Focused Ultrasound (FUS) Mesencephalotomy for Head & Neck Cancer Pain

Inclusion Criteria:

1. Men and women, between 18 and 75 years, inclusive

2. Subjects with head and neck cancer, including one of the following:

• Cancer that arises in the head and neck region: nasal cavity, sinuses, lips,mouth, salivary glands, throat, or larynx (typically squamous cell carcinoma)

• Cancer occurring in the nasopharynx, skin, thyroid gland, and eye

• Lymphoma

• Sarcoma

3. Craniofacial or cervical pain related to the cancer that meets all of the followingcriteria:

• Severe defined by: Worst NPRS score of ≥ 5 out of 10 at current visit and thesubject reports having a similar level of pain for at least the past twomonths.

• Pain is medication-refractory to all three tiers of the WHO cancer pain ladder.Thus, adequate trials of at least 3 prescription medications that will includea 'weak' and a 'strong' opioid. An adequate medication trial is defined as atherapeutic dose of each medication without sufficient effect.

• Duration of greater than 6 months

4. Mesencephalon contralateral to the pain can be targeted by the ExAblate Neurodevice. The region of the mesencephalon must be apparent on MRI. Additional MRIsequences including inversion-recovery and DTI may be utilized to refine the target.

5. Subjects who are able and willing to give consent and able to attend all studyvisits

6. Subjects who are able to communicate sensations during the focused ultrasoundtreatment

Exclusion Criteria:

1. Idiopathic trigeminal neuralgia

2. Trigeminal neuropathic pain from trauma, infection, or iatrogenic

3. Post-herpetic neuralgia

4. Headache syndromes like migraine, cluster headache

5. Temporomandibular joint syndrome

6. Atypical facial pain or pain related to a somatoform disorder

7. Subjects deemed poor candidates by a multidisciplinary team of cancer and palliativecare clinicians:

8. Significant clinician concern about reliability of subject-reportedinformation, such as subject in active process of seeking disability forneuropathic pain

9. Subjects exhibiting any behavior(s) consistent with ethanol or substance abuseas defined by the criteria outlined in the DSM-V as manifested by one (or more)of the following occurring within a 12 month period: Recurrent substance useresulting in a failure to fulfill major role obligations at work, school, orhome (such as repeated absences or poor work performance related to substanceuse; substance-related absences, suspensions, or expulsions from school; orneglect of children or household). Recurrent substance use in situations inwhich it is physically hazardous (such as driving an automobile or operating amachine when impaired by substance use)

10. Recurrent substance-related legal problems (such as arrests for substancerelated disorderly conduct)

11. Continued substance use despite having persistent or recurrent social orinterpersonal problems caused or exacerbated by the effects of the substance (for example, arguments with spouse about consequences of intoxication andphysical fights).

12. Subjects with active psychiatric illness will be excluded. For the purpose of thisstudy, active psychiatric illness includes:

13. Exhibiting current suicide ideation and/or a history of suicide attempt withinpast 2 years

14. been hospitalized for the treatment of a psychiatric illness within the past 2years

15. received transcranial magnetic stimulation for depression treatment

16. received electroconvulsive therapy for depression

17. any presence or history of psychosis

18. Subjects with unstable cardiac status including:

19. Unstable angina pectoris on medication

20. Subjects with documented myocardial infarction within six months of protocolentry

21. Significant congestive heart failure defined with ejection fraction < 40

22. Subjects with unstable ventricular arrhythmias

23. Subjects with atrial arrhythmias that are not rate-controlled

24. Severe hypertension (diastolic BP > 100 on medication)

25. Subjects with standard contraindications for MR imaging such as non-MRI compatibleimplanted metallic devices including cardiac pacemakers, size limitations, etc.

26. On medications that increases the bleeding risk, based on the published guidelineswhich are currently recognized by the American Society of Regional Anesthesia andPain Medicine, American Academy of Pain Medicine and the North AmericanNeuromodulation Society (Reg Anesth Pain Med 2015;40: 182-212); specifically:

27. Aspirin or another antiplatelet medication (clopidogrel, prasugrel,ticlopidine, abciximab) for the last 7 days prior to treatment.

28. Oral, subcutaneous or intravenous anticoagulant medications, such as oralvitamin K inhibitors for the last 7 days, non-vitamin K inhibitor oralanticoagulant (dabigatran, apixaban, rivaroxaban) for the last 72 hours.

29. Intravenous or subcutaneous heparin-derived compounds for the last 48 hours.

30. Individuals who are not able or willing to tolerate the required prolongedstationary supine position during treatment (can be up to 4 hours of total tabletime.)

31. Subjects participating or have participated in another clinical trial in the last 30days

32. Subjects with risk factors for intraoperative or postoperative bleeding from adocumented coagulopathy or if their serum coagulation studies (platelet count, PT,PTT, and INR) exceed the institutional laboratory limits.

33. Subjects with brain tumors or any significant intracranial mass.

34. Any illness that in the investigator's opinion preclude participation in this study

35. Pregnancy or lactation

36. Legal incapacity or limited legal capacity

37. Subjects with a deep brain stimulation implant

38. Skull density ratio, calculated from the baseline non-contrasted head CT, is lessthan 0.4

39. History of hemorrhagic stroke or cerebrovascular event within the past year oftreatment exhibiting incomplete resolution

40. Subjects whose primary pain is other than craniofacial neuropathic pain.

41. Patients deemed high risk because of their airway for the procedure as evaluated byanesthesia.