Varian ProBeam Proton Therapy System China Clinical Trial (Hefei)
Phase: NA
Conditions: Tumor, Solid
Sponsor: Varian, a Siemens Healthineers Company

Varian ProBeam Proton Therapy System China Clinical Trial (Hefei) 
version number:1.4, version date:2022.06.10 
Privacy Statement 
All information in this scheme is owned byOwned by the sponsor, only for the investigator and its authorized 
personnel, institutional medical device clinical trial management department, institutional ethics committee 
and supervision and management department and other relevant personnel for review. It is strictly forbidden 
to disclose any information to third parties unrelated to this study without the sponsor's written permission, 
except for the necessary explanation when signing the informed consent form with the subject of this study. 
Protocol number: VAR-2021-03 
 
Varian ProBeam Proton Therapy System China Clinical Trial 
(Hefei). 
(Prospective, two-centered, single- group target value method) 
 
 
Name of the medical device 
for investigation 
Proton therapy system 
Model 
ProBeam 
Management categories for 
investigational medical 
devices 
Class III medical devices 
Class III medical devices subject to 
clinical trial approval 
Yes□   No 
Similar products in China 
Yes□   No 
Protocol version number and 
date 
Version number: 1 4, Version date: 2022.06 
10 
Clinical trial institutions 
Anhui Provincial Hospital 
researcher 
Zhang Hongyan 
Sponsor 
Varian Medical Systems Trading (Beijing) 
Co., Ltd 
agent 
NA 
 

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Directory 
List of abbreviations .............................................................................................. 3 
Protocol summary.................................................................................................. 7 
1 Sponsor information ......................................................................................... 13 
1.1 Name of the sponsor .............................................................................. 13 
1.2 Sponsor address ..................................................................................... 13 
1.3 The name, address, contact information and relevant qualification 
documents of the agent ................................................................................ 13 
2 Purpose and content of clinical trial ................................................................. 13 
2.1 Objective ............................................................................................... 13 
2.2 content ................................................................................................... 14 
3 Overall design ................................................................................................... 15 
3.1 Trial design ............................................................................................ 15 
4 Statistical considerations .................................................................................. 33 
4.1 Statistical design, methods, and analytical protocols ............................ 33 
4.2 Sample size calculation ......................................................................... 33 
4.3 The level of significance and power of clinical trials ........................... 34 
4.4 Expected shedding rate .......................................................................... 34 

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4.5 Criteria for passing/failing clinical trial results ..................................... 34 
4.6 Criteria and reasons for terminating trials on statistical grounds ......... 35 
4.7 Statistical methods of data, together with methods of dealing with 
missing, unused or erroneous data and irrational data ................................ 35 
4.8 Procedures for reporting deviations from the original statistical plan .. 38 
4.9 Selection criteria and rationale for participants included in the analysis
 ..................................................................................................................... 38 
4.10 Covariate and subgroup analysis ......................................................... 39 
 
 

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List of abbreviations 
Abbreviatio
ns 
Full spelling in English 
Chinese translation 
3DCRT 
3-Dimensional Conformal Radiation Therapy 
3D conformal radiation therapy 
ADL 
Activities of Daily Living 
Daily activities 
AE 
Adverse Events 
Bad Incident 
WHITE 
Serum Albumin 
Serum albumin 
OLD 
Alanine Aminotransferase 
Alanine aminotransferase 
APTT 
Activated Partial Thromboplastin Time 
Activation of partial thromboplastin 
time 
AST 
Aspartate Aminotransferase 
Glutamate aminotransferase 
GOOD 
Blood Urea Nitrogen 
Urea nitrogen 
Ccr 
Endogenous Creatinine Clearance Rate 
Creatinine clearance 
CFDA 
China Food and Drug Administration 
State Food and Drug Administration 
CH 
Chordoma 
Chordoma 
CK-MB 
Creatine Kinase Isoenzymes-MB 
Creatine kinase isoenzymes 
CP 
Child-Pugh 
- 
CR 
Complete Response 
Complete remission 
CRA 
Clinical Research Associate 
Clinical monitor 
CRF 
Case Report Form 
Case report form 
CTCAE 
Common Terminology Criteria for Adverse 
Events 
Common terminology criteria for 
adverse events 
cTn 
Cardiac Troponin 
Troponin 
CTV 
Clinical Target Volume 
Clinical targets 
DART 
Dynamic Adaptive Radiation Therapy 
Dynamically adapted radiotherapy 
techniques 
DIPS 
Digital Imaging Positioning System 
Digital image positioning system 
DOR 
Duration of Response 
Duration of mitigation 
DRR 
Digitally Reconstruction Radiograph 
Digitally reconstructed radiography 
DVH 
Dose Volume Histogram 
Volume dose histogram 
EC 
Ethics Committee 
Ethics Committee 
ECOG 
Eastern Cooperative Oncology Group 
Eastern U.S. Oncology Collaborative 
Group 
eCRF 
Electronic Case Report Form 
Electronic case report form 

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Abbreviatio
ns 
Full spelling in English 
Chinese translation 
EDC 
Electronic Data Capture System 
Electronic data collection systems 
ERA 
Erythrocyte 
Urine red blood cell count 
FAS 
Full Analysis Set 
Full analysis set 
FPG 
Fasting Plasma Glucose 
Fasting blood sugar 
GCP 
Good Clinical Practice 
Good Clinical Trial Management 
Practice for Medical Devices 
GLU 
Glucose 
Urine sugar 
GTV 
Gross Tumor Volume 
Gross tumor area 
HBV 
Hepatitis Virus B 
Hepatitis B virus 
HCG 
Human Chorionic Gonadotropin 
Blood pregnancy test 
HCV 
Hepatitis Virus C 
Hepatitis C virus 
HGB 
Hemoglobin 
haemoglobin 
HIV 
Human Immunodeficiency Virus 
Human immunodeficiency virus 
ICF 
Informed Consent Form 
Informed consent 
IGRT 
Image-Guided Radiation Therapy 
Image-guided radiation therapy 
IMPT 
Intensity Modulated Proton Therapy 
Conformal intensity-modulated proton 
therapy 
IMRT 
Intensity Modulated Radiation Therapy 
Conformal intensity-modulated 
radiation therapy 
INR 
International Normalized Ratio 
International standardized ratio 
LET 
Linear Energy Transfer 
Linear energy transfer 
LEU 
Leucocyte 
Urine white blood cell count 
LGG 
Low-Grade Glioma 
Low-grade glioma 
LVEF 
Left Ventricular Ejection Fractions 
Left ventricular ejection fraction 
Mb 
Myoglobin 
myoglobin 
NEUT 
Neutrophil 
Neutrophils 
NMPA 
National Medical Products Administration 
State Drug Administration 
NPC 
Nasopharyngeal Carcinoma 
Nasopharyngeal carcinoma 
NSCLC 
Non-Small-Cell Lung Cancer 
Non-small cell lung cancer 
NYHA 
New York Heart Association 
New York Heart Society 
OAR 
Organ at Risk 
Endangers organs 

