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Precise positioning of patients for radiation therapy.

We have developed a number of immobilization schemes which permit precise daily positioning of patients for radiation therapy. Pretreatment and post-treatment radiographs have been taken with the patient in the treatment position and analyzed to determine the amount of intratreatment movement. Studies of patients in the supine, seated and decubitus positions indicate mean movements of less than 1 mm with a standard deviation of less than 1mm. Patients immobilized in the seated position with a bite block and a mask have a mean movement of about 0.5 mm +/- 0.3 mm (s.d.), and patients immobilized in the supine position with their necks hyperextended for submental therapy evidence a mean movement of about 1.4 mm +/- 0.9 mm (s.d.). With the exception of those used for the decubitus position, the immobilization devices are simply fabricated out of thermoplastic casting materials readily available from orthopedic supply houses. A study of day-to-day reproducibility of patient position using laser alignment and pretreatment radiographs for final verification of position indicates that the initial laser alignment can be used to position a patient within 2.2 mm +/- 1.4 mm (s.d.) of the intended position. These results indicate that rigid immobilization devices can improve the precision of radiotherapy, which would be advantageous with respect to both tumor and normal tissue coverage in certain situations.

Casts, Surgical↗

Intensity-modulated radiation therapy (IMRT): the radiation oncologist's perspective.

Intensity-modulated radiation therapy (IMRT) is a new and evolving technological advance in high-precision radiation therapy. It is an extension of 3-dimensional conformal radiotherapy (3D-CRT) that allows the delivery of highly complex isodose profiles to the target while minimizing radiation exposure to surrounding normal tissues. Clinical data on IMRT are emerging and being collected, as more institutions are implementing or expanding the use of IMRT. However, the currently available IMRT and its applications are far from being well understood and established. In some circumstances, it remains impractical and too costly. This article discusses some practical issues from the radiation oncologist's perspective.

Attitude of Health Personnel↗

[Sepsis in hemato-oncologic patients].

The general approach regarding the treatment of sepsis in patients with oncological or haematological malignancies does not differ significantly from that in immunocompetent individuals, however, there are several specialities. The main causes of severe infections in cancer patients include deranged cellular or humoral immunity due to the underlying disease, severe neutropenia as a consequence of cytostatic regimens, lesions of the mucosal barriers due to adverse effects of antineoplastic agents, and violations of the integument by therapeutic interventions. Due to the impaired host defense, life threatening infections can occur more often in these patients, thereby limiting the benefits of antineoplastic therapy. On this account precise and intensive therapy has to be initiated in the early stages of sepsis. In the following, we will not primarily focus on sepsis specific treatment modalities, but merely try to elucidate in more detail the pathomechanisms and special features with regard to infectious complications and specific treatment.

Antineoplastic Agents↗

The use of medical images in planning and delivery of radiation therapy.

The authors provide a survey of how images are used in radiation therapy to improve the precision of radiation therapy plans, and delivery of radiation treatment. In contrast to diagnostic radiology, where the focus is on interpretation of the images to decide if disease is present, radiation therapy quantifies the extent of the region to be treated, and relates it to the proposed treatment using a quantitative modeling system called a radiation treatment planning (RTP) system. This necessitates several requirements of image display and manipulation in radiation therapy that are not usually important in diagnosis. The images must have uniform spatial fidelity: i.e., the pixel size must be known and consistent throughout individual images, and between spatially related sets. The exact spatial relation of images in a set must be known. Radiation oncologists draw on images to define target volumes; dosimetrists use RTP systems to superimpose quantitative models of radiation beams and radiation dose distributions on the images and on the sets of organ and target contours derived from them. While this mainly uses transverse cross-sectional images, projected images are also important, both those produced by the radiation treatment simulator and the treatment machines, and so-called "digital reconstructed radiographs," computed from spatially related sets of cross-sectional images. These requirements are not typically met by software produced for radiologists but are addressed by RTP systems. This review briefly summarizes ongoing work on software development in this area at the University of Washington Department of Radiation Oncology.

Computer Communication Networks↗

Precision medicine in combating antimicrobial resistance: A comprehensive review.

