Lesion-Allocated Therapy for Multiple Metastases and Tumor-Zoned Treatment for Bulky Tumors: A Phase II Study of Iodine-125 Seed Implantation Combined With Cryoablation in High-Burden Metastatic Disease

Inclusion Criteria:

* Age ≥18 years;
* Histologically or cytologically confirmed solid malignancy with metastatic disease not amenable to curative surgery or definitive curative-intent radiotherapy;
* High-burden metastatic disease, defined as: Multiple metastases: ≥3 metastatic lesions on imaging, and at least 2 measurable lesions (RECIST v1.1) planned as protocol target lesions; and Bulky lesion: at least 1 lesion meeting bulky criteria (e.g., longest diameter ≥7 cm or tumor volume ≥100 mL, per protocol) designated as the bulky index lesion;
* At least 2 and up to 5 prespecified target lesions are suitable for protocol local therapy and can be assigned per protocol (lesion allocation and/or tumor zoning);
* ECOG performance status 0-2;
* Adequate organ function;
* Willing and able to provide written informed consent.

Exclusion Criteria:

* Lesions requiring emergent surgical decompression or other urgent intervention that cannot be deferred to protocol timelines;
* Target lesions not safely accessible for percutaneous cryoablation and/or 125I seed implantation (e.g., no feasible needle path, unacceptable risk to critical structures despite protective maneuvers);
* Active, uncontrolled infection; uncontrolled pleural effusion/ascites requiring frequent drainage (unless stabilized);
* Severe cardiopulmonary comorbidity prohibiting anesthesia/sedation or percutaneous intervention (e.g., unstable angina, recent MI, uncontrolled arrhythmia, severe COPD with high oxygen requirement);
* Prior local therapy to the same bulky index lesion that would confound response assessment (prior treatment to other non-index lesions may be allowed);
* Uncontrolled CNS metastases (symptomatic, requiring escalating steroids, or not stable after local therapy). Stable treated brain metastases may be allowed per protocol;
* Any condition that, in the investigator's judgment, would compromise protocol compliance or make participation unsafe.