Machine learning (ML) is a burgeoning field of medicine with huge resources being applied to fuse computer science and statistics to medical problems. Proponents of ML extol its ability to deal with ...large, complex and disparate data, often found within medicine and feel that ML is the future for biomedical research, personalized medicine, computer‐aided diagnosis to significantly advance global health care. However, the concepts of ML are unfamiliar to many medical professionals and there is untapped potential in the use of ML as a research tool. In this article, we provide an overview of the theory behind ML, explore the common ML algorithms used in medicine including their pitfalls and discuss the potential future of ML in medicine.
Prediction of radiobiological response is a major challenge in radiotherapy. Of several radiobiological models, the linear-quadratic (LQ) model has been best validated by experimental and clinical ...data. Clinically, the LQ model is mainly used to estimate equivalent radiotherapy schedules (e.g. calculate the equivalent dose in 2 Gy fractions, EQD
), but increasingly also to predict tumour control probability (TCP) and normal tissue complication probability (NTCP) using logistic models. The selection of accurate LQ parameters α, β and α/β is pivotal for a reliable estimate of radiation response. The aim of this review is to provide an overview of published values for the LQ parameters of human tumours as a guideline for radiation oncologists and radiation researchers to select appropriate radiobiological parameter values for LQ modelling in clinical radiotherapy.
We performed a systematic literature search and found sixty-four clinical studies reporting α, β and α/β for tumours. Tumour site, histology, stage, number of patients, type of LQ model, radiation type, TCP model, clinical endpoint and radiobiological parameter estimates were extracted. Next, we stratified by tumour site and by tumour histology. Study heterogeneity was expressed by the I
statistic, i.e. the percentage of variance in reported values not explained by chance.
A large heterogeneity in LQ parameters was found within and between studies (I
> 75%). For the same tumour site, differences in histology partially explain differences in the LQ parameters: epithelial tumours have higher α/β values than adenocarcinomas. For tumour sites with different histologies, such as in oesophageal cancer, the α/β estimates correlate well with histology. However, many other factors contribute to the study heterogeneity of LQ parameters, e.g. tumour stage, type of LQ model, TCP model and clinical endpoint (i.e. survival, tumour control and biochemical control).
The value of LQ parameters for tumours as published in clinical radiotherapy studies depends on many clinical and methodological factors. Therefore, for clinical use of the LQ model, LQ parameters for tumour should be selected carefully, based on tumour site, histology and the applied LQ model. To account for uncertainties in LQ parameter estimates, exploring a range of values is recommended.
The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 °C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, ...where temperatures beyond 50 °C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors.
Schematic overview of clinically proven heating techniques used for various indications and tumor locations.
Background: Superficial hyperthermia is applied in combination with radiotherapy for e.g. melanoma and recurrent breast cancer, using both capacitive and radiative systems. In this paper, numerical ...simulations are applied to address the question which technique yields the most favourable heating characteristics.
Methods: A 434 MHz contact flexible microstrip applicator (CFMA type 4H, size 19.6 × 19.6 cm
2
) and a capacitive system consisting of two circular electrodes with diameter 15 and 25 cm were modelled. The water bolus of the CFMA was filled with deionised water and for capacitive heating both saline and deionised water were modelled. Specific absorption rate (SAR) and temperature simulations were performed for a perfused muscle-equivalent phantom and phantoms with a 1 cm thick superficial fat layer, assuming cylindrical target regions. Subsequently, a real patient model with a chest wall recurrence was studied with the target assumed to have muscle-like properties, fat properties or heterogeneous properties as derived from the CT Hounsfield Units.
Results: Phantom simulations showed that high SAR peaks occur around the bolus edges with capacitive heating. Power absorption below the fat layer is substantially higher for radiative heating and unless the target region is limited to the fat layer, radiative heating yields better target coverage in terms of SAR and temperature. Patient simulations showed that the T
90
for radiative heating was 0.4-1.1 °C higher compared with capacitive heating.
Conclusions: Radiative heating yields more favourable SAR and temperature distributions for superficial tumours, compared with capacitive heating, especially within heterogeneous tissues. Higher tumour temperatures are achieved without occurrence of treatment limiting hot spots.
Aim
To assess the connection between mitophagy and hypoxia‐induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of ...mitophagy‐related apoptosis.
Methodology
Hypoxia‐induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC‐1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN‐induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved‐poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t‐test were used for data analysis.
Results
Hypoxia‐induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia‐augmented apoptotic activity. Simvastatin alleviated hypoxia‐induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts.
Conclusions
The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis.
The high cost and energy intensity of virgin carbon fiber manufacture provides an opportunity to recover substantial value from carbon fiber reinforced plastic wastes. In this study, we assess the ...life cycle environmental implications of recovering carbon fiber and producing composite materials as substitutes for conventional and proposed lightweight materials in automotive applications (e.g., steel, aluminum, virgin carbon fiber). Key parameters for the recycled carbon fiber materials, including fiber volume fraction and fiber alignment, are investigated to identify beneficial uses of recycled carbon fiber in the automotive sector. Recycled carbon fiber components can achieve the lowest life cycle environmental impacts of all materials considered, although the actual impact is highly dependent on the design criteria (λ value) of the specific component. Low production impacts associated with recycled carbon fiber components are observed relative to lightweight competitor materials (e.g., aluminum, virgin carbon fiber reinforced plastic). In addition, recycled carbon fiber components have low in-use energy use due to mass reductions and associated reduction in mass-induced fuel consumption. The results demonstrate environmental feasibility of the CFRP recycling materials, supporting the emerging commercialization of CF recycling technologies and identifying significant potential market opportunities in the automotive sector.