Antimicrobial resistance (AMR) represents one of the most pressing threats to global public health, undermining the effectiveness of modern antimicrobial therapy and challenging decades of medical progress. This comprehensive review examines the transition from broad-spectrum empirical therapy toward precision medicine as an integrated framework for improving antimicrobial use and combating AMR. Precision medicine seeks to tailor treatment decisions by combining pathogen-specific genomic and resistance data with relevant host characteristics to optimize therapy while limiting unnecessary antimicrobial exposure and the selective pressures that drive resistance. The review synthesizes advances reported from 2020, highlighting established and emerging approaches including rapid molecular diagnostics, next-generation sequencing, CRISPR-based detection, machine learning (ML)-assisted decision support, precision dosing, and targeted therapeutics such as bacteriophage therapy, antimicrobial peptides, and bacterial proteolysis-targeting chimeras. Rather than functioning as isolated technologies, these approaches achieve their greatest clinical value when integrated within antimicrobial stewardship programs and a One Health framework that recognizes the interconnected human, animal, and environmental drivers of resistance. Despite considerable progress, important challenges remain, including equitable access to advanced technologies, interpretation of increasingly complex datasets, workforce and infrastructure limitations, and evolving regulatory pathways for novel diagnostics and therapeutics. This review concludes that while precision medicine is not a standalone solution, its successful implementation will depend on coordinated integration of diagnostics, host factors, computational tools, pharmacological optimization, and stewardship strategies to improve patient outcomes while preserving the long-term effectiveness of existing antimicrobials.

Antimicrobial resistance↗

Future of veterinary radiation oncology.

Rapid developments in technology will have a profound effect on veterinary radiation oncology. These developments include computer-enhanced, three-dimensional treatment planning and smaller, more compact, more reliable radiation equipment, primarily linear accelerators. For treatment of all veterinary patients, the linear accelerators need electron capability. Although fractionated therapy will remain the standard from of treatment, new modalities, including a highly precise single-dose treatment called radiosurgery, and a precise fractionated therapy called conformal therapy, will be utilized more in the future.

Animals↗

The role of radiotherapy in the management of cancer--an overview.

Artificial X-rays were first produced in Germany in 1895 and used for cancer almost immediately. During the century since this remarkable discovery, radiation therapy has now become the most imporantant non-surgical modality in cancer: over 50% of all cancer patients now receive radiotherapy at some point during the illness. Radiation therapy has increasingly replaced surgical resection for primary control of a variety of solid tumours, particularly where surgical excision is accompanied by severe long-term tissue loss or psychological morbidity. Frequent examples include cancers of the breast, head and neck (especially larynx, naso- and other pharyngeal sites), and locally advanced cancer of the cervix. Combinations of surgery and radiotherapy are increasing used, for example in the preferred management of most cancers of the breast, by wide local surgical excision, breast preservation and postoperative radiotherapy. In rectal carcinoma as well, there is clear evidence of survival improvement in locally advanced cases when surgical excision is followed by routine pelvic irradiation. In other circumstances, radiation is routinely combined with chemotherapy, as for example in the standard management of small cell lung cancer. Anal carcinoma is also best treated by radical radiochemotherapy, avoiding surgical excision (with permanent colostomy) in the majority of patients. In both the developed and developing world, these are all common tumours, with the result that in 1990, almost half a million patients were treated with radiation therapy in the United States of America. Recent technical advances, both in imaging and therapy beam precision, have greatly improved the therapeutic ratio and accuracy of modern radiotherapy. Radiation therapy continues to progress on a rational scientific basis, with a secure clinical role for the foreseable future.

Antineoplastic Agents↗

Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties.

Sixteen patients (18 hips) were treated with localized radiation therapy limited to periarticular regions surrounding the femoral neck by shielding the prosthesis and the adjacent regions to prevent heterotopic bone formation around the uncemented prosthesis. All hips received 1500 rads. Eight of these hips were irradiated after excising severe heterotopic bone, five because they developed extensive heterotopic ossification in the opposite hip, and five others because they were considered to be at high risk for developing heterotopic ossification. Only two of the 18 hips developed a small amount of heterotopic bone after localized periarticular radiation. All wounds healed primarily. No progressive radiolucencies developed at the bone-prosthesis interface. There was only one trochanteric nonunion of six trochanteric osteotomies. Localized periarticular radiation therapy with precision shielding of the prosthetic components and adjacent skeletal structures is an effective means to prevent heterotopic bone formation around cementless total hip arthroplasties. It also has the advantage of not adversely affecting the healing of the trochanteric osteotomy.

