PET/CT-Guided Biological Target Volume Delineation and Dose Optimization for Radioactive Seed Implantation Therapy in Malignant Tumors

Li Min

Status: Not yet enrolling

Conditions: Malignant Tumors

Treatments: Procedure: PET/CT-Guided Radioactive Seed Implantation; Procedure: PET/CT-Guided Radioactive Seed Implantation (Biological Dose Optimization); Procedure: CT-Guided Radioactive Seed Implantation; Procedure: Tumor-Specific PET/CT-Guided Radioactive Seed Implantation (PSMA/FAPI Subgroup)

Study type: Interventional

Funder types: Other

Identifiers

NCT07327515

960HP20251026

Details and patient eligibility

About

This prospective, open-label Phase I/II trial evaluates a PET/CT-guided planning strategy for radioactive seed implantation therapy in malignant solid tumors. The approach integrates metabolic information from PET/CT into brachytherapy planning to improve the accuracy of biological target volume delineation, enhance dose coverage, and support biologically informed dose delivery. Eligible participants are assigned to one of three arms: conventional CT-guided implantation, PET/CT-guided standard-dose implantation, or PET/CT-guided biologically optimized implantation. All participants undergo image-guided treatment followed by post-implant dosimetric verification and standardized clinical follow-up.

Primary endpoints include technical success rate, dosimetric superiority, and 6-month local control. Secondary endpoints include dosimetric indices (D90, V100, conformity index, homogeneity index), pain relief, quality of life (EORTC QLQ-C30), treatment-related adverse events (CTCAE v5.0), progression-free survival (PFS), failure-free survival (FFS), and overall survival (OS). Exploratory analyses will evaluate associations between baseline PET metabolic parameters (SUVmax, metabolic tumor volume) and clinical outcomes, assess the feasibility of SUV-guided dose painting, and compare the performance of tumor-specific tracers (such as PSMA and FAPI) with FDG for target delineation and treatment response prediction.

The central hypothesis is that PET/CT-guided planning-particularly when incorporating biological dose optimization-will achieve superior dosimetric performance and improved local control and survival outcomes compared with conventional CT-guided implantation.

Full description

This prospective, open-label Phase I/II trial evaluates a molecular-imaging-guided optimization strategy that integrates PET/CT into radioactive seed implantation therapy to improve target delineation accuracy, biological precision, and therapeutic efficacy in malignant solid tumors. Conventional CT-guided planning relies primarily on anatomical visualization and geometric dose coverage but does not incorporate intratumoral biological heterogeneity, which may result in uneven dose distribution and increased risk of local recurrence. To address this limitation, the trial incorporates PET/CT-based biological target volume (BTV) delineation and standardized uptake value (SUV)-driven dose modulation to achieve individualized, biologically optimized treatment planning.

Eligible participants with measurable solid tumors suitable for percutaneous implantation are assigned to one of three groups: (1) conventional CT-guided implantation, (2) PET/CT-guided implantation with standard dosing, and (3) PET/CT-guided implantation with biological dose optimization based on metabolic activity quantified by SUV measures. PET/CT is used to identify metabolically active sub-volumes for selective dose escalation while sparing normal tissues, achieved by adjusting seed activity or spatial distribution to deliver intensified irradiation to high-SUV tumor regions. In addition to standard 18F-FDG PET/CT, tumor-specific tracers are evaluated in selected subgroups to enhance lesion visualization and biological characterization, including 18F-PSMA for prostate cancer, 68Ga-FAPI for pancreatic, colorectal, and fibrotic tumors, 18F-FES for ER-positive breast cancer, and 18F-FMISO or 18F-FAZA for hypoxia detection and targeted dose escalation.

Primary endpoints include technical success rate, dosimetric superiority, and 6-month local control defined by imaging and clinical criteria. Secondary endpoints include dosimetric parameters (D90, V100, conformity index, homogeneity index), pain relief, quality of life (EORTC QLQ-C30), treatment-related adverse events (CTCAE v5.0), and time-to-event outcomes including progression-free survival (PFS), failure-free survival (FFS), and overall survival (OS). Exploratory analyses evaluate correlations between baseline PET parameters (SUVmax, metabolic tumor volume, total lesion glycolysis), radiomics features, and clinical outcomes, as well as early metabolic response (ΔSUVmax at 4-6 weeks) as a predictor of local control.

The central hypothesis is that PET/CT-guided biological optimization will enhance dosimetric conformity, improve local tumor control and survival outcomes, reduce recurrence, and contribute to better symptom relief and quality-of-life measures. Overall, the trial aims to establish a personalized, molecular-imaging-based framework for radioactive seed implantation therapy in malignant solid tumors.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years.
2. Pathologically or clinically confirmed malignant tumor (solid tumor, lymphoma, or leukemia with a localized lesion suitable for radioactive seed implantation).
3. Tumor site accessible for image-guided implantation, with a target lesion visible on CT or PET/CT.
4. Life expectancy of at least 6 months.
5. Ability to undergo PET/CT imaging (FDG or tumor-specific tracers such as PSMA or FAPI).
6. Signed written informed consent.

Exclusion criteria

1. Pregnant or breastfeeding women.
2. Uncontrolled infection or active systemic inflammatory disease.
3. Severe cardiopulmonary dysfunction that contraindicates interventional procedures (e.g., heart failure, severe COPD).
4. Coagulation disorders (INR > 1.5 or platelet count < 50 × 10⁹/L).
5. Known allergy or intolerance to radiopharmaceuticals or iodinated contrast media.
6. Prior radiation therapy overlapping with the planned implantation area.
7. Participation in another clinical trial within the past 30 days that may interfere with study results.
8. Any medical or psychosocial condition considered unsuitable for study participation by the investigators (e.g., poor compliance, unstable clinical status).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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90 participants in 4 patient groups

CT-Guided Radioactive Seed Implantation

Active Comparator group

Description:

CT-guided 125I seed brachytherapy with a standard dose prescription. Target delineation based on contrast-enhanced CT. Post-implant dosimetry will verify D90, V100, V150, and organ-at-risk constraints.

Treatment:

Procedure: CT-Guided Radioactive Seed Implantation

PET/CT-Guided Radioactive Seed Implantation - Standard Dose

Experimental group

Description:

PET/CT-guided 125I seed implantation using PET/CT to support anatomical target delineation without SUV-based biological sub-volume definition. A standard uniform-dose prescription is applied. Post-implant dosimetry verifies target coverage and organ-at-risk constraints.

Treatment:

Procedure: PET/CT-Guided Radioactive Seed Implantation

PET/CT-Guided Radioactive Seed Implantation - Biological Dose Optimization

Experimental group

Description:

PET/CT-guided 125I seed implantation incorporating SUV-based biological sub-volume identification. High-SUV regions receive selective dose escalation through adjustments in seed activity or spatial seed distribution while maintaining organ-at-risk constraints.

Treatment:

Procedure: PET/CT-Guided Radioactive Seed Implantation (Biological Dose Optimization)

Specific PET/CT-Guided Radioactive Seed Implantation (PSMA/FAPI Subgroup)

Experimental group

Description:

Tumor-specific PET tracers such as PSMA and FAPI are used in selected subgroups to enhance lesion visualization and biological characterization for planning 125I seed implantation. Additional tracers are not currently in clinical use within the department but may be incorporated in future protocol amendments as availability allows.

Treatment:

Procedure: Tumor-Specific PET/CT-Guided Radioactive Seed Implantation (PSMA/FAPI Subgroup)