Surgical Strategy of NSCLC Patients After Neo-adjuvant or Induction Treatment
Conditions: Non-small Cell Lung Cancer, Surgery
Sponsor: Ruijin Hospital

1 
Annex 3. 
Ruijin Hospital of Shanghai 
Jiaotong University School of 
Medicine 
Programme of Scientific 
Research Projects Involving 
Human Subjects 
 
(Applicable to prospective studies) 
 
 
Surgical strategies after neoadjuvant or 
induction chemoimmunotherapy in operable 
Study Name:           non-small cell lung cancer                                   
 
 
Programme No . :    NA 
  
Principal Investigator:    Hecheng Li 
 
Affiliation(s):     Department of Thoracic                                  
 
 
 
Ruijin Hospital of Shanghai Jiao 
Tong University  School of Medicine 
10th July 2023 
Version number: 2.0 

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1.   Research Summary 
1.1   Abstracts 
Study title：            Surgical strategies after neoadjuvant or induction 
chemoimmunotherapy in operable small cell lung cancer 
Research Brief:                 Lung cancer is one of the most common malignant tumors worldwide 
and has the highest mortality rate among malignant tumors. In recent 
years, with the gradual development of therapeutic modalities such as 
targeted therapy and immunotherapy, the overall survival of lung cancer 
patients have improved significantly. However, late tumor staging at the 
time of diagnosis often leaves patients with only pneumonectomy, 
which affects the prognosis with a higher rate of postoperative 
complications than lobectomy, poorer quality of life, and the possible 
loss of the opportunity to continue adjuvant therapy. 
Our group proposes to conduct this single-arm prospective clinical 
study to investigate the feasibility, safety, and prognosis of the 
conversion from pneumonectomy to lobectomy after neoadjuvant or 
induction therapy in patients with operable non-small cell lung 
cancer. 
 
Study Objective ：       Primary objective: to investigate the feasibility of switching to 
lobectomy after neoadjuvant/induced chemoimmunotherapy in patients 
with operable non-small cell lung cancer requiring pneumonectomy 
at first diagnosis (R0 resection rate of lobectomy). 
Secondary objective: to investigate the perioperative and long-term 
outcomes of patients with operable non-small cell lung cancer who 
were evaluated to undergo pneumonectomy at first diagnosis and 
switched to neoadjuvant or induction chemoimmunotherapy and 
subsequent lobectomy. 
Study population:                   50 cases 
1） Patients  voluntarily  participated  in  this  study,  had  good  compliance,  could 
cooperate with the trial requirements to complete observation and follow-up, 
and signed the informed consent form; 
2） Be over  18 and under 75 years of age, and is open to both men and women; 
3） Pathologically   confirmed  non-small   cell   lung   cancer   and   clinical   stage 
T2-4N0-2,   potentially   need   pneumonectomy,   neoadjuvant,   or   induction 
Chemo-immunotherapy 
4） ASA rating: I-III. 
5） Cardiac function assessment was adequate for radical lung cancer surgery with 
normal liver and kidney function. 
Study unit/location ：     This is a multicenter study with 4 centers proposed to participate in. 
Study interventions ：        Patients  enrolled will  further undergo relevant examinations (including chest 
enhancement  CT,  PET-CT  (optional),  cranial  MR,  bronchoscopy,  cardiac 
ultrasound,  pulmonary  function,  electrocardiogram,  and  blood  tests)  and  be 
checked   for  contraindications  to   surgery,  then  be   evaluated  whether  be 

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amenable to surgical treatment after multidisciplinary discussion (Department 
of  thoracic   surgery,   department   of  respiratory   medicine,   department   of 
radiology).   Open   or  minimally  invasive  radical  lung  cancer  surgery  and 
systematic lymph node dissection will be performed on eligible patients. The 
perioperative complications, lymph node dissection, R0 clearance rate, 3-year 
event-free survival rate, overall and disease-free survival time, quality of life, 
and pulmonary function will be recorded and analyzed. 
Study duration ：            5 years 

 
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Duration of subject participation : 3 years 
 
1.2 Technology roadmap 
 
 
 
 
Baseline investigations 
Demographics, medical history,   
physical examination, blood 
biochemistry,  ancillary test 
 
 
 
 
 
 
 
Those with severe cardiac, pulmonary, hepatic or 
renal dysfunction who cannot tolerate surgery ;  
Those with uncontrollable neurological or  
psychiatric disorders or mental disorders, poor 
compliance, inability to cooperate and describe 
the response to treatment; 
Those with a history of other malignant tumors and 
a history of thoracic surgery. 
 
 
 
Those who have serious adverse reactions during 
treatment and discontinue treatment ； 
Those who undergo neoadjuvant or induction  
targeted or radiation therapy   
Those who undergo emergency or palliative surgery 
due to lung abscess, hemoptysis, etc. 
 
 
 
 
 
 
 
Those with severe cardiac, pulmonary, hepatic, or renal  
dysfunction who cannot tolerate the surgery. 
 
 
 
Record perioperative data, tumor resection status, and perioperative complications   
Record postoperative complications at 30 days, 90 days      
Record long-term follow-up data including overall survival time, disease-free   
survival time, preserved pulmonary function and quality of life . 
 
 
Enroll and sign informed  
consent according
to    
inclusion criteria 
 
 
Neoadjuvant/induction    
therapy based on biopsy  
pathology
results 
 
 
Preoperative examination  
history，physical   
examination， and ancillary 
tests of organ function 

 
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2. Background of the Study 
2.1 Significance of the study 
Lung cancer is one of the most common malignant tumors worldwide, and the number of 
new lung cancer cases is expected to be as high as  1.8 million worldwide in 2019  [1]. The 
mortality rate of lung cancer is the highest among malignant tumors, and one-fifth of all 
malignant tumor deaths worldwide are due to lung cancer [1]. 
In recent years, lobectomy is no longer the only option for some early-stage lung cancer 
patients.  Sub-lobe resection  can achieve better protection of lung function with the  same 
prognosis. Meanwhile, with the gradual development of targeted therapy, immunotherapy 
and other treatment modalities, more patients benefit from preoperative tumor downstaging. 
However, pneumonectomy is  still preferred  as the  first choice for operable patients with 
tumors  invading  the  main  pulmonary  artery  and  main  bronchus,  even  achieving  tumor 
downstaging  after  neoadjuvant therapy.  Pneumonectomy  is  often  associated  with  higher 
rates of perioperative complications and mortality than lobectomy, and a higher proportion 
of patients  undergoing  total pneumonectomy  are  lost  to  postoperative  adjuvant  therapy, 
which may have an impact on long-term survival. There is currently no evidence to support 
the decision to convert to lobectomy in this population. 
We propose to conduct a single-arm prospective clinical study to investigate the feasibility, 
safety,  perioperative  and  long-term  outcomes   of  surgery  (converting  to   lobectomy  of 
pneumonectomy) in patients with locally progressive operable non-small cell lung cancer 
after neoadjuvant therapy. 
 