Adult↗

Immunological treatment of liver tumors.

Although multiple options for the treatment of liver tumors have often been described in the past, including liver resection, radiofrequency ablation with or without hepatic pump insertion, laparoscopic liver resection and the use of chemotherapy, the potential of immunotherapy and gene manipulation is still largely unexplored. Immunological therapy by gene manipulation is based on the interaction between virus-based gene delivery systems and dendritic cells. Using viruses as vectors, it is possible to transduce dendritic cells with genes encoding tumor-associated antigens, thus inducing strong humoral and cellular immunity against the antigens themselves. Both chemotherapy and radiation therapy have the disadvantage of destroying healthy cells, thus causing severe side-effects. We need more precisely targeted therapies capable of killing cancer cells while sparing healthy cells. Our goal is to establish a new treatment for solid liver tumors based on the concept of cytoreduction, and propose an innovative algorithm.

Algorithms↗

[Treatment policies with active intention on radiation therapy in brain tumors and tolerance dose of the nervous system].

For the treatment of brain tumors, radiation tolerance on the central nervous tissues is one of the most serious limiting factor, because glioblastoma has been considered as radioresistant. Radiation therapy in commonly employed dosages for malignant gliomas carries a risk of injury to surrounding cerebral tissues. Therefore, precision radiation therapy concerning that radiation field co-inside with the tumorous lesion is essentially important to intend obtaining an improvement of the local control rate without delayed radiation injuries. In this paper, a review of literatures as for radiation tolerance on the central nervous system and treatment policies with active intention for brain tumors are discussed.

Astrocytoma↗

Verification of electron beam therapy with storage phosphor images: precision of field placement.

Portal verification images were generated from the photon contamination in electron beams produced by a linear accelerator during treatment of patients receiving high-energy electron radiation therapy (8-14 MeV). An experimental storage phosphor system was used to record the images and display them on laser-printed film. Images were obtained from four or more treatment fractions from 21 cases of head and neck cancer. Precision in field placement was estimated by determining the position of a selected anatomic landmark relative to the center of the field for each series of images. The average standard deviation in the field-position measurements was 3.8 mm. Several procedural problems were also detected and corrected after review of the verification images. The results indicate that the emphasis placed on monitoring and control of field-positioning error in high-energy electron treatments should be similar to the emphasis placed on this aspect of error in photon treatment.

Electrons↗

Importance of precise positioning for proton beam therapy in the base of skull and cervical spine.

Using proton beam therapy, high doses have been delivered to chordomas and chondrosarcomas of the base of skull and cervical spine. Dose inhomogeneity to the tumors has been accepted in order to maintain normal tissue tolerances, and detailed attention to patient immobilization and to precise positioning has minimized the margins necessary to ensure these dose constraints. This study examined the contribution of precise positioning to the better dose localization achieved in these treatments. Three patients whose tumors represented different anatomic geometries were studied. Treatment plans were developed which treated as much of the tumor as possible to 74 Cobalt-Gray-Equivalent (CGE) while maintaining the central brain stem and central spinal cord at less than or equal to 48 CGE, the surface of the brain stem, surface of the spinal cord, and optic structures at less than or equal to 60 CGE, and the temporal lobes at less than or equal to 5% likelihood of complication using a biophysical model of normal tissue complication probability. Two positioning accuracies were assumed: 3 mm and 10 mm. Both proton beam plans and 10 MV X ray beam plans were developed with these assumptions and dose constraints. In all cases with the same positioning uncertainties, the proton beam plans delivered more dose to a larger percentage of the tumor volume and the estimated tumor control probability was higher than with the X ray plans. However, without precise positioning both the proton plans and the X ray plans deteriorated, with a 12% to 25% decrease in estimated tumor control probability. In all but one case, the difference between protons with good positioning and poor positioning was greater than the difference between protons and X rays, both with good positioning. Hence in treating these tumors, which are in close proximity to critical normal tissues, attention to immobilization and precise positioning is essential. With good positioning, proton beam therapy permits higher doses to significantly more of the tumor in these sites than do X rays.

