Magnetic Hyperthermia Research Articles

Clinical effectiveness of combined whole body hyperthermia and external beam radiation therapy (EBRT) versus EBRT alone in patients with painful bony metastases: A phase III clinical trial study

PurposeTo evaluate the response rate, pain relief duration, and time it took for pain to decline or resolve after radiation therapy (RT) with or without fever-range Whole Body Hyperthermia (WBH) in bony metastatic patients with mainly primary tumor of prostate and breast cancer leading to bone pain. Materials & methodsBony metastatic patients with pain score ≥4 on the Brief Pain Inventory (BPI) underwent RT of 30 Gy in 10 fractions in combination with WBH with nursing care under medical supervision versus RT-alone. WBH application time was 3-4 h in three fractions with at least 48-h intervals. All patients were stratified primary site, breast or prostate cancer vs others, BPI score, and exclusion criteria. The primary endpoint was complete response (CR) (BPI equal to zero with no increase of analgesics) within two months of follow-up. ResultsBased on this study, the RT-alone group showed the worst pain. The study was terminated after the enrollment of a total of 61 patients, 5 years after the first enrollment (April 2016 to February 2021). Finally, the CR rate in RT + WBH revealed the most significant difference with RT-alone, 47.4% versus 5.3% respectively within 2 months post-treatment (P-value <0.05). The time of complete pain relief was 10 days for RT + WBH, while the endpoint was not reached during the RT-alone arm. Pain progression or stable disease was observed in half of the patients in RT-alone group within 4 weeks after treatment. However, this score was near zero in RT + WBHT patients in two months post-treatment. ConclusionsWBH plus RT showed significant increases in pain relief and shorter response time in comparison with RT-alone for patients with bone metastatic lesions.

Influence of Controlled Dipolar Interaction for Polymer-Coated Gd-Doped Magnetite Nanoparticles toward Magnetic Hyperthermia Application.

To maximize heat release from immobilized nanoparticles (NPs), a detailed understanding of the controlled dipolar interaction is essential for challenging magnetic hyperthermia (MH) therapies. To design optimal MH experiments, it is necessary to precisely determine magnetic states impacted by the inevitable concurrence of magnetic interactions under a common experimental form. In this work, we describe how the presence of dipolar interaction significantly alters the heating mechanism of host materials when NPs are embedded in them for MH applications. The concentration of the NPs and the intensity of their interaction can profoundly impact the amplitude and shape of the heating curves of the host material. The heating capability of interacting NPs might be enhanced or diminished, depending on their concentration within the host material. We propose chitosan- and dextran-coated Gd-doped Fe3O4 NPs directing dipole interactions effective for the linear regime to enlighten the pragmatic trends. The outcomes of our study may have substantial implications for cancer therapy and could inspire novel approaches for maximizing the effectiveness of MH.

Nonmetallic graphite for tumor magnetic hyperthermia therapy

Magnetic hyperthermia therapy (MHT) has garnered immense interest due to its exceptional spatiotemporal specificity, minimal invasiveness and remarkable tissue penetration depth. Nevertheless, the limited magnetothermal heating capability and the potential toxicity of metal ions in magnetic materials based on metallic elements significantly impede the advancement of MHT. Herein, we introduce the concept of nonmetallic materials, with graphite (Gra) as a proof of concept, as a highly efficient and biocompatible option for MHT of tumors in vivo for the first time. The Gra exhibits outstanding magnetothermal heating efficacy owing to the robust eddy thermal effect driven by its excellent electrical conductivity. Furthermore, being composed of carbon, Gra offers superior biocompatibility as carbon is an essential element for all living organisms. Additionally, the Gra boasts customizable shapes and sizes, low cost, and large-scale production capability, facilitating reproducible and straightforward manufacturing of various Gra implants. In a mouse tumor model, Gra-based MHT successfully eliminates the tumors at an extremely low magnetic field intensity, which is less than one-third of the established biosafety threshold. This study paves the way for the development of high-performance magnetocaloric materials by utilizing nonmetallic materials in place of metallic ones burdened with inherent limitations.