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Abbreviatio
ns 
Full spelling in English 
Chinese translation 
WHETHER 
Occult Blood Test 
Occult blood test 
OIS 
Oncology Information System 
Radiation therapy management 
software 
OPC 
Oropharyngeal Cancer 
Oropharyngeal cancer 
ORR 
Objective Response Rate 
Objective response rate 
THE 
Overall Survival 
Overall lifetime 
PBS 
Pencil Beam Scanning 
Pen beam scanning 
PD 
Progressive Disease 
Disease progression 
PFS 
Progression-free Survival 
Progression-free survival 
PLT 
Platelet 
platelet 
PPS 
Per-Protocol Set 
Conforms to the scenario set 
PR 
Partial Response 
Partial remission 
FOR 
Protein 
Urine protein 
PRV 
Planning Organ-at-Risk Volume 
Plan to endanger organs 
PSA 
Prostate Specific Antigen 
Prostate-specific antigen 
PSI 
Paul Scherrer Institute 
Paul Scheller Institute, Switzerland 
PT 
Prothrombin Time 
Prothrombin time 
PTC 
Proton Treatment Console 
Proton therapy console 
PTV 
Planning Target Volume 
Plan the target 
QA 
Quality Assurance 
quality assurance 
QOL 
Quality-of-Life 
Quality of life assessment 
RBC 
Red Blood Cell 
erythrocyte 
RBE 
Relative Biological Effectiveness 
Relative biological effects 
RECIST 1.1 
Response Evaluation Criteria in Solid Tumors 
RECIST Version 1.1 
Tumor efficacy evaluation criteria 
version 1.1 
RVR 
Remaining Volume at Risk 
Remaining danger areas 
SAE 
Serious Adverse Events 
Serious adverse events 
SBRT 
Stereotactic Body Radiation Therapy 
Stereotactic radiosurgery 
SCIC 
Second Channel Integrity Check 
Second integrity check 
SCLC 
Small Cell Lung Cancer 
Small cell lung cancer 

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Abbreviatio
ns 
Full spelling in English 
Chinese translation 
Scr 
Serum Creatinine 
creatinine 
SD 
Stable Disease 
The disease is stable 
SDV 
Source Data Validation 
Raw data verification 
SLD 
Sum of Longest Diameter 
The sum of the longest diameters of 
the tumor 
SOBP 
Spread-out Bragg Peak 
Extend Bragg Peak 
SOP 
Standard Operating Procedure 
Standard operating procedures 
SS 
Safety Set 
Security datasets 
ETC 
Serum Total Bilirubin 
Total serum bilirubin 
TV 
Treated Volume 
Treatment area 
ULN 
Upper Limit of Normal 
Upper limit of normal value 
VMAT 
Volumetric-Modulated Arc Therapy 
Volumetric rotational intensity-
modulated radiotherapy 
WBC 
White Blood Cell 
white blood cell 
WHO 
World Health Organization 
World Health Organization 

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Protocol summary 
The name of 
the 
experiment 
Varian ProBeam Proton Therapy System China Clinical Trial (Hefei). 
Device 
name Investigational medical device: proton therapy system (hereinafter referred to as 
ProBeam). 
Manage 
categories 
Class III (classification: 05 radiotherapy equipment--01 radiotherapy equipment--02 
medical light ion therapy system). 
Scope 
of 
application 
Proton therapy system provide precision radiation therapy protons for lesions, tumors, 
and conditions in the patient's body that require radiation therapy. 
Scope of the 
test 
Cancer patients, including tumors of the nervous system, head and neck, chest, 
abdomen, spine, pelvis, limbs, etc 
Trial 
design Prospective, two-centered, single-group target value method 
Trial 
and 
long-term 
follow-up 
purposes 
Clinical trial (screening-short-term follow-up): The data obtained by using Proton Beam 
system (ProBeam) for radiation therapy in tumor patients compared with the target value 
to evaluate the effectiveness and safety of ProBeam for radiation therapy in tumor 
patients to provide clinical basis for product registration application.  
Long-term follow-up: The long-term efficacy and safety of ProBeam for radiation 
therapy in cancer patients were evaluated by using the long-term follow-up data of 
ProBeam for radiation therapy in cancer patients.  
Sample 
size 
47 cases.  
Among them, the number of head and neck, chest, abdomen, spine and pelvic tumors 
is distributed as evenly as possible.  
Intensity modulated Proton Therapy (IMPT) technology and respiratory gating 
technology should be used and verified in this study.  
clinical 
trial 
Number 
of 
institutions 
2 
The expected 
duration 
of 
the 
participant's 
participation 
The screening period from signing the informed consent form to enrollment is 
expected to be 4 weeks, the treatment period is 1~8 weeks, and the short-term 
follow-up and long-term follow-up after the last treatment are divided into 
short-term follow-up and long-term follow-up, and the maximum duration 
of expected participation of each subject from screening to the end of short-term 
follow-up is 12 weeks +3 months. Long-term follow-up continued after the end of the 
short-term follow-up until the fifth year after the end of the last radiotherapy.  
Expected 
overall 
duration 
of 
clinical trials 
and long-term 
follow-up 
The first subject is expected to be enrolled in December 2021, and the clinical trial 
institution expects to enroll 8-18 subjects per month, for a total enrollment time of 
about 4 months, and the last 1 subject ends the trial (short-term follow-up) is End In 
September 2022, the overall duration of the clinical trial included all working 
hours before, during and after the start of all clinical trials, and the overall duration of 
the clinical trial was 16 months.  

