Robotic Bronchoscopy With CBCT Image Fusion for Pulmonary Nodule Diagnosis in People Living With HIV

Официальное название

Clinical Application and Promotion of Full-Situational Awareness Bronchoscopic Robot Combined With CBCT-Based Multimodal Image Fusion for the Diagnosis and Management of Pulmonary Nodules in People Living With HIV: A Multicenter Open-Label Controlled Study

Обзор

This multicenter study evaluates a full-situational awareness robotic bronchoscopy system combined with CBCT-based multimodal image fusion for diagnosing lung nodules in people living with HIV (PLWH). Lung nodules are small lesions that may be benign or cancerous. In PLWH, accurate diagnosis is especially important but challenging. In this study, participants will be assigned to one of two groups: * Experimental group: Robotic bronchoscopy with real-time full-situational awareness and CBCT image fusion; * Control group: Electromagnetic navigation-guided bronchoscopy combined with radial endobronchial ultrasound (EBUS). In both groups, rapid on-site cytologic evaluation (ROSE) will be performed to confirm tissue adequacy. For participants confirmed to have lung cancer and meeting safety criteria, an exploratory transbronchial cryoablation will be performed during the same procedure. The study aims to compare diagnostic accuracy and safety between the two approaches and to explore the feasibility of immediate cryoablation for early-stage lung cancer in PLWH.

Подробное описание

Background Lung cancer is a leading cause of cancer mortality worldwide. Early detection and differentiation of pulmonary nodules are critical for survival. In people living with HIV (PLWH), pulmonary nodules carry a higher risk of malignancy, yet percutaneous biopsy is often contraindicated due to coagulation abnormalities or immunosuppression, and conventional bronchoscopy yields variable diagnostic rates (30%-70%) for peripheral nodules ≤3 cm. Electromagnetic navigation bronchoscopy (ENB) improves accessibility but lacks real-time intraoperative image feedback, while cone-beam CT (CBCT) provides intraoperative 3D imaging without dynamic fusion to robotic navigation. Existing robotic bronchoscopes improve stability but have limited distal fine control in complex airways.

Preclinical and early clinical data suggest that full-situational awareness bronchoscopic robots (FSABR) integrated with CBCT-based multimodal image fusion can construct a dynamically updated 3D lung model, compensate for respiratory-induced target displacement, and improve tool-in-lesion accuracy and biopsy yield. However, clinical evidence-especially in PLWH-remains lacking.

Study Design

This is a prospective, multicenter, randomized (1:1), open-label, parallel-group controlled trial conducted at Shanghai Public Health Clinical Center and collaborating centers. Eligible PLWH with pulmonary nodules ≤3 cm (malignant risk ≥50% by CT) will be randomly assigned to:

* Experimental arm: FSABR with CBCT-based multimodal image fusion guidance for targeted biopsy; * Control arm: ENB-guided bronchoscopy with radial endobronchial ultrasound (r-EBUS) localization for targeted biopsy.

In both arms, rapid on-site evaluation (ROSE) will be performed to confirm specimen adequacy. For participants with ROSE-confirmed malignancy meeting predefined anatomic and clinical safety criteria, exploratory transbronchial cryoablation will be performed during the same procedure. This therapeutic component is hypothesis-generating only.

Procedures Peripheral nodules will be localized by intraoperative imaging (CBCT in the experimental arm; r-EBUS in the control arm). Targeted biopsy will be performed using a 1.1-mm cryoprobe (typically 3 freeze-thaw cycles or until adequate tissue is obtained). Cryoablation (3 cycles × 12 min) will be attempted only in ROSE-positive patients with early-stage peripheral lung cancer deemed suitable by the operator. Follow-up includes chest CT at post-procedure day 1 and month 1 for all patients, and additional serial CT at 3, 6, 12, and 24 months for patients undergoing cryoablation, together with HIV virologic monitoring (viral load and CD4 count).

Objectives The primary objective is to compare the diagnostic yield (proportion of cases with a definitive benign or malignant histocytologic diagnosis) between the FSABR-CBCT arm and the ENB-r-EBUS arm. Secondary objectives include: tool-in-lesion rate, nodule visualization rate, ROSE adequacy, specimen quality, procedural times, safety (pneumothorax, bleeding, infection, HIV-related events), and feasibility/safety of same-session cryoablation. Sensitivity, specificity, positive and negative predictive values, and accuracy for malignancy will also be calculated using final histopathology or 6-12-month imaging follow-up as reference standard.

