# Model Predictive Control and Its Role in Biomedical Therapeutic Automation: A Brief Review
## 3 MPC in Biomedical Applications
### Cancer
#### 3.5.2 Hyperthermia Therapy  
Mild hyperthermia is a non-toxic therapy process for the treatment of cancer cells. The process involves heating specific targeted tissues of the body, usually consisting of the surroundings of the tumor cells, to temperatures of 39 to 45 degree Celsius for up to 90 min. The rest of the patient body is kept at the normal functioning temperature. Various research trials have established hyperthermia as an effective cancer therapy [130]. For instance, hyperthermal therapy displayed a complete response in cervical cancer  
Figure 12: Tumor eradication by the employment of oncolytic viruses in conjunction with an impulsive nonlinear estimating and predictive control strategy. diagnosed human subjects under randomized Phase III trials [131]. In fact, the results of these trials showed an approximately double complete-response rate in comparison to that of radiation therapy. Hyperthermia therapy has proven effective in attaining higher control of metastatic or recurrent malignant melanoma [132] and other tumors as well [133]. Hyperthermic treatment involves the temporal cumulative application of elevated temperatures on the target tissues. In this therapy, the relationship between time and temperatures is established using the relationship given by [PERSON] [134]. Intra-treatment temperatures are typically monitored using catheterized point-wise temperature sensors placed at certain discrete points of/around the tumor [135,136]. Non-invasive magnetic resonance temperature measurements are employed to obtain a more detailed spatial temperature distribution [13,137]. However, extended hyperthermic treatments cause patient discomfort, leading to non-sustained temperature levels. Moreover, during these treatments, maintaining the desired thermal dose is challenging due to unknown and altering body fluid rates and other various factors not taken into consideration. One of the solutions to these issues is to apply higher temperature (about 57 degree Celsius) for a shorter duration [138, 139, 140, 141]. Such high-power, short-duration therapies include high-temperature hyperthermia, coagulation necrosis and thermal ablation therapy. Magnetic resonance-guided high-intensity focused ultrasound (MR- HIFU) is one of the most prominent technologies deployed for such treatments. Appropriate feedback controllers are needed to maintain the desired thermal distribution over the duration of the therapy despite unknown disturbances and plant-model mismatch. Therefore, MR-HIFU implementations include feedback controller-assisted temperature control schemes. These control schemes typically include binary strategies to regulate the sonic intensities and radiation durations using PID-based models. The major drawbacks associated with these controllers are their default constraints and incapacity to consider the future thermal behavior of the patient body. Hence, proportional, multipoint adaptive and linear quadratic regulator control systems have also been used for simulating temperature control during hyperthermia treatments [142]. However, these control systems are typically designed around standard hyperthermia treatments. In a real-life scenario, a tissue at a high temperature continues to acquire thermal dosage even after the radiation is switched off. This indicates an integral relationship between temperature and dose. Hence, the control mechanism should consider predicting future temperature values to prevent overdose. In this regard, MPCs can provide optimum control in hyperthermal treatments. Researchers have suggested MPCs as a superior scheme to control thermal dose parameters while considering multiple heating locations and intensities simultaneously [130]. The contributing variables make it difficult to sustain a specified temperature in the spatial distribution of the target tissue. Hence, the solution to the problem is to reduce the number of control parameters using an MPC.