Polyethylene Glycol as Surface Modification of Magnetite Nanoparticle Coated Silica a Potentially Hyperthermia Therapy Material

Local hyperthermia therapy is one of the cancer treatments by implementing heat from a temperature of 41-45°C on cancer cells. This method is believed to reduce the risk of normal cells around the cancer cells from dying. The form of hyperthermia therapy itself is in ferrofluid. During its development, superparamagnetic nanoparticles of iron oxide have attracted various studies because of their good magnetic properties and good biocompatibility. However, the poor particle interactions and their tendency to aggregation make coatings on superparamagnetic necessary. Therefore, silica coating on the superparamagnetic surface is carried out to reduce the risk of aggregation and increase the biocompatibility of the material. Polyethylene glycol functionalization was also applied to improve the biocompatibility of the material, as well as being a carrier for ferrofluid. The test was carried out using the magnetite co-precipitation synthesis method and the formation of a sol-gel silica coating. Variations applied in this experiment are the effects of TEOS concentration as a source of silica and the ratio of particles to PEG. The addition of silica was proven to increase the value of the magnetic moment to 51.55 emu/g. The addition of TEOS as a source of silica in iron (III) nanoparticles has an effect on increasing the magnetic attraction, decreasing the surface tension value, reducing particle size, and decreasing the SAR value. Functionalization of polyethylene glycol has the effect of reducing the magnetic moment, increasing and decreasing hydrophobicity, increasing the surface tension value, and reducing the particle size of iron (III) oxide nanoparticles. This shows that magnetic nanoparticles coated with silica with polyethylene glycol functionalization are proven to generate heat when given AC current with the SAR value and the highest temperature is found in iron (III) oxide which gets 3ml silica coating with a PEG ratio of 2:5 at a temperature of 32.2°C. and SAR value of 87.63 W/mg

A Validated Methodological Approach to Prove the Safety of Clinical Electromagnetic Induction Systems in Magnetic Hyperthermia

The present study focuses on the development of a methodology for evaluating the safety of MNH systems, through the numerical prediction of the induced temperature rise in superficial skin layers due to eddy currents heating under an alternating magnetic field (AMF). The methodology is supported and validated through experimental measurements of the AMF’s distribution, as well as temperature data from the torsos of six patients who participated in a clinical trial study. The simulations involved a computational model of the actual coil, a computational model of the cooling system used for the cooling of the patients during treatment, and a detailed human anatomical model from the Virtual Population family. The numerical predictions exhibit strong agreement with the experimental measurements, and the deviations are below the estimated combined uncertainties, confirming the accuracy of computational modeling. This study highlights the crucial role of simulations for translational medicine and paves the way for personalized treatment planning.

Protease-Mediated T1 Contrast Enhancement of Multilayered Magneto-Gadolinium Nanostructures for Imaging and Magnetic Hyperthermia.

In this work, we constructed a multifunctional composite nanostructure for combined magnetic hyperthermia therapy and magnetic resonance imaging based on T1 and T2 signals. First, iron oxide nanocubes with a benchmark heating efficiency for magnetic hyperthermia were assembled within an amphiphilic polymer to form magnetic nanobeads. Next, poly(acrylic acid)-coated inorganic sodium gadolinium fluoride nanoparticles were electrostatically loaded onto the magnetic nanobead surface via a layer-by-layer approach by employing a positively charged enzymatic-cleavable biopolymer. The positive-negative multilayering process was validated through the changes occurring in surface ζ-potential values and structural characterization by transmission electron microscopy (TEM) imaging. These nanostructures exhibit an efficient heating profile, in terms of the specific absorption rates under clinically accepted magnetic field conditions. The addition of protease enzyme mediates the degradation of the surface layers of the nanostructures with the detachment of gadolinium nanoparticles from the magnetic beads and exposure to the aqueous environment. Such a process is associated with changes in the T1 relaxation time and contrast and a parallel decrease in the T2 signal. These structures are also nontoxic when tested on glioblastoma tumor cells up to a maximum gadolinium dose of 125 μg mL-1, which also corresponds to a iron dose of 52 μg mL-1. Nontoxic nanostructures with such enzyme-triggered release mechanisms and T1 signal enhancement are desirable for tracking tumor microenvironment release with remote T1-guidance and magnetic hyperthermia therapy actuation to be done at the diseased site upon verification of magnetic resonance imaging (MRI)-guided release.

An agent-based model for studying the temperature changes on environments exposed to magnetic fluid hyperthermia

Magnetic fluid hyperthermia (MFH) is a technique whose results show promise in the treatment against cancer, but which still faces obstacles such as controlling the spatial distribution of temperature. The present study developed an agent-based model in order to simulate the temperature changes in an aqueous environment submitted to the magnetic fluid hyperthermia technique. The developed model was built with its parameters based on the clinical treatment protocol for glioblastoma multiforme (GBM). Using thermodynamic properties of magnetic fluid and tissues, we define a specific thermal parameter (α) and evaluate its influence, together with the intensity of the external magnetic field (H), on the dynamics of the temperature of the cancer environment. The temperature evolution generated by the model was in accordance with experimental results known from the subject literature. The parameters evaluation indicates that the temperature stabilization of the tumor environment during MFH treatment is due to the local interactions of energy diffusion, as well as indicating that the α-parameter is a key factor for controlling the temperature and heating speed.

