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Mittal, S., F. John, A. Naveh, Z. Bomzon, G. R. Barger, and C. Juhasz. "P14.69 Evaluation of electric field intensity delivered by Tumor-Treating Fields therapy to PET-defined metabolic volumes in recurrent glioblastomas." Neuro-Oncology 21, Supplement_3 (August 2019): iii83—iii84. http://dx.doi.org/10.1093/neuonc/noz126.304.
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Abstract BACKGROUND Tumor-Treating Fields (TTFields) therapy is a clinical treatment option for patients with newly-diagnosed and recurrent glioblastomas. Electric field intensities (EFIs) delivered to the tumor mass may affect treatment responses. In this study, we used the patients’ neuroimaging data to create realistic head models and evaluate: (i) the magnitude of EFIs delivered to the tumor mass; (ii) factors affecting the EFI values; and (iii) factors affecting treatment responses as assessed by amino acid PET. MATERIAL AND METHODS Fourteen recurrent glioblastomas in 9 patients were evaluated with α-[11C]-methyl-L-tryptophan (AMT)-PET before and up to 3 months after TTFields therapy (mean follow-up: 2.3 months). Individual MRI and CT scans were used to create patient-specific realistic head models and simulate TTFields delivery to the tumors. For each direction of treatment (antero-posterior, left-right), two 9-disk transducer arrays were simulated using disks placed according to the patients’ NovoTAL System™ based treatment plan. To generate TTFields, an alternating voltage difference (200V peak-to-peak, 200 kHz) was imposed on the outer surfaces of the disks. The simulations were performed using the Sim4Life V3.0 (ZMT-Zurich) quasi-electrostatic solver. The field intensities were normalized to simulate 2A peak-to-peak current supplied by the device. 3D EFI maps were created and fused with the pre- and post-TTFields PET images to measure EFIs delivered to the PET-defined metabolic tumor volume. Interval changes of static AMT uptake and kinetic PET variables were also evaluated. RESULTS The mean EFI delivered to the tumors varied between 1.34–2.43 V/cm (mean: 1.86 V/cm). Fronto-parietal tumors received higher mean EFI than temporal lobe tumors (p=0.05). Most tumors showed decreasing (n=9) or stable (n=4) AMT uptake on follow-up PET imaging after TTFields therapy. Higher EFIs delivered to the tumors (r=-0.56, p=0.04) and concomitant bevacizumab treatment (n=7, p=0.01) were associated with a greater PET response. On tracer kinetic analysis, the AMT uptake responses correlated with transport rate changes (p=0.04). CONCLUSION TTFields treatment of recurrent glioblastomas delivers variable EFIs to the metabolic tumor volume. Treatment responses on PET are driven by decreased amino acid transport rates, whose magnitude is associated with higher EFIs delivered to the tumor mass and also with concomitant antiangiogenic treatment in those with combined therapy. (The cost of the PET scans was supported by a grant from NovoCure Ltd., Haifa, Israel)
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Steiner, Katherine C., Veronica Davila, Charlotte K. Kent, Janice K. Chaw, Lyn Fischer, and Jeffrey D. Klausner. "Field-Delivered Therapy Increases Treatment for Chlamydia and Gonorrhea." American Journal of Public Health 93, no. 6 (June 2003): 882–84. http://dx.doi.org/10.2105/ajph.93.6.882.
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Bomzon, Zeev, Noa Urman, Hadas Sara Hershkovich, Eilon David Kirson, Ariel Naveh, Reuven Shamir, Eduard Federov, Cornelia Wenger, and Uri Weinberg. "A general approach to optimizing tumor treating fields therapy." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e14668-e14668. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14668.
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e14668 Background: Tumor Treating Fields (TTFields) are alternating electric fields used to non-invasively treat cancer. TTFields are delivered via transducer arrays placed on the skin close to the tumor. Post-hoc analysis [1] has shown that delivering higher field power to the tumor and increasing usage (percent of time patient is actively treated) improve patient survival. Thus, optimizing the position of arrays to maximize TTFields power at the tumor could improve survival. At the same time, minimizing the array area to maximize patient comfort and consequently maximizing usage is also likely to improve survival. However, optimizing TTFields delivery is non-trivial since the field distribution is influenced by array positioning and geometry, the anatomy of the patient and the heterogeneous electric properties of different tissues. Here we present a general approach to optimizing Tumor Treating Fields using numerical simulations. Methods: Delivery of TTFields to the brains, lungs and abdomens of realistic computational models was investigated. The effect of the transducer array size and position on the field distribution within the phantoms was analyzed, and an approach for optimizing TTFields delivery developed. Results: Field power is generally highest in the region between the arrays, with larger arrays generally delivering higher field power. Anatomical features such as bones, the spine or a resection cavity significantly influence the field within this region. A general approach to optimizing TTFields delivery is: Maximize field power by using the largest arrays possible. To maximize patient comfort, array size are chose so that significant portions of the skin in the region of disease are not covered by the arrays. Place virtual arrays on a realistic computational model of the patient such that the tumor is located between them and simulate TTFields delivery to the patient. Apply an iterative algorithm to shift the arrays around their initial positions until field power in the tumor bed is maximized. Conclusions: We have developed a general approach to optimizing delivery of TTFields to the tumor. Effective TTFields treatment planning is expected to improve patient outcome. [1] Ballo et. al., submitted to RED Journal 2018.
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Inyang, Samuel Okon, and Alan Chamberlain. "Qualitative analysis of irregular fields delivered with dual electron multileaf collimator: A Monte Carlo study." Polish Journal of Medical Physics and Engineering 22, no. 1 (March 1, 2016): 5–9. http://dx.doi.org/10.1515/pjmpe-2016-0002.
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Abstract The use of a dual electron multileaf collimator (eMLC) to collimate therapeutic electron beam without the use of cutouts has been previously shown to be feasible. Further Monte Carlo simulations were performed in this study to verify the nature and appearance of the isodose distribution in water phantom of irregular electron beams delivered by the eMLC. Electron fields used in this study were selected to reflect those used in electron beam therapy. Results of this study show that the isodose distribution in a water phantom obtained from the simulation of irregular electron beams through the eMLC conforms to the pattern of the eMLC used in the delivery of the beam. It is therefore concluded that the dual eMLC could deliver isodose distributions reflecting the pattern of the eMLC field that was used in the delivery of the beam.
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Wroe, Andrew, Anatoly Rosenfeld, and Reinhard Schulte. "Out-of-field dose equivalents delivered by proton therapy of prostate cancer." Medical Physics 34, no. 9 (August 7, 2007): 3449–56. http://dx.doi.org/10.1118/1.2759839.
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Attenburrow, Mary Jane, and Katharine Smith. "Internet-delivered therapy for anxiety disorders: a solution to unequal access to treatment?" BJPsych Advances 21, no. 5 (September 2015): 291–94. http://dx.doi.org/10.1192/apt.21.5.291.
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SummaryAnxiety disorders are common, often have a chronic course and frequently coexist with other psychiatric disorders. Psychological therapy is recommended as first-line treatment, but equitable access remains a challenge. This month's Cochrane Corner review assesses the evidence for the efficacy of therapist-supported cognitive-behavioural therapy (CBT) for anxiety disorders delivered via the internet. Although internet delivery of therapy is attractive for many reasons, and the results of this preliminary review suggest that it is efficacious, this is a rapidly expanding field. Further updates of this review will include more evidence to support or refute the use of this new method of treatment delivery, either alongside or in preference to standard face-to-face CBT.
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Hazelton, Christine, Alex Pollock, Glyn Walsh, and Marian C. Brady. "Scanning training for rehabilitation of visual field loss due to stroke: Identifying and exploring training tools in use." British Journal of Occupational Therapy 82, no. 8 (November 8, 2018): 502–11. http://dx.doi.org/10.1177/0308022618809900.
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IntroductionVisual field loss affects one fifth of stroke survivors, limiting daily activities and reducing quality of life. Scanning training is a commonly used intervention, but there is variation in how this is delivered. This study aimed to identify the scanning training tools used in Scotland and describe their training parameters, delivery and suitability for use with stroke survivors.MethodAn email survey identified scanning training tools used in Scotland. Two expert panel meetings gained consensus on the motor, language and cognitive skills required to use each scanning training tool. Video capture techniques gathered objective measures of training parameters.ResultsTen scanning training tools were identified. These tools used four delivery methods: paper-based, computer software, web-based and specialised equipment. They aimed to improve reading, perception or general visual skills. Fast, saccadic eye movements were most frequently targeted: two interventions also encouraged head movements. Session duration, frequency and therapist support varied considerably. The level of motor, language and cognitive skills required for each tool was determined.ConclusionScanning training tools used in Scotland vary in delivery modality, functional abilities required for use and visual skills trained. This information will support clinical decision-making and inform future research on training effectiveness and feasibility.
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Wroe, Andrew, Anatoly Rosenfeld, and Reinhard Schulte. "Erratum: “Out-of-field dose equivalents delivered by proton therapy of prostate cancer”." Medical Physics 35, no. 7Part1 (June 26, 2008): 3398. http://dx.doi.org/10.1118/1.2940156.
