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Results for “precision treatment”

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At least 19 recordsLinked to original sources
PubMed1994

Three-dimensional conformal radiotherapy. Precision treatment of lung cancer.

Three-dimensional conformal radiotherapy is a mode of precision radiation treatment that currently is being integrated into the multidisciplinary management of lung cancer. 3-DCRT represents a technical improvement in comparison with conventional treatment. This has been achieved without the use of innovations in accelerator hardware that are currently being developed and tested. When these technical advances are widely available for clinical use, they will be integrated with the current 3-DCRT systems, which are for the most part composed of improvements in software. Thus, 3-DCRT is a modality in a state of flux that should have great clinical potential in the future. The accurate dose volume histogram data available with current 3-DCRT systems will facilitate strategies to predict and prevent radiation pneumonitis.

Carcinoma, Non-Small-Cell Lung↗
PubMed2002

High-dose, high-precision treatment options for boosting cancer of the nasopharynx.

PURPOSE: The aim of the study is to define the role and type of high-dose, high-precision radiation therapy for boosting early staged T1,2a, but in particular locally advanced, T2b-4, nasopharyngeal cancer (NPC). MATERIALS AND METHODS: Ninety-one patients with primary stage I-IVB NPC, were treated between 1991 and 2000 with 60-70Gy external beam radiation therapy (ERT) followed by 11-18Gy endocavitary brachytherapy (ECBT) boost. In 1996, for stage III-IVB disease, cisplatinum (CDDP)-based neoadjuvant chemotherapy (CHT) was introduced per protocol. Patients were analyzed for local control and overall survival. For a subset of 18 patients, a magnetic resonance imaging (MRI) scan at 46Gy was obtained. After matching with pre-treatment computed tomogram, patients (response) were graded into four categories; i.e. LD (T1,2a, with limited disease, i.e. disease confined to nasopharynx), LRD (T2b, with limited residual disease), ERD (T2b, with extensive residual disease), or patients initially diagnosed with T3,4 tumors. Dose distributions for ECBT (Plato-BPS v. 13.3, Nucletron) were compared to parallel-opposed three-dimensional conformal radiation therapy (Cadplan, Varian Dosetek v. 3.1), intensity modulated radiation therapy (IMRT) (Helios, Varian) and stereotactic radiotherapy (SRT) (X-plan, Radionics v. 2.02). RESULTS: For stage T1,2N0,1 tumors, at 2 years local control of 96% and overall survival of 80% were observed. For the poorest subset of patients, well/moderate/poorly differentiated T3,4 tumors, local control and overall survival at 2 years with CHT were 67 and 67%, respectively, vs. local control of 20% and overall survival of 12% without CHT. For LD and LRD, conformal target coverage and optimal sparing can be obtained with brachytherapy. For T2b-ERD and T3,4 tumors, these planning goals are better achieved with SRT and/or IMRT. CONCLUSIONS: The dosimetric findings, ease of application of the brachytherapy procedure, and the clinical results in early staged NPC, necessitates ERT combined with brachytherapy boost to be the therapy of preference for LD and LRD. For locally advanced T3,4 tumors, our current protocol indicates neoadjuvant chemotherapy in conjunction with high cumulative doses of radiotherapy (81Gy); IMRT and/or SRT to be the preferred technique for boosting the primary tumor.

Brachytherapy↗
PubMed2026

The emerging landscape of polymerase θ in tumor pathogenesis and precision treatment.