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The first subject is expected to start long-term follow-up in May 2022 and the last 
one subject to end long-term follow-up in June 2027, and the overall duration 
of long-term follow-up in clinical trials includes all clinical runs, After all working 
hours ended, the total long-term follow-up period for clinical studies was 
approximately 62 months.  
Primary 
effectiveness 
Evaluation 
indicators 
Disease Control Rate (DCR). 
Evaluation time: 3 months ± 7  days after the last treatment.  
Definition of indicators: Complete  Response (CR), Partial Response (PR), Stable 
Disease (SD) for disease control; No biochemical recurrence at the end of prostate 
cancer treatment, no regional lymph nodes or distant metastases, considered disease 
control. Proportion of participants who developed disease control three months after 
the end of the last radiotherapy. Participants who discontinued the trial for any reason 
(except loss to follow-up) before the end of radiation therapy were considered to have 
progression (PD) or uncontrolled.  
Evaluation methodology: Response Evaluation Criteria in Solid Tumors RECIST 
Version 1.1 (RECIST 1.1) by an independent imaging review team Changes in 
tumour CT or MRI imaging before and after treatment were assessed.  At 3 months 
of radiographic evaluation, if PD is found, PET-CT is required to confirm it.  
The 
main 
safety 
evaluation 
index 
(1) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 toxicity 
ratio 
Evaluation time: 3 months ± 7 days after the end of the last treatment.  
Indicator definition: Proportion of subjects with grade 3 toxicity during the 
trial cycle.  
Evaluation methodology: Investigators recorded AEs that occurred during the 
clinical trial cycle and graded them according to CTCAE V5.0.  
(2) CTCAE grade 4 and 5 toxicity ratio 
Evaluation time: the entire clinical trial cycle. 
Indicator definition: Proportion of subjects with toxicity of grade 4 and 5 during 
the trial cycle.  
Evaluation methodology: Investigators recorded AEs that occurred during the 
clinical trial cycle and graded them according to CTCAE V5.0.  
Secondary 
effectiveness 
Evaluation 
indicators 
(1) Objective Response Rate (ORR) (1 month± 7 days, 3 months, ± 7 days after the 
end of the last treatment). 
(2) Duration of Response (DOR) (3 months ± 7  days) after the end of the last 
treatment 
(3) DCR (1 month ± 7 days after the end of the last treatment).  
(4) Tumor markers (if required) (screening period, 1 month ± 7 days, 2 months± 7 
days, 3 months±7 after the end of the last treatment days).  
(5) Tumor-specific symptoms (screening period, 1 month ± 7 days, 2 mon ths± 7 days, 
3 months±7 days).  
(6) Product usability evaluation (ProBeam system, radiotherapy management software 
(OIS), radiotherapy planning software (Eclipse)) (the day of completion of the last 
treatment). 

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Secondary 
safety 
Evaluation 
indicators 
(1) CTCAE grade 1 and 2 toxicity ratio (3 months ± 7 days after the end of the last 
treatment). 
(2) Laboratory tests [screening period, treatment period on the 1st day of each week 
(Monday to Sunday is considered as 1 calendar week, the day of the first treatment 
of each natural week) before treatment or -1 day, 3 days after the end of the last 
treatment, 1 Months ±7 days, 2 months ±7 days, 3 months ±7 days].  
(3) Eastern Cooperative Oncology Group (ECOG) physical status grading [screening 
period, treatment period 1st day of each week (Monday to Sunday is regarded as 1 
natural week, On the day of the first treatment of each calendar week) before or -1 
day before treatment, within 3 days after the end of the last treatment, 1 month± 7 
days, 2 months±7 days, 3 months ±7 days].  
(4) Tumor recurrence rate (3 months ± 7 days after the end of the last treatment).  
(5) Incidence of adverse events (AEs) (3 months ± 7 days after the end of the last 
treatment). 
(6) The incidence of Serious Adverse Events (SAEs) (3 months ± 7 days after the end 
of the last treatment). 
(7) Incidence of device defects (after last treatment) 
Eligibility 
criteria 
Inclusion Criteria (Major Criteria): 
(1) 18≤ age≤ 80 years; 
(2) First-diagnosed patients with tumors of the nervous system, head and neck, 
chest, abdomen, spine, pelvic cavity, limbs, etc. by tissue/cell pathology; 
(3) ECOG physical condition is graded as 0 to 2; 
(4) Women of childbearing had negative results in the blood pregnancy test 
(Human Chorionic Gonadotropin, HCG) 7 days prior to the first treatment; 
(5) The subject or subject's guardian is able to understand the purpose of the 
study, demonstrate sufficient compliance with the protocol and sign informed 
consent form. 
 
Exclusion Criteria (Major Criteria): 
(1) The subject with radiotherapy contraindications, including the known genetic 
tendencies that increase the sensitivity of normal tissue radiotherapy or the 
accompanying diseases that lead to hypersensitivity to radiotherapy; 
(2) The subject with other uncontrolled tumors except that to be treated according 
to medical history or the investigator's estimation, or with other malignant tumors 
within five years prior to enrollment; 
(3) Implanted pacemakers or other metal prosthesis within the scope of proton 
therapy; 
(4) Other situations that investigator determines not suitable for enrollment. 
Specifications 
for the use of 
investigational 
medical device 
All subjects used the investigational medical device: ProBeam for radiation therapy.  

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Statistical 
analysis 
Statistical analysis with SAS 9.4 software.  
All data are described statistically, including baseline data, all efficacy measures, 
and all safety data. The measurement data give the mean, standard deviation, 
minimum, maximum, median, 25th quantile and 75th quantile; The counting data 
gives the frequency and composition ratio.  
Effectiveness analysis 
DCR was calculated and the Clopper-Pearson method was used to calculate the 95% 
confidence interval for tumor disease control. ORR was calculated and the Clopper-
Pearson method was used to calculate the objective response rate 95% confidence 
interval.  Descriptive statistics on the percentage change from baseline of the 
measurable sum of the longest diameter (SLD). The Waterfall Chart was made by 
the maximum percentage reduction in SLD per participant compared to the 
screening period.  
The Kaplan-Meier method was used to calculate the median duration of response, 
median progression-free survival, median survival, and overall survival, and plotted K-
M curves (long-term follow-up data).  
Safey analysis 
Descriptive statistics were used to classify organ systems in MedDRA medical terms, 
and the incidence, occurrence, and severity of adverse events, adverse 
reactions, and serious adverse events were summarized.  
Laboratory indicators, ECOG physical status grading and other safety-related indicators 
were compared and evaluated before and after treatment, and clinical evaluation [no 
clinical significance, clinically significant (tends to normal), clinically significant (tends 
to be abnormal), not checked], CTCAE grade evaluation before and after treatment 
cross-tab.  
The central effect is considered in the analysis process, and the general linear model is 
used for the measurement data and CMH for the counting data.  
The baseline data analysis was performed using the Full Analysis Set (FAS); 
Effectiveness analysis uses FAS and Per Protocol Set (PPS); Security analysis uses the 
Safety Set (SS).  

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Trial flowchart 

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受试者招募
知情同意书签署
是
接受检查及评估
不纳入研究
否
筛选
受试者
筛选失败
不通过
通过
纳入研究
（全部受试者使用试验
用器械）
设计放射治疗计划
实施放射治疗
进行检查及评估
（放射治疗期访视）
继续治疗？
是
否
进行检查及评估
（放射治疗结束后随访期）

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The body of the protocol 
1 Sponsor information 
1.1 Name of the sponsor 
Varian Medical Systems Trading (Beijing) Co., Ltd 
1.2 Sponsor address 
No. 8 Yuncheng Street, Beijing Economic and Technological Development Zone, Beijing, 2nd floor, area B, 3rd floor 
1.3 The name, address, contact information and relevant qualification documents of the agent 
NA 
2 Purpose and content of clinical trial 
2.1 Objective 
Clinical trial (screening-short-term follow-up): The data obtained by using Proton Beam equipment (ProBeam) for radiation 
therapy in tumor patients compared with the target value to evaluate the effectiveness and safety of ProBeam for radiation therapy 
in tumor patients to provide clinical basis for product registration application.  
Long-term follow-up: The long-term efficacy and safety of ProBeam for radiation therapy in cancer patients were evaluated 
by using the long-term follow-up data of ProBeam for radiation therapy in cancer patients.  