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Bechir, Edwin Sever, Farah Bechir, and Bogdan Vladila. "Effects of Electromagnetic Field Use on Jaw Bone Densification." Revista de Chimie 69, no. 12 (January 15, 2019): 3705–9. http://dx.doi.org/10.37358/rc.18.12.6824.
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The working hypothesis started from the premise of the benefits of the electromagnetic field therapy (EMFT) benefits in order to densify the periodontal bone tissues. The objective of this study was to quantify the results of using this therapy with the Electronic Doctor Stem Generator (EDSG) in the densification of affected alveolar bone tissues by clinical and radiological examinations. The study was performed on 30 patients, who benefited from adjuvant therapy in the electromagnetic field (EMF) with the EDSG device after performing the specific dental treatments. We applied these very low-frequency EMF bioactivation treatment delivered by EDSG device, 30 daily exposures for a 2-hour interval. The results proved the appreciable reduction of teeth mobility, the reduction of periodontal pockets depth and the bone regeneration in the regions exposed to the EMF produced by EDSG device. EMF adjuvant therapy with EDSG device is an innovative, atraumatic and non-invasive therapy.
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Omichi, Ryotaro, Seiji B. Shibata, Cynthia C. Morton, and Richard J. H. Smith. "Gene therapy for hearing loss." Human Molecular Genetics 28, R1 (June 22, 2019): R65—R79. http://dx.doi.org/10.1093/hmg/ddz129.
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Abstract Sensorineural hearing loss (SNHL) is the most common sensory disorder. Its underlying etiologies include a broad spectrum of genetic and environmental factors that can lead to hearing loss that is congenital or late onset, stable or progressive, drug related, noise induced, age related, traumatic or post-infectious. Habilitation options typically focus on amplification using wearable or implantable devices; however exciting new gene-therapy-based strategies to restore and prevent SNHL are actively under investigation. Recent proof-of-principle studies demonstrate the potential therapeutic potential of molecular agents delivered to the inner ear to ameliorate different types of SNHL. Correcting or preventing underlying genetic forms of hearing loss is poised to become a reality. Herein, we review molecular therapies for hearing loss such as gene replacement, antisense oligonucleotides, RNA interference and CRISPR-based gene editing. We discuss delivery methods, techniques and viral vectors employed for inner ear gene therapy and the advancements in this field that are paving the way for basic science research discoveries to transition to clinical trials.
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Moskowitz, Chaya S., Joanne F. Chou, Suzanne L. Wolden, Jonine L. Bernstein, Jyoti Malhotra, Danielle Novetsky Friedman, Nidha Z. Mubdi, et al. "Breast Cancer After Chest Radiation Therapy for Childhood Cancer." Journal of Clinical Oncology 32, no. 21 (July 20, 2014): 2217–23. http://dx.doi.org/10.1200/jco.2013.54.4601.
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Purpose The risk of breast cancer is high in women treated for a childhood cancer with chest irradiation. We sought to examine variations in risk resulting from irradiation field and radiation dose. Patients and Methods We evaluated cumulative breast cancer risk in 1,230 female childhood cancer survivors treated with chest irradiation who were participants in the CCSS (Childhood Cancer Survivor Study). Results Childhood cancer survivors treated with lower delivered doses of radiation (median, 14 Gy; range, 2 to 20 Gy) to a large volume (whole-lung field) had a high risk of breast cancer (standardized incidence ratio [SIR], 43.6; 95% CI, 27.2 to 70.3), as did survivors treated with high doses of delivered radiation (median, 40 Gy) to the mantle field (SIR, 24.2; 95% CI, 20.7 to 28.3). The cumulative incidence of breast cancer by age 50 years was 30% (95% CI, 25 to 34), with a 35% incidence among Hodgkin lymphoma survivors (95% CI, 29 to 40). Breast cancer–specific mortality at 5 and 10 years was 12% (95% CI, 8 to 18) and 19% (95% CI, 13 to 25), respectively. Conclusion Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial.
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Habib, Saffiya, and Moganavelli Singh. "Recent Advances in Lipid-Based Nanosystems for Gemcitabine and Gemcitabine–Combination Therapy." Nanomaterials 11, no. 3 (February 27, 2021): 597. http://dx.doi.org/10.3390/nano11030597.
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The anti-metabolite drug gemcitabine is widely used for the treatment of a variety of cancers. At present, gemcitabine is administered as a hydrochloride salt that is delivered by slow intravenous injection in cycles of three or four weeks. Although regarded as a ‘front-line’ chemotherapeutic agent, its efficacy is hampered by poor target cell specificity, sub-optimal cellular uptake, rapid clearance from circulation, the development of chemoresistance, and undesirable side-effects. The use of organic, inorganic, and metal-based nanoparticles as delivery agents presents an opportunity to overcome these limitations and safely harness optimal drug efficacy and enhance their therapeutic indices. Among the many and varied nano delivery agents explored, the greatest body of knowledge has been generated in the field of lipid-mediated delivery. We review here the liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, exosomes, lipid-polymer hybrids, and other novel lipid-based agents that have been developed within the past six years for the delivery of gemcitabine and its co-drugs.
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LEE, Tim W. R., David A. MATTHEWS, and G. Eric BLAIR. "Novel molecular approaches to cystic fibrosis gene therapy." Biochemical Journal 387, no. 1 (March 22, 2005): 1–15. http://dx.doi.org/10.1042/bj20041923.
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Gene therapy holds promise for the treatment of a range of inherited diseases, such as cystic fibrosis. However, efficient delivery and expression of the therapeutic transgene at levels sufficient to result in phenotypic correction of cystic fibrosis pulmonary disease has proved elusive. There are many reasons for this lack of progress, both macroscopically in terms of airway defence mechanisms and at the molecular level with regard to effective cDNA delivery. This review of approaches to cystic fibrosis gene therapy covers these areas in detail and highlights recent progress in the field. For gene therapy to be effective in patients with cystic fibrosis, the cDNA encoding the cystic fibrosis transmembrane conductance regulator protein must be delivered effectively to the nucleus of the epithelial cells lining the bronchial tree within the lungs. Expression of the transgene must be maintained at adequate levels for the lifetime of the patient, either by repeat dosage of the vector or by targeting airway stem cells. Clinical trials of gene therapy for cystic fibrosis have demonstrated proof of principle, but gene expression has been limited to 30 days at best. Results suggest that viral vectors such as adenovirus and adeno-associated virus are unsuited to repeat dosing, as the immune response reduces the effectiveness of each subsequent dose. Nonviral approaches, such as cationic liposomes, appear more suited to repeat dosing, but have been less effective. Current work regarding non-viral gene delivery is now focused on understanding the mechanisms involved in cell entry, endosomal escape and nuclear import of the transgene. There is now increasing evidence to suggest that additional ligands that facilitate endosomal escape or contain a nuclear localization signal may enhance liposome-mediated gene delivery. Much progress in this area has been informed by advances in our understanding of the mechanisms by which viruses deliver their genomes to the nuclei of host cells.
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Wong, Ru Xin, Jacqueline Faught, Melissa Gargone, William Myers, Matthew Krasin, Austin Faught, and Sahaja Acharya. "Cardiac-Sparing and Breast-Sparing Whole Lung Irradiation Using Intensity-Modulated Proton Therapy." International Journal of Particle Therapy 7, no. 4 (March 1, 2021): 65–73. http://dx.doi.org/10.14338/ijpt-20-00079.1.
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Abstract Purpose Whole lung irradiation (WLI) is indicated for certain pediatric patients with lung metastases. This study investigated whether WLI delivered as intensity-modulated proton therapy (IMPT) could significantly spare the heart and breasts when compared with conventional WLI delivered with anteroposterior/posteroanterior photon fields and with intensity-modulated photon therapy (IMRT) WLI. Materials and Methods Conventional, IMRT, and IMPT plans were generated for 5 patients (aged 5-22 years). The prescription dose was 16.5 GyRBE in 1.5-GyRBE fractions. Conventional plans used 6-MV photons prescribed to the midline and a field-in-field technique to cover the planning target volume (the internal target volume [ITV] + 1 cm). IMRT plans used 6-MV photons with a 7-beam arrangement with dose prescribed to the planning target volume. IMPT plans used scenario-based optimization with 5% range uncertainty and 5-mm positional uncertainty to cover the ITV robustly. Monte Carlo dose calculation was used for all IMPT plans. Doses were compared with paired Student t test. Results The ITV Dmean was similar for the IMPT, conventional, and IMRT plans, but the IMPT plans had a lower Dmin and a higher Dmax at tissue interfaces than conventional plans (Dmean ratio: 0.96, P > .05; Dmin ratio: 0.9, P < .001; Dmax ratio: 1.1, P = .014). Dmeans for breast and heart substructures were lower with IMPT plans than with conventional/IMRT plans (heart ratios, 0.63:0.73; left ventricle ratios, 0.61:0.72; right ventricle ratios, 0.45:0.57; left atrium ratios, 0.79:0.85; right atrium ratios, 0.81:0.86; left breast ratios, 0.40:0.51; right breast ratio, 0.46:0.52; all P < .05). Conclusions IMPT resulted in comparable ITV coverage and lower mean doses to the heart and breasts when compared with other techniques. Whole lung irradiation delivered as IMPT warrants prospective evaluation in pediatric patients.
