Research on New Intelligent Diagnosis and Treatment Technologies for Early Lung Cancer Based on Multimodal Imaging Bronchoscopy Navigation
Phase: NA
Conditions: Lung Cancer, Peripheral Pulmonary Nodules
Sponsor: Jisong Zhang

Study protocol 
 
 
Official Title of the study: Research on New Intelligent Diagnosis and Treatment 
Technologies for Early Lung Cancer Based on Multimodal Imaging Bronchoscopy 
Navigation 
Affiliation: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine 
Department: Department of Respiratory and Critical Care Medicine 
Date of the document: May 20, 2024 
 
 

Research on new intelligent diagnosis and treatment technologies for early lung 
cancer based on multimodal imaging bronchoscopy navigation 
 
 
Background 
Lung cancer is one of the malignant tumors with the highest incidence and mortality 
rates worldwide. From the 1970s to the present, the mortality rate of lung cancer in 
China has been climbing year by year, and currently lung cancer ranks first in China in 
terms of incidence rate and mortality rate. Meanwhile, data show that 75% of lung 
cancer patients are already in advanced stage when they are diagnosed. The 5-year 
survival rate of advanced lung cancer in China is only 16.1%, while the 5-year survival 
rate of early lung cancer patients can reach 73%. Therefore, improving the early 
diagnosis rate of lung cancer will greatly reduce the mortality rate of lung cancer. 
Regular chest computed tomography (CT) in the population can detect a large 
number of nodular lung lesions, and data show that lung nodules are detected in 
approximately 25% of the population on routine screening, most of which (96.4%) are 
benign. Further examination of these high-risk lung nodules is effective in improving 
early lung cancer detection and reducing mortality by approximately 20%. CT-guided 
percutaneous lung puncture is the mainstay of conventional diagnosis of lung nodules, 
and the risk of complications is a major concern. Its complications include 
pneumothorax, hemoptysis, and needle tract metastasis, among which the incidence of 
pneumothorax is 12.3% and hemoptysis is 20%. In recent years, the use of navigational 
tracheoscopy for peripheral lung nodule biopsy has gradually increased in the clinic 
due to good safety and accuracy. 2020 CHEST published a meta-analysis on 
navigational tracheoscopy, the incidence of pneumothorax is only 2%, which is 
obviously advantageous compared with the traditional methods. 
Even so, navigational bronchoscopy techniques have limitations in the 
management of peripheral lung nodules. Navigation bronchoscopy has limitations in 
the diagnosis and treatment of peripheral lung nodules. Data show that the overall 
diagnostic rate of navigation bronchoscopy for biopsy of peripheral lung nodules is 

80%, which is lower than that of traditional CT-guided percutaneous lung puncture, 
especially for near-pleural foci and foci with a diameter of less than 1 cm. There are 
three reasons for this. First, the current mainstream navigation system based on CT 
images does not have enough ability to recognize airways smaller than 3 mm, and 
intraoperative blindness exists in some of the small airway areas, resulting in failure or 
inaccuracy of preoperative bronchoscopic path planning in some areas. Second, the 
current mainstream bronchoscopy equipment apex outer diameter is generally around 
4-5mm, which cannot enter the finer distal small airways, and it is difficult to reach 
some peripheral lesions close to the subpleural area, which makes it difficult to increase 
the biopsy positivity rate of this part of the lesion. Third, the small airways around the 
lesions are in a collapsed state due to various reasons such as sputum stasis, insufficient 
inspiration or breath holding during the acquisition of CT images, so it is difficult for 
preoperative CT to truly reflect the situation of the patient's airway, which ultimately 
results in the difference between the real-time observation of the distribution of the 
airway and the pathway of the preoperative planning, and makes it impossible to realize 
the accurate guidance in the intraoperative period. 
To improve the diagnostic rate of lung nodules by navigational bronchoscopy, this 
project has conducted a preliminary exploration to address the three main issues 
mentioned above. The preliminary research found that the mainstream whole-lung 
navigation systems on the market, including The SPiN Thoracic Navigation System 
magnetic navigation system from Veran, the virtual bronchoscopic navigation (VBN) 
System from Lungpro of Broncus, and the Super Dimension Electromagnetic 
Navigation System from Medtronic, are all similar, although there are differences in the 
operation process. Despite the differences in operation procedures, the core technology 
of computerized virtual bronchial tree imaging is similar, and all of them are suboptimal 
for the reconstruction of small airways less than 3 mm. The main reason is that for small 
airways less than 3 mm, the airway features are not obvious or missing, which are 
difficult to be extracted by the existing navigation algorithms. To address this problem, 
on the basis of the existing algorithms to recognize airway segments, deep learning 
technology is added to do super-resolution reconstruction of the original CT by super-

resolution convolutional neural network (SRCNN), so as to enhance the visual features 
of the airway smaller than 3mm, and link the 3D-VNET network model with its own 
attention mechanism to intelligently recognize more small airway segments smaller 
than 3mm. 
 