2.2 Background 
For operable early lung cancer, sub-lobe resection has been demonstrated to achieve similar 
oncologic  outcomes compared with lobectomy  [2,  3], while preserving the  lung function. 
Pneumonectomy  remains   the  standard  surgical  procedure   for  patients  whose   surgical 
strategies  are  pneumonectomy  initially,   although  tumor  downstaging   after  neoadjuvant 
therapy. More evidence is needed to determine whether the extent of surgical resection can 
be reduced for these patients. 
Although pneumonectomy  ensures  a  good  R0  clearance  rate,  it  is  associated with  a 
higher rate of perioperative complications and mortality than lobectomy. 355 patients with 
pneumonectomy  were  retrospectively  analyzed  by  Gregory  D.  Jones'  team  [4],  and  the 
mortality rates were 3.7%, 4.5%, and 6.8% at in-hospital, 30 days, and 90 days, respectively, 
for  non-oncological  causes.  30-   and   90-day  readmission  rates  were   13%   and    19%, 
respectively.  The  rate  of readmission within  30  and  90  days was  13% versus  19%, with 
cardiopulmonary complications being the most common cause. In retrospective studies  [5-8], 
the 30-day complication and mortality rates for total lung resection were 30% and 5%-8%, 
compared with 4%-10% and 0%-3% for lobectomy. In addition, the 90-day mortality rate 
after total lung resection can be  1-2 times higher than the  30-day mortality rate  [9-10]. A 
controlled study published in the Annals of Surgery in 2022  [11]  compared postoperative 

 
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complications and mortality rates between pneumonectomy  and lobectomy by propensity 
score matching, and showed that the complication rates of grade III or higher and mortality 
at 90 days were significantly higher in the group of pneumonectomy than lobectomy (21% 
vs.  13%  and  6.9% vs.  1.9%, respectively),  The three  complications with the highest rates 
were hypoxemic respiratory failure, bronchopleural fistula, and intrathoracic hemorrhage. In 
addition,  cardiovascular  complications  were  significantly  higher  in  the  pneumonectomy 
group. 
Marc Riquet's team  [12] retrospectively  analyzed the  10-year  survival  of  1466 patients 
undergoing pneumonectomy, and the 5-year and  10-year survival rates were 32% and  19%, 
respectively. In the analysis of risk factors affecting long-term  survival, the  investigators 
found  that  patients'  general  physical  status  and  tumor  biology  were  closely  related  to 
prognosis, and that the occurrence of nonfatal postoperative  complications  independently 
increased the long-term risk of death, which was considered to be indicative of the fragility 
of patients' general physical status. The investigators compared the long-term survival of 
patients in the lobectomy versus pneumonectomy groups using propensity score analysis. 
Cumulative nonneoplastic mortality at 2 years was twice as high in the pneumonectomy 
group as in the lobectomy group (21% versus  11%), and cumulative nonneoplastic mortality 
at  5 years was 24% versus  13%  in  the pneumonectomy group  and 2% in the lobectomy 
group, with the risk  of nonneoplastic  death  increasing by  9%  in  pneumonectomy  group 
versus 2% in lobectomy group over the postoperative period. The risk of non-tumor death 
increased by 9% in the total pneumonectomy group and by 2% in the lobular group at  1-2 
years. The most common causes of death in both groups were pneumonia and myocardial 
infarction, both  of which were  significantly  higher  in  the pneumonectomy  group.  These 
non-oncologic deaths are attributable to the impaired general health status of patients after 
pneumonectomy. A prospective controlled cohort study by Ulrik Sartipy's team  [13] found 
that patients  in  the pneumonectomy  group  had  a  more pronounced  decrease  in  strength 
scores than those in the lobectomy group (-32% vs. -17%). Recovery from this decline in 
strength  scores  was  different  between  the two  groups,  with Bram  Balduyck's team  [14] 
finding that strength scores in patients who underwent lobectomy returned to baseline levels 
within  1 month after surgery, which supports the idea that adjuvant therapy is often initiated 
in  the  first  month  after   surgery,  whereas  in  patients  who  underwent  pneumonectomy, 
strength  scores  did  not return to baseline  levels  after  1  year  of follow-up.  The  physical 
strength   scores  did  not  return  to  baseline  after   1   year   of follow-up.   Patients  with 
pneumonectomy were more likely to have dyspnea, pain, and shoulder dyskinesia than those 
with lobectomy. Because  of the decline in general physical  status  and  strength  scores,  a 
significant proportion of patients undergoing pneumonectomy did not receive postoperative 
adjuvant therapy. In the study by Filippo Lococ's team  [15], nearly half of the patients did 
not receive postoperative adjuvant therapy, although the benefit of postoperative adjuvant 
chemotherapy on long-term survival has been demonstrated in clinical studies  [16]. Recent 
advances in neoadjuvant/adjuvant  combination  of immuno-  and  chemotherapy  [17]  have 

 
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increased  the  rate  of  long-term  survival  benefit  in  patients  with  operable  lung  cancer, 
whereas  the  loss  of  access  to  adjuvant  therapy  in  pneumonectomy  patients  potentially 
compromises their long-term survival benefit. 
According  to  the  existing  clinical  studies,  patients  after  pneumonectomy  face  higher 
perioperative complications and mortality, and their long-term survival is impaired due to 
the loss of adjuvant therapy or non-tumor factors, and their quality of life scores are also 
lower. Taking into account the high efficiency and downstaging rate of neoadjuvant therapy 
for  lung  cancer,  strict  patient  screening  was  performed to reduce  surgical  trauma  while 
ensuring   R0   resection   (from   pneumonectomy   to   lobectomy/sleeve    lobectomy   after 
neoadjuvant therapy ). Reduce perioperative complications and mortality in this population 
and  increase  the  proportion   of  postoperative  adjuvant  therapy   for  potential  long-term 
survival benefits and improved quality of life. Prospective evidence is lacking. Therefore, 
our group would like to conduct this single-arm prospective clinical study to explore the 
safety, feasibility, and long-term outcome of reducing the scope of surgery after neoadjuvant 
therapy for locally progressive NSCLC, in order to lay the foundation for further research 
and clinical application. 
 