Synthesis of Mesoporous Core Shell Magnetite Bioactive Glass Nanoparticles for Magnetic Hyperthermia Treatment of Cancer

AbstractMultiple biological advances have made use of bioactive glass (BG) nanoparticles (NPs) in regenerative medicine, bone and tooth repair, drug and gene transfer, cancer treatment, and cosmetics. Normal biocompatible coatings alongside hydrocarbons, polymers, and silica significantly affect fundamental attributes of NPs. In this study, we synthesized a novel mesoporous BG NPs with magnetite core shell (AMAG_BG) using L‐arginine as a template processing magnetic hyperthermia (MH). BG network coverage on magnetite (AMAG) NPs were orchestrated first time by bio‐inspired synthesis in watery dissolvable. AMAG and AMAG_BG NPs were characterized by utilizing FE‐SEM, HR‐TEM, and BET analysis. The elemental composition of L‐arginine templated magnetite (AMAG) and AMAG_BG NPs was also determined by XPS and EDX analysis. Characteristics of AMAG_BG were contrasted with bare AMAG NPs in morphology, particle size, porosity, and composition. The fabricated BG NPs′ in‐vitro bioactivity and heat studies were successfully monitored after interaction with simulated bodily fluid (SBF). Magnetic studies and in‐vitro heat studies together demonstrated the behavior of BG NPs towards MH treatment of cancerous cells. Cytotoxicity tests on AMAG_BG NPs using U2OS and human blood cells with appropriate control experiments revealed biocompatibility. The study represents magnetic and thermal property‐dependent sustainable synthetic process of AMAG BG NPs for cancer treatment.

Design of miniatured MRI coils for MRI‐guided tumor diagnosis and hyperthermia therapy

AbstractIn this paper, the researchers offer a miniatured design of microstrip lines based on magnetic resonance imaging (MRI) coils that can be utilized to detect tumor tissues and to restore those tissues after radiotherapy. A 61.67% reduction in size was achieved in the MRI array dimensions when compared to the previously reported MRI coils. The reliability of the design specifications was verified. The proposed MRI coils could contribute two resonant modes. Primarily, these MRI coils were suitable for homogenous magnetic field and they enable radio frequency (RF) heating by generating a concentrated electric field |E|. The collective temperature and specific absorption ratio (SAR) have been estimated at Larmor frequency. In this study, it was possible to create a uniform magnetic flux density |B1| field operating at 500 MHz. These proposed coils were excited at 8.06 GHz. When simulating cancer in a biological system, healthy tissues were introduced into a Class A scenario and malignant tissues were introduced into a Class B scenario. According to these two scenarios, tumor tissues were magnetically (|B1|) homogeneous with a 44.1% standard deviation with rapidly raised temperature at 4.77°C. These MRI coils delivered an impact on diagnostic imaging and parallelly restored the cancerous tissues by hyperthermia.

Promote lipolysis in white adipocytes by magnetic hyperthermia therapy with Fe3O4 microsphere-doped hydrogel

Obesity has become an ongoing global crisis, since it increases the risks of cardiovascular disease, type 2 diabetes, fatty liver, cognitive decline, and some cancers. Adipose tissue is closely associated with the disorder of lipid metabolism. Several efforts have been made toward the modulation of lipid accumulation, but have been hindered by poor efficiency of cellular uptake, low safety, and uncertain effective dosage. Herein, we design an Fe3O4 microsphere-doped composite hydrogel (Fe3O4 microspheres @chitosan/β-glycerophosphate/collagen), termed as Fe3O4@Gel, as the magnetocaloric agent for magnetic hyperthermia therapy (MHT), aiming to promote lipolysis in white adipocytes. The experimental results show that the obtained Fe3O4@Gel displays a series of advantages, such as fast sol–gel transition, high biocompatibility, and excellent magneto-thermal performance. MHT, which is realized by Fe3O4@Gel subjected to an alternating magnetic field, leads to reduced lipid accumulation, lower triglyceride content, and increased mitochondrial activity in white adipocytes. This work shows that Fe3O4@Gel-mediated MHT can effectively promote lipolysis in white adipocytes in vitro, which provides a potential approach to treat obesity and associated metabolic disorders.