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Tang, Gordon, and E. Antonio Chiocca. "Gene transfer and delivery in central nervous system disease." Neurosurgical Focus 3, no. 3 (September 1997): E4. http://dx.doi.org/10.3171/foc.1997.3.3.5.
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Gene transfer offers the potential to explore basic physiological processes and to intervene in human disease. The central nervous system (CNS) presents a fertile field in which to develop novel therapeutic modalities to treat intractable and pervasive malignant tumors and neurodegenerative disease. The extension of gene therapy to the CNS, however, faces the delivery obstacles of a target population that is postmitotic and isolated behind a blood-brain barrier (BBB). Approaches to this problem have included grafting of genetically modified cells to deliver novel proteins or introducing genes by viral or synthetic vectors geared toward the CNS cell population. Direct inoculation and bulk flow, as well as osmotic and pharmacological disruption, have been used to circumvent the BBB's exclusionary role. Once the gene is delivered, myriad strategies have been used to affect a therapeutic result. Genes activating prodrugs are the most common antitumor approach. Other approaches focus on activating immune responses, targeting angiogenesis, and influencing apoptosis and tumor suppression. At this time, therapy directed at neurodegenerative diseases has centered on ex vivo gene therapy for supply of trophic factors to promote neuronal survival, axonal outgrowth, and target tissue function. Despite early promise, gene therapy for CNS disorders will require advancements in methods for delivery and long-term expression before becoming feasible for human disease.
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Mijanović, Olja, Ana Branković, Anton V. Borovjagin, Denis V. Butnaru, Evgeny A. Bezrukov, Roman B. Sukhanov, Anastasia Shpichka, Peter Timashev, and Ilya Ulasov. "Battling Neurodegenerative Diseases with Adeno-Associated Virus-Based Approaches." Viruses 12, no. 4 (April 18, 2020): 460. http://dx.doi.org/10.3390/v12040460.
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Neurodegenerative diseases (NDDs) are most commonly found in adults and remain essentially incurable. Gene therapy using AAV vectors is a rapidly-growing field of experimental medicine that holds promise for the treatment of NDDs. To date, effective delivery of a therapeutic gene into target cells via AAV has been a major obstacle in the field. Ideally, transgenes should be delivered into the target cells specifically and efficiently, while promiscuous or off-target gene delivery should be minimized to avoid toxicity. In the pursuit of an ideal vehicle for NDD gene therapy, a broad variety of vector systems have been explored. Here we specifically outline the advantages of adeno-associated virus (AAV)-based vector systems for NDD therapy application. In contrast to many reviews on NDDs that can be found in the literature, this review is rather focused on AAV vector selection and their testing in experimental and preclinical NDD models. Preclinical and in vitro data reveal the strong potential of AAV for NDD-related diagnostics and therapeutic strategies.
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Albarqi, Hassan A., Ananiya A. Demessie, Fahad Y. Sabei, Abraham S. Moses, Mikkel N. Hansen, Pallavi Dhagat, Olena R. Taratula, and Oleh Taratula. "Systemically Delivered Magnetic Hyperthermia for Prostate Cancer Treatment." Pharmaceutics 12, no. 11 (October 25, 2020): 1020. http://dx.doi.org/10.3390/pharmaceutics12111020.
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Herein, we report a novel therapy for prostate cancer based on systemically delivered magnetic hyperthermia. Conventional magnetic hyperthermia is a form of thermal therapy where magnetic nanoparticles delivered to cancer sites via intratumoral administration produce heat in the presence of an alternating magnetic field (AMF). To employ this therapy for prostate cancer tumors that are challenging to inject intratumorally, we designed novel nanoclusters with enhanced heating efficiency that reach prostate cancer tumors after systemic administration and generate desirable intratumoral temperatures upon exposure to an AMF. Our nanoclusters are based on hydrophobic iron oxide nanoparticles doped with zinc and manganese. To overcome the challenges associated with the poor water solubility of the synthesized nanoparticles, the solvent evaporation approach was employed to encapsulate and cluster them within the hydrophobic core of PEG-PCL (methoxy poly(ethylene glycol)-b-poly(ε-caprolactone))-based polymeric nanoparticles. Animal studies demonstrated that, following intravenous injection into mice bearing prostate cancer grafts, the nanoclusters efficiently accumulated in cancer tumors within several hours and increased the intratumoral temperature above 42 °C upon exposure to an AMF. Finally, the systemically delivered magnetic hyperthermia significantly inhibited prostate cancer growth and did not exhibit any signs of toxicity.
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Rong, Yi, Tasha Fahner, and James S. Welsh. "Hypofractionated Breast and Chest Wall Irradiation Using Simultaneous in-field Boost IMRT Delivered via Helical Tomotherapy." Technology in Cancer Research & Treatment 7, no. 6 (December 2008): 433–39. http://dx.doi.org/10.1177/153303460800700604.
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Although helical tomotherapy has been described as a means of administering accelerated partial breast irradiation, its practicality in routine whole breast irradiation as part of breast conserving therapy or chest wall irradiation has been questioned. In this technical note we describe our method of whole breast or chest wall irradiation using helical tomotherapy based image-guided, hypofractionated, simultaneous in-field boost intensity modulated radiation therapy. We have observed that excellent dose-distributions can be achieved with helical tomotherapy through a careful selection of treatment planning parameters. Dose homogeneity to the whole breast and simultaneously targeted lumpectomy region appears superior to conventional “tangents” with minimal hot or cold spots. Dose-volume histogram analysis documents effective reduction of high dose to critical sensitive structures (heart and lung) although a greater volume of these non-target organs receives low dose compared to what is typical with tangential beams. Treatment planning is efficient and is usually completed within one to two hours, although physician contouring requires more time and attention than non-IMRT approaches. Pretreatment megavoltage CT (MVCT) imaging has proved invaluable in aiding set-up and engenders greater confidence that the planned IMRT dose distributions are truly being delivered. In some situations, MVCT can provide visual feedback when a seroma or overall breast volume has changed significantly since simulation, thereby identifying cases where replanning might be prudent. Treatment is brief, typically completed in 6 to 9 minutes. Initial clinical application has confirmed the feasibility and practicality of helical tomotherapy as an efficient means of administering radiation therapy for routine breast-conserving therapy and post-mastectomy chest wall irradiation. A simultaneous in-field boost technique reduces the length of the overall course by about a week thereby adding convenience and reducing costs. Further refinements of our technique are being explored and formal prospective clinical evaluation is underway.
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Arle, Jeffrey, Eric Wong, Anders Korshoej, Socrates Dokos, Ze’ev Bomzon, and Kristen Carlson. "SCIDOT-52. IN SITU DELIVERY OF TUMOR TREATING FIELDS THERAPY IN GLIOBLASTOMA PATIENTS." Neuro-Oncology 21, Supplement_6 (November 2019): vi282. http://dx.doi.org/10.1093/neuonc/noz175.1187.
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Abstract The efficacy of Tumor-Treating Fields (TTFields) rests on the result of a large-scale clinical trial that demonstrated an increase in the survival of newly diagnosed glioblastoma patients when combined with temozolomide chemotherapy. Overall survival now extends to over 60 months in some of our patients when dexamethasone, which we suspected of interference with TTFields effects, is replaced with celecoxib to control tumor-associated inflammation. The transcranial method of delivering TTFields has not changed in light of ongoing advances in deep brain stimulation (DBS) and transcranial electric stimulation (TES), notably that the resistivity of the skull is the principle obstacle to placing therapeutic electric field strength of 2 V/cm into target tumor sites and variation in skull thickness is the main difference in TES efficiency across individuals. Realistic human head finite element modeling (FEM) predicted that surgical craniectomy beneath TTFields’ electrodes would enhance field strength at target tumor sites. Here we show that 2 V/cm can be reliably delivered to tumor sites using minimally-invasive DBS cylindrical leads or ribbon electrode arrays, pre- or post-resection. Two objections arise to the in situ method: 1) Will TTFields stimulate axons in situ? 2) Will field strength exceed safety limits for cell damage? Neural stimulation modeling and experiments show that TTFields’ frequency of 200 kHz, 1–3 orders of magnitude higher than ion channel time constants, is too high to stimulate them. Furthermore, 2 V/cm is well below cell damage limits of 700 V/mm. Thus we propose a new delivery method to improve tumor control in glioblastoma patients and to provide valuable information on TTFields’ effects via cell studies using in situ electric fields at 200 kHz.
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Zhao, Nan, Ruijie Yang, Yuliang Jiang, Suqing Tian, Fuxin Guo, and Junjie Wang. "A Hybrid IMRT/VMAT Technique for the Treatment of Nasopharyngeal Cancer." BioMed Research International 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/940102.
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Hybrid IMRT/VMAT technique which combined intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) was developed for the treatment of nasopharyngeal cancer (NPC). Two-full-arc VMAT (2ARC-VMAT), 9-field IMRT (9F-IMRT), and Hybrid IMRT/VMAT plans for NPC were compared in terms of the dosimetric quality, sparing of organs at risk (OARs), and delivery efficiency. The Hybrid IMRT/VMAT technique can improve the target dose homogeneity and conformity compared with 9F-IMRT and 2ARC-VMAT. It can reduce the dose delivered to the TMJ, mandible, temporal lobe, and unspecified tissue with fewer MUs compared with 9F-IMRT and dose delivered to parotids, brainstem, and spinal cord compared with 2ARC-VMAT technique. The mean delivery time of Hybrid plans was shorter than that of 9F-IMRT plans (408 s versus 812 s;P=0.00) and longer than that of 2ARC-VMAT plans (408 s versus 179 s;P=0.00). Hybrid IMRT/VMAT technique could be a viable radiotherapy technique with better plan quality.