Hyperthermia treatment planning is increasingly used in clinical applications and recommended in quality assurance guidelines. Assistance in phase-amplitude steering during treatment requires ...dedicated software for on-line visualization of SAR/temperature distributions and fast re-optimization in response to hot spots. As such software tools are not yet commercially available, we developed Adapt2Heat for on-line adaptive hyperthermia treatment planning and illustrate possible application by different relevant real patient examples.
Adapt2Heat was developed as a separate module of the treatment planning software Plan2Heat. Adapt2Heat runs on a Linux operating system and was developed in C++, using the open source Qt, Qwt and VTK libraries. A graphical user interface allows interactive and flexible on-line use of hyperthermia treatment planning. Predicted SAR/temperature distributions and statistics for selected phase-amplitude settings can be visualized instantly and settings can be re-optimized manually or automatically in response to hot spots.
Pretreatment planning E-Field, SAR and temperature calculations are performed with Plan2Heat and imported in Adapt2Heat. Examples show that Adapt2Heat can be helpful in assisting with phase-amplitude steering, e.g., by suppressing indicated hot spots. The effects of phase-amplitude adjustments on the tumor and potential hot spot locations are comprehensively visualized, allowing intuitive and flexible assistance by treatment planning during locoregional hyperthermia treatments.
Adapt2Heat provides an intuitive and flexible treatment planning tool for on-line treatment planning-assisted hyperthermia. Extensive features for visualization and (re-)optimization during treatment allow practical use in many locoregional hyperthermia applications. This type of tools are indispensable for enhancing the quality of hyperthermia treatment delivery.
Hyperthermia treatment planning can be supportive to ensure treatment quality, provided reliable prediction of the heating characteristics (i.e., focus size and effects of phase-amplitude and ...frequency steering) of the device concerned is possible. This study validates the predictions made by the treatment planning system Plan2Heat for various clinically used phased-array systems.BACKGROUNDHyperthermia treatment planning can be supportive to ensure treatment quality, provided reliable prediction of the heating characteristics (i.e., focus size and effects of phase-amplitude and frequency steering) of the device concerned is possible. This study validates the predictions made by the treatment planning system Plan2Heat for various clinically used phased-array systems.The evaluated heating systems were AMC-2, AMC-4/ALBA-4D (Med-Logix srl, Rome, Italy), BSD Sigma-30, and Sigma-60 (Pyrexar Medical, Salt Lake City, UT, USA). Plan2Heat was used for specific absorption rate (SAR) simulations in phantoms representing measurement set-ups reported in the literature. SAR profiles from published measurement data based on E‑field or temperature rise were used to compare the device-specific heating characteristics predicted by Plan2Heat.METHODSThe evaluated heating systems were AMC-2, AMC-4/ALBA-4D (Med-Logix srl, Rome, Italy), BSD Sigma-30, and Sigma-60 (Pyrexar Medical, Salt Lake City, UT, USA). Plan2Heat was used for specific absorption rate (SAR) simulations in phantoms representing measurement set-ups reported in the literature. SAR profiles from published measurement data based on E‑field or temperature rise were used to compare the device-specific heating characteristics predicted by Plan2Heat.Plan2Heat is able to predict the correct location and size of the SAR focus, as determined by phase-amplitude settings and operating frequency. Measured effects of phase-amplitude steering on focus shifts (i.e., local SAR minima or maxima) were also correctly reflected in treatment planning predictions. Deviations between measurements and simulations were typically < 10-20%, which is within the range of experimental uncertainty for such phased-array measurements.RESULTSPlan2Heat is able to predict the correct location and size of the SAR focus, as determined by phase-amplitude settings and operating frequency. Measured effects of phase-amplitude steering on focus shifts (i.e., local SAR minima or maxima) were also correctly reflected in treatment planning predictions. Deviations between measurements and simulations were typically < 10-20%, which is within the range of experimental uncertainty for such phased-array measurements.Plan2Heat is capable of adequately predicting the heating characteristics of the AMC‑2, AMC-4/ALBA-4D, BSD Sigma-30, and Sigma-60 phased-array systems routinely used in clinical hyperthermia.CONCLUSIONPlan2Heat is capable of adequately predicting the heating characteristics of the AMC‑2, AMC-4/ALBA-4D, BSD Sigma-30, and Sigma-60 phased-array systems routinely used in clinical hyperthermia.
Capacitive devices are used for hyperthermia delivery, initially mainly in Asia, but nowadays also increasingly in Europe. Treatment planning can be very useful to determine the most effective ...patient-specific treatment set-up. This paper provides a validation of GPU-based simulations using Plan2Heat for capacitive hyperthermia devices.
Validation was first performed by comparing simulations with an analytical solution for a spherical object placed inside a uniform electric field. Resolution was 5, 2.5 or 1 mm. Next, simulations for homogeneous and inhomogeneous phantom setups were performed for Thermotron RF8 and Celsius TCS capacitive heating devices at 2.5 mm resolution. Also different combinations of electrode sizes were evaluated. Normalized SAR profiles were compared to phantom measurements from the literature. Possible clinical use of treatment planning was demonstrated for an anal cancer patient, evaluating different treatment set-ups in prone and supine position.
Numerical and analytical solutions showed excellent agreement. At the center of the sphere, the error was 5.1%, 2.9% and 0.2% for a resolution of 5, 2.5 and 1 mm, respectively. Comparison of measurements and simulations for both Thermotron RF8 and Celsius TCS showed very good agreement within 5% for all phantom set-ups. Simulations were capable of accurately predicting the penetration depth; a very relevant parameter for clinical application. The patient case illustrated that planning can provide insight by comparing effectiveness of different treatment strategies.
Plan2Heat can rapidly and accurately predict heating patterns generated by capacitive devices. Thus, Plan2Heat is suitable for patient-specific treatment planning for capacitive hyperthermia.
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