MRI-Guided Focused Ultrasound Radiosensitization for Patients With Malignant Melanoma

The objective of this study is to examine the safety profile and therapeutic efficacy of MRI-guided focused ultrasound microbubble therapy and radiotherapy in humans.

Inclusion Criteria:Age ≥18 yearsAll biopsy-confirmed malignant melanoma of the skin, including metastatic lesions.Stage I-IV malignant melanoma, per AJCC guidelines (8th Edition).Patient referred for palliative radiotherapy/ standard radiotherapy/ neoadjuvant radiotherapy/SBRT/ hypofractionation.Patient on immunotherapy.Able to understand and give informed consent.Weight <140kgTarget lesion visible by non-contrast MRI.Target lesion accessible for MRg-FU procedure.Able to communicate sensation during MRg-FU treatment.Creatinine within normal institutional limits or creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above the institutional upper limit of normalExclusion Criteria:Pregnant or lactating women may not participate due to the embryotoxic effects of protocol treatment. Women/ men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.Unable to have contrast-enhanced MRI scan - the standard of care criteriaTarget lesion involves the skin surface causing ulceration, bleeding or dischargeSevere cardiovascular, neurological, renal or hematological chronic diseaseECOG (Eastern Cooperative Oncology Group) Performance Status ≥ 3. Unable to tolerate required stationary position during treatmentCardiac disease or unstable hemodynamics, including myocardial infarction within six months, unstable angina, congestive heart failure, ejection fraction < 50%, cardiac shunts, cardiac arrhythmia and cardiac pacemaker.Contraindication to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation like cisapride, erythromycin, tricyclic antidepressants, Class IA and III antiarrhythmic agents and some antipsychotics like haloperidol, droperidol, quetiapine, thioridazine, ziprasidone.Severe hypertension (diastolic BP > 100 mmHg)History of bleeding disorder, coagulopathySeverely impaired renal function with estimated glomerular filtration rate < 30ml/min/1.73m2 and/or on dialysis