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Kirsh, Bonnie, Lynn Cockburn, and Rebecca Gewurtz. "Best Practice in Occupational Therapy: Program Characteristics that Influence Vocational Outcomes for People with Serious Mental Illnesses." Canadian Journal of Occupational Therapy 72, no. 5 (December 2005): 265–79. http://dx.doi.org/10.1177/000841740507200503.
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Background. Despite the known benefits of work for people with mental illnesses, vocational outcomes of this group remain poor. Attempts at comparing the efficacy of various models of service delivery have met with limited success due to variations across studies. Purpose. The purpose of this paper is to provide information about key characteristics related to outcomes in the field of vocational rehabilitation for people with serious mental illnesses. Method. A comprehensive review of literature published between 1990 and 2003 was conducted, resulting in 39 articles for analysis. Results. A set of twelve characteristics was identified that appear to influence vocational outcomes across models. These characteristics relate to the types of services offered, the manner in which services are delivered, and the work environment. Practice Implications. The authors suggest these characteristics can be incorporated across models and practice settings. The findings are discussed in terms of implications for best practice in occupational therapy.
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Chen, Thomas, Clovis da Fonseca, and Axel Schönthal. "Intranasal Perillyl Alcohol for Glioma Therapy: Molecular Mechanisms and Clinical Development." International Journal of Molecular Sciences 19, no. 12 (December 6, 2018): 3905. http://dx.doi.org/10.3390/ijms19123905.
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Intracranial malignancies, such as primary brain cancers and brain-localized metastases derived from peripheral cancers, are particularly difficult to treat with therapeutic agents, because the blood-brain barrier (BBB) effectively minimizes brain entry of the vast majority of agents arriving from the systemic circulation. Intranasal administration of cancer drugs has the potential to reach the brain via direct nose-to-brain transport, thereby circumventing the obstacle posed by the BBB. However, in the field of cancer therapy, there is a paucity of studies reporting positive results with this type of approach. A remarkable exception is the natural compound perillyl alcohol (POH). Its potent anticancer activity was convincingly established in preclinical studies, but it nonetheless failed in subsequent clinical trials, where it was given orally and displayed hard-to-tolerate gastrointestinal side effects. Intriguingly, when switched to intranasal delivery, POH yielded highly promising activity in recurrent glioma patients and was well tolerated. As of 2018, POH is the only intranasally delivered compound in the field of cancer therapy (outside of cancer pain) that has advanced to active clinical trials. In the following, we will introduce this compound, summarize its molecular mechanisms of action, and present the latest data on its clinical evaluation as an intranasally administered agent for glioma.
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Turton, Ailie J., Jayne Angilley, Verity Longley, Philip Clatworthy, and Iain D. Gilchrist. "Search training for people with visual field loss after stroke: A cohort study." British Journal of Occupational Therapy 81, no. 5 (December 19, 2017): 255–65. http://dx.doi.org/10.1177/0308022617743481.
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Introduction People with visual field loss after stroke often experience difficulties in everyday activities. The purpose of this study was to assess the acceptability of search training as used within occupational therapy and the feasibility of possible measures for use in a future trial. Method Nine participants took part in a goal oriented intervention that was delivered three times a week for 3 weeks. Patient reports of acceptability and outcomes using the Visual Function Questionnaire-25 were collected. Participants’ room-search behaviour before and after the intervention was recorded using a head-worn camera. Results Eight participants completed nine treatment visits. All participants reported improved awareness and attention to the blind side during activities following the intervention. Seven participants’ change scores on the Visual Function Questionnaire-25 exceeded six points. Patterns of head-direction behaviour and overall room-search times were variable across patients; markedly, improved performance was only evident in the most severely affected participant. Conclusion The intervention was acceptable. The Visual Function Questionnaire-25 is a feasible measure for assessing patient-reported outcomes. While the room search was informative about individuals’ behaviour, more sophisticated methods of gaze tracking would allow search processes to be determined in real-world activities that are relevant to patients’ goals.
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Hayes, F. A., E. I. Thompson, L. Parvey, B. Rao, L. Kun, D. Parham, and H. O. Hustu. "Metastatic Ewing's sarcoma: remission induction and survival." Journal of Clinical Oncology 5, no. 8 (August 1987): 1199–204. http://dx.doi.org/10.1200/jco.1987.5.8.1199.
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Eighteen patients with previously untreated metastatic Ewing's sarcoma (ES) entered a protocol designed to evaluate the response rate to cyclophosphamide and doxorubicin induction therapy delivered before delayed surgery and delayed lower dose, limited-field radiation therapy, (RT), and maintenance chemotherapy. With chemotherapy and delayed surgery, 14 of 18 were rendered free of gross tumor. RT was delivered to the primary site of 11 of these responding patients, plus four of those not free of gross disease. Following RT, two more attained complete clinical remission. Site of primary or metastases did not influence outcome; however, the size of the primary at diagnosis did appear to do so. Ten patients remain disease-free 16 to 82 months (median, 47 months) from diagnosis.
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Chen, Thomas C., and Gregory A. Helm. "Introduction to gene therapy in neurological surgery." Neurosurgical Focus 8, no. 4 (April 2000): 1–5. http://dx.doi.org/10.3171/foc.2000.8.4.1.
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Gene therapy is an exciting new discipline in which neurosurgery and neurosurgeons can have a direct impact on both patient care and emerging scientific developments. Unlike other organs, the brain is unique in that it has a blood–brain barrier, often preventing efficient systemic gene delivery to the area of interest. Therefore, not only is gene delivery required, but it will often need to be accomplished in a local and specific manner. Although brain neoplasms have been the most commonly studied application of genetic therapeutics in neurological surgery, there are many other potential applications of this technology to neurosurgical disorders, including spinal instability, neurodegenerative disease, neurogenetic diseases, central nervous system (CNS) injury, aneurysms, trauma, stroke, and epilepsy. As the field of gene therapy for the CNS develops from the preclinical setting to clinical trials to mainstream therapy, the need for safe and specific gene delivery will be increasingly apparent. Neurosurgeons are in an enviable position as there is nobody more qualified to address the issue of how a gene can be delivered to the central nervous system. Not only do we have the training to operate on the nervous system and its coverings, but we have the ability to recognize and take care of complications that may arise from these procedures. However, the neurosurgeon's role in gene therapy for the brain and spine should not be confined to gene delivery only. Instead, we also need to understand and have a role in deciding what genes could have therapeutic utility in our patients. Herein lies our challenge in gene therapy: how can we as neurosurgeons interface with our basic science colleagues to address rapidly all of the problems that are blocking the advancement of nucleic acid therapeutics into the clinical setting.
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Zeevi, Oshrit, Zeev Bomzon, and Tal Marciano. "NIMG-65. STUDY OF LOCAL PERTURBATION IN COMPUTATIONAL MODELLING ON TUMOR TREATING FIELDS (TTFIELDS) THERAPY." Neuro-Oncology 22, Supplement_2 (November 2020): ii162. http://dx.doi.org/10.1093/neuonc/noaa215.678.
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Abstract INTRODUCTION Tumor Treating Fields (TTFields) are an approved therapy for glioblastoma (GBM). A recent study combining post-hoc analysis of clinical trial data and extensive computational modelling demonstrated that TTFields dose at the tumor has a direct impact on patient survival (Ballo MT, et al. Int J Radiat Oncol Biol Phys, 2019). Hence, there is rationale for developing TTFields treatment planning tools that rely on numerical simulations and patient-specific computational models. To assist in the development of such tools is it important to understand how inaccuracies in the computational models influence the estimation of the TTFields dose delivered to the tumor bed. Here we analyze the effect of local perturbations in patient-specific head models on TTFields dose at the tumor bed. METHODS Finite element models of human heads with tumor were created. To create defects in the models, conductive spheres with varying conductivities and radii were placed into the model’s brains at different distances from the tumor. Virtual transducer arrays were placed on the models, and delivery of TTFields numerically simulated. The error in the electric field induced by the defects as a function of defect conductivity, radius, and distance to tumor was investigated. RESULTS Simulations showed that when a defect of radius R is placed at a distance, d >7R, the error is below 1% regardless of the defect conductivity. Further the defects induced errors in the electric field that were below 1% when σrR/d < 0.16, where σrR/d < 0.16, where σr = (σsphere – σsurrounding)/(σsphere + σsurrounding).σsurroundings is the average conductivity around the sphere and σsphere is the conductivity of the sphere. CONCLUSIONS This study demonstrates the limited impact of local perturbations in the model on the calculated field distribution. These results could be used as guidelines on required model accuracy for TTFields treatment planning.
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Gutin, Philip H., and Eric T. Wong. "Noninvasive Application of Alternating Electric Fields in Glioblastoma: A Fourth Cancer Treatment Modality." American Society of Clinical Oncology Educational Book, no. 32 (June 2012): 126–31. http://dx.doi.org/10.14694/edbook_am.2012.32.122.