DNA polymerase θ (Polθ) has emerged as a central yet paradoxical regulator of genome stability and tumor progression. Unlike conventional DNA repair factors, Polθ governs an error-prone double-strand break repair pathway-termed theta-mediated end joining (TMEJ)-which becomes essential for survival in homologous recombination (HR)-deficient cancers while simultaneously fueling genomic instability. This review presents a comprehensive and updated synthesis of Polθ's structural architecture, regulatory networks, and context-dependent functions across major malignancies, including ovarian, breast, lung, and colorectal cancers. We highlight recently uncovered mechanisms, such as the iron-FTH1/FTL-POLQ-RAD51 axis in platinum-resistant ovarian cancer, the differential POLQ regulation under methionine restriction in BRCA1-mutant breast cancer, and the identification of germline POLQ mutations defining a novel hereditary colorectal cancer subtype. Beyond DNA repair, we integrate emerging evidence linking Polθ to replication stress tolerance, base excision repair, and immune modulation via type I interferon activation and macrophage polarization. The review also provides a critical evaluation of current Polθ inhibitors-including ART558, RP-6685, novobiocin, and AB25583-focusing on their mechanisms, synthetic lethality profiles, and ability to overcome PARP inhibitor resistance. By bridging molecular mechanisms with tumor biology and therapeutic translation, this review offers a unique framework for understanding Polθ as both a prognostic biomarker and a precision oncology target, with implications for combination therapies involving radiotherapy, immunotherapy, and chemotherapy.

Cancer therapy↗
PubMed1990

Clinical applications of a CT-simulator: precision treatment planning and portal marking in breast cancer.

Breast cancer is frequently treated with radiation using opposed tangent portals to the involved breast, including the chest wall. Presented is a method for simulating such treatment fields on a CT simulator. A short series of CT images provides a three dimensional model for treatment planning prior to marking the patient. Gantry and collimator angles, as well as wedges or custom blocks, are determined in the planning stage. Upon receipt of an approved treatment plan, the portals are available for simulation. The cross-hair laser and computerized bed movement in the CT simulator aid in marking the entrance of the radiation fields on the patient's skin. Discussion of the clinical application of the described technique is included.

Breast Neoplasms↗
PubMed1998

Fractionated high dose rate brachytherapy moulds--a precise treatment for carcinoma of the pinna.

BACKGROUND AND PURPOSE: The aim of this paper is to describe a fractionated high dose rate brachytherapy procedure for the treatment of small superficial cancers of the pinna and to report the outcome in a small series of patients. MATERIALS AND METHODS: Thirteen patients with superficial cancers of the pinna, not invading cartilage, have been treated and in the majority of cases the tumour thickness was determined by a transdermal ultrasound measurement. For the single-plane moulds the prescribed surface dose was 45 Gy in eight fractions over 5 days and the moulds were constructed such that the full thickness of the disease, as determined by the ultrasound measurement, would lie within the 80% isodose surface. One case was treated with a sandwich mould and in this case the dose was reduced to 42.5 Gy. The treatment machine was a high dose rate microselectron, which contains a single stepping iridium source. RESULTS: The radiation reactions were of moderate severity, but were limited to the high dose volume. In all cases there was complete tumour resolution and rapid healing occurred leaving a barely perceptible scar. There were no recurrences over a minimum follow-up time of 18 months and there were no late radiation complications in this period. CONCLUSIONS: The treatment of superficial carcinoma of the pinna by means of HDR moulds is a safe and reliable technique. In this small series of patients there was total tumour control with excellent cosmesis.

Brachytherapy↗
PubMed1990

[Diverticular disease of the colon, the indications for and results of elective surgical treatment].

Precise criteria were prospectively used to indicate surgery in patients with diverticular disease of the colon: a) anatomical deformity of the sigmoid (ADS), including stenosis and fistulae with presence of contrast media extraluminally; b) recurrent acute diverticulitis (RAD); c) prior diverticulitis with perforation (DP) and d) recurrent GI bleeding (GIB). 42 patients were operated on according to these criteria, from 1978 to 1988, 26 males and 16 females, with a mean age of 61 years (range 31 to 93). ADS was the indication in 22 patients (52%), with fistulae present in 9. RAD was the indication in 16 patients (37%), DP in 9 patients (21%) and GIB in 5%. All patients were submitted to either ample sigmoid resection or left hemicolectomy. All patients were followed, with a mean of 43 months for the series. Only 1 patient died after surgery from pulmonary embolism. Late clinical evaluation revealed absence of preoperative symptoms and signs. We feel that surgical treatment of diverticular disease of the colon is warranted with the criteria described, with good immediate and longterm results.

Adult↗
PubMed2005

[Circadian rhythm study from anticipatory behavior to drug treatment].