 
Reference 
 
1.  1.Fitzmaurice C, Akinyemiju TF et al. Global, Regional, and National Cancer Incidence, Mortality, 
Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer    
Groups,  1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 
2018; 4(11):1553–1568. 
 
2. Hisashi Saji, Morihito Okada, Masahiro Tsuboi et. al Segmentectomy versus lobectomy in 
small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, 
phase 3, randomised, controlled, non-inferiority trial Lancet 2022; 399:  1607–17 
 
3. Nasser Altorki, M.D. , Xiaofei Wang, Ph.D, David Kozono, M.D et. al Lobar or Sublobar Resection 
for Peripheral Stage IA Non–Small-Cell Lung Cancer n englj med 388;6 
 
4.Jones G, Tan KS, Caso R, et al. Time-varying analysis of readmission and mortality during the first 
year after pneumonectomy. J Thorac Cardiovasc Surg. 2020 
 
5.Shapiro M, Swanson SJ, Wright CD, et al. Predictors of major morbidity and mortality after 
pneumonectomy utilizing the Society for Thoracic Surgeons General Thoracic Surgery Database. Ann 
Thorac Surg. 2010;90:927–934. 
 
6.Yang J, Xia Y, Yang Y, et al. Risk factors for major adverse events of video assisted thoracic surgery 
lobectomy for lung cancer. Int J Med Sci. 2014;11:863–869 

 
8 
 
7.Kozower BD, Sheng S, O’Brien SM, et al. STS database risk models: predictors of mortality and   
major morbidity for lung cancer resection. Ann Thorac Surg. 2010;90:875–881. discussion 881–873 
 
8.Pricopi C, Mordant P, Rivera C, et al. Postoperative morbidity and mortality after pneumonectomy: a 
30-year experience of 2064 consecutive patients. Interact Cardiovasc Thorac Surg. 2015;20: 316–321 
 
9.Schneider L, Farrokhyar F, Schieman C, et al. Pneumonectomy: the burden of death after discharge 
and predictors of surgical mortality. Ann Thorac Surg. 2014;98:1976–1981. discussion  1981–1972 
 
 
 
10. Kim AW, Boffa DJ, Wang Z, et al. An analysis, systematic review, and meta-analysis of the 
perioperative mortality after neoadjuvant therapy and pneumonectomy for non-small cell lung cancer. J 
Thorac Cardiovasc Surg. 2012;143:55–63 
 
11.Gregory D. Jones, MD, Raul Caso, MD, Kay See Tan, PhD et.al Propensity-matched Analysis 
Demonstrates Long-term Risk of Respiratory and Cardiac Mortality After Pneumonectomy 
 
Compared With Lobectomy for Lung Cancer Ann Surg 2022;275:793–799 
 
12.Marc Riqueta, Pierre Mordanta , Ciprian Pricopia et. al, A review of250 ten-year survivors after 
pneumonectomy for non-small-cell lung cancer. European Journal of Cardio-Thoracic Surgery 45 
(2014) 876–881 
 
13.Ulrik Sartipy et. al Prospective population-based study comparing quality of life after 
pneumonectomy and lobectomy European Journal of Cardio-thoracic Surgery 36 (2009)  1069—1074 
 
14.Bram Balduyck, MD, Jeroen Hendriks, MD, PhD, Patrick Lauwers, MD et.al Quality of Life after 
Lung Cancer Surgery: A Prospective Pilot Study comparing Bronchial Sleeve Lobectomy with 
Pneumonectomy J Thorac Oncol. 2008;3:  604 –608 
 
15. Filippo Lococo , Carolina  Sassorossi , Dania Nachira et.al Prognostic Factors and Long-Term 
Survival in Locally Advanced NSCLC with Pathological Complete Response after Surgical Resection 
Following Neoadjuvant Therapy Cancers 2020,  12, 3572 
 
16.The International Adjuvant Lung Cancer Trial Collaborative Group Cisplatin-Based Adjuvant 
Chemotherapy in Patients with Completely Resected Non–Small-Cell Lung Cancer N Engl J Med 
2004;350:351-60 
 
17.Patrick M Forde,Jonathan Spicer , Shun Lu et.al Neoadjuvant Nivolumab plusChemotherapy in 
Resectable Lung Cancer NEnglJ Med. 2022 May 26; 386(21):  1973–1985 
 
2.3 Expected results of the research 
1) Expected to publish 2-3 papers in SCI/EI indexed journals. 
2)  Expected  to  participate   in  international  academic  conferences   1-2   times,  national 

 
9 
 
conferences 3-4 times. 
 
 
2.4 Risk/benefit assessment 
2.4.1 Known potential risks 
Radical  lung  cancer  surgery  is  a widely practiced treatment  for  early  stage  lung  cancer, 
including   pneumonectomy,   double   lobectomy,   sleeve   lobectomy    and   lobectomy   or 
segmental  resection,  etc.  The  common  potential  risks   are  perioperative   complications, 
including intraoperative  or postoperative bleeding, persistent air leakage, lung infections, 
pleural effusions, and an increase in the rate of local recurrence. 
 
2.4.2 Known Potential Benefits 
Narrowing   surgical   resection    in   cases    that   do   well     on   neoadjuvant    or   induced 
chemoimmunotherapy preserves lung function, potentially reducing the risk of perioperative 
complications,  and  death.  It  protects  the  patient's  general   state  of  health,  reduces  the 
incidence  of long-term  non-tumor   deaths,  maintains   a  high  physical   strength   score, 
facilitates adjuvant therapy follow-up, and may result in a long-term survival benefit for the 
patient. 
 