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Overview: Tumor treating fields (TTF) therapy is a novel antimitotic, electric field–based treatment for cancer. This nonchemical, nonablative treatment is unlike any of the established cancer treatment modalities, such as surgery, radiation, and chemotherapy. Recently, it has entered clinical use after a decade of intensive translational research. TTF therapy is delivered to patients by a portable, battery-operated, medical device using noninvasive transducer arrays placed on the skin surface surrounding the treated tumor. TTF therapy is now a U.S. Food and Drug Administration (FDA)–approved treatment for patients with recurrent glioblastoma (GBM) who have exhausted surgical and radiation treatments. This article will introduce the basic science behind TTF therapy, its mechanism of action, the preclinical findings that led to its clinical testing, and the clinical safety and efficacy data available to date, as well as offer future research directions on this novel treatment modality for cancer.
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Odell-Miller, Helen. "Embedding Music and Music Therapy in Care Pathways for People with Dementia in the 21st Century—a position paper." Music & Science 4 (January 1, 2021): 205920432110204. http://dx.doi.org/10.1177/20592043211020424.
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Unique music therapy interventions are discussed from a clinical educational and research perspective, demonstrating a current position on music therapy for people living with dementia and their carers. The position paper, adapted from the keynote lecture given at the workshop “Music Selves and Societies” at Cambridge University in 2018, outlines current research and practice across music and music therapy fields, focussing upon embedding music in daily life and care for people living with dementia. Worldwide, around 50m people have dementia; this is estimated to increase to 75.6m in 2030 and 135.5m in 2050. This results in increased demand for long-term care and a need for heightened awareness and capacity for home care in local settings. Distinctions between interventions delivered by music therapists (direct music therapy) and interventions delivered by musicians or carers arising from training from music therapists (indirect music therapy) are discussed. Political and strategic developments for music and dementia are summarized, highlighting the need for increased training in the field and access to music at all stages of dementia. Case study examples are presented to highlight emerging practices and research; for example, couples attending music therapy groups in a rural community setting (Together in Sound) improved relationships and attitudes for people living with dementia. An international trial investigating reading and music interventions for people living with dementia and their homebased family carers (Homeside) is introduced, alongside practice and research in care homes where music therapy had been found to reduce agitation and improve carers’ well-being. Research shows music therapy interventions address personalized needs linked to daily lived experiences. However, indirect music therapy is needed to reach all who can benefit from music and are living with dementia. It is concluded that high quality, accessible music interventions should be embedded in care, and further research is needed to ascertain best practice.
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Mehta, M. P., S. P. Tannehill, S. Adak, L. Martin, D. G. Petereit, H. Wagner, J. F. Fowler, and D. Johnson. "Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: results of Eastern Cooperative Oncology Group 4593." Journal of Clinical Oncology 16, no. 11 (November 1998): 3518–23. http://dx.doi.org/10.1200/jco.1998.16.11.3518.
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PURPOSE To assess the feasibility, toxicity, and efficacy of hyperfractionated accelerated radiation therapy (HART) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Thirty patients from six institutions with stage IIIA or IIIB NSCLC were enrolled between November 1993 and August 1995. Radiation therapy (total dose, 57.6 Gy in 36 fractions) was delivered over 15 days with the use of three daily fractions with a 4-hour interval between fractions and an 8-hour interval between on-cord fields. Patients were not treated on weekends. RESULTS Twenty-eight patients (93%) completed radiation therapy. Treatment-related toxicities of grade 3 or greater included esophagitis in six patients and grade 3 skin reaction in three patients. The overall objective response rate was 54%, and the response rate within the radiation field was 64%. With a minimum follow-up of 19 months in surviving patients, the median survival and 1-year survival rate are 13 months and 57%, respectively. The median relapse-free survival and 1-year relapse-free survival rate are 7 months and 23%, respectively. No transverse myelitis or late toxicities of grade 4 or greater have been observed. CONCLUSION HART, delivered to a total dose of 57.6 Gy over 15 total days, is practical and well tolerated. Survival appears similar to that seen with modern combined modality regimens. A phase III trial is under way.
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Hale, L. A., and C. J. Eales. "Consulting the South African experts in physiotherapeutic stroke rehabilitation." South African Journal of Physiotherapy 57, no. 2 (May 31, 2001): 32–40. http://dx.doi.org/10.4102/sajp.v57i2.504.
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This paper presents the opinions of expert physiotherapists on what constitutes optimal stroke rehabilitation in South Africa. Data were collected by the use of the Delphi technique. Consensus was reached after two rounds, and the respondents’ views are summarised and discussed within the framework of South African health care. Results showed that physiotherapy was felt to be very important after stroke, and the survey created a profile of the skills that physiotherapists may require in order to work in this field. However, no new or innovative methods by which appropriate rehabilitation services could be delivered in South Africa were generated by the survey.The Delphi technique is described and its use in this survey considered.
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Ranasinghe, Mark, Karlheinz Peter, and James McFadyen. "Thromboembolic and Bleeding Complications in Transcatheter Aortic Valve Implantation: Insights on Mechanisms, Prophylaxis and Therapy." Journal of Clinical Medicine 8, no. 2 (February 25, 2019): 280. http://dx.doi.org/10.3390/jcm8020280.
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Transcatheter aortic valve implantation (TAVI) has emerged as an important alternative to surgical aortic valve repair (SAVR) for patients with severe aortic stenosis. This rapidly advancing field has produced new-generation devices being delivered with small delivery sheaths, embolic protection devices and improved retrieval features. Despite efforts to reduce the rate of thrombotic complications associated with TAVI, valve thrombosis and cerebral ischaemic events post-TAVI continue to be a significant issue. However, the antithrombotic treatments utilised to prevent these dreaded complications are based on weak evidence and are associated with high rates of bleeding, which in itself is associated with adverse clinical outcomes. Recently, experimental data has shed light on the unique mechanisms, particularly the complex haemodynamic changes at sites of TAVI, that underpin the development of post-TAVI thrombosis. These new insights regarding the drivers of TAVI-associated thrombosis, coupled with the ongoing development of novel antithrombotics which do not cause bleeding, hold the potential to deliver newer, safer therapeutic paradigms to prevent post-TAVI thrombotic and bleeding complications. This review highlights the major challenge of post-TAVI thrombosis and bleeding, and the significant issues surrounding current antithrombotic approaches. Moreover, a detailed discussion regarding the mechanisms of post-TAVI thrombosis is provided, in addition to an appraisal of current antithrombotic guidelines, past and ongoing clinical trials, and how novel therapeutics offer the hope of optimizing antithrombotic strategies and ultimately improving patient outcomes.
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Contreras, Jessika, Amar Srivastava, Anupama Chundury, Julie K. Schwarz, Stephanie Markovina, Premal H. Thaker, L. Stewart Massad, et al. "Long-term outcomes of intensity-modulated radiation therapy (IMRT) and high dose rate brachytherapy as adjuvant therapy after radical hysterectomy for cervical cancer." International Journal of Gynecologic Cancer 30, no. 8 (June 11, 2020): 1157–61. http://dx.doi.org/10.1136/ijgc-2020-001412.
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ObjectiveCompared with 3D-planned pelvic radiation, intensity-modulated radiation therapy (IMRT) has been shown to reduce acute toxicity in cervical cancer patients after radical hysterectomy. This study evaluated late toxicity and patterns of failure after post-operative pelvic IMRT interdigitated weekly with high dose rate brachytherapy.MethodsThis retrospective study included 53 cervical cancer patients treated between January 2006 and August 2019 with radical hysterectomy, lymphadenectomy, and post-operative IMRT and high dose rate brachytherapy. The decision to include chemotherapy was made by the treating gynecologic oncologist based on patient-specific criteria including positive pelvic lymph nodes, positive surgical margins, or positive parametrial invasion. The actuarial rates of genitourinary and gastrointestinal toxicity, vaginal cuff/regional nodal/distant failure, and overall survival were calculated using the Kaplan–Meier method.ResultsMedian follow-up was 70 months (range 5.4–148) months and age at diagnosis was 47 (range 24–73) years. The 2018 International Federation of Gynecology and Obstetrics (FIGO) clinical stages were IB1 (n=19), IB2 (n=7), IIB (n=7), IIIC1 (n=19), and IIIC2 (n=1). Median radiation dose delivered in 160 cGy daily fractions was 5120 (range 4640–5120) cGy. Median brachytherapy dose prescribed to the vaginal surface delivered in six weekly fractions was 2400 (range 1200–4800) cGy. Concurrent chemotherapy was delivered in 35 (66%) patients. There were no acute grade >3 genitourinary or gastrointestinal toxicities. Late grade >3 occurred in two (3.8%) patients, including a small bowel obstruction and a ureteral stricture. The 5-year actuarial rate for gastrointestinal or genitourinary toxicity was 1.9%. There were no vaginal cuff recurrences. The 5-year actuarial rates for regional nodal failure, distant failure outside the radiation field, any failure, and overall survival were 11%, 11%, 14%, and 85%, respectively.ConclusionsPost-operative IMRT with high dose rate brachytherapy for patients with cervical cancer is associated with excellent outcomes and limited rates of radiation-related non-hematologic toxicity.