Additive Manufacturing of Iron Carbide Incorporated Bioactive Glass Scaffolds for Bone Tissue Engineering and Drug Delivery Applications.

In this study, we have synthesized a bioactive glass with composition 45SiO2-20Na2O-23CaO-6P2O5-2.5B2O3-1ZnO-2MgO-0.5CaF2 (wt %). Further, it has been incorporated with 0.4 wt % iron carbide nanoparticles to prepare magnetic bioactive glass (MBG) with good heat generation capability for potential applications in magnetic field-assisted hyperthermia. The MBG scaffolds have been fabricated using extrusion-based additive manufacturing by mixing MBG powder with 25% Pluronic F-127 solution as the binder. The saturation magnetization of iron carbide nanoparticles in the bioactive glass matrix has been found to be 80 emu/g. The morphological analysis (pore size distribution, porosity, open pore network modeling, tortuosity, and pore interconnectivity) was done using an in-house developed methodology that revealed the suitability of the scaffolds for bone tissue engineering. The compressive strength (14.3 ± 1.6 MPa) of the MBG scaffold was within the range of trabecular bone. The in vitro test using simulated body fluid (SBF) showed the formation of apatite indicating the bioactive nature of scaffolds. Further, the drug delivery behaviors of uncoated and polycaprolactone (PCL) coated MBG scaffolds have been evaluated by loading an anticancer drug (Mitomycin C) onto the scaffolds. While the uncoated scaffold demonstrated the drug's burst release for the initial 80 h, the PCL-coated scaffold showed the gradual release of the drug. These results demonstrate the potential of the proposed MBG for bone tissue engineering and drug delivery applications.

Curcumin Nanocarriers with a Focus on Cellular Uptake Studies – An Innovative Cancer Therapy

Once a dye, curcumin (CUR) has transformed into a versatile therapeutic agent with antioxidative, anti-inflammatory, and anticancer properties. Despite its potent anticancer effects, CUR encounters challenges such as poor solubility and a short circulation half-life. To address this, researchers utilize nanocarriers like nanoparticles, liposomes, and micelles for efficient CUR delivery. With its multifaceted anticancer activity, CUR holds promise as a cancer therapeutic. Recent studies concentrate on crafting nanocarriers tailored for size, charge, and functionalization, offering adaptable tools for combinational cancer therapy. The synergistic combination of CUR with chemotherapy, magnetic nano hyperthermia, or photodynamic therapy amplifies the efficacy of malignancy treatment. The investigation into CUR-loaded nanocarriers, whether used alone or in combination with other modalities, aims to enhance cancer treatment outcomes, highlighting the diverse potential of curcumin in contemporary therapeutic strategies. This research underscores the importance of combinational drug delivery therapies, providing a renewed perspective on the versatile applications of curcumin in modern medicine.

Investigation of gadolinium doped manganese nano spinel ferrites via magnetic hypothermia therapy effect towards MCF-7 breast cancer

Magnetic spinel ferrite nanoparticles (MSF-NPs) are potential candidates for biomedical applications, especially in cancer diagnosis and therapy due to their excellent physiochemical and magnetic properties. In the current study, MSF-NPs were fabricated by sol-gel auto combustion method. The crystal structure and surface morphology were confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The magnetic properties were studied by VSM (vibrating sample magnetometer). As increasing Gd3+ concentration, the saturation magnetization values decreased from (17.8-2.3) emu/g, while the coercivity decreased from (499-133) Oe at room temperature. Finally, the fabricated MSF-NPs were tested against anticancer activity by MTT assay. The IC50 = 21.27 μg/mL value was observed, showing the strong antiproliferative activity of these nanoparticles. These results suggested that the obtained MSF-NPs would be useful for remote-controlled hyperthermia therapy for cancer treatment and MRI application due to their excellent magnetic properties. These distinct properties make MSF-NPs most suitable for cancer treatment and bright Contrast Agents (T1-MRI).