Study purpose and design 
To improve the problems of recognition, extraction, and three-dimensional 
reconstruction of 2-3mm small airways that have not been solved by mainstream 
navigation software on the market through deep learning methods based on the VBN 
navigation system, and evaluate the accuracy of the improved navigation system and 
the original navigation system in the diagnosis of peripheral pulmonary lesions (PPL) 
through a randomized controlled trial. 
 
Study population 
Subjects for this single-center randomized controlled trial were recruited from August 
2023 to December 2024 at the Sir Run Run Shaw Hospital, Zhejiang University School 
of Medicine. 
 
Inclusion and exclusion criteria 
Inclusion criteria: (1) aged 18 years or above; (2) patients with one or more peripheral 
lung nodules suspected to be lung cancer or poorly absorbing lesions on conventional 
anti-infective therapy; (3) patients with nodule diameters ≤30 mm (diameters 
mentioned in the text are the average of the maximum and minimum diameters; (4) the 
nodules were pure ground glass nodules, partially solid nodules, or solid nodules; (5) 
the nodule is surrounded by lung parenchyma and is not visible in the bronchial lumen 
above the segment.  
Exclusion criteria: (1) preoperative judgment that it is difficult for the patient to benefit 
from bronchoscopic biopsy (e.g., high risk of bleeding due to perivascular encasement 
of the lesion, difficulty in reaching the airway adjacent to the lesion due to previous 
lung surgery, etc.); (2) those with incomplete clinical data; (3) those with missing visits 

after biopsy. 
 
Interventions 
After stratification according to the size of the lesion and the proportion of solid 
components in the lesion (≥50%, <50%), the eligible subjects were randomized into the 
new navigation system group (experimental group) and the old navigation system group 
(control group) in a 1:1 ratio. All included subjects underwent transnavigation-guided 
bronchoscopic lung biopsy at the respiratory endoscopy center. For pre-biopsy 
navigation path planning, the small airway reconstruction system-pro (SARS-pro) (self-
developed by our team) was used in the experimental group and the conventional VBN 
system (LungPro; Bronchus Corporation) in the control group. The SARS-pro 
navigation system is an augmented reality optical navigation system based on VBN, 
which upgrades the small airway tree reconstruction navigation system through deep 
learning and multiple trainings. 
 
Outcomes 
The primary outcome was the diagnostic positive yield of the different navigation 
systems for PPL. The second outcome was the adverse events (hemoptysis, 
pneumothorax, and mediastinal emphysema) of the subjects.  
 
Ethical approval and informed consent statement 
The trial was approved by the Ethics Committee of the Sir Run Run Shaw Hospital, 
Zhejiang University School of Medicine (approval number: 2024-1000) (See the 
attachment "Ethics Approval Document"). For statistical analysis, subject identities 
were expressed as codes, which did not involve disclosure of subjects' privacy and 
personal information, and the study did not involve commercial interests, so informed 
consent was waived by the Ethics Committee (See the attachment " Informed consent 
form"). 

Statistical analysis plan 
 
 
Official Title of the study: Research on New Intelligent Diagnosis and Treatment 
Technologies for Early Lung Cancer Based on Multimodal Imaging Bronchoscopy 
Navigation 
Date of the document: May 20, 2024 
 
 

Research on New Intelligent Diagnosis and Treatment Technologies for Early 
Lung Cancer Based on Multimodal Imaging Bronchoscopy Navigation 
 
 
Statistical analysis 
For sample size calculation, a study reported a deep learning-based airway 
segmentation algorithm based on 40 CT images. Based on the benefit of a larger sample 
size in deep learning, the sample size in this study was set to 100. For subject 
characteristics, the quantitative data were tested for normality using the skewness and 
kurtosis methods, and the homogeneity of variance was tested using the Levene test. 
Normal distribution measurement data were described as mean and standard deviation 
[Mean (±SD)], and t test or t' test was utilized for comparison between groups. Non-
normal data were summarized as median and interquartile range [M (Q₁, Q₃)], and 
group comparisons were made using the Wilcoxon rank sum test. Count data were 
reported as the number of cases and composition ratio [n (%)], and the chi-square test 
or the Fisher exact test was utilized for comparison between groups. Data cleaning was 
accomplished using Python 3.9.12 (Python Software Foundation, Delaware, USA), and 
the difference comparison was completed by R version 4.3.3 (R Foundation for 
Statistical Computing, Vienna, Austria). Statistical significance was set to P<0.05. 
 