Adult↗

Priorities in renal replacement programs.

The various alternative programs in renal replacement therapy have precise meritocratic ranking which unfortunately is still largely ideal today. New directions and scientific plans (bioartificial kidney, new immunomodulators, gene therapy) have to be followed to make today's ideal ranking become reality.

Genetic Therapy↗

Molecular aspects of bladder cancer III. Prognostic markers of bladder cancer.

The current pathological and clinical parameters provide important prognostic information, yet still have limited ability to predict the true malignant potential of most bladder tumors. In the last years, investigation of the basic mechanisms involved in carcinogenesis and tumor progression by molecular biology has provided a host of markers which are of potential diagnostic or prognostic value for bladder carcinoma. These markers may serve as tools for early and accurate prediction of tumor recurrence, progression and development of metastases and for prediction of response to therapy. The precise prediction of tumor biological behavior would facilitate treatment selection for patients who may benefit from radical surgical treatment or adjuvant therapy. We provide a current, comprehensive review of the literature on bladder tumor markers with a special emphasis on their prognostic potential. The literature suggests that currently no single marker is able to accurately predict the clinical course of bladder tumors and thus would serve as a reliable prognosticator. A combination of prognostic markers could predict which superficial tumors need an aggressive form of therapy and which invasive tumors require adjuvant therapy. Altogether, the most promising markers are, at this point, Ki-67 and p53 expression as well as matrixmetalloproteinase complex and angiogenesis.

Biomarkers, Tumor↗

[Clinical bacteriology and empiric therapy for hospital-acquired pneumonia in the elderly at a national leprosarium].

Hospital-acquired pneumonia is one of the most important fatal respiratory diseases in the elderly. Prompt and precise empiric therapy is essential for recovery. Fourteen isolates from twelve elderly lepromatous leprosy patients (9 men, 3 women, mean age of 75.8 years) with hospital-acquired pneumonia were studied. Subsequently, empiric therapy with gentamicin and beta-lactams for nosocomial pneumonia in the elderly was examined. Fourteen types of bacteria isolated from expectorated sputum specimens consisted mainly of ten strains of gram-negative bacilli (71%) six of Klebsiella pneumoniae, one each of Citrobacter freundii, Enterobacter agglomerans, Serratia liquefaciens, and Aeromonas hydrophilia and four strains of gram-positive cocci (29%) two of Staphylococcus sp., one each of Streptococcus sp. and Streptococcus pneumoniae. Methicillin-resistant Staphylococcus aureus and Pseudomonas sp. were not detected. Resistance rates of the etiologic agents to the antibiotics showed that gentamicin was 7.7%, ceftazidime 0%, and cefmetazole 23.1%. Cephalosporins were superior to penicillins. As a result of empiric therapy, six elderly leprosy patients with nosocomial pneumonia were cured and one improved temporarily. This study shows the necessity of specific empiric therapy for hospital-acquired pneumonia in a hospital with many elderly patients. The combination of gentamicin and beta-lactams is of value as an initial antibiotic therapy for hospital-acquired pneumonia in the elderly.

Aged↗

[Depressions resistant to tricyclic antidepressive treatment and hypothyroidism].

The relationship between thyroid disorders and depression is well known. This type of endocrine disease is mainly observed in patients with depression resistant to appropriate antidepressor therapy. Three clinical forms of this association may be distinguished: hypothyroidism in a patient with depression but without a previous psychiatric history; a relapse of depression in a manico depressive patient who has developed hypothyroidism; the finding of slight thyroid dysfunction (increased TSH response after injection of TRH) in a patient with depression. The frequency of the association of hypothyroidism and resistant depression underlines the need to perform thyroid function tests in all depressed patients who do not respond normally to appropriate antidepressor therapy. The precise mechanism of the resistance of depressive symptoms to tricyclic antidepressors is unclear. Several arguments point to an effect of triiodothyronine on central noradrenergic receptors. In practice, significant hypothyroidism implies substitute therapy. Minor thyroid dysfunction (abnormal TRH test alone) may require the association of tricyclic antidepressors and thyroid hormone although the indications and precise dosages of this drug association have not been established.