Heterostructure nanozymes with sustainable tumor microenvironment regulation and reinforced hyperthermia-responsive catalytic activities for orchestrated osteosarcoma catalytic therapy

Catalytic therapy employing nanozymes has evoked extensive exploration as a promising regimen for cancer theranostics, with specific reactivity in response to tumor microenvironment (TME). However, inherently deficient catalytic efficiency and instability compromise their anticancer efficacy, thus limiting biomedical applications. Herein, we report a novel gold-based heterostructure nanozyme (ATP@IR) with dual enzymes-mimicking activities and illustrious photothermal effect for bone tumor catalytic treatment, aiming at obtaining balanced synergism of catalytic therapy and hyperthermia. With the advantage of its unique tipping-deposition heterostructure structure, ATP@IR nanozymes expedite the electron-hole pair separation and produce massive hot electron, leading to illustrious photothermal effect for tumor hyperthermia treatment. Intriguingly, ATP@IR nanozymes display both intrinsic peroxidase (POD)-mimicking (Km: 39.56 mM) and catalase (CAT)-mimicking activities under weakly acidic TME, which could breakdown endogenous H2O2 into deleterious hydroxyl radicals (·OH) and simultaneously replenish oxygen, realizing efficient tumor ablation and hypoxia alleviation. Meanwhile, elevated oxygen level is leveraged to synergistically produce more reactive oxygen species by reacting with ICG for enhanced photodynamic efficacy. Benefiting from phenomenal thermal conversion efficiency (η = 73.6 %), the dual enzyme-mimicking activities of nanozymes are dramatically improved upon mild hyperthermia when exposure to laser, which actualize hyperthermia-augmented catalytic treatment. Impressively, the potent antitumor efficacy is demonstrated by in vivo xenograft osteosarcoma models without causing lung metastasis. Accordingly, this work provides a reasonable strategy by integrating nanocatalytic treatment, hyperthermia treatment, and TME modulation for efficient treatment of osteosarcoma.

Ferrimagnetic devitrified glass doped with copper by ion exchange: Microstructure, bioactivity and antibacterial properties

In this work, the ion-exchange technique in molten salts was investigated to introduce copper ions in a bioactive and ferrimagnetic devitrified glass. This approach aimed to develop a magnetic and bioactive material for oncologic bone implants, able to join the ability to promote bone bonding to hyperthermic therapy while simultaneously lowering the risk of developing post-surgery infections. The ion-exchange approach was developed in order to overcome experimental critical issues related to the influence of copper introduction as a starting reagent, during the material synthesis, on magnetite nucleation.The magnetic devitrified glass was prepared by melt and quenching route, followed by ion exchange in a mixture of molten sodium and copper nitrates, in three different Na/Cu molar ratios (20, 200, 2000). The obtained samples were analysed in terms of morphology, composition, ability to release heat, bioactivity and antibacterial properties. The results revealed that copper ion-exchange involved both sodium and calcium ions and the precipitation of few amounts of copper oxide aggregates occurred. The crystalline nature of the starting material and its ability to reach the temperature needed for hyperthermia, under exposition to an alternating magnetic field, were not affected. A bacteriostatic effect was obtained by samples with the highest copper amount and the copper doping did not affect the bioactivity of the glass ceramic.

The impact of fractional derivative on thermomechanical interactions in two-dimensional skin tissues throughout hyperthermia treatment

This work aims to study the influence of fractional derivatives and thermal relaxation time on two-dimensional biological tissues using an eigenvalue-based approach. Understanding the heat transfer mechanism and its thermomechanical interactions with the skin tissue of patients is crucial for the successful implementation of thermal treatment procedure. The study employs Laplace and Fourier transforms, and the resulting formulations are applied to human tissues undergoing regional hyperthermia treatment for tumor therapy. The numerical inversion process for Laplace and Fourier transformations utilizes the Stehfest numerical inverse method. The results demonstrate that thermal relaxation time and fractional order parameter significantly influence all analyzed distributions. The numerical findings suggest that thermo-mechanical waves propagate through the skin tissue over finite distances, which helps mitigate the unrealistic predictions made by the Pennes' model.

Urchin-like Fe3O4@Bi2S3 Nanospheres Enable the Destruction of Biofilm and Efficiently Antibacterial Activities.

Biofilm-associated infections (BAIs) have been considered a major threat to public health, which induce persistent infections and serious complications. The poor penetration of antibacterial agents in biofilm significantly limits the efficiency of combating BAIs. Magnetic urchin-like core-shell nanospheres of Fe3O4@Bi2S3 were developed for physically destructing biofilm and inducing bacterial eradication via reactive oxygen species (ROS) generation and innate immunity regulation. The urchin-like magnetic nanospheres with sharp edges of Fe3O4@Bi2S3 exhibited propeller-like rotation to physically destroy biofilm under a rotating magnetic field (RMF). The mild magnetic hyperthermia improved the generation of ROS and enhanced bacterial eradication. Significantly, the urchin-like nanostructure and generated ROS could stimulate macrophage polarization toward the M1 phenotype, which could eradicate the persistent bacteria with a metabolic inactivity state through phagocytosis, thereby promoting the recovery of implant infection and inhibiting recurrence. Thus, the design of magnetic-driven sharp-shaped nanostructures of Fe3O4@Bi2S3 provided enormous potential in combating biofilm infections.

