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

NCT ID: NCT07327515

Last Updated: 2026-01-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-31

Study Completion Date

2028-06-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Malignant Tumors

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants are assigned in parallel to three groups: CT-guided, PET/CT-guided standard dose, and PET/CT-guided biological dose optimization. Exploratory cohorts may use tumor-specific PET tracers, including PSMA, FAPI, and other emerging agents, to refine biological targeting and predictive modeling.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Due to the procedural nature of seed implantation, participants and treating clinicians cannot be blinded. However, independent radiologists and nuclear medicine physicians who evaluate imaging outcomes (e.g., tumor response, PET metabolic parameters, local control) will be blinded to group allocation and treatment details. Blinded image review will include: (1) PET/CT parameter assessment (SUVmax, MTV, TLG), (2) Radiographic response evaluation (RECIST 1.1 criteria), (3) Dosimetric verification (D90, V100, V150). All imaging data will be anonymized before evaluation to minimize potential bias in efficacy and dosimetric assessments.

Study Groups

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CT-Guided Radioactive Seed Implantation

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.

Group Type ACTIVE_COMPARATOR

CT-Guided Radioactive Seed Implantation

Intervention Type PROCEDURE

CT-guided implantation of 125I radioactive seeds for localized treatment of malignant tumors. The target area is delineated on contrast-enhanced CT images, and seeds are implanted according to a treatment planning system (TPS) with a prescribed dose of about 100 Gy. Post-procedure dosimetry will confirm D90, V100, and V150, as well as organ-at-risk (OAR) dose constraints.

PET/CT-Guided Radioactive Seed Implantation - Standard Dose

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.

Group Type EXPERIMENTAL

PET/CT-Guided Radioactive Seed Implantation

Intervention Type PROCEDURE

PET/CT-guided 125I seed implantation performed using PET/CT fusion to support anatomical target delineation without SUV-based biological sub-volume definition. A standard uniform-dose treatment plan is implemented, and post-implant dosimetric evaluation is used to confirm target coverage and compliance with organ-at-risk constraints.

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

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.

Group Type EXPERIMENTAL

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

Intervention Type PROCEDURE

PET/CT-guided 125I seed implantation for the treatment of malignant tumors. The biological target volume (BTV) is defined using 18F-FDG PET/CT fused with planning CT to improve target accuracy and tumor coverage. The prescribed dose is approximately 100 Gy. Post-implant verification includes D90, V100, and OAR constraints.

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

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.

Group Type EXPERIMENTAL

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

Intervention Type PROCEDURE

125I seed brachytherapy guided by tumor-specific PET/CT imaging. Tracers such as PSMA (for prostate cancer) and FAPI (for pancreatic, colorectal, and fibrotic tumors) identify biologically active regions for targeted dose escalation. High-uptake areas (SUVmax \> threshold determined by tracer characteristics) receive escalated doses of approximately 120-150 Gy through increased seed density or activity, while normal tissues remain within tolerance limits.

Interventions

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PET/CT-Guided Radioactive Seed Implantation

PET/CT-guided 125I seed implantation performed using PET/CT fusion to support anatomical target delineation without SUV-based biological sub-volume definition. A standard uniform-dose treatment plan is implemented, and post-implant dosimetric evaluation is used to confirm target coverage and compliance with organ-at-risk constraints.

Intervention Type PROCEDURE

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

PET/CT-guided 125I seed implantation for the treatment of malignant tumors. The biological target volume (BTV) is defined using 18F-FDG PET/CT fused with planning CT to improve target accuracy and tumor coverage. The prescribed dose is approximately 100 Gy. Post-implant verification includes D90, V100, and OAR constraints.

Intervention Type PROCEDURE

CT-Guided Radioactive Seed Implantation

CT-guided implantation of 125I radioactive seeds for localized treatment of malignant tumors. The target area is delineated on contrast-enhanced CT images, and seeds are implanted according to a treatment planning system (TPS) with a prescribed dose of about 100 Gy. Post-procedure dosimetry will confirm D90, V100, and V150, as well as organ-at-risk (OAR) dose constraints.

Intervention Type PROCEDURE

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

125I seed brachytherapy guided by tumor-specific PET/CT imaging. Tracers such as PSMA (for prostate cancer) and FAPI (for pancreatic, colorectal, and fibrotic tumors) identify biologically active regions for targeted dose escalation. High-uptake areas (SUVmax \> threshold determined by tracer characteristics) receive escalated doses of approximately 120-150 Gy through increased seed density or activity, while normal tissues remain within tolerance limits.

Intervention Type PROCEDURE

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Li Min

OTHER

Sponsor Role lead

Responsible Party

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Li Min

Vice Director

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Min Li, Dr.

Role: STUDY_DIRECTOR

Locations

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The 960th Hospital of People's Liberation Army (PLA)

Jinan, Shandong, China

Site Status

Countries

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China

Central Contacts

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Min Li, Dr.

Role: CONTACT

0531-51665482

Min Li, Dr.

Role: CONTACT

Facility Contacts

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Min Li, Dr.

Role: primary

0531-51665482

Other Identifiers

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960HP20251026

Identifier Type: -

Identifier Source: org_study_id

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