This open-label, randomized Phase II trial evaluates whether a strategy-based, multimodal local treatment approach improves local control compared with single-modality local therapy in patients with high-burden metastatic disease characterized by multiple metastases and at least one bulky lesion.
In the experimental arm, prespecified target lesions are prospectively allocated to either iodine-125 (125I) seed implantation or cryoablation using protocol-defined anatomic and technical suitability criteria, and at least one bulky index lesion is treated using a tumor-zoned approach (e.g., core debulking with cryoablation and peripheral/high-risk margin control with 125I seeds) under predefined organ-at-risk constraints. The control arm treats all prespecified target lesions with a single local modality (either 125I seed implantation alone or cryoablation alone), with standardized supportive care and follow-up.
The primary objective is to determine whether the "lesion allocation plus tumor zoning" strategy can improve local control of treated target lesions with acceptable safety. Imaging-based efficacy endpoints are evaluated using protocol-defined criteria with standardized blinded independent imaging review. Key secondary endpoints include local progression-free survival of the bulky index lesion, overall response rate (RECIST), progression-free survival, time to systemic progression (including new lesions), overall survival, tumor-burden reduction metrics, technical success, and re-intervention rates. Safety is assessed throughout the study using CTCAE v5.0, including monitoring for procedure-related and radiation-related complications. Exploratory analyses assess dosimetry-outcome relationships, zonal response patterns within bulky lesions, imaging/radiomics biomarkers, and peripheral blood biomarker dynamics.
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);
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);
Li Min
Lead sponsor
Jinan Military General Hospital
Sponsor institution