This clinical trial evaluates the safety and effectiveness of spatiotemporal stereotactic body radiation therapy (ST-SBRT) in treating patients with solid tumors that have spread to other parts of the body (polymetastatic). SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. ST-SBRT is designed to deliver radiation directly to the core of the tumor, while keeping the radiation exposure of the area around the tumor at minimal dosage.

PRIMARY OBJECTIVE:

I. To conduct a first evaluation of the toxicity and efficacy of ST-SBRT, targeting polymetastatic lesions as small as 2.0 cm.

SECONDARY OBJECTIVES:

I. To describe feasibility using:

Ia. Percentage of patients with screen failure; Ib. Number of ST-SBRT fractions given per subject; Ic. Percentage of treatment fractions that require adaptation.

II. To summarize:

IIa. Percentage of subjects with clinical response in non-irradiated lesions (abscopal effect); IIb. Duration of earliest clinical response; IIc. Frequency of late toxicity; IId. 1-year overall survival; IIe. 3-month change in total tumor volume; IIf. 3-month change in quality of life per Functional Assessment of Cancer Therapy (FACT)-General (G).

III. To evaluate whether a lesion's irradiation status is associated with its change in volume after 4 weeks.

IV. To compare alternate guidelines (Immune-Modified Response Evaluation Criteria in Solid Tumors [iRECIST], Immune-related Response Evaluation Criteria In Solid Tumors [irRECIST], Positron Emission Tomography [PET] Response Criteria in Solid Tumors [PERCIST]) against Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 for ability to detect clinical response in irradiated and non-irradiated lesions.

V. To evaluate whether, at 3 months after first treatment fraction, the net change in total tumor volume is associated with net change in quality of life (FACT-G).

EXPLORATORY OBJECTIVE:

I. To identify serologic markers correlated with net change in lesion volume.

OUTLINE:

Patients undergo ST-SBRT on study. Patients also undergo collection of blood samples at screening and on study and undergo computed tomography (CT) at screening, on study, and during follow up.

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative

  • Assent, when appropriate, will be obtained per institutional guidelines

• Age: >= 18 years

• Karnofsky performance status > 60

• Poly-metastatic disease, > 5 lesions, and with at least one lesion > 2.0 cm, with limited treatment options, and ineligible for or in progression under the standard systemic therapy

• Pre-screening assessment confirms that the intervention can be administered without exceeding dose constraint guidelines

• Patients with brain metastases can be included but brain metastases must be treated prior to enrollment and follow up magnetic resonance imaging (MRI) 3 months after treatment shows stable findings

• Spinal cord metastases are allowed as long as treatment with or without radiation is completed

• Prior radiotherapy in general is allowed, as long as the composite plan meets dose constraints

• Life expectancy >= 3 months in the opinion of the treating investigators

• Off systemic therapy for at least one month prior and one month after study intervention

Exclusion Criteria:

• Judgement by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements
• Those not eligible for SBRT after review by a radiation oncologist
• Serous medical comorbidities precluding radiotherapy
• Unable to undergo a CT scan
• Pregnant and/or breastfeeding women are excluded from this study as these agents may have the potential for teratogenic or abortifacient effects. Female patients of childbearing potentially must have a negative urine or serum pregnancy test within 72 hours prior to receiving therapy
• On active systemic therapy
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)