Antidepressive Agents, Tricyclic↗

Osteoporosis in men treated with androgen deprivation therapy for prostate cancer.

PURPOSE: We surveyed the growing literature on osteoporosis secondary to androgen deprivation therapy and provide suggestions regarding its identification and treatment. MATERIALS AND METHODS: We reviewed pertinent studies of male osteoporosis, osteoporotic fracture incidence or bone mineral density loss as a possible side effect of prostate cancer treatment and potential therapies for this side effect. RESULTS: Hypogonadism is a well-known cause of secondary osteoporosis in men. There is evidence of decreased bone mineral density with all types of androgen deprivation therapy, presumably due to its anti-testosterone effect. Bone mineral density loss is 3% to 5% yearly in the first few years of androgen deprivation therapy with an increase in osteoporotic fracture incidence. There are little data on potential treatments, although bisphosphonates and intermittent androgen deprivation therapy may have salutary effects. CONCLUSIONS: Osteoporosis is an important and debilitating side effect of androgen deprivation therapy, although precise estimates of its incidence, degree and cost are not completely elucidated. Until more data are available, it is prudent for all men beginning androgen deprivation therapy to receive calcium and vitamin D, and maintain a moderate exercise regimen. Baseline and at least 1 followup bone density measurement seem appropriate with bisphosphonate treatment a possibility in those in whom osteoporosis develops. More research is needed to explore the effect of bisphosphonates, calcium and vitamin D supplementation, exercise, calcitonin, selective estrogen re-uptake inhibitors, estrogens and intermittent androgen deprivation therapy on the course of androgen deprivation therapy induced osteoporosis. The osteoporotic fracture incidence and bone mineral density should be regularly incorporated into studies involving the hormonal treatment of prostate cancer.

Androgen Antagonists↗

Core-based portal image registration for automatic radiotherapy treatment verification.

PURPOSE: Portal imaging is the most important quality assurance procedure for monitoring the reproducibility of setup geometry in radiation therapy. The role of portal imaging has become even more critical in recent years due to the migration of three-dimensional (3D) treatment planning technology, including high-precision conformal therapy, from the research setting to routine clinical practice. Unfortunately, traditional methods for acquiring and interpreting portal images suffer from a number of deficiencies that contribute to the well-documented observation that many setup errors go undetected, and some persist for a clinically significant portion of the prescribed dose. Significant improvements in both accuracy and efficiency of detecting setup errors can, in principle, be achieved by using automatic image registration for on-line screening of images obtained from electronic portal imaging devices (EPIDs). METHODS AND MATERIALS: This article presents recent developments in a method called core-based image analysis that shows great promise for achieving the desired improvements in error detection. Core-based image analysis is a fundamental computer vision method that is capable of exploiting the full power of EPIDs by providing for on-line detection of setup errors via automatic registration of user-selected anatomical structures. We describe a robust method for automatic portal image registration based on core analysis and demonstrate an approach for assessing both accuracy and precision of registration methods using realistic, digitally reconstructed portal radiographs (DRPRs) where truth is known. RESULTS: Automatic core-based analysis of a set of 20 DRPRs containing known, random field positioning errors was performed for a patient undergoing treatment for prostate cancer. In all cases, the reported translation was within 1 mm of the actual translation with mean absolute errors of 0.3 mm and standard deviations of 0.3 mm. In all cases, the reported rotation was within 0.6 degree of the actual rotation with a mean absolute error of 0.18 degree and a standard deviation of 0.23 degree. CONCLUSION: Our results, using digitally reconstructed portal radiographs that closely resemble clinical portal images, suggest that automatic core-based registration is suitable as an on-line screening tool for detecting and quantifying patient setup errors.

Humans↗