2.4.2 Assessment of potential risks/benefits 
It has been shown in retrospective studies that total pneumonectomy is only performed when 
lobectomy is difficult to achieve R0 resection and is associated with higher perioperative 
complications  and  mortality  than  lobectomy,  with  a  significant  impact  on  the  patient's 
general  state  of health  and  strength  scores,  which  may  contribute  to impaired long-term 
survival.  In  patients  who  do  well  on  neoadjuvant  or  induction  therapy,  conversion  to 
lobectomy can potentially reduce the incidence of perioperative adverse events, reduce the 
risk of immediate and long-term non-tumor death, protect the patient's general health and 
strength  scores,  and  increase  the  patient's   chances  of  receiving  postoperative  adjuvant 
therapy, thereby reducing the risk of tumor-related death. 
Risk-minimizing measures:  Select patients with  good results  of neoadjuvant  or induction 
therapy  according  to   strict  admission  criteria,  review  the  tracheoscopic  biopsy  before 
surgery to clarify the status of the bronchus to be preserved, take frozen pathology to clarify 
the status of the nearest incision margins during the surgery to decide the actual surgical 
method,  and  maintain  adjuvant  therapy  after  the  surgery  to  minimize  the  possibility  of 
increasing the risk of local recurrence. Postoperatively, the patient's vital  signs, drainage, 
and air leakage were closely observed to ensure perioperative safety. 
Preoperative and intraoperative reassessment 
1 Bronchoscopic biopsy of bronchial mucosa to be preserved/EBUS to assess the condition 
of the outer wall of the preserved bronchus. 
2 In cases of main pulmonary artery invasion prior to neoadjuvant therapy, intraoperative 

 
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freezing is performed to assess the status of the arterial wall at the site of original invasion. 
3 For cases with transverse  fissure  invasion, pulmonary  fissure margins were  frozen  for 
pathologic evaluation. 
 
3. Information on the principal investigator 
3.1 Name, qualifications, and contact information of the principal investigator 
Name:Li Hecheng 
Sex:Male 
Age: 48 years old 
Specialty:Thoracic Surgery 
Title:Chief Physician 
Administrative Position:Chief of Department 
GCP Training:Yes 
Contact:lihecheng2000@hotmail.com(E-mail);13917113402(Mobile) 
 
No. 
Name 
Gender（ M/F） 
Age（y）  
 
GCP （ Y/N 
) 
 
1 
ZX.Yin 
M 
37 
 
Thoracic 
Y 
Sub-I,CRC 
2 
XF.Zhang 
M 
28 
 
Thoracic 
Y 
Sub-I,CRC 
3 
RS.Jin 
M 
37 
 
Thoracic 
Y 
Sub-I,CRC 
4 
XY.Chen 
M 
38 
 
Thoracic 
Y 
Sub-I 
5 
NC.Zhang 
M 
36 
 
Thoracic 
Y 
Sub-I 
6 
SJ.Yu 
M 
30 
 
Thoracic 
Y 
Sub-I 
7 
YQ.Cao 
F 
26 
 
Thoracic 
Y 
Sub-I 
8 
CQ.Li 
M 
38 
 
Thoracic 
Y 
Sub-I 
9 
DP.Han 
M 
38 
 
Thoracic 
Y 
Sub-I 
10 
YJ.Zhang 
M 
38 
 
Thoracic 
Y 
Sub-I 
11 
K.Chen 
M 
38 
 
Thoracic 
Y 
Sub-I 
12 
HL.Du 
M 
42 
 
Thoracic 
Y 
Sub-I 
 
 
4. Aims of the study 
Primary   objective:   to   investigate   the   feasibility   of   conversion   to   lobectomy    after 
neoadjuvant/induced  chemoimmunotherapy  in patients with  operable non-small  cell  lung 

 
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cancer who are required to undergo pneumonectomy at first diagnosis (R0 resection rate). 
Secondary objective: to investigate the perioperative  and long-term outcomes  of patients 
with operable non-small cell lung cancer who were evaluated to undergo pneumonectomy at 
first  diagnosis  and   switched  to  neoadjuvant   or   induction  chemoimmunotherapy   and 
subsequent lobectomy. 
5. Research design 
5.1 Overall design 
In this single-arm, open-label, multicenter, prospective clinical trial, 50 cases of operable 
non-small-cell lung cancer requiring pneumonectomy were proposed to be enrolled. Patients 
will be treated with neoadjuvant or inductive combination therapy of immuno- and chemo- 
by   evaluation   from   multidisciplinary   discussion   (Department    of  Thoracic    Surgery, 
department  of Respiratory  Medicine,  department  of  Radiology),  than  undergo   open  or 
minimally invasive radical surgery for lung cancer and systematic lymph node dissection. 
Peri-operative complications, lymph node dissection, R0 resection rate, and postoperative 
short-term and long-term efficacy outcomes will be recorded and evaluated. 
Participating centers: 
1 Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 
2 Shanghai General Hospital of Shanghai Jiao Tong University School of Medicine 
3 The Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine 
4 Huadong Hospital, Fudan University Medical College, Shanghai, China 
 
 
5.2 Defining study endpoints 
The  study is completed if the  subject  completes  all phases of the  study according to the 
protocol, if he or she is no longer being examined, or if the last  subject has had the  last 
follow-up visit. 
A subject completes the study if he or she completes all phases of the study, including the 
last follow-up visit or the last treatment or examination specified in the protocol. 
 
Primary study endpoints 
l Tumor R0 resection rate (lobectomy) 
Secondary study endpoints 
l Overall survival (OS, unit:month) 
l Disease-free survival (DFS, unit: month) 
l Surgical Evaluation Indicators. 
     Surgical  time  (unit:  minutes),  intraoperative  bleeding  (unit:  ml),  intraoperative 
blood transfusion (unit: ml) 
     Incidence of intraoperative accidents 
     Lymph  node  dissection:  total  number   of  lymph  node   dissection  (unit:  one), 
number  of lymph  node  dissection  stations  (intrapulmonary,hilar  and  ipsilateral 

 
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mediastinal lymph nodes), and the number of lymph nodes cleared at each station 
(unit: one). 
l Perioperative, 30-day, 90-day complication rates, mortality rates 
l Quality of Survival and Pulmonary Function Evaluation at Admission, Discharge, 30 
Days, and 90 Days 
     Quality of Life Score: Scored using the short form-36 (SF-36) and recorded on a 
100-point scale. 
     Resting oxygen saturation (unit: percentage) 
     Lung function: Tidal volume, Vital capacity, Forced vital capacity, first second 
vital capacity. 
     Tidal volume, Vital capacity, Forced Expiratory Volume In  1s, all in ml. 
 
