Michael D. Sherar

Bio: Michael D. Sherar is an academic researcher from University Health Network. The author has contributed to research in topics: Attenuation coefficient & Attenuation. The author has an hindex of 36, co-authored 94 publications receiving 5585 citations. Previous affiliations of Michael D. Sherar include University of Western Ontario & Keele University.

Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials

Abstract: *MRC Cyclotron Unit, Hammersmith Hospital, London, United Kingdom; +MRC Cancer Trials Office, Cambridge, United Kingdom; *Departments of Hyperthermia and Statistics, Daniel den Hoed Cancer Center, Rotterdam,The Netherlands; “Department of Radiotherapy, Academic Medical Center, Amsterdam,The Netherlands; apartments of Radiation Oncology, Biostatistics, and Clinical Physics, Princess Margaret Hospital/Ontario Cancer Institute, University of Toronto, Canada purpose: Claims for the value of hyperthermia as an adjunct to radiotherapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of thii form of treatment, randomized phase III trials were needed. Methods and Materials: Five randomized trials addressing this question were started between 1988 and 1991. In these trials, patients were eligible if they had advanced prhnary or recurrent breast cancer, and local radiotherapy was indicated in preference to surgery. In addition, heating of the lesions and treatment with a prescribed (re)irradiation schedule had to be feasible and informed consent was obtained. The primary endpoint of ail trials was local complete response. Slow recruitment led to a decision to collaborate and combii the trial rest&s in one analysis, and report them simuhaneously in one publication. Interim analyses were carried out and the trials were closed to recruitment when a previously agreed statistically sign&ant difference in complete response rate was observed in the two larger trials. Results: We report on pretreatment characteristics, the treatments received, the local response observed, duration of response, time to local failure, distant progression and survival, and treatment toxicity of tbe 306 patients randomized. The overali CR rate for RT alone was 41% and for the combined treatment arm was 59%, giving, after stratification by trial, an odds ratio of 2.3. Not alI trials demonstrated an advantage for the combined treatment, although tbe 95% confidence intervals of the different trials all contain the pooled odds ratio. The greatest effect was observed in patients with recurrent lesions in previously irradiated areas, where further irradiation was limited to low doses. Conclusion: The combined result of the five trials has demonstrated the efficacy of hyperthemia as an adjunct to radiotherapy for treatment of recurrent breast cancer. The implication of these encouraging results is that hyperthermia appears to have an important role in the clinical management of this disease, and there should be no doubt that further studies of the use of hypertbermia are warranted. Breast cancer, Hyperthermia, Radiotherapy, Randomized trial. Reprint requests to: Jill B. Whaley, MRC Cancer Trials Office, 5 Shaftesbury Road, Cambridge CB2 2BW UK Accepted for publication 6 March 1996.

A theoretical comparison of energy sources--microwave, ultrasound and laser--for interstitial thermal therapy.

Abstract: A number of heating sources are available for minimally invasive thermal therapy of tumours. The purpose of this work was to compare, theoretically, the heating characteristics of interstitial microwave, laser and ultrasound sources in three tissue sites: breast, brain and liver. Using a numerical method, the heating patterns, temperature profiles and expected volumes of thermal damage were calculated during standard treatment times with the condition that tissue temperatures were not permitted to rise above 100 degrees C (to ensure tissue vaporization did not occur). Ideal spherical and cylindrical applicators (200 microm and 800 microm radii respectively) were modelled for each energy source to demonstrate the relative importance of geometry and energy attenuation in determining heating and thermal damage profiles. The theoretical model included the effects of the collapse of perfusion due to heating. Heating patterns were less dependent on the energy source when small spherical applicators were modelled than for larger cylindrical applicators due to the very rapid geometrical decrease in energy with distance for the spherical applicators. For larger cylindrical applicators, the energy source was of greater importance. In this case, the energy source with the lowest attenuation coefficient was predicted to produce the largest volume of thermally coagulated tissue, in each tissue site.

Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo.