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Holdman, Y. I., and E. V. Titovich. "HUMAN BODY ANTHROPOMORPHIC PHANTOM UTILISATION FOR THE COMPLEX TESTING OF RADIATION THERAPY TECHNOLOGICAL PROCESS." Doklady BGUIR, no. 7-8 (December 29, 2019): 133–40. http://dx.doi.org/10.35596/1729-7648-2019-126-8-133-140.
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The rapid development of technologies in the field of radiation therapy allows us nowadays to implement precision and most clinically effective radiotherapy techniques for oncological patient’s treatment to minimize the irradiation of normal tissues and improve local tumor control. An important condition for the implementation of the justification principle is strict compliance with the requirements for the accuracy of the dose delivered. High standards of radiation treatments performed are guaranteed by the development and strict compliance with the quality assurance (QA) program in the radiological department. However, due to QA programmes specificity, standardized and worldwide used tests included in the quality management system are trivial mechanical and dosimetric tests that can’t define the presence and magnitude of the integral error in the dose delivered to the patient, which arises as a result of the execution of sophisticated radiation therapy procedures, as well as to take into account the complexity of the implementation of modern methods of treatment. The aim of the work is to develop a method of complex dosimetric testing of the radiation therapy process (end-to-end audit), based on the utilization of the anthropomorphic phantom of the original design. The result of this work is the creation of the modified anthropomorphic phantom for precision dosimetric measurements, designed for testing the following technological procedures of the radiation therapy process: a computer tomography acquisition; a computerized treatment planning system, including a contouring module and dose distribution calculation algorithm; imaging systems integrated with radiation treatment units; dosimetric and technical characteristics of the radiation treatment units. Regular dosimetric testing of the radiation therapy technological process (end-to-end audit) with utilization of the technique proposed by the authors, based on the developed anthropomorphic phantom usage, will allow to assess the accuracy of dose distribution delivered to patients with all major malignant tumors localizations.
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Gleeson, Ferga, Erik Tryggestad, Nicholas Remmes, Chris Beltran, Jon Kruse, Michael Haddock, Christopher Hallemeier, Andrew Storm, and Michael Levy. "Knowledge of endoscopic ultrasound-delivered fiducial composition and dimension necessary when planning proton beam radiotherapy." Endoscopy International Open 06, no. 06 (June 2018): E766—E768. http://dx.doi.org/10.1055/a-0588-4800.
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Abstract Background and study aims Little consideration has been given to selection of endoscopic ultrasound-guided fiducials for proton radiotherapy and the resulting perturbations in the therapy dose and pattern. Our aim was to assess the impact of perturbations caused by six fiducials of different composition and dimensions in a phantom gel model. Materials and methods The phantom was submerged in a water bath and irradiated with a uniform 10 cm × 10 cm field of 119.7 MeV monoenergetic spot scanning protons delivered through a 45 mm range shifter. The proton “Bragg Peak” was evaluated. Results Dose perturbations manifesting as dose reductions up to 30 % were observed. A carbon composite (1 × 5 mm) and gold (0.4 × 10 mm) fiducial with backload potential rather than dedicated EUS pre-loaded gold fiducial needles had the best performance in terms of minimizing the dose perturbation. Conclusions Our data demonstrate that a carbon composite fiducial has a less untoward effect on proton therapy dose distribution than dedicated EUS pre-loaded gold fiducial needles. Such information is important to consider when selecting fiducials specifically for proton therapy.
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Eley, John G., Kenneth R. Hogstrom, Kenneth L. Matthews, Brent C. Parker, and Michael J. Price. "Potential of discrete Gaussian edge feathering method for improving abutment dosimetry in eMLC-delivered segmented-field electron conformal therapy." Medical Physics 38, no. 12 (November 23, 2011): 6610–22. http://dx.doi.org/10.1118/1.3660289.
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2019, CIDESD. "Abstracts presented at International Congress CIDESD 2019." Motricidade 15, S1 (January 28, 2019): 1–237. http://dx.doi.org/10.6063/motricidade.16967.
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The International Congress of CIDESD 2019 aims to provide a valuable opportunity for delegates to share, learn from and contribute to the most recent advances in Sports, Exercise and Health Sciences in a refreshing professional and social scenery.
We have put together a programme that includes plenary sessions delivered by leading experts in the field, free communication sessions organised across our key research areas, industry exhibition, research projects showcase, and plenty of networking opportunities! Additionally, we will offer a set of thoughtfully designed pre-congress workshops.
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Wang, Shutao, Cheng-Chia Wu, Hairong Zhang, Maria Eleni Karakatsani, Yi-Fang Wang, Yang Han, Kunal R. Chaudhary, Cheng-Shie Wuu, Elisa Konofagou, and Simon K. Cheng. "Focused ultrasound induced-blood–brain barrier opening in mouse brain receiving radiosurgery dose of radiation enhances local delivery of systemic therapy." British Journal of Radiology 93, no. 1109 (May 1, 2020): 20190214. http://dx.doi.org/10.1259/bjr.20190214.
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Objective: Investigate the temporal effects of focused ultrasound (FUS)-induced blood–brain barrier (BBB) opening in post-radiotherapy mouse brains. Methods and materials: C57B6 mice without tumors were used to simulate the scenario after gross total resection (GTR) of brain tumor. Radiation dose of 6 Gy x 5 was delivered to one-hemisphere of the mouse brain. FUS-induced BBB-opening was delivered to the irradiated and non-irradiated brain and was confirmed with MRI. Dynamic MRI was performed to evaluate blood vessel permeability. Two time points were selected: acute (2 days after radiation) and chronic (31 days after radiation). Results: BBB opening was achieved after FUS in the irradiated field as compared to the contralateral non-irradiated brain without any decrease in permeability. In the acute group, a trend for higher gadolinium concentration was observed in radiated field. Conclusion: Localized BBB-opening can be successfully achieved without loss of efficacy by FUS as early as 2 days after radiotherapy. Advances in knowledge: Adjuvant radiation after GTR is commonly used for brain tumors. Focused ultrasound facilitated BBB-opening can be achieved without loss of efficacy in the post-irradiated brain as early as 2 days after radiation therapy. This allows for further studies on early application of FUS-mediated BBB-opening.
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Joo, Ji Hyeon, and Jong Hoon Kim. "Stereotactic body radiation therapy for local control of liver metastases from colorectal cancer." Journal of Clinical Oncology 34, no. 4_suppl (February 1, 2016): 662. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.662.
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662 Background: Although possible candidates for surgical treatment are increasing, majority of colorectal cancer patients with liver metastases are ineligible for surgery. In our institution, SBRT for liver metastatic colorectal carcinoma has been adopted since 2005. By reviewing the treatment outcomes of relatively large cohorts treated with homogeneous technique, we aimed to report patterns of recurrence and the most effective dose fractionation schedule. Methods: Seventy patients with colorectal liver metastases were treated with SBRT from 2005 to 2014. Total number of treated lesions was 103. Median tumor size was 2.5 cm, with ≥ 3 cm in 42 (41%) lesions. Prescribed doses were biologically equivalent dose (BED) ≥ 112 Gy10, but, if small bowel is adjacent to target volume, dose was decreased according to the normal tissue tolerance dose. Prescription doses relevant to BED ≥ 112 Gy10 were ≥ 45 Gy in 3 fractions or ≥ 60 Gy in 5 fractions, in this study. Results: Median follow-up period was 34.2 months (range, 5.3-121.8). The 2-year local control rate was 92% when full prescription dose was delivered, and 73% if compromised dose group was included. On prognostic factor analysis for local control, N-stage (P= 0.008), and BED (P= 0.001) were significant factors. Overall survival rate was 86% for BED ≥ 112 Gy10 group, and 73% for total cohort. The major pattern of failure was out-of-field intrahepatic progression. On multivariate analysis, N stage (P= 0.001), lesion size (P= 0.010) and number of treated hepatic lesions (P< 0.001) were significant factors for intrahepatic control. Conclusions: Liver SBRT was an effective treatment option for colorectal liver metastases. If BED ≥ 112 Gy10 was delivered, we could expect long-term survival in substantial portion of patients. Major pattern of failure was out-of-field intrahepatic progression, which was related to number of treated hepatic lesions, lesion size and N-stage.
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Kos, Bor, Juan Luis Vásquez, Damijan Miklavčič, Gregers G. G. Hermann, and Julie Gehl. "Investigation of the mechanisms of action behind Electromotive Drug Administration (EMDA)." PeerJ 4 (August 24, 2016): e2309. http://dx.doi.org/10.7717/peerj.2309.
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ObjectiveBladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved.Material and MethodsElectromotive Drug Administration involves applying intravesical mitomycin C with direct current of 20 mA delivered through a catheter electrode for 30 min. For numerical electric field computation we built a 3-D nonhomogeneous patient specific model based on CT images and used finite element method simulations to determine the electric fields in the whole body.ResultsResults indicate that highest electric field in the bladder wall was 37.7 V/m. The mean electric field magnitude in the bladder wall was 3.03 V/m. The mean magnitude of the current density in the bladder wall was 0.61 A/m2.ConclusionsThe present study shows that electroporation is not the mechanism of action in EMDA. A more likely explanation of the mechanism of action is iontophoretic forces increasing the mitomycin C concentration in the bladder wall.