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2.2 content 
This clinical trial is a prospective study, carried out in 2 clinical trial institutions, and 47 patients with tumors of the nervous 
system, head and neck, chest, abdomen, spine, pelvis, limbs and other tumors were selected as study subjects, all using 
investigational medical devices, and designed for a single group of target values. The research device involved in this trial is the 
proton therapy device (ProBeam), a medical device for investigation. Short-term follow-up is: 1 visit during the screening period 
(within 4 weeks before the first treatment), 2~9 visits during the treatment period according to the length of treatment weeks 
(1~8 weeks), and 3 after the last treatment 3 visits within a month; Long-term follow-up was 11 visits over a period of 3~5 
months after the end of the last treatment. The main efficacy evaluation index was DCR 3 months after the end of the last 
treatment, and the main safety evaluation index was the proportion of CTCAE grade 3 toxicity in the entire short-term follow-
up clinical trial cycle and CTCAE 4 in the entire short-term follow-up clinical trial cycle The proportion of grade 5 toxicity 
reactions, the collected data were analyzed and compared with the target values, and the effectiveness and safety of ProBeam in 
proton radiation therapy for patients with tumors such as nervous system, head and neck, chest, abdomen, spine, pelvis, and 
extremities were evaluated.  Tumor remission, recurrence, survival, device-related adverse events and serious adverse events 
were summarized 6 months, 1 year, 2 years and 5 years after the last treatment. To assess the long-term efficacy and safety of 
ProBeam for radiation therapy in patients with oncology.  

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3 Overall design 
3.1 Trial design 
3.1.1 Trial and long-term follow-up purposes 
3.1.1.1 Main purpose 
To evaluate whether the main efficacy evaluation index of ProBeam in radiotherapy for cancer patients reached the target 
value 3 months after the end of the last treatment. The main safety evaluation index: whether the proportion of CTCAE grade 3 
toxicity is lower than the acceptable value, and whether CTCAE grade 4 and 5 toxic reactions occur.  
3.1.1.2 Secondary purposes 
When evaluating the use of ProBeam in radiation therapy for tumor patients, the secondary effectiveness evaluation 
indicators ORR, DOR, DCR, tumor markers (if necessary), tumor-specific symptoms, and product usability evaluation are 
actually the actual situation.  
When evaluating the use of ProBeam in radiation therapy in tumor patients, the proportion of secondary safety evaluation 
indicators CTCAE grade 1 and 2 toxicity, laboratory tests, ECOG physical status grade, tumor recurrence rate, adverse 
event rate, serious adverse event rate, The actual situation of the incidence of device defects.  
3.1.1.3 Long-term follow-up purposes 
To evaluate the effectiveness of ProBeam for radiotherapy in tumor patients, the evaluation indexes were 6 months, 1 year, 
2 years, 5 years of DCR The actual situation of ORR, DOR, PFS, OS.  

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After ProBeam was used in radiotherapy for tumor patients, the safety evaluation index was 6 months, 1 year, 2 years, and 
5 years of device-related AE and device-related treatment SAE, the actual situation of tumor recurrence rate.  
3.1.2 Choice of trial method and justification 
This trial was designed using the prospective, two-center, single-group target value method. 
(1) Prospective study: Adopt a research approach that traces from the present to the future. Prospective studies can 
establish cause and effect; There are unified diagnosis, detection and evaluation standards for the obtained data, so the 
data processing is controllable. 
(2) Two centers: Select 2 clinical trial institutions to carry out the clinical trial. More cases than single-center trials can be 
obtained in the same amount of time, thus shortening the duration of clinical trials.  
(3) Single-group target value method: Because the same device of the experimental medical device is radioactive and 
difficult to obtain, the existing treatment method is not feasible due to objective conditions, so the single-group target 
value method is adopted. Moreover, the applicable population and main evaluation indicators of experimental medical 
devices can be fully defined and relatively stable; The main evaluation index adopts the effective rate mentioned in 
the "Guidelines for the Technical Review of Clinical Evaluation of Proton Carbon Ion Therapy System" (CFDA 
Circular No. 4 [2018]), which is relatively objective and reproducible. According to the Guidelines for the Technical 
Review of Clinical Evaluation of Proton Carbon Ion Therapy Systems, the target value of therapeutic response rate for 
experimental medical devices should be at least 80%, and the expected value should be 95%. Among them, the 
effective definition is: CR+PR+SD (complete response CR, partial response PR, disease stable SD), which is basically 
consistent with the definition of tumor disease control rate in this clinical trial. Therefore, no control group was set up 
in this clinical trial, and the single-group target value method was used to evaluate whether the tumor disease control 
rate reached the target value (80%) and the main safety evaluation index CTCAE 3 when ProBeam was used in 

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radiotherapy for tumor patients Whether the proportion of grade toxicities is less than acceptable (5%) and whether 
the proportion of CTCAE grade 4 and 5 toxicities is acceptable (0%).  
3.1.3 Diagnostic and therapeutic methods of medical devices for investigation 
All subjects used ProBeam, an investigational medical device. The investigator formulated an individualized radiotherapy 
plan according to the actual clinical situation of the subjects, and the use of experimental medical devices is detailed in the 
product manual.  
The specific treatment process is: preoperative assessment to determine the indications (radiotherapist)→ signing of the 
informed consent form for radiotherapy (radiotherapist)→ selection and production of postural immobilization devices 
(radiotherapist, radiotherapist, physicist) → CT/MRI Simulation positioning (radiotherapist, radiotherapist, physicist)→ target 
and normal organ delineation (radiotherapist)→ radiotherapy plan design (physicist)→ radiotherapy plan review and 
authorization for executable plans (radiotherapist, physicist), → treatment plan validation (physicist), → proton radiation therapy 
(radiotherapist). First treatment, radiotherapist and physicist are present) → post-treatment efficacy evaluation (radiotherapist, 
independent imaging review team) → follow-up (radiotherapist).  
Subjects will receive radiotherapy with reference to the dose and segmentation prescribed by the trial, and the expected 
radiotherapy cycle of each subject is 1~8 weeks. 
 