Abstract: A new non-invasive method for monitoring apoptosis has been developed using high frequency (40 MHz) ultrasound imaging. Conventional ultrasound backscatter imaging techniques were used to observe apoptosis occurring in response to anticancer agents in cells in vitro, in tissues ex vivo and in live animals. The mechanism behind this ultrasonic detection was identified experimentally to be the subcellular nuclear changes, condensation followed by fragmentation, that cells undergo during apoptosis. These changes dramatically increase the high frequency ultrasound scattering efficiency of apoptotic cells over normal cells (25- to 50-fold change in intensity). The result is that areas of tissue undergoing apoptosis become much brighter in comparison to surrounding viable tissues. The results provide a framework for the possibility of using high frequency ultrasound imaging in the future to non-invasively monitor the effects of chemotherapeutic agents and other anticancer treatments in experimental animal systems and in patients.

Hyperthermia in combined treatment of cancer

Abstract: Hyperthermia, the procedure of raising the temperature of tumour-loaded tissue to 40-43 degrees C, is applied as an adjunctive therapy with various established cancer treatments such as radiotherapy and chemotherapy. The potential to control power distributions in vivo has been significantly improved lately by the development of planning systems and other modelling tools. This increased understanding has led to the design of multiantenna applicators (including their transforming networks) and implementation of systems for monitoring of E-fields (eg, electro-optical sensors) and temperature (particularly, on-line magnetic resonance tomography). Several phase III trials comparing radiotherapy alone or with hyperthermia have shown a beneficial effect of hyperthermia (with existing standard equipment) in terms of local control (eg, recurrent breast cancer and malignant melanoma) and survival (eg, head and neck lymph-node metastases, glioblastoma, cervical carcinoma). Therefore, further development of existing technology and elucidation of molecular mechanisms are justified. In recent molecular and biological investigations there have been novel applications such as gene therapy or immunotherapy (vaccination) with temperature acting as an enhancer, to trigger or to switch mechanisms on and off. However, for every particular temperature-dependent interaction exploited for clinical purposes, sophisticated control of temperature, spatially as well as temporally, in deep body regions will further improve the potential.

Magnetic resonance imaging device

Abstract: By using a multiple receiving coil composed of receiving coils, an imaging portion of a subject is subjected to a first pulse sequence to create n sensitivity images (701 to 703) fewer than the examination images. When these sensitivity images are created, an NMR signal is measured for only the low-frequency region of the k space. A second pulse sequence from which a phase encode step is removed is conducted to create m (m>n) examination images (704, 705) of the subject by using the receiving coils. When sensitivity distributions (707, 708) of the receiving coils are determined for the sensitivity images (701 to 703), and if there are no sensitivity distributions corresponding to the slice positions of the examination images (704, 705), they are determined by slice interpolation using the sensitivity distributions (701 to 703), and the aliasing artifacts of the examination images (704, 705) are removed by matrix operation by using the sensitivity distributions (707, 708).

The cellular and molecular basis of hyperthermia.

Abstract: In oncology, the term 'hyperthermia' refers to the treatment of malignant diseases by administering heat in various ways. Hyperthermia is usually applied as an adjunct to an already established treatment modality (especially radiotherapy and chemotherapy), where tumor temperatures in the range of 40-43 degrees C are aspired. In several clinical phase-III trials, an improvement of both local control and survival rates have been demonstrated by adding local/regional hyperthermia to radiotherapy in patients with locally advanced or recurrent superficial and pelvic tumors. In addition, interstitial hyperthermia, hyperthermic chemoperfusion, and whole-body hyperthermia (WBH) are under clinical investigation, and some positive comparative trials have already been completed. In parallel to clinical research, several aspects of heat action have been examined in numerous pre-clinical studies since the 1970s. However, an unequivocal identification of the mechanisms leading to favorable clinical results of hyperthermia have not yet been identified for various reasons. This manuscript deals with discussions concerning the direct cytotoxic effect of heat, heat-induced alterations of the tumor microenvironment, synergism of heat in conjunction with radiation and drugs, as well as, the presumed cellular effects of hyperthermia including the expression of heat-shock proteins (HSP), induction and regulation of apoptosis, signal transduction, and modulation of drug resistance by hyperthermia.

Optical Coherence Tomography of the Human Retina

Abstract: Objective: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. Design: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. Setting: Research laboratory. Participants: Convenience sample of normal human subjects. Main Outcome Measures: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. Results: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10-??m depth resolution. Conclusion: Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.