is from G-actin, to p300 antigen, to epidermal growth factor receptor (EGFR), to p185 (neu oncogene product), to DNA aneuploidy and, finally, to visual morphology.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Knowledge-based decision support for patient monitoring in cardioanesthesia.

An approach to generating 'intelligent alarms' is presented that aggregates many information items, i.e. measured vital signs, recent medications, etc., into state variables that more directly reflect the patient's physiological state. Based on these state variables the described decision support system AES-2 also provides therapy recommendations. The assessment of the state variables and the generation of therapeutic advice follow a knowledge-based approach. Aspects of uncertainty, e.g. a gradual transition between 'normal' and 'below normal', are considered applying a fuzzy set approach. Special emphasis is laid on the ergonomic design of the user interface, which is based on color graphics and finger touch input on the screen. Certain simulation techniques considerably support the design process of AES-2 as is demonstrated with a typical example from cardioanesthesia.

Anesthesia↗

3-D comparative study of proton vs. x-ray radiation therapy for rectal cancer.

To assess the usefulness of proton beams for treatment of patients with rectal cancer, we have performed comparative 3D treatment planning for proton beam and x-ray beam therapy. Three common x-ray techniques (AP-PA, 3-field, and 4-field box), a proton beam only plan, and a proton boost plan were compared. The plan which would have been treated without the aid of the 3D planning system was also simulated. Dose distributions were analyzed and dose-volume histograms computed for the target volumes and critical normal tissues. Analyses of these plans demonstrate that the proton beam techniques reduce the volume of small bowel irradiated. This may allow higher doses to be delivered to the tumor, with a probable increase in local control, or a reduction in normal tissue complications probability. All the plans developed with the 3D planning system treated significantly less bowel than the one planned without it.

Aged↗

Radiotherapy treatment planning using the ACTA-scanner.

Computerized tomography is useful in radiotherapy treatment planning in the following ways: (1) Its image provides the most accurate possible contour of the patient and demonstrates the internal structures in their proper relation to each other. (2) The tumor and its extension are accurately demonstrated. (3) Corrections for tissue heterogeneities can be accomplished in one of two ways, either by arbitrary assignment of densities to tissues or by direct scanning with a therapy source. This latter procedure is under investigation. (4) The computer can be programmed to demonstrate summations of dose delivered from multiple fields.

Dose-Response Relationship, Radiation↗

EEG-brain mapping. A method to optimize therapy in schizophrenics using absolute power and center frequency values.

In this study EEG-spectral parameters like mean alpha-power values and center frequency values are computed as maps and compared using significant probability mapping. The parameters are used to describe changes of the functional state of the brain after neuroleptic depot injection (Haldol-Decanoate) in schizophrenic patients. The absolute alpha-power increased significantly (p < 0.01), especially within the first week after injection mostly in the left hemispheric regions. The center frequency decreased most significantly (p < 0.02) between the first and second week after haldol depot injection at the right occipital regions. Both parameters are efficient to describe functional changes correlated with clinical symptomatology, even 3-5 days earlier. Thus, EEG power and center frequency mapping can be used very efficiently to estimate the optimal time between sequential neuroleptic depot injections.

Adult↗

Computer-aided tumour classification and treatment selection in breast cancer.

In order to provide a common basis for treatment decisions and the future evaluation of breast cancer therapy, the breast cancer protocol used in our clinic was formulated for the computer. A system for the simulation of clinical reasoning was used which allows the physician to express the medical logic as a series of inferences to be confirmed or rejected on the basis of Boolean combinations of medical criteria. The system enables the physician to rearrange these criteria into a questionnaire for complete and accurate recording of patient data. These data are then fed into the computer to produce a patient status report and treatment recommendations. The data from 26 patients in various stages of breast cancer have been processed by the computer and the computer's conclusions compared to the assessment made by a junior physician in our department. In three cases the staging was not identical, in 15 cases the treatment decisions were not identical and in all cases investigations were left out by the physician. The system has been of considerable value in standardising patient examination and treatment and in training inexperienced physicians.

Breast Neoplasms↗

Computer use in diagnosis, prognosis, and therapy.

