MR guided cancer treatment system for an elevated therapeutic index – A macroscopic approach

Abstract

Adjuvant therapy for cancer usually refers to surgery followed by chemotherapy and/or radiation treatment to decrease the risk of recurrence. But still, the absolute benefit for survival obtained with adjuvant therapy compared with control is only approximately 6%. The objective of this analysis is to formulate a non-invasive multimodal cancer treatment system related to cancer stem cells and hypoxic fractions of solid tumors, emphasizing MRI monitoring and guidance, to elevate the therapeutic index. Tumor hypoxia is a therapeutic concern since it can reduce the effectiveness of drugs and radiotherapy, where well oxygenated cells requiring one third of the dose of hypoxic cells to achieve a given level of cell killing. Cancer stem cells might be the cause of tumor recurrence, sometimes many years after the appearance of the successful treatment of a primary tumor. Thus, the primary objective of such a treatment system will be to provide sufficient selective toxicity to both kill cancer stem cells and cells of hypoxic fractions of the tumor. Active tumor targeting with the use of liposomally encapsulated drugs is the starting point of the treatment procedure. The system facilitates quality assurance means by MR monitoring of drug accumulation and drug release, in real time. Cavitation involves the nucleation, growth and oscillation of gaseous cavities. Selective drug release and/or hyperthermia are achieved by ultrasound induced cavitation well defined to the tumor region. Hyperthermic effects, increased vascularization and subsequent increase in pO2 levels to hypoxic regions, can be monitored by MRI. MRI monitoring of key physiological parameters facilitates optimization related to approximate real time concomitant treatments, including correct timing and various combinations of drug therapy, hyperthermia, ionizing radiation, ablation, other treatment options, before or after surgery. The likelihood of an improved therapeutic index with the use of such a system seems compelling. Further research related to optimal timing, combinations of responses between liposomally encapsulated drug dosage, ultrasound exposure, hyperthermia, pO2 response time, ionizing radiation fractionation and treatment time, have to be conducted.