Effect of Al3+ doping on magnetic properties of Zn-Mn ferrite nanoparticles for magnetic induction hyperthermia

Magnetic induction hyperthermia with self-regulated temperature is an advanced technology capable of automatically regulating hyperthermia temperature through a magnetic phase transition, which has a promising application prospect. This paper investigated the effects of Al3+ doping on the magnetic properties and Curie temperature of Zn-Mn ferrite. The specific saturation magnetization and Curie temperatures of Zn0.5Mn0.5AlxFe2-xO4 (0 ≤ x ≤ 0.6) nanoparticles decrease linearly with increment of Al3+ content. The magnetic heating experiments exhibit that the synthesized nanoparticles can raise the temperature of agar phantom to above 42 °C and self-regulate the temperature below their Curie temperatures, demonstrating their potential for self-regulated temperature hyperthermia. Additionally, in vitro cell experiments confirm the nanoparticles’ good biocompatibility.

Magneto-photothermal synergy applied to gold-coated magnetic nanoparticles

In this work, we describe the synthesis of magnetic nanoparticles with a suitable size for easy cellular internalization, avoiding their rapid renal excretion (less than 5 nm) and accumulation in the liver (more than 100 nm). The nanoparticles are functionalized with a biocompatible polymer (low molecular weight, branched polyethylenimine, PEI), and this treatment allows their functionalization with a shell of gold particles in order to improve their ability to absorb electromagnetic radiation in the visible and near infrared wavelength regions. As a result, the magnetic nanostructures are potential agents of local heating (hyperthermia) by exposing them to alternating magnetic fields (magnetic hyperthermia) or to light of the suitable wavelength (photothermia). Magnetic hyperthermia experiments demonstrate that both types of particles can reach the desired temperature range for cell apoptosis, with the difference of a shorter time needed when gold is absent. The released thermal energy is measured by the SAR (specific absorption rate, in W/g), and the values found are promising, up to 600 W/g in the case of uncoated particles. Regarding the photothermia response under the IR radiation, it is comparable for gold-coated and uncoated magnetic particles, but it is enhanced by a factor of almost 10 when the incident light is visible (blue-green) and the particles are provided with their gold shell. Improvements related to the selection of gold particles with resonant absorbance in the infrared are under investigation.

Biological treatment evaluation in thermoradiotherapy: application in cervical cancer patients.

Hyperthermia treatment quality is usually evaluated by thermal (dose) parameters, though hyperthermic radiosensitization effects are also influenced by the time interval between the two modalities. This work applies biological modelling for clinical treatment evaluation of cervical cancer patients treated with radiotherapy plus hyperthermia by calculating the equivalent radiation dose (EQDRT, i.e., the dose needed for the same effect with radiation alone). Subsequent analyses evaluate the impact of logistics. Biological treatment evaluation was performed for 58patients treated with 23-28fractions of 1.8-2 Gy plus 4-5 weekly hyperthermia sessions. Measured temperatures (T50) and recorded time intervals between the radiotherapy and hyperthermia sessions were used to calculate the EQDRT using an extended linear quadratic (LQ) model with hyperthermic LQ parameters based on extensive experimental data. Next, the impact of a30-min time interval (optimized logistics) as well as a4‑h time interval (suboptimal logistics) was evaluated. Median average measured T50 and recorded time intervals were 41.2 °C (range 39.7-42.5 °C) and 79 min (range 34-125 min), respectively, resulting in amedian total dose enhancement (D50) of 5.5 Gy (interquartile range [IQR] 4.0-6.6 Gy). For 30-min time intervals, the enhancement would increase by ~30% to 7.1 Gy (IQR 5.5-8.1 Gy; p < 0.001). In case of 4‑h time intervals, an ~ 40% decrease in dose enhancement could be expected: 3.2 Gy (IQR 2.3-3.8 Gy; p < 0.001). Normal tissue enhancement was negligible (< 0.3 Gy), even for short time intervals. Biological treatment evaluation is auseful addition to standard thermal (dose) evaluation of hyperthermia treatments. Optimizing logistics to shorten time intervals seems worthwhile to improve treatment efficacy.