 
5.3 Determination of sample size 
This study is a prospective observational clinical study, and the purpose of the study is to 
evaluate  the  feasibility  and  long-term  outcome   of pnuemonectomy  to  lobectomy   after 
neoadjuvant or induction chemoimmunotherapy for locally progressive non-small cell lung 
cancer. Due to the lack of previous reference data, the sample size was not calculated based 
on hypothesis testing, and 50 patients were enrolled. 
6 Study population 
6.1 Inclusion criteria 
The study subjects should meet the following criteria: 
1) The patients voluntarily participate in the study, have good compliance, can cooperate 
with the requirements of the experiment to complete the observation and follow-up, and sign 
the informed consent form. 
2) Aged over  18 years old, under 75 years old; male and female are not limited; 
3)  Pathologically  confirmed  non-small   cell  lung   cancer  with  clinical  stage  T2-4N0-2, 
resectable non-small  cell lung cancer, potentially needing pneumonectomy  and receiving 
neoadjuvant or induction therapy. 
4) ASA score: Grade I-III; 
5)  The  cardiopulmonary  function  evaluation  can  meet  the  requirements  for  radical  lung 
cancer surgery, and the liver and kidney functions are normal. 
 
 
6.2 Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from this study; 
1) Those with serious cardiac, pulmonary, hepatic, and renal dysfunctions, unable to tolerate 
the surgery; 
2) Those with uncontrollable neurological or psychiatric diseases or mental disorders, poor 
compliance, and being unable to cooperate and describe the treatment response. 
3)Those who  are  going to undergo  emergency  surgery  or palliative  surgery  due  to  lung 

 
13 
 
abscess or hemoptysis. 
4) Those who have been treated, or are undergoing neoadjuvant or induction radiotherapy or 
targeted therapy. 
5) Those who have a combined history of other malignant tumors 
6) Those who have a history of thoracic surgery 
7) Those who are pregnant or breastfeeding women 
8) Patients of childbearing age who refuse to use contraception. 
 
 
6.3 Recruitment 
Source of study subjects: outpatients 
Recruitment  location:  Thoracic  Surgery  and  Respiratory  Medicine  Clinic  of participant 
centers. 
Recruitment  method:  Through  WeChat  public  number,  departmental  website  and  other 
online channels to publish recruitment information. 
The researchers conducted a study on the lungs of patients attending outpatient clinics. After 
preliminary evaluation of lung cancer patients in the outpatient clinic of Ruijin Hospital and 
identification of those who are potentially eligible for enrollment, as well as improvement of 
chest  CT,  PET-CT （ optional  ） ,  cardiac  ultrasound,  lung  function  and  other  auxiliary 
examinations,  and  after  it  is  clear  that  they  are  eligible  for  enrollment,  subjects  will  be 
informed of the study and will sign an informed consent form. 
Measures to strengthen the compliance of the study subjects: The researchers contacted the 
study  subjects  or their  families through the Internet or telephone, informing them of the 
schedule of the treatment program and reminding them of the follow-up visits. 
 
6.4 Methods of Study Subject Allocation 
This study is a single-arm clinical trial and does not involve the allocation of study subjects 
to the enrollment group. 
 
7. Research interventions 
7.1 Giving the research intervention 
7.1.1 Description of the research intervention 
After the patients were enrolled in the group, further relevant examinations (bronchoscopy, 
chest enhanced CT, PET-CT (optional), cranial MR, cardiac ultrasound, pulmonary function, 
electrocardiogram, and blood test) were completed, contraindications to surgery were ruled 
out,  and  they  were  evaluated  to  receive  neoadjuvant/induced  chemo-immuntherapy  after 
multidisciplinary  discussion  (thoracic   surgery,  respiratory  medicine,  pathology).  After 
completion  of treatment,  the  patient  is  reassessed  and  discussed  multidisciplinaryly  for 
surgical  feasibility.  Open  or  minimally  invasive  (thoracoscopic-assisted,  robotic-assisted) 
radical lung cancer surgery with  systemic lymph node dissection is performed, including 

 
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pneumonectomy, lobectomy, combined lobectomy, and sleeve lobectomy (with or without 
pulmonary  angioplasty/sleeve).  Based  on  the   surgical  pathology   and  guidelines,  the 
postoperative    adjuvant    treatment     and    follow-up    plan    was     individualized    after 
multidisciplinary discussion. 
 
7.1.2 Dosage and method of administration 
No drug trials were involved in this study. 
 
 
7.1.3 Methods of establishing, preserving, and unblinding test drug codes and breaking 
the blind in emergency situations 
This study does not involve blinding. 
 
7.1.4 Items and number of clinical and laboratory examinations to be conducted 
Postoperative follow-up in January, follow-up in March, follow-up every three months 
thereafter, and follow-up every six months after one year postoperatively, with blood routine, 
biochemistry, tumor indexes, and chest CT examination at each follow-up. In the first year 
after surgery, head MR was performed every half a year and PET-CT （optional ） was 
repeated every year; after one year after surgery, head MR was performed every half a year 
and PET-CT（optional） was performed every year. 
7.2 Preparation/handling/storage/responsibility 
7.2.1 Responsibility 
No drug trials were involved in this study. 
7.2.2 Composition, appearance, packaging and labeling 
This study did not involve drug testing. 
7.2.3 Product storage and stability 
This study does not involve drug testing. 
7.2.4 Preparation 
This study does not involve drug trials. 
7.3 Measures to reduce bias: randomization and blinding 
This study was a single-arm study and did not involve randomization grouping and blinding. 
 
7.4 Follow-up and compliance 
The patients will be followed up in one and three months after surgery. Then every 
three months in first year, every six months after one year of operation, with blood routine, 
biochemistry, tumor indexes, and chest CT examination at each visit. Within one year after 
surgery, head MR was performed every six months and PET-CT was performed at one year, 
and after one year after surgery, head MR was performed every six months and PET-CT was 
performed every year. 
The researchers  will  contact  the  study  participants  or  their  families  via  the  Internet  or 
telephone to inform them of the treatment schedule and remind them of follow-up visits. 

 
15 
 
 
7.5 Commitment to research intervention 
During the perioperative period, relevant  complications  and examination test results 
were recorded by the treating doctors and nursing staff, and after discharge, a specialized 
After discharge from the hospital, specialists will be assigned to conduct follow-up visits 
and record them in the case report form (CRF). 
 