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Davies, Roger, Kieran O’Dea, and Anthony Gordon. "Immune therapy in sepsis: Are we ready to try again?" Journal of the Intensive Care Society 19, no. 4 (April 4, 2018): 326–44. http://dx.doi.org/10.1177/1751143718765407.
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Immune therapy to ease the burden of sepsis has thus far failed to consistently improve patient outcomes. Advances in cancer immune therapy and awareness that prolonged immune-suppression in sepsis can leave patients vulnerable to secondary infection and death have driven resurgence in the field of sepsis immune-therapy investigation. As we develop and evaluate these novel therapies, we must learn from past experiences where single-mediator targeted immune therapies were blindly delivered to heterogeneous patient cohorts with complex and evolving immune responses. Advances in genomics, proteomics, metabolomics, and point-of-care technology, coupled with a better understanding of sepsis pathogenesis, have meant that personalised immune-therapy is on the horizon. Here, we review the complex immune pathogenesis in sepsis and the contemporary immune therapies that are being investigated to manipulate this response. An outline of the immune biomarkers that may be used to support this approach is also provided.
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Obaidat, Ihab M., Venkatesha Narayanaswamy, Sulaiman Alaabed, Sangaraju Sambasivam, and Chandu V. V. Muralee Gopi. "Principles of Magnetic Hyperthermia: A Focus on Using Multifunctional Hybrid Magnetic Nanoparticles." Magnetochemistry 5, no. 4 (December 6, 2019): 67. http://dx.doi.org/10.3390/magnetochemistry5040067.
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Hyperthermia is a noninvasive method that uses heat for cancer therapy where high temperatures have a damaging effect on tumor cells. However, large amounts of heat need to be delivered, which could have negative effects on healthy tissues. Thus, to minimize the negative side effects on healthy cells, a large amount of heat must be delivered only to the tumor cells. Magnetic hyperthermia (MH) uses magnetic nanoparticles particles (MNPs) that are exposed to alternating magnetic field (AMF) to generate heat in local regions (tissues or cells). This cancer therapy method has several advantages, such as (a) it is noninvasive, thus requiring surgery, and (b) it is local, and thus does not damage health cells. However, there are several issues that need to achieved: (a) the MNPs should be biocompatible, biodegradable, with good colloidal stability (b) the MNPs should be successfully delivered to the tumor cells, (c) the MNPs should be used with small amounts and thus MNPs with large heat generation capabilities are required, (d) the AMF used to heat the MNPs should meet safety conditions with limited frequency and amplitude ranges, (e) the changes of temperature should be traced at the cellular level with accurate and noninvasive techniques, (f) factors affecting heat transport from the MNPs to the cells must be understood, and (g) the effect of temperature on the biological mechanisms of cells should be clearly understood. Thus, in this multidisciplinary field, research is needed to investigate these issues. In this report, we shed some light on the principles of heat generation by MNPs in AMF, the limitations and challenges of MH, and the applications of MH using multifunctional hybrid MNPs.
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Slassi, Noureddine, Hmad Ouabi, and Naïma El Khayati. "Comparison of an in-house developed monitor unit double-check program for 3D conformal radiation therapy and treatment planning system verification." Journal of Radiotherapy in Practice 18, no. 03 (January 8, 2019): 251–61. http://dx.doi.org/10.1017/s1460396918000742.
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AbstractAimThe treatment planning system (TPS) plays a key role in radiotherapy treatments; it is responsible for the accurate determination of the monitor unit (MU) needed to be delivered to treat a patient with cancer. The main goal of radiotherapy is to sterilise the tumour; however, any imprecise dose delivered could lead to deadly consequences. The TPS has a quality assurance tool, an independent program to double check the MU, evaluate patient plan correctness and search for any potential error.Materials and methodsIn this work, a comparison was carried out between a MU calculated by TPS and an independent in-house-developed monitor unit calculation program (MUCP). The program, written in Cplusplus (C++ Object-Oriented), requires a database of several measured quantities and uses a recently developed physically based method for field equivalence calculation. The ROOT CERN data analysis library has been used to establish fit functions, to extend MUCP use to a variety of photon beams. This study presents a new approach to checking MU correctness calculated by the TPS for a water-like tissue equivalent medium, using our MUCP, as the majority of previous studies on the MU independent checks were based on the Clarkson method. To evaluate each irradiated region, four calculation points corresponding to relative depths under the water phantom were tested for several symmetric, asymmetric, irregular symmetric and asymmetric field cases. A comparison of MU for each radiation fields from readings of the TPS and the MUCP was undertaken.ResultsA satisfactory agreement has been obtained and within the required standards (3%). Additional experimental measurements of dose deposited in a water phantom showed a deviation of <1·6%.FindingsThe MUCP is a useful tool for basic and complex MU verification for 3D conformal radiation therapy plans.
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Wong, Bradley, David Christie, James Hellyer, Corinne Henningsen, Tania Brogmus, and Gerald B. Fogarty. "Volumetric modulated arc therapy (VMAT) for extensive skin field cancerisation (ESFC) – exploring the limits of treatment volumes with a case series of backs." International Journal of Radiology & Radiation Therapy 7, no. 6 (November 27, 2020): 184–92. http://dx.doi.org/10.15406/ijrrt.2020.07.00286.
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Skin field cancerisation arises from prolonged sun exposure and increases with age. Multiple areas of the skin can be involved resulting in poor quality of life and cosmesis and even death. The long-term efficacy of traditional treatments such as topical creams is disappointing. Volumetric modulated arc therapy (VMAT) is a relatively new radiation technique that allows the definitive treatment of large convex fields. Extra dose can also be delivered simultaneously using a boost technique to proven areas of macroscopic invasive disease. In what we believe is the first publication of its kind, we present a retrospective case series of 15 patients with 21 areas treated with VMAT to the back. Treatment is feasible but areas of skin cancerisation over 800 cm2 should not be treated in one course but broken into smaller fields separated by adequate breaks. Care should be taken when treating large areas of the spine as pancytopenia may result and routine blood counts between treatment courses should be considered. More research is warranted to confirm the dose and efficacy outcomes, but this technique may represent a new therapeutic option for patients with extensive skin field cancerisation of the back.
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van Marlen, Patricia, Max Dahele, Michael Folkerts, Eric Abel, Ben J. Slotman, and Wilko Verbakel. "Ultra-High Dose Rate Transmission Beam Proton Therapy for Conventionally Fractionated Head and Neck Cancer: Treatment Planning and Dose Rate Distributions." Cancers 13, no. 8 (April 13, 2021): 1859. http://dx.doi.org/10.3390/cancers13081859.
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Transmission beam (TB) proton therapy (PT) uses single, high energy beams with Bragg-peak behind the target, sharp penumbras and simplified planning/delivery. TB facilitates ultra-high dose-rates (UHDRs, e.g., ≥40 Gy/s), which is a requirement for the FLASH-effect. We investigated (1) plan quality for conventionally-fractionated head-and-neck cancer treatment using spot-scanning proton TBs, intensity-modulated PT (IMPT) and photon volumetric-modulated arc therapy (VMAT); (2) UHDR-metrics. VMAT, 3-field IMPT and 10-field TB-plans, delivering 70/54.25 Gy in 35 fractions to boost/elective volumes, were compared (n = 10 patients). To increase spot peak dose-rates (SPDRs), TB-plans were split into three subplans, with varying spot monitor units and different gantry currents. Average TB-plan organs-at-risk (OAR) sparing was comparable to IMPT: mean oral cavity/body dose were 4.1/2.5 Gy higher (9.3/2.0 Gy lower than VMAT); most other OAR mean doses differed by <2 Gy. Average percentage of dose delivered at UHDRs was 46%/12% for split/non-split TB-plans and mean dose-averaged dose-rate 46/21 Gy/s. Average total beam-on irradiation time was 1.9/3.8 s for split/non-split plans and overall time including scanning 8.9/7.6 s. Conventionally-fractionated proton TB-plans achieved comparable OAR-sparing to IMPT and better than VMAT, with total beam-on irradiation times <10s. If a FLASH-effect can be demonstrated at conventional dose/fraction, this would further improve plan quality and TB-protons would be a suitable delivery system.
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Owen, Tymothy E., Gaynor Williams, Zoann Nugent, Morel Rubinger, and Naseer Ahmed. "Single Institution Outcomes for Early Stage Follicular Lymphomas Treated with Radiation Therapy Alone as Initial Therapy." Blood 110, no. 11 (November 16, 2007): 4457. http://dx.doi.org/10.1182/blood.v110.11.4457.4457.