This study is expected to provide evidence on the clinical utility of full-situational awareness robotic bronchoscopy with intraoperative CBCT fusion in a vulnerable population and to explore the feasibility of a "diagnose-and-treat" strategy for early lung cancer in PLWH.

Вмешательства

• Процедура Robotic bronchoscopy with CBCT-guided multimodal image fusion and targeted cryobiopsy
  Participants undergo peripheral pulmonary nodule biopsy using a full-situational awareness bronchoscopic robot. Intraoperative cone-beam CT (CBCT) and multimodal image fusion are used for real-time navigation. ROSE is performed. If ROSE confirms malignancy and safety criteria are met, exploratory transbronchial cryoablation is done in the same session. If robotic navigation fails to obtain a definitive diagnosis, percutaneous transthoracic needle biopsy (PTNB) may be used as rescue.
• Процедура Electromagnetic navigation bronchoscopy with radial EBUS and targeted cryobiopsy
  Participants undergo peripheral pulmonary nodule biopsy using electromagnetic navigation bronchoscopy (ENB) with radial endobronchial ultrasound (r-EBUS) localization. ROSE is performed. If ROSE confirms malignancy and safety criteria are met, exploratory transbronchial cryoablation is done in the same session. If ENB-rEBUS fails to obtain a definitive diagnosis, percutaneous transthoracic needle biopsy (PTNB) may be used as rescue.

Первичные конечные точки

• Diagnostic Yield [Срок оценки: From initial bronchoscopic biopsy through final histopathologic or 12-month imaging confirmation]

Вторичные конечные точки (8)

• Tool-in-Lesion Rate [Срок оценки: Intraoperative (at time of biopsy attempt)]
• Nodule Visualization Rate [Срок оценки: Intraoperative]
• ROSE Adequacy [Срок оценки: Intraoperative]
• Qualified Cryobiopsy Specimen Rate [Срок оценки: Intraoperative (immediate pathologic assessment)]
• Cryoablation Success (Exploratory) [Срок оценки: Intraoperative]
• Complete / Partial Ablation Response Rate [Срок оценки: 6 months and 12 months post-procedure]
• Procedure Time [Срок оценки: Intraoperative]
• Safety - Overall Adverse Event Rate [Срок оценки: From procedure through 30 days post-procedure (through 24 months for ablated patients regarding delayed complications)]

Критерии участия

Критерии включения

• Confirmed diagnosis of HIV infection; on stable antiretroviral therapy (ART) for ≥6 months with plasma HIV viral load <50 copies/mL.
• Presence of at least one pulmonary nodule ≤3 cm in maximum diameter on thin-section CT; radiological features suggestive of malignancy (e.g., part-solid or solid nodule with spiculation, lobulation, or vessel convergence) with estimated pretest probability of malignancy ≥50%.
• Age 18-70 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Life expectancy ≥6 months.
• Voluntary written informed consent obtained prior to any study procedure; willingness and ability to comply with scheduled visits, procedures, and follow-up requirements.

Критерии исключения

• Active pulmonary tuberculosis or Pneumocystis jirovecii pneumonia requiring acute treatment at the time of screening.
• Coagulation disorder: International Normalized Ratio (INR) >1.5 or platelet count <50 × 10\^9/L.
• Prior definitive treatment for the target pulmonary nodule (e.g., surgical resection, radiotherapy, ablation, or systemic anti-tumor therapy).
• Unstable ART status: not on continuous ART or HIV viral load ≥50 copies/mL within 3 months prior to enrollment.
• Target lesion already diagnosed definitively by previous percutaneous biopsy or surgical pathology.
• Severe cardiopulmonary dysfunction:

• Forced Expiratory Volume in 1 second (FEV1) <50% predicted; or
• New York Heart Association (NYHA) Class III-IV heart failure.
• Pregnancy or breastfeeding.
• Participation in another interventional clinical trial within the past 3 months.
• Inability to complete follow-up (e.g., no fixed residence, unstable contact information).
• Any other condition that, in the investigator's judgment, would make the participant unsuitable for enrollment or pose unacceptable risk (including significant airway abnormality preventing safe navigation).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07663656 · SPHCC-FSABR-CBCT-HIVPN-OC-2026 · SHDC12025140

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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