 
 
screening 
period 
 
Peri- 
operative 
period 
Follow-up 
3 
months 
6 
months 
9 
months 
1 
year 
1.5 
years 
2 
years 
2.5 
years 
3 
years 
Informed consent 
× 
 
 
 
 
 
 
 
 
Base-line 
× 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
× 
 
 
 
 
 
 
 
 
 
 
Test 
Physical 
Examination 
× 
× 
 
 
 
 
 
 
 
Complete 
Blood Count 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Blood 
Biochemical 
Analysis 
 
× 
 
× 
 
× 
 
× 
× 
 
× 
 
× 
 
× 
 
× 
 
× 
Tumor  Bio- 
marker 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Chest CT 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
PET-CT 
× 
 
 
 
× 
 
× 
 
× 
Cephalic 
MR 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.  Discontinuation  of  the  research  intervention   and  discontinuation/withdrawal  of 
research subjects 
8.1 Discontinuation of the research intervention 
The investigator should consider discontinuing the study intervention if the subject develops. 
1) patients with serious unintended adverse reactions or complications that do not improve 
significantly after symptomatic treatment and cannot be continued. patients who are unable 
to continue the study intervention. 
2)  Patients  who  are  unable  to  tolerate  the  study  intervention  for  non-treatment  related 
reasons. 
3) Laboratory test values that, in the judgment of the investigator, are clinically significant. 
After  discontinuation  of the  study  intervention,  patients may  continue to  complete  other 
parts  of the  treatment  regimen,  including  chemotherapy,  radiotherapy,  targeted  therapy, 
immunotherapy,  etc.,  and will be treated in accordance with the  study protocol. therapy, 
targeted therapy, immunotherapy, etc., and will be scheduled for examination and follow-up 
according to the study protocol. 
 
8.2 Suspension/withdrawal of research subjects 
The researcher may discontinue or withdraw a research subject if the subject is. 
1) pregnancy 

 
16 
 
2) apparent noncompliance with the study intervention. 
3) if clinical side effects, abnormal laboratory tests, or other clinical conditions occur that 
make continued participation in the study is no longer in the best interest of the subject. 
4) Disease progression such that discontinuation of the study intervention is warranted. 
5) The subject meets the exclusion criteria (emerging or confirmed). 
6) the subject is unable to receive the study intervention for a certain period of time. 
 
The  reason  for  discontinuation/withdrawal  of the   subject   from  the   study   should  be 
documented on the case report form, and subjects who signed the informed consent, were 
randomized, but did not receive the study intervention will be replaced. Subjects who signed 
informed consent, were randomized, received the study intervention and were subsequently 
withdrawn will or will not be replaced. 
 
8.3 Loss of Follow-Up 
Subjects will be followed up for a period of 3 years. Lost visits will be considered to occur 
when the subject stops scheduled follow-up visits, fails to complete the procedures specified 
in the study, or cannot be contacted by the investigator. 
The  investigator  will   follow  the   established  follow-up  plan,  complete  telephone   and 
outpatient  follow-up  regularly,  and  communicate  with  the  subject  on  a  regular  basis  to 
minimize lost visits. 
 
9. Evaluation of study outcomes 
9.1 Evaluation of primary and secondary outcomes 
Primary Study Endpoints 
R0 Resection rate (lobectomy): the proportion of patients with complete tumor removal by 
lobectomy, as evaluated by thepathologic findings of postoperative lung cancer specimens; 
Secondary study endpoints 
1) Lymph node dissection:Record the total number of lymph node dissection, the number of 
stations of lymph node dissection, and the number of lymph node dissection at each station  
during the operation, and evaluate them according to the pathologic results. 
2)  Perioperative  indicators:Record  the  duration  of  surgery,  intraoperative  bleeding,  the 
incidence  of intraoperative  accidents,  evaluated  by   surgical  records   and  perioperative 
clinical manifestations, laboratory tests, physical examination;. 
3)   Postoperative   short-term   efficacy   indicators:   record   the   length    of  postoperative 
hospitalization   (days),   survival   within   30   days   after   surgery,   and   evaluate   through 
postoperative follow-up; 
4) Perioperative  complication rate: Evaluated by  clinical manifestations,  laboratory tests, 
and physical examination. 
5)  3-year  disease-free  survival  rate:  defined  as  the proportion  of patients without tumor 
recurrence or metastasis 3 years after surgery, evaluated by postoperative follow-up. 
6) 3-year overall  survival rate: defined as the proportion of patients who are still alive 3 
years after surgery, and evaluated by postoperative follow-up. 

 
17 
 
 
9.2 Safety and other evaluations 
The main methods of safety evaluation of the study intervention include. 
1) Clinical presentation; 
2) Physical examination; 
3) Vital signs (e.g., temperature, pulse, blood pressure); 
4) Routine blood and blood biochemistry tests. 
 
9.3 Adverse Events and Serious Adverse Events 
9.3.1 Definition of Adverse Events (AE) 
This refers to all adverse medical events that occur after a subject has undergone radical 
lung cancer surgery, which may be manifested by signs, symptoms, disease, or abnormal 
laboratory tests, but are not necessarily causally related to the trial intervention. 
 
9.3.2 Definition of Serious Adverse Event (SAE) 
means an adverse medical event resulting in death, life-threatening, permanent or serious 
disability  or  loss  of  function,  the  need  for  hospitalization  of the  subject,  or  prolonged 
hospitalization  after  the  subject  has  undergone  radical  lung  cancer  surgery.  A   serious 
adverse   event   (SAE)   is   defined   as   an   adverse   medical   event   resulting   in   death, 
life-threatening,  permanent  or  serious  disability  or  loss   of  function,  hospitalization  or 
prolonged hospitalization after radical lung cancer surgery. 
9.3.3 Classification of adverse events 
9.3.3.1Severity of the incident 
1) Mild: Symptoms and signs are easily tolerated by the patient. Symptoms may be ignored 
or disappear when the patient is distracted. 
2) Moderate:  Symptoms  cause  discomfort but  are tolerable. They  cannot be ignored and 
interfere with concentration. 
3) Severe: Symptoms interfere with daily activities. 
 
9.3.3.2Relevance to research interventions 
1) Unrelated: A condition that occurs in a subject that is clearly related to other factors such 
as the subject's clinical status, treatment, or concomitant medications. 
2) Unlikely to be related: What happens to the subject is likely to be caused by other factors 
such as the subject's clinical condition, treatment, or concomitant medications, but not by a 
known response to the intervention. 
3) Possibly Related: What happens to the subject is sometimes related to the intervention or 
is a known response, but may also result from other factors such as the subject's clinical 
condition, treatment, or concomitant medications. 
4) Likely Related: The subject has a condition that is sometimes related to the intervention, 
is a known response, and cannot be explained by other factors such as the subject's clinical 
status, treatment, or concomitant medications. 
5) Highly Likely to be Relevant: The subject is experiencing a condition that is sometimes 

 
18 
 
related to the intervention, is a known response, and cannot be explained by other factors 
such as the subject's clinical status, treatment, or concomitant medications. There may also 
be one or more of the following: i) immediate onset after the intervention; ii) improvement 
after discontinuation of the intervention; iii) reoccurrence after a second intervention; iv) a 
positive reaction at the site of the intervention. 
 