3.1.3.1 Enrollment time 
The investigators obtained the informed consent of the participants and signed the ICF, which was then screened according 
to the inclusion criteria. If the patient meets all the inclusion criteria of this trial and does not meet any of the exclusion criteria, 

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the case is included in this trial, and the time of enrollment of the subject is used as the treatment on the day of the first treatment, 
and a unique enrollment number is obtained in the order of enrollment.  
3.1.3.2 The number of subjects required for the clinical trial 
After screening according to the inclusion criteria, it is expected that a total of 47 subjects will be included in this clinical 
trial, all of whom will be treated with investigational medical devices.  
3.1.4 Effectiveness evaluation methods 
If it is not possible to follow up at the clinical trial center according to the visit arrangement due to the epidemic, the clinical 
examination can be examined by other tertiary hospitals, and the test results will be transmitted back to the clinical trial center 
for evaluation; The carrier of imaging data in the outer hospital is not limited, and it is necessary to ensure that the imaging 
department of the center can be opened and read.  
3.1.4.1 The main effectiveness evaluation indicators and the methods and time selection of their evaluation, recording and 
analysis 
(1) Tumor disease control rate (DCR). 
Reason for selection: According to the clinical trial effectiveness evaluation in the "Guidelines for the Review of Clinical 
Evaluation Technologies of Proton Carbon Ion Therapy System" (CFDA Circular No. 4 [2018]): "In view of the local 
characteristics of radiotherapy, it is recommended that the efficacy evaluation should be based on local control, and according to 
the different diseases, the common standards in clinical research, such as the efficacy evaluation criteria for solid tumors, should 
be reasonably adopted RECIST。 The efficacy evaluation can be divided into complete response CR, partial response PR, 
disease stable SD, disease progression PD, and the effective definition is: "CR+PR+SD." ”； Due to the particularity of the 
disease, the evaluation method recommended in the relevant diagnosis and treatment guidelines is selected. The tumor disease 

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control rate was selected as the main effectiveness evaluation index, which was relatively objective and reproducible, and adopted 
the common standard in clinical research, which was widely recognized and applied by clinicians.  
Definition of indicators: the occurrence of CR, PR and SD after the end of treatment is disease control; No biochemical 
recurrence at the end of prostate cancer treatment, no regional lymph nodes or distant metastases, considered disease control. 
Proportion of participants who developed disease control three months after the end of the last radiotherapy.  
Metric type: Qualitative. 
Data collection time: screening period, 3 months ± 7 days after the end of the last treatment.  
Evaluation time: 3 months ± 7 days after the end of the last treatment.  
Site of evaluation: Tumor receiving radiation therapy. 
Evaluation method: The changes in tumor CT or MRI imaging before and after treatment were evaluated by an independent 
imaging review panel according to RECIST 1.1.  At 3 months of radiographic evaluation, if PD is found, PET-CT is required to 
confirm it.  
Calculation formula: DCR = number of disease control subjects / total number of subjects× 100%. 
Criteria: See RECIST 1.1 for details. At the time of 3-month imaging evaluation, if the patient is found to have PD, PET-
CT examination is required to confirm it, if progress is confirmed, it is recorded as PD, if progress cannot be confirmed, it may 
be false progression, and it is recorded as SD. If prostate cancer does not have biochemical recurrence, PET-CT examination is 
not required, and there is no metastasis by default, which is regarded as tumor control, and if biochemical recurrence occurs, it 
is regarded as tumor not controlled, and PET-CT is required to confirm tumor metastasis.  

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Note: Participants who aborted the trial for any reason (except loss to follow-up) before the end of the last radiation therapy 
were considered to have disease progression (PD) or were not controlled. Disease site evaluation uses the same approach as 
baseline, including consistent contrasted/non-contrast scans and prompt scanning. If changes are needed, the case must be 
discussed with a radiologist to determine whether an alternative approach is possible. If not, the objective situation in the future 
is unclear.  
3.1.4.2 Secondary effectiveness evaluation indicators and their methods and timing of evaluation, recording, analysis 
(1) Objective response rate (ORR). 
Reason for selection: The Guidelines for the Review of Clinical Evaluation Technologies of Proton Carbon Ion Therapy 
Systems (CFDA Circular No. 4 [2018]) recommends the use of the latest version of the commonly used evaluation criteria for 
radiation oncology as the clinical trial evaluation criteria, so RECIST 1.1 is used  Relevant indicators as effectiveness evaluation 
criteria; Due to the particularity of the disease, the evaluation method recommended in the relevant diagnosis and treatment 
guidelines is selected. All of them can directly measure the effect of radiotherapy and are widely recognized and applied by 
clinicians.  
Definition of indicators: CR or PR after the end of treatment is considered objective remission, prostate cancer has no 
biochemical recurrence at the end of the last treatment, and no regional lymph nodes or distant metastasis are considered objective 
remission. Proportion of participants who experienced objective remission at each time point after the end of the last treatment.  
Metric type: Qualitative. 
Data collection time: screening period, 1 month± 7 days, 3 months, ± 7 days after the end of the last treatment.  
Evaluation time: 1 month± 7 days, 3 months, ± 7 days after the last treatment.  

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Site of evaluation: Tumor receiving radiation therapy. 
Evaluation method: The changes in tumor CT or MRI imaging before and after treatment were evaluated by an independent 
imaging review panel according to RECIST 1.1.  At 3 months of radiographic evaluation, if PD is found, PET-CT is required to 
confirm it.  
Calculation formula: ORR = number of subjects in objective response / total number of subjects × 100%. 
Criteria: See RECIST 1.1 for details. At the time of 3-month imaging evaluation, if the patient is found to have PD, PET-
CT examination is required to confirm it, if progress is confirmed, it is recorded as PD, if progress cannot be confirmed, it may 
be false progression, and it is recorded as SD. If prostate cancer does not have biochemical recurrence, PET-CT examination is 
not required, and there is no metastasis by default, which is regarded as objective remission, and if biochemical recurrence occurs, 
it is regarded as not objectively remission, and PET-CT is required to confirm tumor metastasis.  
Note: Participants who aborted the trial for any reason (other than loss to follow-up) before the end of the last radiotherapy 
were considered to have not responded objectively. Disease site evaluation uses the same approach as baseline, including 
consistent contrasted/non-contrast scans and prompt scanning. If changes are needed, the case must be discussed with a 
radiologist to determine whether an alternative approach is possible. If not, the objective situation in the future is unclear.  
(2) Time to sustained remission (DOR). 
Reason for selection: The Guidelines for the Review of Clinical Evaluation Technologies of Proton Carbon Ion Therapy 
Systems (CFDA Circular No. 4 [2018]) recommends the use of the latest version of the commonly used evaluation criteria for 
radiation oncology as the clinical trial evaluation criteria, so RECIST 1.1 is used  Relevant indicators as effectiveness evaluation 
criteria; Due to the particularity of the disease, the evaluation method recommended in the relevant diagnosis and treatment 

