Clinical Research Directory

Inclusion Criteria: * Age at least 18 years at consent. * Histologically or cytologically confirmed solid malignancy. A repeat biopsy of a radiographically typical metastasis is not required in a participant with an established cancer diagnosis when the multidisciplinary team documents that biopsy would not change care. * One index lesion with a maximum three-dimensional diameter of at least 7.0 centimeters on baseline planning computed tomography or co-registered diagnostic imaging, measured in any orthogonal plane. * Planning gross tumor volume of the index lesion at least 100 cubic centimeters, documented before randomization. * A target symptom clinically attributable to the index lesion and rated at least 4 on a 0-to-10 numeric rating scale at baseline. Allowed categories are pain, pressure/fullness, dyspnea, dysphagia, bleeding burden or lesion-related functional limitation. Another symptom requires documented confirmation by the Principal Investigator or a qualified delegated physician that attribution is reliable; exact wording is fixed before randomization. * The treating radiation oncologist judges that local radiotherapy is appropriate and its expected benefit is not outweighed by its burden. * Eastern Cooperative Oncology Group performance status 0-3. * Investigator-estimated life expectancy at least 12 weeks, supported by a locally accepted prognostic tool where available. * Planning computed tomography and technical review confirm that all three randomized regimens could meet every hard organ-at-risk constraint and every mandatory target-coverage minimum, and the lesion can accommodate at least three complete protocol-conforming LATTICE high-dose regions. * Ability to undergo simulation, immobilization and image guidance, and receive one fraction daily on five consecutive working days, with planned completion within seven calendar days of the first fraction and a protocol-permitted maximum of ten calendar days after a documented interruption. * Adequate clinical stability and laboratory status for treatment, including the protocol tumor lysis syndrome risk assessment and laboratory panel. * For participants of childbearing potential, a negative pregnancy test according to institutional policy and agreement to avoid pregnancy during the protocol-defined radiation-risk period. * Ability to understand study procedures and provide written informed consent. Reading or electronic-completion assistance is allowed if responses remain the participant's own. Exclusion Criteria: * A primary central nervous system tumor, brain metastasis or spinal-canal/intramedullary target requiring a central nervous system-specific stereotactic protocol. * Hematologic malignancy, including lymphoma, leukemia or myeloma, as the index lesion. * An oncologic emergency in which randomization could delay required decompression, stabilization, surgery, embolization, hemostatic intervention or immediate conventional radiotherapy. Examples include unstable spinal cord or cauda equina compression, impending airway loss, uncontrolled life-threatening bleeding, bowel perforation or an unstable pathological fracture. * Previous radiotherapy to the index lesion with clinically relevant overlap. Overlapping reirradiation is excluded in the current protocol; a future separately approved amendment would be required to permit it. * Inability to meet a hard organ-at-risk constraint or a mandatory target-coverage minimum in any arm, place the required number of compliant high-dose regions, or adequately visualize or manage target motion. * An arrangement in which a critical serial organ or hollow-viscus organ would enter a high-dose region and safe deletion of that region or translation of the locked grid would leave fewer than three valid regions. * Eastern Cooperative Oncology Group performance status 4 or estimated life expectancy less than 12 weeks. * Pregnancy or breastfeeding when treatment poses clinically relevant fetal or infant risk. * A genetic or connective-tissue condition associated with unacceptable radiosensitivity when the investigator considers hypofractionation unsafe. * Uncontrolled infection, bleeding disorder, metabolic abnormality, organ failure or another illness that makes protocol radiotherapy unsafe. * Clinical or laboratory tumor lysis syndrome at baseline. * Concurrent investigational radiosensitizer or systemic treatment whose timing cannot meet protocol washout or hold requirements, unless prospectively approved by the Principal Investigator before randomization. * Another condition that, in the investigator's documented judgment, prevents reliable consent, protocol treatment or primary-outcome collection and cannot be addressed by reasonable support or the telephone contingency.