Precise, rhythmic, daily change of the internal milieu is a conspicuous feature of all living organisms. It affects temporal patterns of all kinds of behaviors during a day and deeply influences both the social structure and daily life of individual human beings. These daily variations arise from the internal circadian mechanisms. Three functions of the endogenous clock are discriminated as rhythm generation, entrainment to light-dark cycle and output from the clock. The endogenous clock is localized in the suprachiasmatic nucleus (SCN) in mammals. Recent papers demonstrated strong expression of clock genes such as Per1, Per2 and Per3 in the SCN. Circadian oscillation is basically regulated by the transcription/translation feedback system of the Per gene in mammals. As serotonin/antidepressant and GABA/benzodiazepine drugs affect the light and non-light-induced entrainment, these drugs can regulate the circadian oscillation of clock genes and environmental stimuli-induced change of Per gene expression in the SCN. There are two main stimuli that entrain circadian rhythm, the light-dark cycle (LD) and restricted feeding. Light resets the circadian clock with induction of Per1 and Per2 gene in the SCN, the locus of a main oscillator. Mice were allowed access to food for 4 h during daytime (7 h in advance of feeding time) under LD or constant darkness. The peaks of mPer1 and mPer2 mRNA in the cerebral cortex and liver were advanced 6-12 h after 6 days of RF, whereas those in SCN were unaffected. The increase of mPer expression by RF treatment was observed in SCN-lesioned mice. The present results suggest that RF strongly entrained the expression of mPer and clock-controlled genes in the cerebral cortex and liver without affecting light-dependent SCN clock function.

Animals↗
PubMed2003

Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part I: Treatment modalities of radiation therapy.

BACKGROUND: Treatment of childhood low-grade gliomas is a challenging issue owing to their low incidence and the lack of consensus about "optimal" treatment approach. MATERIAL AND METHODS: Reports in the literature spanning 60 years of radiation therapy, including orthovoltage, megavoltage and recently modern high-precision treatments, were reviewed with respect to visual function, survival, prognostic factors, dose prescriptions, target volumes, and treatment techniques. Based on these experiences, future strategies in the management of childhood low-grade glioma are presented. RESULTS: Evaluation of published reports is difficult because of inconsistencies in data presentation, relatively short follow-up in some series and failure to present findings and results in a comparable way. Even with the shortcomings of the reports available in the literature, primarily concerning indications, age at treatment, dose response, timing and use of "optimal" treatment fields, radiation therapy continues to play an important role in the management of these tumors achieving long-term survival rates up to 80% or more. Particularly in gliomas of the visual pathway, high local tumor control and improved or stable visual function is achieved in approximately 90% of cases. Data on dose-response relationships recommend dose prescriptions between 45 and 54 Gy with standard fractionation. There is consensus now to employ radiation therapy in older children in case of progressive disease only, regardless of tumor location and histologic subtype. In younger children, the role of radiotherapy is unclear. Recent advances in treatment techniques, such as 3-D treatment planning and various "high-precision" treatments achieved promising initial outcome, however with limited patient numbers and short follow-ups. CONCLUSIONS: Radiation therapy is an effective treatment modality in children with low-grade glioma regarding tumor control and improvement and/or preservation of neurologic function or vision, respectively. More prospective studies are needed to address the impact of modern radiation therapy technologies (including intensity-modulated radiotherapy) on outcome especially in the very young and to define the role of radiation therapy as a part of a comprehensive treatment approach. The forthcoming prospective trial SIOP/GPOH LGG RT 2003 is addressing this issue.

Adolescent↗
PubMed2026

MET-Aberrant non-small cell lung cancer: from kinase dependence to cell-surface targetability-mechanistic basis and biomarker framework for bispecific antibodies and antibody-drug conjugates.

