This is a phase 0, pilot prospective study to determine the feasibility of combined irreversible electroporation (IRE) and radiation therapy in subjects with lung tumors with metastatic cancer of any histology. These are subjects who have advanced disease (stage IV) or previously treated disease that has become progressive, recurrent, or metastatic.

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed metastatic cancer of any histology. There must be a lung tumor present, although the lung tumor does not specifically need to have been biopsied.

• Patients must have advanced disease (stage IV) or previously treated disease that has become progressive, recurrent, or metastatic.

• Patients may have received any number of prior systemic or local therapies. There will be no prespecified washout period prior to IRE. However, systemic therapy will be halted while receiving IRE and radiation, and can be restarted following completion of radiation therapy.

• Up to 3 lesions may be included for treatment. The selected lesion(s) should be amenable to ablation and irradiation and patients will be eligible for ablation and irradiation in the judgment of the treating radiologist and radiation oncologist. If more than one lesion is selected, they should be separated by at least 5 cm to minimize lung irradiation. The target lesion for treatment by IRE and radiation will be a tumor not previously treated by radiation. This target lesion must be measurable, defined as the ability to be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >10 mm with spiral CT scan. The upper limit to the target lesion is 6 cm maximal diameter, but it also must be planned to be encompassed entirely by an IRE ablative zone. Any number of IRE probes will be allowed such that the entire tumor can be ablated.

• Must be age ≥ 18 years. Children are excluded from this study but will be eligible for future pediatric trials, if applicable.

  1. Both men and women and members of all races and ethnic groups are eligible for this trial. Non-English speaking, deaf, hard of hearing and illiterate individuals are eligible for this trial.

• Performance status: ECOG performance status ≤2 (Karnofsky ≥50%).

• Life expectancy of ≥3 months.

• Adequate organ and marrow function as defined below. Labs should be performed within 14 days of treatment.

  1. Platelets ≥50,000/mcL
  2. Hemoglobin ≥8 g/dL
  3. Absolute neutrophil count ≥1,000/mcL
  4. INR <1.5

• Female patients of childbearing potential must have a negative urine or serum pregnancy during screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

• The effects of ionizing radiation (i.e. radiation therapy) on the developing human fetus are known to have the potential for congenital abnormalities and fetal harm. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and until completion of radiation therapy. Should a woman become pregnant or suspect she is pregnant during this period, she should inform her treating physician immediately.

  1. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  1. Has not undergone a hysterectomy or bilateral oophorectomy; or
  2. Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

• Patients must not have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis.

• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

• Patient's whose target lesion has been previously treated with radiation therapy.
• Patients who have not recovered from adverse events due to prior anti-cancer therapy administered.
• Patients may not be receiving any other investigational agents 2 weeks prior to enrollment and until end of all therapeutic interventions.
• Patients with cardiac arrhythmias, pacemakers, or implanted defibrillator.
• Patients with epilepsy.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients must not be pregnant due to the potential for congenital abnormalities and fetal harm caused by ionizing radiation.
• Patients with disease amenable to curative intent therapy.
• Patient has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin.