title: A new noninvasive approach in breast cancer therapy using magnetic resonance imaging-guided focused ultrasound surgery.
abstract: An ideal vision of modern medicine includes tumor surgery with the human body remaining completely intact. A noninvasive therapy could avoid infections and scar formation; it would require less anesthesia, reduce recovery time, and possibly also reduce costs. This study investigated whether human breast cancer can be effectively treated with a novel combination of image guidance and energy delivery, noninvasive magnetic resonance imaging (MRI)-guided focused ultrasound (FUS). We have developed a FUS therapy unit guided by MRI for the treatment of human breast tumors in a clinical 1.5 T MR scanner. With interactive target segmentation on MRI, defined volumes could be noninvasively treated in a single session with on-line MR temperature control. The ultrasound waves were focused through the intact skin and resulted in the localized thermal tissue ablation at a maximum temperature of 70 degrees C. The therapy principle was first demonstrated in sheep breast in vivo and was then applied in a patient with core biopsy-proven invasive breast cancer 5 days before breast-conserving surgery. MRI proved suitable to delineate the breast cancer, served as stereotactic treatment planning platform, and delineated the FUS-related tissue changes such as interruption of tumor blood flow. Furthermore, MRI localized the hot spot in the tumor and measured temperature elevation during the treatment. This allowed us to monitor the efficacy and safety of FUS therapy. Immunohistochemistry of the resected specimen demonstrated that FUS homogeneously induced lethal and sublethal tumor damage with consecutive up-regulation of p53 and loss of proliferative activity. This effect was realized without anesthesia and damage to the surrounding healthy tissue or systemic effects. Overall, our results show that noninvasive MRI-guided therapy of breast cancer is feasible and effective. Thus, MRI-guided FUS may represent a new strategy for the neoadjuvant, adjuvant, or palliative treatment in selected breast cancer patients and in patients with other soft-tissue tumors.
authors.affiliation: Deutsches Krebsforschungszentrum (dkfz), Division of Radiation Oncology, D-69120 Heidelberg, Germany. p.huber@dkfz-heidelberg.de
authors.forename: P E
authors.initials: PE
authors.lastname: Huber
authors.forename: J W
authors.initials: JW
authors.lastname: Jenne
authors.forename: R
authors.initials: R
authors.lastname: Rastert
authors.forename: I
authors.initials: I
authors.lastname: Simiantonakis
authors.forename: H P
authors.initials: HP
authors.lastname: Sinn
authors.forename: H J
authors.initials: HJ
authors.lastname: Strittmatter
authors.forename: D
authors.initials: D
authors.lastname: von Fournier
authors.forename: M F
authors.initials: MF
authors.lastname: Wannenmacher
authors.forename: J
authors.initials: J
authors.lastname: Debus
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000601:surgery*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000000981:diagnostic imaging / Q000601:surgery*; D008875:Middle Aged; D012756:Sheep; D014463:Ultrasonography