Data management and confidentiality 
(1) The data is stored in the hospital's server with strict security protection and is not 
accessible to external networks; (2) All information related to the identity of the CT's 
patients is kept confidential, and the relevant information is not disclosed to the public 
outside of the scope permitted by relevant laws and/or regulations. 
 
 
 

Ethics Committee Approval (Original Chinese version) 
 
 
Official Title of the study: Research on New Intelligent Diagnosis and Treatment 
Technologies for Early Lung Cancer Based on Multimodal Imaging Bronchoscopy 
Navigation 
Affiliation: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine 
Department: Department of Respiratory and Critical Care Medicine 
Date of the document: June 6, 2024 
 

Ethics Committee Approval (English translation version) 
 
 
Official Title of the study: Research on New Intelligent Diagnosis and Treatment 
Technologies for Early Lung Cancer Based on Multimodal Imaging Bronchoscopy 
Navigation 
Affiliation: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine 
Department: Department of Respiratory and Critical Care Medicine 
Date of the document: June 6, 2024 
 
 
 

Ethics Committee Approval Letter of Sir Run Run Shaw Hospital, Zhejiang 
University School of Medicine 
 
Approval No: Sir Run Run Shaw Hospital Ethical Review 2024 Study No. 1000 (Abbreviation: 2024-
1000) 
Study Title 
Research on new intelligent diagnosis and treatment technologies for early 
lung cancer based on multimodal imaging bronchoscopy navigation 
Sponsor 
No 
Acceptance Number 
2024-2289-01 
Principal 
Investigator 
Enguo Chen 
Responsible 
Department 
Department of 
Respiratory Medicine 
Category of Review 
Initial review 
Type of Review 
Quick review 
Date of Review 
2024.06.06 
Location of Review 
/ 
Items Reviewed 
See the attachment 
Evaluation 
This ethics committee believes that the submitted review materials comply 
with ethical norms and agrees to conduct clinical research. 
Decision 
The committee's review resolution on the project is: Consent 
Chair signature 
 
Date of issue 
 
Stamp of EC 
Stamped by the Ethics Review committee. 
Period of Validity 
This clinical study shall be initiated in our hospital within one year from 
the date of the initial review and approval by this ethics review committee. 
Continue Review 
The review frequency is once every 12 months from the date of approval 
of this research. The first time is on June 5, 2025. Please submit the 
research progress report one month before the expiration of the approval 
document. The Ethics Review committee has the right to change the 
frequency of follow-up reviews according to the actual progress. 
Statement 
The responsibilities, composition of personnel, operating procedures and 
records of this ethics review committee comply with the "Ethical Review 

Measures for Biomedical Research Involving Humans", the "International 
Ethical Guidelines for Research Related to Human Health", the 
"Declaration of Helsinki", international ethical guidelines such as GCP 
and ICH-GCP, and relevant domestic laws and regulations. 
Precautions 
l. Please follow the ethical principles in the relevant laws, regulations and rules of China. 
2. Please conduct the study in accordance with the clinical research protocol, informed consent form 
and recruitment materials approved by the Ethics Review Committee to protect the health and rights 
of the subjects. Any modification of the study protocol, informed consent form, recruitment materials, 
etc. must be reviewed and approved by the Ethics Review Committee before implementation. 
3. SAE/SUSARs occurring in this institution and safety update reports during the research and 
development period shall be submitted to the Ethics Review Committee in a timely manner in 
accordance with the latest requirements of NMPNGCP, and SAE/SUSARs occurring in other centers 
in China and abroad shall be summarized and evaluated periodically and then submitted to the Ethics 
Review Committee. 
4. The Ethics Review Committee has the right to make a new decision on the evaluation based on the 
reports. 
5. Regardless of whether the study is started or not, please submit the study progress report 1 month 
before the due date of the follow-up review. 
6. The sponsor should submit a summary of the center's research progress report to the Ethics Review 
Committee of the group leader. The applicant is requested to submit a written report to this Ethics 
Review Committee in a timely manner when any situation arises that may significantly affect the 
conduct of the study or increase the risk to the subjects. 
7. When the study enrolls subjects who do not meet the inclusion criteria or meet the exclusion criteria, 
withdraws subjects from the study in accordance with the rules for discontinuation of the study, 
administers incorrect treatments or dosages, or administers combinations of medications prohibited 
by the protocol, etc., and conducts the study without complying with the protocol, or violates the 
principles of GCP by potentially adversely affecting the rights and interests of subjects or their health 
as well as the scientific validity of the study, the applicant, the Supervisory Reviewer, or the 