Computers are used to influence diagnostic and therapeutic decisions. The computer's information-handling capabilities allow it to serve as a reliable extension of the physician's memory and expander of the physician's information and synthesized knowledge resources. Computers have been used to facilitate decisions through organization of patient data, improved classification of patients, decision analysis in clinical settings, and simulation of expert clinical reasoning. Computer programs are more successful in narrow, constrained, single arenas of medicine with much underlying pathophysiologic understanding and where decisions are based largely on hard laboratory data. New models of synthetic reasoning that simulate expert clinical behavior show promise of supporting complicated decisions concerning problems of multiple diseases. All systems are confronted by problems of consensus and authority of the underlying information used.

Computers↗

[Marker-evidence for documentation and evaluation of findings and treatment in fractures of the facial skull].

A special form is presented by means of which clinical findings and therapy of fractures of the visceral cranium are documented in such a way that the data can be fed into a computer and be evaluated. Like similar forms for cheilognathopalatoschisis and tumors of the jaw and face area the present form is meant for a special field or specific problems and is not to replace the traditional case history.

Diagnosis, Computer-Assisted↗

[A computer-controlled monitoring and therapy system for shock compensation in severe burns (author's transl)].

A computer-controlled control loop for the automatic diagnosis of shock and infusion therapy is reported. External information (off-line) and vital parameters measured with serial devices (on-line) are used by the computer for the automatic control of infusion pumps. By this method the critical shock phase could be prevented in five seriously burned patients. The construction of the system also permits its use in other shock conditions.

Blood Pressure↗

Investigating the potential of three-dimensional treatment planning.

3-D treatment planning has received a great deal of attention in the radiation therapy community over the last several years. This new technology makes use of the continuous improvements in computer hardware and graphics capabilities, along with major improvements in treatment planning software, to provide a fully three dimensional simulation of the patient, radiation beams, and dose distributions which are used for radiation therapy of various cancers. With these capabilities, the physician and treatment planner may now optimize the radiation beams used to treat the patient much more effectively than in the past, when only a limited description of the patient, beams, and doses was available. This paper describes several of the new capabilities of these 3-D planning systems, some research studies which are currently being performed to evaluate the usefulness of the new technology, and finally some of the costs associated with its implementation.

Computer Simulation↗

[Computerized planning of radiotherapy].

The hypophysis was studied by MR tomography in 148 patients with the most prevalent diseases of the hypothalamohypophyseal system and in 13 ones with primary hypothyrosis. The findings evidence a great variety of changes in the MRT picture in the examinees. The method permits a reliable diagnosis of hypophyseal macroadenoma and of an 'empty' sella turcica. Qualitative and quantitative criteria for MRT diagnosis of these conditions are suggested. The diagnostic value of MRT for the detection of macroadenomas is still to be researched. The method was effectively used for a dynamic follow-up of the hypophyseal status in the course of pathogenetic therapy; the formation of an 'empty' sella turcica is possible against the background of dopamine agonist therapy and substitution therapy of primary hypothyrosis.

Adolescent↗

[Conformal technics by the movement of bars in pendular fields. 1. Prototype realization and the possible applications].

The growing interest for conformal radiotherapy originates from the need of giving the prescribed dose to the target volume, by sparing, at the same time, surrounding healthy tissues and organs. More dose to the target volume with respect to the healthy tissues always increases the curative possibilities of the treatment. However, the development of conformal techniques implies an increased complexity of the treatment and the solution of many technical and dosimetric problems. In our Institute we are developing new conformal techniques, based on the use of moving bars driven by a computer-controlled system in arc therapy. This paper refers to the conclusion of the preliminary part of our work: a movement (translating or rotating) of bars in arc therapy seems to have good chances to tailor dose distribution in a relatively simple way. We realized two mechanical systems driven by computer for translating and rotating movements of a bar. The two techniques have been tested by TLD and film dosimetry on acrylic phantoms. We present the results of these tests, and describe technical problems and the clinical possibilities of this method.

Equipment Design↗

[The effectiveness of treatment for breast cancer patients].

