A Phase I Trial of Palliative Spatially Fractionated (GRID) Radiotherapy Using Intensity Modulated Proton Therapy

Inclusion Criteria: * Histologically or cytologically confirmed cancer diagnosis. * Planning to undergo palliative radiotherapy to unresectable or metastatic target lesion ≥ 4.5 cm in any dimension as measured with radiographic imaging or with calipers by clinical exam. * Cohort A: 10 patients with lesions that have been previously irradiated. * Cohort B: 10 patients with lesions that have not been previously irradiated. * ECOG performance status ≤ 3 * At least 18 years of age. * Radiotherapy is known to be teratogenic. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 6 months after completion of the study * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: * Patients with tumors in need of urgent surgical intervention, such as life-threatening bleeding or those at high risk for pathologic fracture and amenable to surgical intervention. * Patients with a superficial target lesion ≤ 1 cm deep to skin surface who initially had a superficial lesion irradiated, if the target lesion was in the area of the prior irradiation. * Currently receiving any cytotoxic cancer therapy regimens or VEGF inhibitors that will overlap with the proton GRID administration. * Cytotoxic chemotherapy and VEGF inhibitors prior to radiotherapy or planned after radiotherapy delivery are allowed at the discretion of the treating radiation oncologist. This includes continuing a treatment plan which was initiated prior to the start of radiotherapy. A 2-week washout is recommended, but not required. * Pregnant. Women of childbearing potential must have a negative pregnancy test within 20 days of study entry. * Patients with HIV are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.