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guidelines is selected. They are all commonly used indicators for the evaluation of tumor treatment effects, and are widely 
recognized and applied by clinicians.  
Indicator definition: the time between the first assessment of the tumour as CR or PR and the time between the first 
assessment of PD or death from any cause.  
Indicator type: quantitative. 
Data collection time: 1 month± 7 days, 3 months, ± 7 days after the end of the screening period, until tumor progression or 
subject death.  
Evaluation time: 3 months ± 7 days after the last treatment.  
Site of evaluation: Tumor receiving radiation therapy. 
Evaluation method: The changes in tumor CT or MRI imaging before and after treatment were evaluated by an independent 
imaging review panel according to RECIST 1.1.  At 3 months of radiographic evaluation, if PD is found, PET-CT is required to 
confirm it.  
Calculation formula: DOR = time to death from PD or any cause on the first assessment - time to CR or PR for the first 
assessment;  
Criteria: See RECIST 1.1 for details. At the time of 3-month imaging evaluation, if the patient is found to have PD, PET-
CT examination is required to confirm it, if progress is confirmed, it is recorded as PD, if progress cannot be confirmed, it may 
be false progression, and it is recorded as SD.  
Note: If no tumor progression or death is observed during the follow-up period after the end of radiotherapy, the formula is: 
DOR > last visit time after the end of the last radiotherapy - CR or PR time for first assessment. Others are the same as ORR.  

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(3) Tumor disease control rate (DCR). 
Reason for selection: DCR 3 months after the end of the last treatment was the primary evaluation index, and DCR at other 
follow-up time was used as a secondary evaluation index.  
Definition of indicators: the occurrence of CR, PR and SD after the end of treatment is disease control; No biochemical 
recurrence at the end of prostate cancer treatment, no regional lymph nodes or distant metastases, considered disease control.  
Proportion of participants who developed disease control at one month after the end of the last treatment.  
Metric type: Qualitative. 
Data collection time: screening period, 1 month ± 7 days after the end of the last treatment.  
Evaluation time: 1 month ± 7 days after the last treatment.  
Site of evaluation: Tumor receiving radiation therapy. 
Evaluation method: The changes in tumor CT or MRI imaging before and after treatment were evaluated by an independent 
imaging review panel according to RECIST 1.1.  At 3 months of radiographic evaluation, if PD is found, PET-CT is required to 
confirm it.  
Calculation formula: DCR = number of disease control subjects / total number of subjects × 100%. 
Criteria: See RECIST 1.1 for details. At the time of 3-month imaging evaluation, if the patient is found to have PD, PET-
CT examination is required to confirm it, if progress is confirmed, it is recorded as PD, if progress cannot be confirmed, it may 
be false progression, and it is recorded as SD. If prostate cancer does not have biochemical recurrence, PET-CT examination is 
not required, and there is no metastasis by default, which is regarded as tumor control, and if biochemical recurrence occurs, it 
is regarded as tumor not controlled, and PET-CT is required to confirm tumor metastasis.  

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Note: Participants who aborted the trial for any reason (other than loss to follow-up) before the end of the last radiotherapy 
were considered to have PD or was uncontrolled. Disease site evaluation uses the same approach as baseline, including consistent 
contrasted/non-contrast scans and prompt scanning. If changes are needed, the case must be discussed with a radiologist to 
determine whether an alternative approach is possible. If not, the objective situation in the future is unclear.  
(4) Tumor markers (if needed) 
Reason for selection: The Guidelines for the Review of Clinical Evaluation Technologies of Proton Carbon Ion Therapy 
System (CFDA Circular No. 4, 2018) suggests that changes in tumor markers and functional imaging parameters should be used 
as reference factors for effectiveness evaluation.  
Data collection and evaluation time: screening period, 1 month ± 7 days, 2 months± 7 days, 3 months±7 months after the 
end of the last treatment Sky.  
Evaluation method: tumor marker examination is performed, and the investigator judges that the tumor marker (before and 
after radiotherapy) is reported as clinically significant changes. 
Note: Researchers choose relevant indicators according to the disease, and the scheme is not uniformly stipulated. 
(5) Tumor-specific symptoms 
Reason for selection: The Guidelines for the Review of Clinical Evaluation Technologies of Proton Carbon Ion Therapy 
Systems (CFDA Circular No. 4 of 2018) suggests that clinical manifestations should be recorded during follow-up.  
Data collection and evaluation time: screening period, 1 month ± 7 days, 2 months± 7 days, 3 months±7 months after the 
end of the last treatment Sky.  

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Methodology: Symptoms are recorded according to the type of disease, which may include, but are not limited to, the 
following: pain, swallowing function, mobility, bleeding, visual acuity, appetite/weight, superficial lymph node size, and the 
investigator judges that the symptoms (before and after radiotherapy) are clinically significant.  
Note: Researchers record relevant symptoms according to the disease, and the plan is not uniformly stipulated. 
(6) Product usability evaluation (ProBeam system, radiotherapy management software (OIS), radiotherapy planning 
software (Eclipse)). 
Reason for selection: Routine effectiveness indicators of medical device clinical trials. 
Indicator type: quantitative, open-ended question. 
Data collection and evaluation time: the day the last treatment was completed. 
Evaluation method: Researchers using the corresponding function scored according to the Likrt scale and collected open-
ended questions to evaluate the overall feeling of ease of use during treatment.  
 
3.1.5 Safety evaluation methods 
If it is not possible to follow up at the clinical trial center according to the visit arrangement due to the epidemic, the clinical 
examination can be examined by other tertiary hospitals, and the test results will be transmitted back to the clinical trial center 
for evaluation; The carrier of imaging data in the outer hospital is not limited, and it is necessary to ensure that the imaging 
department of the center can be opened and read.  

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3.1.5.1 The main safety evaluation indicators and the methods and time selection of their evaluation, recording and 
analysis 
(1) CTCAE 3 toxicity ratio 
Reason for selection: According to the Guidelines for the Technical Review of Clinical Evaluation of Proton Carbon Ion 
Therapy System (CFDA Circular No. 4 of 2018), if the proportion of CTCAE grade 3 acute toxic reactions exceeds 5%, it is 
considered as a clinical trial failure, so it is selected  The proportion of CTCAE grade 3 toxicity is used as the main safety 
evaluation index, and CTCAE is a commonly used safety evaluation standard in radiation oncology, which is widely recognized 
and applied by clinicians.  
Indicator definition: Proportion of subjects with grade 3 toxicity during the trial cycle.  
Metric type: Qualitative. 
Data collection time: the entire clinical trial cycle. 
Evaluation time: 3 months ± 7 days after the last treatment.  
Evaluation methodology: Investigators recorded AEs that occurred during the clinical trial cycle and graded them according 
to CTCAE V5.0.  
Calculation formula: proportion of CTCAE grade 3 toxicities = (number of subjects with CTCAE grade 3 toxicity in the 
test cycle) / total number of subjects × 100%. 
Judging criteria: See CTCAE V5.0 for details.  
(2) CTCAE Grade 4 and 5 toxicity ratio 