MET-aberrant non-small cell lung cancer (NSCLC) is not a uniform therapeutic entity. Its biology, diagnostic pathways, and treatment sensitivity differ across MET exon 14 skipping alteration (METex14), MET amplification, and MET overexpression. This heterogeneity cannot be fully explained by conventional event-based classification and is reflected in the distinct clinical activity of MET tyrosine kinase inhibitors (MET-TKIs), bispecific antibodies (BsAbs), and antibody-drug conjugates (ADCs). With the emergence of antibody-based therapies, MET has evolved from a signaling driver to a cell-surface target for receptor modulation and payload delivery. We therefore propose a clinically anchored two-dimensional framework for interpreting therapeutic relevance in MET-aberrant NSCLC: kinase dependence and cell-surface targetability. Neither dimension should be regarded as a directly measurable binary variable. Kinase dependence is inferred from genomic and treatment-contextual proxies, most strongly METex14 and, more conditionally, high-level focal MET amplification. Cell-surface targetability is approximated by drug-specific IHC assessment of assay-defined c-MET protein expression; however, receptor internalization, intracellular trafficking, and payload delivery capacity remain incompletely measurable in routine clinical practice. Within this framework, MET-TKIs have the most evidence-supported established role in tumors with evidence of MET-driven kinase dependence. EGFR × MET BsAbs have demonstrated clinical activity in broad post-osimertinib EGFR-mutant NSCLC, while EGFR/MET co-dependence or MET-mediated bypass activation provides a mechanistic rationale for their use; MET-defined preferential benefit remains to be prospectively established. MET-directed antibody-drug conjugates (MET-ADCs) are supported in drug- and assay-defined populations with high c-MET protein overexpression, although the predictive relevance of delivery-related factors remains hypothesis-generating. Accordingly, MET testing should shift from single-event detection to platform-oriented stratification: next-generation sequencing (NGS) for driver alterations and resistance profiles, fluorescence in situ hybridization (FISH) for high-level focal amplification, and immunohistochemistry (IHC) for surface expression relevant to antibody-based therapies. This framework is intended to organize current biological and clinical evidence rather than to replace drug-specific companion diagnostics, regulatory indications, or prospectively validated treatment-selection algorithms. Precision treatment of MET-aberrant NSCLC is thus moving from event-based drug selection toward mechanism-based therapeutic matching. Future priorities include standardizing biomarkers, defining optimal target populations, and aligning biological subtypes, diagnostic strategies, and therapeutic platforms.

Antibody-drug conjugate↗
PubMed1995

Ultrasound biomicroscopic imaging of the effects of YAG laser cycloablation in postmortem eyes and living patients.

PURPOSE: The authors performed a series of experiments designed to determine if early effects of YAG laser cycloablation could be detected by ultrasound biomicroscopy in postmortem eyes and living patients. They also designed an apparatus that allowed simultaneous ultrasound biomicroscopic imaging of YAG laser cycloablation. METHODS: Treated and untreated regions of postmortem eyes treated with YAG cycloablation were imaged and compared. Treatment was placed at varying distances from the limbus in postmortem eyes and the resulting effects imaged. Histologic examinations were performed after imaging. Six living patients had ultrasound biomicroscopy before and after YAG cycloablation. An apparatus combining contact YAG laser and ultrasound biomicroscopy was used in postmortem eyes. RESULTS: Early treatment effects imaged included ciliary epithelial disruption, ciliary epithelial separation, and bubble formation. Ultrasound biomicroscopic findings varied with the distance of treatment from the limbus and were maximal below the treatment site. Results of histologic examination showed close correlation to the ultrasound biomicroscopic images. Similar findings to those found in postmortem eyes were found in living patients after treatment. The apparatus combining contact YAG and ultrasound biomicroscopy allowed realtime imaging of effects of YAG laser cycloablation. CONCLUSIONS: The ability of ultrasound biomicroscopy to detect changes associated with cyclodestructive procedures potentially could provide us with a method of improving treatment precision and correlating treatment effect with clinical response.

Cadaver↗
PubMed1991

[Management of unilateral vocal cord paralysis].

The phoniatric analysis evaluates the importance of the vocal disorder and the appearance of the larynx what permets to find five clinical cases. For each one, there is a precise treatment: no treatment, rehabilitation with precises exercises in each case, collagen injection, early or secondary to rehabilitation. The rehabilitation will be intensive and done as soon as possible. It is based on a well known body proprioception. Intrinsic laryngeal muscles work, breathing exercises, exercises aimed at restoring the laryngeal sphincter will precede the pure vocal work. Author's experience shows that the results are good if rehabilitation is well indicated from the beginning and the patient with good motivations.

