(1) Background: Modulated electro-hyperthermia (mEHT) is a mild to moderate, capacitive-coupled heating technology that uses amplitude modulation to enhance the cell-killing effects of the treatment. We present three year survival results and a cost effectiveness analysis from an ongoing randomised controlled Phase III trial involving 210 participants evaluating chemoradiotherapy (CRT) with/without mEHT, for the management of locally advanced cervical cancer (LACC) in a resource constrained setting (Ethics Approval: M120477/M704133; ClinicalTrials.gov ID: NCT033320690). (2) Methods: We report hazard ratios (HR); odds ratio (OR), and 95% confidence intervals (CI) for overall survival and disease free survival (DFS) at two and three years in the ongoing study. Late toxicity, quality of life (QoL), and a cost effectiveness analysis (CEA) using a Markov model are also reported. (3) Results: Disease recurrence at two and three years was significantly reduced by mEHT (HR: 0.67, 95%CI: 0.48–0.93, p = 0.017; and HR: 0.70, 95%CI: 0.51–0.98, p = 0.035; respectively). There were no significant differences in late toxicity between the groups, and QoL was significantly improved in the mEHT group. In the CEA, mEHT + CRT dominated the model over CRT alone. (4) Conclusions: CRT combined with mEHT improves QoL and DFS rates, and lowers treatment costs, without increasing toxicity in LACC patients, even in resource-constrained settings.

Background: Modulated electro-hyperthermia (mEHT) is unique due to its combination of thermal and non-thermal effects. Method: This report summarizes the literature on the effects of mEHT observed in vitro and in vivo. Results: The thermal and electrical heterogeneity of tissues allows the radiofrequency signal to selectively target malignant tissue. The applied modulation appears to activate various apoptotic pathways, predominantly leading to immunogenic cell death (ICD). ICD promotes the release of damage-associated molecular patterns, potentially producing tumour-specific antigen-presenting cells. This abscopal-type effect may target distant metastases while treating the primary tumour locally. This immune memory effect is like vaccination mechanisms. Conclusions: The application of mEHT has the potential to expand from local to systemic disease, enabling the simultaneous treatment of micro- and macro-metastases.

Cancer in low- and middle-income countries (LMICs) is associated with late-stage diagnoses and poor survival, compounded by limited access to screening, diagnostic tools, and treatment. The high prevalence of HIV further complicates outcomes, especially in sub-Saharan Africa. Hyperthermia has emerged as a valuable adjunct to treatment in high-income countries, particularly for locally advanced cancers such as cervical and head and neck tumours, which are common in resource-constrained settings. Uptake of hyperthermia in LMICs has however been limited. A phase III randomised controlled trial in a South African public hospital demonstrated that modulated electro-hyperthermia (mEHT), a capacitively coupled heating technique, was feasible in this setting. The trial, the first to assess hyperthermia in Africa and to include HIV-positive participants, found that adding mEHT to chemoradiotherapy significantly improved 5-year disease-free survival (32% vs. 14%; HR:0.73; 95%CI:0.53-1.00; p=0.049 ); reduced recurrence, and improved quality of life without increasing toxicity. Benefits were observed equally in HIV-positive and HIV-negative participants. A cost-effectiveness analysis indicated an 82.2% probability of cost savings over three years, primarily due to fewer recurrences and residual disease and improved quality of life. Given its affordability, ease of integration, and lack of additional toxicity, mEHT represents a promising adjunct to chemoradiation in LMICs. Further replication in LMICs beyond sub-Saharan Africa is needed to confirm generalisability to diverse healthcare settings.

Cancer biology is a constantly evolving field of study due to the dynamic and complex nature of biological systems. The unique role of in vitro assays in cell biology has led to numerous transformations in our understanding of the functional and structural details of the cells and tissues that comprise these systems. However, the traditional monolayer assays have been reported to fall short of the in vivo physiology of cells. This has led to the development of 3D cell models, such as spheroids and organoids, that aim to recapitulate the intricate structural and functional behaviour of in vivo tumours. This review describes passive methods of spheroid formation (scaffold-free and scaffold-based) and the limitations that have driven the development of engineered active design methods to increase the physiological relevance of the model. Traditional assays need to be modified to evaluate these models, accounting for their architecture, density, and microenvironment gradients. Current developments in performing 3D cell assays include increased reagent concentration and incubation periods; however, many protocols still require single-cell analysis. We present a review of assay developments that maintain the spatial and contextual information that makes the 3D models physiologically relevant. Additionally, we introduce the advances in microscopy techniques that provide deeper visualisation of these models.

Therapeutic hyperthermia is typically applied using radiative or capacitive heating devices. Capacitive heating applies electrode pairs positioned on the patient to increase the tumor temperature and is considered a user-friendly method for relatively easy application of hyperthermia to both superficial and deep-seated tumor sites. However, this heating technique also has some limitations that are mainly inherent to the physics of capacitively induced heating. This review provides an overview of the principles of capacitive heating devices and the factors influencing the power absorption and resulting temperature distribution in the patient. Device parameters that strongly influence the achieved temperature distribution include the electrode sizes, the water bolus temperature for skin cooling, the cooling medium, and the output power. These parameters vary in commercially available devices. Complete characterizations of most of the commercially available capacitive devices are still lacking. Sparse phantom measurements in the literature characterizing capacitive devices indicate that therapeutic heating is at least possible for superficial tumors and tumors at intermediate depth. The dominant E‑field orientation with capacitive heating induces preferential subcutaneous fat heating, which limits deep heating and makes it most effective for slender patients (i.e., fat layer thickness < 1.5–2 cm). Numerical simulations have been helpful in optimizing device design, particularly in terms of bolus cooling, and are increasingly used for patient-specific treatment planning. Based on the physical characteristics and present literature, it can be concluded that appropriate patient selection is important to ensure effective and responsible use of capacitive heating devices.