The study of late results of treatment in 1166 patients with breast cancer permitted to find the percentage of a 5-year survival to be equal to 55.58, 37.93% of patients survived for 10 years, 28.25% -- for 15 years. In the first stage a 5-year survival was 87.20%, while in the second and third -- 57.7% and 31.56% of patients survived for 5 years, accordingly. The modern methods of radiotherapy (radiosurgical method, interstitial gamma therapy with Au-198 granules, distance grammatherapy on the machine LUCH) enhanced the efficacy of therapeutic measures in patients with widespread breast cancer. A complex diagnosis -- cytology, non-contrast mammography and mathematical analysis by means of a computer contributes to recognition of early forms of breast cancer.

Adenocarcinoma↗

Enlarged acid-base and blood gas calculations by electronical data computing in the blood gas laboratory.

A rapid anaysis of parameters of the acid-base equilibrium and blood gases during open heart surgery and emergency therapy is absolutely necessary. Computing of the several parameters of the acid-base status by slide rules or nomograms is time consuming and can be shortened by computer applications. The central blood gas laboratory consists of a blood gas analyzer for PO2, PCO2 and pH, an electronic desktop calculator, a four color X-Y-plotter and two data lines to the cardiac surgery unit and to the intensive care unit. The time needed for computing and feedback of the parameters could be decreased to one quarter. In addition to numerical data printout, a graphical representation of the several parameters is possible on a X-Y-plotter and includes the Rahn-Fenn-O2-CO2-Diagram with venous admixture, ventilation perfusion ratio, alveolar dead space ventilation and the standard and actual oxygen dissociation curve as well as the pH/HCO3- Acid-Base nomogram. Furthermore, a computer diagnosis of the actual disturbances can be plotted.

Acid-Base Equilibrium↗

[Electronic data processing in the clinical nuclear medicine].

Computer techniques as introduced into clinical nuclear-medicine 12 years ago, were first exclusively used for scintigraphic purposes. Through the development of a comprehensive pilot system for nuclear medical data processing on the basis of two Siemens Process control computers it could be demonstrated, that besides of scintigraphy there are also other important fields for computer application, e.g. in function diagnostics and therapy planning.

Bayes Theorem↗

[Quantitative fluorometry at the ocular fundus (author's transl)].

Description of a videodensitometric method for the quantitative evaluation of fluorescence angiography photographs using the Quantimet 720 image analysis computer system. The clinical value of the new method is demonstrated in a case of central serous retinopathy. With the aid of these measurements the activity of leakage points can be assessed more exactly than by mere subjective inspection of the gained pictures, thus allowing a better control of the effects of a chosen therapy.

Computers↗

Computer assisted monitoring in intensive medicine.

Intensive Medicine is always associated with the problem of handling the mass and assuring the quality of information on vital signs, fluid and blood balance, laboratory data, physiological calculations, etc., required in patient care. A computer based monitoring system for intensive care was introduced in 1973 at the Academic Hospital in Leuven. The basic software was developed at the Peter Bent Brigham Hospital of the Harvard Medical School and the medical division of the Hewlett Packard Company; the computer used was a H.P. 2100 central processor with 32K of core memory. Initially, the program allowed mainly acquisition, storage and retrieval of bedside monitored and manual data of cardiac and circulatory function. Very soon however, the software was extended and modified by the division of "Medical Informatics" in order to meet new or different requirements. In the present situation our vision on the use of computer-assisted monitoring has changed and our present program has been extended as follows : 1. On-line collection and retrieval of bedside monitored data including heart rate, arterial blood pressure (systolic-diastolic-mean) left atrial pressure, central venous pressure, pulmonary artery pressure, intracranial pressure. Trend analysis of those data, with calculation of mean values, standard variation and corresponding t-tests. 2. Computer assistance in performing time consuming calculations on off-line data such as : -- clearance-values (renal function), -- temperature-correction of blood-gasvalues, -- hour-to-hour fluid balance, including calculation of in-sensible losses, -- blood-balance. 3. Data transmission of laboratory results as soon as available in the central laboratory through a direct link between laboratory and I.T.U. 4. Computer assisted E.C.G. analysis. The three first objectives are realised, on-line E.C.G.-analysis is being developed. The same computer serves the remotely located medical and coronary care units and one bed in the emergency department. An assessment of computer assistance in intensive therapy, on nursing labor and on quality of patient care is made.

Clinical Laboratory Techniques↗