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Abstract Objectives: Less than 10% patients with follicular lymphoma (FL) have stage I or II disease and radiation therapy is frequently used as the initial treatment modality. There is limited data on the outcomes of such treated patients. This study was undertaken to evaluate the outcome of patients with limited follicular non-Hodgkin’s lymphomas (NHL) at our institution treated with radiation therapy (RT) alone as initial management. Methods: Demographic, histological subtype and treatment factors were retrospectively reviewed from charts of patients treated at CancerCare Manitoba between 1982 and 2003. Thirty-four patients with stage I–II, grade I–II FL treated initially with RT at our institution within the specified time period were analysed. Results: The median follow up time was 7.4 years. RT was delivered using involved or extended field techniques. Doses ranged from 15 Gy to 48 Gy, with a median dose of 35 Gy. The 5 and 10 year overall survival (OS) for all patients is 80% and 64%, respectively. Twelve patients had recurrences, with a median time from radiation to recurrence of 1.43 years. The majority of recurrences were outside the initial treatment field (93%). Patients with stage I versus II disease have had a 5 year freedom from recurrence of 79% and 45%, respectively (P=0.03). Those patients < 60 years versus ≥ 60 years have an OS of 83% and 78%, respectively (P=0.03). Hemoglobin levels and LDH did not predict survival within this data set. Conclusions: After RT alone the 10 year freedom from recurrence may be as high as 52% in patients with early stage FL. There was a significant improvement in OS with age <60. There is also improvement in time to recurrence with Stage I versus Stage II disease. This data is consistent with previously published data on RT for early stage FL.
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Sood, B. M., P. F. Timmins, G. R. Gorla, M. Garg, P. S. Anderson, B. Vikram, and G. L. Goldberg. "Concomitant cisplatin and extended field radiation therapy in patients with cervical and endometrial cancer." International Journal of Gynecologic Cancer 12, no. 5 (2002): 459–64. http://dx.doi.org/10.1136/ijgc-00009577-200209000-00009.
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The purpose of this study is to evaluate the toxicity and safety of concomitant cisplatin (CDDP) and extended field radiation therapy (EFRT) in patients with cervical cancer (CxCA) and endometrial cancer (EnCA). Twenty-five patients were analyzed retrospectively for treatment-related morbidity from 1989 to 1998. Fourteen patients had CxCA and 11 patients had EnCA. Eighteen patients (72%) had surgery prior to radiotherapy and chemotherapy. EFRT was delivered by a four-field technique to the pelvis and para-aortic regions. CDDP at 100 mg/m2 was given over 5 days during 1st and 4th week of EFRT. EFRT dose for EnCA and CxCA was 45 Gy. Toxicity was analyzed using the RTOG toxicity criteria.Twenty-four (96%) of the 25 patients completed the prescribed therapy. Of the 14 patients with CxCA, three (21%) had no toxicity, three (21%) had grade 1–2, and eight (58%) had grade 3–4 hematologic toxicities. Overall six (24%) had grade 3–4 acute gastrointestinal toxicities, three (21%) of these patients were treated for cervix cancer and three (27%) patients were treated for endometrial cancer. The worst (Grade 3–4) toxicities in 15 patients occurred after the 4th week of radiotherapy. In six of 25 (24%) patients radiation treatments had to be delayed due to toxicities. The median delay of treatment was 10.5 days (range 7–31 days). Of the six patients who had grade 3–4 acute gastrointestinal toxicities, four (66%) had undergone exploratory laparotomy and lymph node sampling prior to start of chemoradiation.We conclude that concomitant EFRT and CDDP appears to be safe with moderate but manageable toxicity. Toxicity is most severe after the 4th week of treatment. Morbidity may be worse in patients with prior laparotomy.
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Corradetti, Michael Nino, Eric Xanthopoulos, Surbhi Grover, Annemarie Therese Fernandes, Miranda Kim, Charles B. Simone, John Paul Christodouleas, Lilie L. Lin, and Ramesh Rengan. "A strategy to reduce acute toxicity from chemoradiation therapy for limited-stage small cell lung cancer." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e17534-e17534. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e17534.
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e17534 Background: The standard of care for limited stage SCLC as outlined in the Intergroup 0096 trial involves twice daily radiation therapy, delivered to two out of four fields at a time, which results in high rates of clinically significant acute toxicity. This study examines acute esophagitis and treatment breaks in patients treated with radiation therapy as outlined by Intergroup 0096 vs those treated with a slight modification to this technique. Methods: We identified SCLC patients who received 45 Gy in 1.5 Gy bid fractions from an institutional database. Associations were assessed via Chi-squared test. A break was defined as an interruption of 3+ days. Results: 74 SCLC patients were treated with 3D-conformal radiation therapy from 2004 to 2010. 16 patients did not satisfy criteria described in the Methods and were excluded. 28 patients were treated per Intergroup 0096 with AP/PA fields bid for 1 week followed by AP/PA treatment in the AM and 2 oblique fields in the PM for 2 weeks. 28 patients were treated with the same approach except all four fields were treated with each fraction. Patient characteristics were well distributed as outlined below (Table). 54% of patients had CTCAE grade 3 esophagitis with the Intergroup 0096 approach vs 23% in patients treated with a 4-field approach (p = 0.01). 29% vs 7% patients had a treatment break (p = 0.03). 32% of grade 3 esophagitis patients had breaks vs 8% with esophagitis grades 0 – 2 (p = 0.02). There was no difference in survival or distant/local failure. Conclusions: Grade 3 esophagitis and treatment breaks were reduced in patients receiving continuous 4-field treatment. Future investigation is required to determine whether the observed reduction in breaks could translate to a local control or survival benefit if applied to a larger patient sample. [Table: see text]
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Yoo, Paul Y., Katryne Scott, Filip Myszak, Stephanie Mamann, Amelie Labelle, Melanie Holmes, Andreanne Guindon, and Andre E. Bussieres. "Interventions Addressing Vision, Visual-perceptual Impairments Following Acquired Brain Injury: A Cross-sectional Survey." Canadian Journal of Occupational Therapy 87, no. 2 (January 3, 2020): 117–26. http://dx.doi.org/10.1177/0008417419892393.
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Background. The existing literature on the effectiveness of interventions targeting vision, visual-perceptual impairments following acquired brain injury (ABI) is scarce and unlinked to occupational performance. Purpose. To explore current occupational therapy practice in vision-rehabilitation among adults with ABI in Canada, and to determine the evidence-practice gaps. Methods. An online survey was made available through the Canadian Association of Occupational Therapists (CAOT) website, and disseminated to seven public healthcare institutions in Quebec. The survey collected respondent demographic information, and the types and frequency of treatments delivered. Descriptive statistics were conducted to determine interventions’ frequency. Participant comments were collected and grouped into recurring themes. Findings. Over half (55%) of respondents regularly use evidence-based interventions when addressing visual acuity (VA) and visual field (VF) deficits, but only very few (3%) use it when dealing with oculomotor function and visual stress impairments. Implications. Results gave a glimpse of interventions used and suggested the need for further research in vision rehabilitation.
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Chen, Yi-Jen, Michelle B. Chen, Alan J. Liu, Julian Sanchez, Peter Tsai, and An Liu. "Dosimetric Coverage of the External Anal Sphincter by 3-Dimensional Conformal Fields in Rectal Cancer Patients Receiving Neoadjuvant Chemoradiation: Implications for the Concept of Sphincter-Preserving Radiation Therapy." BioMed Research International 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/578243.
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Background. We evaluated the anatomic location of the external anal sphincter (EAS) to pelvic bony landmarks related to 3-dimensional conformal radiotherapy (3DRT) and studied the dosimetric coverage of the EAS in patients undergoing neoadjuvant chemoradiation for rectal cancer.Methods. Sixty-four consecutive rectal cancer patients treated with neoadjuvant chemoradiation were included. All patients were treated in a prone position on a bellyboard by 3DRT. The inferior border of the RT fields was at least 3–5 cm inferior to the gross tumorous volume (GTV) or at the inferior border of the obturator foramen (IBOF), whichever was more inferior. The EAS was contoured and dose distributions were determined using dose-volume histograms.Results. In 53 out of 64 cases (82.8%), the EAS was completely inferior to the IBOF. In the remaining 11 cases, the EAS was either overlapping the IBOF (10 cases; 15.6%) or completely superior to the IBOF (1 case; 1.7%). The average mean dose delivered to the EAS was 2795 cGy. Lower mean doses were delivered to the EAS when the center of the EAS was located more distant from the GTV.Conclusions. Meticulous planning to define the inferior border of the RT field is recommended to avoid irradiating the EAS.
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Čorović, Selma, Bassim Al Sakere, Vincent Haddad, Damijan Miklavčič, and Lluis M. Mir. "Importance of Contact Surface between Electrodes and Treated Tissue in Electrochemotherapy." Technology in Cancer Research & Treatment 7, no. 5 (October 2008): 393–99. http://dx.doi.org/10.1177/153303460800700507.
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Electrochemotherapy is an effective antitumor treatment employing locally applied high voltage electric pulses delivered through conductive electrodes to the tumor in combination with chemotherapeutic drugs. The efficiency of electrochemotherapy strongly depends on the local electric field distribution inside the target tissue. For successful therapy the entire target tissue has to be exposed to the local electric field strength above the reversible threshold. The aim of this study is to demonstrate the influence of the contact surface between electrode and treated tissue on the coverage of the tumor tissue by sufficiently high local electric field. The electric field distribution is calculated by means of numerical modeling using finite element method. Numerical results are confirmed with in vivo experiments. We demonstrated that the placement of electrodes giving larger electrode-tissue contact surface leads to improved electrochemotherapy outcome. Our results provide guidance on electrochemotherapy for treatment of protruding cutaneous tumors using parallel plate electrodes.