9.3.3.3Anticipation 
Investigators  should  confirm  that  adverse  events  are  expected  or  unanticipated,  and  that 
adverse events may be considered unanticipated if their nature, severity, or 
frequency  are  not  consistent  with  the   risk   information   described  for previous   study 
interventions, they may be considered unintended. 
 
9.3.4 Timing, frequency, follow-up and regression of adverse event assessment 
Time   and  frequency  of adverse  event  assessment:  assessed  every  three   days   during 
hospitalization, and once at each follow-up visit after discharge. 
Follow-up of adverse events: The investigator should follow up the adverse events; observe 
the final regression until the symptoms disappear or stabilize; the investigator should follow 
up the results with the principal investigator and the ethics committee. 
All adverse events should be collected on a case report form (CRF), which should include a 
description of the event, time of occurrence, physician's assessment of severity, relationship 
to the study intervention, and time to resolution/stabilization of the event. 
9.3.5 Adverse event reporting 
Adverse events should be promptly recorded on the Case Report Form (CRF) and regularly 
reported to the Principal Investigator, Ethics Committee:. 
1) description of the adverse event; and 
2) the time of occurrence and duration; and 
3)Whether the adverse event was serious or unintended. 
4) the mode of onset; and 
5) evaluation of severity; and 
6)regression; and 
7)Measures taken in response to the adverse event. 
 
9.3.6 Reporting of Serious Adverse Events 
Serious adverse events should be promptly documented on a Case Report Form (CRF) and 
reported within 24 hours to the Principal Investigator, Ethics Committee. 
1)the description of the adverse event; 
2)time of occurrence and duration; 
3)whether the adverse event was serious or unintended; 
4)mode of onset; 
5)assessment of severity; 
6)regression; 

 
19 
 
7)Measures taken in response to the adverse event. 
 
10. Statistical analysis 
10.1 General methodology 
All  statistical  analyses  were  performed  using   R   software,   and  hypothesis  tests  were 
standardized using two-sided tests, giving the test  statistic and its corresponding p-value. 
p<0.05 was considered  statistically  significant, and 95% confidence intervals were  set as 
required. 
Statistical  description: All  indicators  are  described  according  to  their nature.  Qualitative 
indicators are expressed as frequencies and percentages of categories; metrics provide the 
number of cases, mean, standard deviation, median, minimum and maximum values. 
Statistical  inference:  For   overall   survival  time   and  disease-free   survival  time,   overall 
survival  curves  and  disease-free  survival  curves  were  plotted  using  the  Kaplan-Meier 
method; risk differences between survival and disease-free survival were assessed using the 
Log-Rank test; multivariate analyses were performed using the Cox proportional risk model 
to  assess  the  effect  of subgrouping  (surgical  modality)  and  other  prognostic  factors  on 
survival and disease-free survival. survival and disease-free survival. The t-test was used for 
measures that were normally distributed, and the rank-sum test was used for measures that 
were not normally distributed; the chi-square test was used for between-group comparisons 
of count data, and the Fisher exact probability method was used when necessary. 
 
 
 
10.2 Analysis of Primary and Secondary Study Endpoints 
Primary Endpoints 
Overall   survival   time   (in   months):   Overall   survival   curves   were   plotted  using   the 
Kaplan-Meier method; the difference in survival risk between the two groups was assessed 
using  the  Log-Rank  test  with  95%  confidence  intervals;  multivariate  analyses  were 
performed  using  the  Cox  proportional  risk  model  to  assess  the  effect  of  subgrouping 
(surgical procedure) and other prognostic factors on the survival risk, and 95% confidence 
intervals were given for each factor. A multivariate analysis using the Cox proportional risk 
model was performed to assess the effect of grouping factors (surgical modality) and other 
prognostic factors on survival risk with 95% confidence intervals for each factor. 
Secondary endpoints 
Disease-free survival time (in months): Disease-free survival curves were plotted using the  
Kaplan-Meier  method;  differences  in  the  risk  of  disease-free  survival  between  the  two  
groups were assessed using the Log-Rank test with 95% confidence intervals; multivariate  
analyses were performed using the  Cox  proportional risk model to  assess  the  effect  of 
subgrouping  factors  (surgical  procedure)  and  other prognostic   factors  on  the  risk   of 
disease-free survival, with 95% confidence intervals for each factor. A multivariate analysis  
using the Cox proportional risk model was performed to assess the effect of grouping factors  
(surgical modality) and other prognostic factors on the risk of disease-free  survival with  
95% confidence intervals for each factor. 

 
20 
 
l Surgical evaluation indicators. 
     Surgical time (unit: minutes), intraoperative bleeding (unit: ml), intraoperative blood 
transfusion  (unit:  ml):  all  quantitative  data  not  conforming  to  normal  distribution, 
calculate the median, 25% quartile, 75% quartile, the minimum value, the maximum 
value, and analyze the difference between the two groups by using the rank sum test. 
     Incidence of intraoperative accidents: count data, using chi-square test to analyze the 
difference between the two groups. 
     Lymph node dissection: the total number of lymph node dissection (unit: one) and the 
number  of lymph  node  dissection  at   each  station  (unit:  one)  were  non-normally 
distributed measurements,  and the difference between the two groups was  analyzed 
using   the   rank-sum   test;   the   number     of  stations   of   lymph   node   dissection 
(intrapulmonary, hilar, and ipsilateral mediastinal lymph nodes) was count data, and the 
difference between the two groups was analyzed using the chi-square test. Differences 
between the two groups were analyzed using the chi-square test. 
     Tumor R0 resection rate: count data, using the chi-square test to analyze the difference 
between the two groups. 
l Perioperative, 30-day, and 90-day complication rates, and mortality rates: were count 
data, and differences between the two groups were analyzed using the chi-square test. 
l Quality of Survival and Cardiorespiratory Function Evaluation at Admission, Discharge, 
30 Days, and 90 Days 
     Quality of Life Score SF-36 Scale: Percentage, as a non-normally distributed measure, 
use rank sum test to analyze the difference between the two groups. 
     Resting oxygen saturation (in percent): a non-normally distributed measure, differences 
between the two groups were analyzed using the rank-sum test. 
 