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Reason for selection: According to the Guidelines for the Review of Clinical Evaluation Technologies of Proton Carbon Ion 
Therapy System (CFDA Circular No. 4 of 2018), CTCAE grade 4 and 5 toxicities are considered to be clinical trial failures, so 
4 is selected  The proportion of grade 5 and grade 5 toxicity reactions is used as a safety evaluation index, and CTCAE is a 
commonly used safety evaluation standard in radiation oncology, which is widely recognized and applied by clinicians.  
Indicator definition: Proportion of subjects with toxicity of grade 4 and 5 during the trial cycle.  
Metric type: Qualitative. 
Data collection time: the entire clinical trial cycle. 
Evaluation time: 3 months ± 7 days after the last treatment.  
Evaluation methodology: Investigators recorded AEs that occurred during the clinical trial cycle and graded them according 
to CTCAE V5.0.  
Formula: Proportion of CTCAE grade 4 and 5 toxicities = (number of subjects with CTCAE grade 4 and 5 reactions in the 
test cycle) / total number of subjects × 100% 
Judging criteria: See CTCAE V5.0 for details.  
3.1.5.2 Secondary safety evaluation indicators and their methods and time selection for evaluation, recording and analysis 
(1) CTCAE grade 1 and 2 toxicity ratio 
Reason for selection: The proportion of CTCAE grade 3~5 toxicity reactions 3 months after the end of the last treatment 
was the main safety evaluation index, and the proportion of CTCAE grade 1 and grade 2 toxicity reactions was used as a 
secondary safety evaluation index for auxiliary evaluation.  

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Indicator definition: Proportion of subjects with grade 1 and 2 toxicity during the trial cycle.  
Metric type: Qualitative. 
Data collection time: the entire clinical trial cycle. 
Evaluation time: 3 months ± 7 days after the last treatment.  
Evaluation methodology: Investigators recorded AEs that occurred during the clinical trial cycle and graded them according 
to CTCAE V5.0.  
Calculation formula: proportion of CTCAE grade 1 and 2 toxicities = (number of subjects with CTCAE grade 1 and 2 
toxicities in the test cycle) / Total number of participants× 100%. 
Judging criteria: See CTCAE V5.0 for details.  
(2) Laboratory tests 
Reason for selection: According to the Guidelines for Technical Review of Clinical Evaluation of Proton Carbon Ion 
Therapy System (CFDA Circular No. 4 of 2018), changes in clinical symptoms and signs should be recorded for clinical 
manifestations, tumor improvement (imaging examinations, laboratory test data), etc., and comprehensive analysis should be 
carried out. At the same time, it is a routine safety monitoring index for medical device clinical trials.  
Data collection and evaluation time: screening period, treatment period 1st day per week (Monday to Sunday is regarded as 
1 calendar week, each natural week on the day of the first treatment), before treatment or -1 day (blood count only), 3 days after 
the end of the last treatment, 1 month ± 7 days (except coagulation routine), 2 months± 7 days (except coagulation routine), 3 
months, ± 7 days (except coagulation routine). 。  

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Evaluation items: blood routine, coagulation routine, urine routine, liver function, kidney function. 
Evaluation method: Laboratory tests are performed and the investigator judges clinically significant changes in laboratory 
indicators (before and after radiotherapy). 
(3) ECOG grading of physical status 
Reason for selection: According to the Guidelines for the Review of Clinical Evaluation Technologies of Proton Carbon Ion 
Therapy System (CFDA Circular No. 4 of 2018), the follow-up of subjects should include safety and efficacy evaluation. The 
general condition of the subjects is recommended to be evaluated using the internationally accepted scoring method.  
Data collection time and evaluation time: screening period, treatment period on the first day of each week (every Monday 
to Sunday is regarded as 1 calendar week, each natural week on the day of the first treatment) before treatment or -1 day, 3 days 
after the end of the last treatment, 1 month ± 7 days, 2 months± 7 days, 3 months, ± 7 days.  
Evaluation method: ECOG physical performance status was graded and reported by the investigator to report clinically 
significant changes in the test results (before and after radiotherapy).  
(4) Tumor recurrence rate 
Reason for selection: According to the Guidelines for the Review of Clinical Evaluation Technologies of Proton Carbon Ion 
Therapy System (CFDA Circular No. 4 of 2018), the clinical trial summary report still needs to be submitted 6 months, 1 year 
and 2 months after treatment  The situation in years and 5 years is summarized, including the tumor recurrence rate. Therefore, 
an adjuvant analysis of tumor recurrence rate was also added to short-term follow-up. At the same time, it is a common indicator 
for the safety evaluation of tumor treatment, and is widely recognized and applied by clinicians.  

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Definition of indicators: The tumor recurrence rate is the ratio of the number of subjects with tumor recurrence to the total 
number of subjects. Tumor recurrence refers to tumors that are clinically controlled after radiation therapy and regrow after a 
period of time, in the same nature as the primary tumor. Clinically referred to recurrence mostly refers to local recurrence, such 
as remnant organs, irradiation fields, and affected adjacent organs. Prostate cancer recurrence refers to biochemical recurrence 
and PET-CT is required to confirm tumor metastasis to lymph nodes or distant metastases.  
Metric type: Qualitative. 
Data collection time: screening period, 1 month± 7 days, 3 months, ±7 days after the last treatment.  
Evaluation time: 3 months ± 7 days after the last treatment.  
Evaluation method: The changes in tumor CT or MRI imaging before and after treatment were evaluated by an independent 
imaging review panel according to RECIST 1.1.  At 3 months of radiographic evaluation, if PD is found, PET-CT is required to 
confirm it.  
Calculation formula: tumor recurrence rate = number of subjects with tumor recurrence / total number of subjects × 100%. 
Criteria: See RECIST 1.1 for details. At the time of 3-month imaging evaluation, if the patient is found to have PD, PET-
CT examination is required to confirm it, if progress is confirmed, it is recorded as PD, if progress cannot be confirmed, it may 
be false progression, and it is recorded as SD. If prostate cancer does not have biochemical recurrence, PET-CT examination is 
not required, and there is no metastasis by default, which is regarded as tumor control, and if biochemical recurrence occurs, it 
is regarded as tumor not controlled, and PET-CT is required to confirm tumor metastasis.  
Note: Participants who discontinued the trial for any reason (other than loss to follow-up) before the end of radiotherapy 
were considered to have no oncological disease control. Disease site evaluation uses the same approach as baseline, including 

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consistent contrasted/non-contrast scans and prompt scanning. If changes are needed, the case must be discussed with a 
radiologist to determine whether an alternative approach is possible. If not, the objective situation in the future is unclear.  
(5) Adverse event rate 
Reason for selection: Routine safety monitoring indicators for clinical trials of medical devices. 
Indicator definition: Adverse events are adverse medical events that occur during clinical trials, whether or not related to a 
device. 
Metric type: Qualitative. 
Data collection time: the entire clinical trial cycle. 
Evaluation time: 3 months ± 7 days after the last treatment.  
Evaluation method: The investigator recorded all AEs that occurred.  
Calculation formula: adverse event rate = number of subjects with adverse events in this group / total number of subjects in 
this group× 100%. 
(6) Serious adverse event rate 
Reason for selection: Routine safety monitoring indicators for clinical trials of medical devices. 
Definition: Serious adverse events are those that occur in the course of a clinical trial that result in death or serious 
deterioration of health, including fatal illness or injury, permanent defects in body structure or function, requiring hospitalization 
or prolonged hospital stay, or requiring medical or surgical intervention to avoid permanent defects in body structure or body 
function; Events that lead to fetal distress, fetal death, or congenital anomalies or birth defects. 