investigator shall submit a report on the violation of the protocol. investigator to submit a report on 
the violation of the protocol. 
8. If the applicant suspends or prematurely terminates the clinical study, the applicant is requested to 
submit a report on the suspension or termination of the study in a timely manner. 
9. Upon completion of the clinical study, the applicant is requested to submit a completion report. 
10. All research projects involving the collection of specimens and data from Chinese human genetic 
resources must be approved by the China Human Genetic Resources Management Office before the 
research can be carried out in the Center. 11. 
11. Before the implementation of any research project approved by the Ethics Review Committee, the 
applicant shall register the relevant information of the research project on the clinical research 
registration information system platform of the National Health and Keystone Commission and the 
Center for Drug Control and Prevention in accordance with relevant regulations. 
Attachments: 
1. Application form for initial review (for scientific research) 
2. Principal Investigator's Responsibility Statement 
3. Principal Investigator's Curriculum Vitae 
4. Study protocol (V1.0; 2024.05.20) 
5.Application for exemption/waiver of informed consent form 
6. Science and Technology Program of Zhejiang Province Project No.: 2022C03086. 

Informed Consent Form (Original Chinese version) 
 
 
Official Title of the study: Research on New Intelligent Diagnosis and Treatment 
Technologies for Early Lung Cancer Based on Multimodal Imaging Bronchoscopy 
Navigation 
Affiliation: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine 
Department: Department of Respiratory and Critical Care Medicine 
Date of the document: May 28, 2024 
 

Informed Consent Form (English translation version) 
 
 
Official Title of the study: Research on New Intelligent Diagnosis and Treatment 
Technologies for Early Lung Cancer Based on Multimodal Imaging Bronchoscopy 
Navigation 
Affiliation: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine 
Department: Department of Respiratory and Critical Care Medicine 
Date of the document: May 28, 2024 
 
 

Application Form for Exemption/Signature of Informed Consent Form 
Project Name 
Research on new intelligent diagnosis and treatment technologies for 
early lung cancer based on multimodal imaging bronchoscopy 
navigation 
Clinical research 
category 
□ Sponsor-initiated non-registered clinical studies  
√ Investigator-initiated clinical studies  
Sponsor 
No 
Principal Investigator 
Enguo Chen 
Responsible 
Department 
Department of 
Respiratory 
Medicine 
1. Exemption from informed consent (skip if not applicable) 
□ Research conducted using data or specimens obtained from previous clinical diagnosis and 
treatment, disease surveillance or clinical studies, and where potential subjects have 
signed informed consent forms allowing such data or specimens to be used in other clinical 
studies (not applicable, please skip) 
1 
Please provide the ethics approval number corresponding to the original 
informed consent form or the signed informed consent form. 
2 
Please explain whether this study exceeds the scope permitted by the 
original informed consent letter. 
3 
Please explain whether the privacy and personal identity information of 
the subjects are protected. 
4 
Please specify whether follow-up or obtaining information from the 
subjects again is needed in the future 
√ Research conducted using data or specimens obtained from previous clinical diagnosis and 
treatment, disease surveillance or clinical studies, and where potential subjects have not 
signed the informed consent form allowing such data or specimens to be used in other 
clinical studies (If not applicable, please skip). 
1 
Please explain if the data or specimens used are obtained from previous 
clinical diagnosis and treatment, disease surveillance or clinical 

research. (Yes) 
2 
Please specify whether to use data or specimens that the subjects 
explicitly refused to utilize. (No) 
3 
If informed consent is required as stipulated, the study cannot be 
conducted. (The subjects have the right to know that their data or 
specimens may be used for the study. Their refusal or non-consent to 
participate in the study is not evidence that the study cannot be carried 
out or that informed consent is waived). 
4 
Please explain whether the privacy and personal identity information of 
the subjects are protected. (Yes) 
5 
Whether follow-up is needed in the future or to obtain information from 
the subjects again. (No) 
2. Application for exemption from signing of informed consent Form (Skip if not applicable) 
□The signed informed consent form poses an improper threat to the privacy of the subjects. 
The only record that links the true identity of the subjects and the research is the informed 
consent document. The main risk comes from the leakage of the subjects' identities or personal 
privacy， please explain. 
□In other cases, such as when conducting questionnaire surveys through email, wechat, 
DingTalk or phone calls, if written informed consent has been provided to the subjects or their 
guardians or oral informed consent has been obtained from them, please explain. 
Signature of the principal 
researcher 
 
Date