Lung  function:  Tidal  volume,  Vital  capacity,  Forced  vital  capacity,  Forced  Expiratory 
Volume In  1s, all in ml: were normally distributed measures and analyzed using the student 
The differences between the two groups were analyzed using the student-t test with 95% 
confidence intervals. 
 
10.3 Safety analysis 
Adverse  events  were  coded,  calculated,  and  expressed  using   severity,  frequency,   and 
association  with  intervention.  Adverse  events  leading  to  Adverse  events  leading  to 
discontinuation of the study intervention  should be  listed separately from serious adverse 
events arising from the treatment. 
 
10.4 Descriptive analysis at baseline 
Descriptive statistics were used to analyze the demographic characteristics and laboratory 
indicators of the study population at baseline. 
 
10.5 Subgroup analysis 
For   the    primary   study    endpoints    grouped   by    age,    sex    or   other    demographic, 

 
21 
 
clinicopathologic characteristics, and surgical treatment modalities, a Subgroup analysis was 
performed. 
 
11. Supporting documentation and considerations 
11.1 Informed consent process 
Informed consent should be completed before the subject agrees to participate in the study 
and continue throughout the study. The informed consent form is approved by the Ethics 
Committee  and  should  be  read by the  subject.  The  researcher  will  explain  the research 
process and answer questions from the subject; the subject will be informed of the possible 
risks and their rights. Subjects will be allowed to discuss their participation with their family 
or  guardian  before   agreeing  to  participate.   The  researcher  must  tell  the   subject  that 
participation in the study is voluntary and that he or she may withdraw from the study at any 
time. A copy of the informed consent form may be provided to the participant to keep. The 
rights and welfare of research subjects will be protected, and it is emphasized that the quality 
of their medical care will not be compromised by their refusal to participate in the study. 
 
11.2 Privacy 
Subjects' personal information in the study will be kept confidential. Identifying information 
will not be disclosed outside of the research team unless permission is granted.  Subjects' 
files will be kept in locked filing cabinets and will be accessible only to researchers. To 
ensure that the study is conducted in accordance with the regulations, access to the subjects' 
personal data at the research unit will be provided by government authorities or the Ethics 
Review Committee, as required. 
11.3 Collection and use of specimens and data 
Study data will be obtained by the investigator and stored in the custody of the Department 
of Thoracic  Surgery,  Ruijin  Hospital.  If  the   study  is   completed,  the  retained  clinical 
information and other data may be used for future  studies with the consent of the  study 
participants. 
Storage location:Thoracic Surgery Ward, 4th and 7th floor, Building 6, Ruijin Hospital. 
 
11.4 Quality control and quality assurance 
In  order to ensure that this trial is conducted in  strict  accordance with the clinical  study 
protocol, clinical investigators and clinical sponsors should operate in strict accordance with 
the requirements of the study protocol throughout the clinical trial, and make sure that the 
test procedures are standardized, the test data are accurate and the conclusions of the study 
are reliable. The specific requirements are as follows. 
1) Investigators must be physicians trained in clinical trials and work under the guidance of 
senior professionals; 
2) The clinical ward inspection before the trial must meet the standardized requirements and 
ensure that the resuscitation equipment is complete; 
3) Research centers must  strictly follow the  study protocol and truthfully fill in the case 
observation form; 
4) Supervisors should follow the operating procedures, supervise the conduct of the clinical 

 
22 
 
trial, confirm that all data are recorded and reported correctly and completely, and that all 
case report forms are filled out correctly and are consistent with the original information to 
ensure that the trial is conducted in accordance with the clinical research protocol. Ensure 
that the trial is carried out in accordance with the clinical study protocol. 
5) Ensure that the investigator can be contacted at any time by telephone, fax or e-mail. 
6) In case of serious adverse events, the study should be suspended if necessary. 
 
11.5 Data processing and record keeping 
11. 5.1 Data collection and management 
Completion and handover of the case report form (CRF): All relevant information of the 
case should be recorded in the CRF by the treating physician according to the trial protocol, 
and ensure that the data are recorded in a timely, complete, accurate, and truthful manner. 
the CRF  should not be  altered,  and  if there  is a mistake that needs to be  corrected, the 
correction should be signed and dated. The completed CRF must be reviewed and signed by 
the clinical investigator. If there is any doubt, the investigator must decide whether to make 
changes or not, and no further changes should be made to the CRF after confirmation. The 
completed CRF should be handed over to the data manager for data entry and management. 
All processes should be documented. 
Data  entry  and modification: A  designated  data manager  is responsible  for this process. 
Establish a database system specific to this test. Data entry will be performed after training 
of the data entry personnel and will be done by two people independently using the double 
entry method. 
Generation and resolution of questions: If the data manager has any questions during the 
CRF  review,  data  entry,  or any part  of the data review process, he/she  should  fill out  a 
question form and return it to the supervisor. The researcher should provide a written answer 
to the question on the question form, sign it, and return it to the data manager to correct the 
data; the data manager does not have the authority to modify the original data. The query 
form should be kept in a safe place. 
Data Audit: This is the process of checking and evaluating the data in the database. This 
process is a  special task  of the  data manager, who  should report  on the process  of data 
management and general information, case enrollment and completion (including the list of 
shedding subjects), items involved in determining the population for statistical analysis, and 
issues  that   need  to  be   discussed   and  resolved   (inclusion/exclusion   criteria   checking, 
completeness   checking,    logical    consistency   checking,    outlier    data    checking,    and 
time-window checking, etc.), and should be verified by the principal investigator,  Statistical 
analysts. 
Database  locking:  After  reviewing  the  data  and  confirming  that  the  database  has  been 
created correctly, the principal investigator and the statistical analyst will lock the database. 
In principle, the data should not be modified after locking, but if there is a problem, it can 
only be corrected in the statistical analysis program after confirmation by the study leader. 
All modifications should be documented and explained. Data security should be guaranteed, 
and unrelated personnel should not have access to or modify the data, and the data should be 
backed up. 

 
23 
 
 
11. 5.2 Research data retention 
After the completion of the clinical trial, the investigator will organize the clinical trial data 
and original records and within three months The investigator shall organize the clinical trial 
data and original records and submit them to the office of the clinical trial organization for 
archiving within three months. The minimum period of retention of data after the completion 
of clinical trials is  10 years. 
Data destruction should be licensed by the Clinical Trial Organization of Ruijin Hospital. 
 
11.6 Publication and Data Sharing Conventions 
This clinical trial is a multicenter study and data are shared within each participating center. 
 
11.7 Declaration of conflict of interest 
There are no relevant conflicts of interest.