Humans↗
PubMed1994

Patient positioning for fractionated precision radiation treatment of targets in the head using fiducial markers.

When irradiating targets in the brain, an accurately localised dose is often needed. One crucial moment to achieve this is the positioning of the patient. We have developed a positioning method where the patient is immobilised with a bite block and a head mould, and where the position of the target is determined by X-ray imaging of fiducial markers that are placed in the patient's skull. A method for computing the transformation needed to move the target from the observed to the prescribed position and orientation is described. This method uses the information from two orthogonal X-ray images and takes measurement errors and data from three or more markers into account. Results from using the method clinically in proton beam therapy are given.

Algorithms↗
PubMed2000

Arteriovenous malformations of the orofacial area.

Vascular lesions are pathological residues of the embryonic vascular system and can be divided into two main groups. The first group comprises haemangiomas, which are typical of childhood and involute spontaneously. The second group is formed by lesions without active proliferation, which include, among others, arteriovenous malformations that are congenital and grow proportionately with the subject. The authors present two cases of arteriovenous malformations of the orofacial area and discuss possibilities for modern diagnosis and treatment. Precise diagnosis and effective treatment of vascular lesions should be ensured by a diagnostic and therapeutic team of specialists from several disciplines (maxillofacial, ENT, plastic and general surgeon, paediatrician, haematologist, anaesthesiologist and possibly a neurosurgeon), headed by an intervention radiologist.

Arteriovenous Malformations↗
PubMed1999

Validity of area-under-the-curve analysis to summarize effect in rheumatoid arthritis clinical trials.

There is a continuing interest in increasing the statistical efficiency of the analysis of clinically meaningful endpoints in rheumatology. One issue that is attracting increasing attention is whether the conventional practice of only reporting the outcome at the end of the study (EOS) might be replaced or complemented by a longitudinal summary that better reflects the clinical course of the disease. The area under the curve (AUC) is a summary measure that integrates serial assessments of a patient's endpoint over the duration of the study. We evaluated the utility of AUC as a summary measure for the analysis and reporting of two RA trials: (i) methotrexate combined with cyclosporine versus methotrexate and placebo in partial methotrexate responders in relatively late disease, and (ii) prednisone plus methotrexate plus sulfasalazine versus sulfasalazine alone in relatively early disease. We replicated the published results of each trial first using the conventional EOS and then AUC summaries. For each patient, the changes from baseline over time were transformed into a summary measure by calculating AUC using the trapezium rule and then standardizing it by the study duration. Using an approach similar to the index of responsiveness to change, we scaled treatment differences derived from EOS and AUC summary measures by their standard deviation of the control group. This signal-versus-noise ratio captures the treatment discrimination ability of each summary measure. Compared to EOS and within each treatment group, the AUC summary reported smaller effects (i.e., change from baseline) with reduced errors in the estimates. AUC measures preserved discriminant validity in treatment comparisons and reported smaller but more precise treatment effect estimates. In the COBRA trial with rapidly-acting medications, AUC seemed to be more sensitive than EOS to detect treatment difference. With slow acting medications and in relatively late disease patients as in the cyclosporine trial, EOS was more sensitive to detect treatment difference than was AUC. In this setting, AUC, however, still seemed to be more sensitive than EOS for the two responsive-to-change endpoints: tender joint counts and pain by visual analog scale. AUC integrates repeated assessments during the trial duration into summary measures. Compared to EOS, the report of RA trial results using AUC summary provides smaller estimates of treatment effects but with better precision. AUC summary is likely to preserve treatment group discrimination taking into account the appropriate onset and offset of the drug action. Trial reports using AUC summary have smaller effect sizes. For trials with long acting medications and short duration similar to the cyclosporine trial, AUC still preserves treatment discrimination but may not be as sensitive as EOS. The calculations of AUC require some additional work in the analysis of each endpoint.

Antirheumatic Agents↗