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Metric type: Qualitative. 
Data collection time: the entire clinical trial cycle. 
Evaluation time: 3 months ± 7 days after the last treatment.  
Evaluation methodology: The investigator recorded all SAEs that occurred.  
Calculation formula: Serious adverse event rate = number of subjects with serious adverse events in this group / total number 
of subjects in this group× 100%. 
(7) Incidence of device defects 
Reason for selection: Routine safety monitoring indicators for clinical trials of medical devices. 
Definition of indicators: refers to the unreasonable risk that medical devices may endanger human health and life safety 
under normal use during clinical trials, such as crash. 
Metric type: Qualitative. 
Time of data collection: during treatment. 
Evaluation time: After the last treatment was completed. 
Evaluation methodology: The investigator recorded all device defects that occurred. 
Calculation formula: incidence of device defects = number of occurrences of device defects / number of times of device use 
× 100%.

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4 Statistical considerations 
4.1 Statistical design, methods, and analytical protocols 
This study was a prospective, two-center, single-group target value trial. 
All statistical analysis methods are described in detail in the statistical 
analysis plan. A first draft of the statistical analysis plan is formed after the 
protocol and eCRF are finalized and will be finalized prior to database locking.  
4.2 Sample size calculation 
4.2.1 Total sample size 
This clinical trial intends to enroll 47 subjects. The sample size determination 
process is as follows: 
This clinical study is designed for clinical verification of a single group of 
target values, and the tumor disease control rate, the main effectiveness evaluation 
index, is used as the basis for sample size estimation. According to the Guidelines 
for the Review of Clinical Evaluation Technologies of Proton Carbon Ion Therapy 
System (CFDA Circular No. 4 of 2018), the target value is set at 80%, and the 
bilateral significance level is 0.05, and the power degree 80%, applying the 
sample size estimation professional software PASS 15.0, calculated by the above 
parameters, the test group needs a sample size of at least 42 cases. Considering 
that about 10% of cases may be dropped or lost to follow-up during clinical 
validation, the sample size of the experimental group was expanded to 47 cases.  

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4.3 The level of significance and power of clinical trials 
The significance level α (bilateral) = 0.05, and the power was 80%.  
4.4 Expected shedding rate 
In the sample size estimation process, the expected shedding rate is 10%.  
This dropout rate refers to the proportion of participants who ultimately 
could not be included in the primary analysis. Shedding subjects are subjects who 
have been identified by the investigator as having serious protocol deviations. 
May include, but is not limited to, the following: the subject violates the inclusion 
criteria; Participants were not treated with experimental devices; Participants used 
concomitant medications/devices that are prohibited by the protocol; lack of data 
on key evaluation indicators; Participants did not obtain any data, etc.  
4.5 Criteria for passing/failing clinical trial results 
The target value of the main effectiveness evaluation index (tumor disease 
control rate) of the trial was 80%, and if the lower limit of the 95% confidence 
interval of the test results was greater than 80%, the tumor disease control rate of 
the experimental group reached the target.  
If the main safety evaluation index of the trial (the proportion of CTCAE 
grade 3 toxic reactions) is greater than 5%, the clinical trial fails.  
If the trial has CTCAE grade 4 and 5 toxicity, the clinical trial fails.  

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4.6 Criteria and reasons for terminating trials on statistical grounds 
No interim analysis was performed in this study and therefore criteria for 
termination of the trial for statistical reasons were not established. 
4.7 Statistical methods of data, together with methods of dealing with 
missing, unused or erroneous data and irrational data 
4.7.1 Data statistical methods 
Statistical analysis with SAS 9.4 software.  
All data are described statistically, including demographics, baselines, all 
efficacy measures, and all safety data. The measurement data give the mean, 
standard deviation, minimum, maximum, median, 25th quantile and 75th quantile; 
The counting data gives the frequency and the corresponding percentage.  
Effectiveness Analysis: 
The number and percentage of cases achieving DCR were calculated, and 
the Clopper-Pearson method was used to calculate the 95% confidence interval 
for tumor disease control rate. ORR was calculated and the Clopper-Pearson 
method was used to calculate the objective response rate 95% confidence interval. 
Descriptive statistics on the percentage change from baseline of the sum of the 
longest diameter (SLD) of the measurable tumor. The Waterfall Chart was made 
by the maximum percentage reduction in SLD per patient compared to the 
screening period.  

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The Kaplan-Meier method was used to calculate the median duration of 
response, median progression-free survival, median survival, and overall survival, 
and plotted K-M curves (long-term follow-up data).  
For tumor markers, compare and evaluate the changes before and after 
treatment, and give clinical evaluation [no clinical significance, clinically 
significant (tend to normal), clinically significant (tend to be abnormal), not 
checked].  
Safety Analysis: 
Descriptive statistics were used to classify organ systems in MedDRA 
medical terms, and the incidence, occurrence, and severity of adverse events, 
adverse reactions, and serious adverse events were summarized.  
Laboratory indicators, ECOG physical status classification and other safety-
related indicators were compared and evaluated before and after treatment, and 
clinical evaluation ([no clinical significance, clinically significant (tending to 
normal), clinically significant (tending to abnormal), not checked], CTCAE grade 
evaluation before and after treatment cross-table.  
4.7.2 Missing, unused, or erroneous data (including mid-exit and 
evacuation) and unreasonable data 
All missing, unused or erroneous data (including mid-exit and withdrawal) 
and unreasonable data will be discussed and finalized by investigators and 

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biostatisticians during the blinding review phase. The basic statistical principles 
of these data processing are as follows: 
(1) Describe the details of each shedding case; 
(2) Missing data from baseline, which can not be estimated; 
(3) The missing values of DCR and primary safety evaluation indicators 
(proportion of CTCAE grade 3 toxicities, proportion of CTCAE grade 
4 and 5 toxicities) at 3 months after the end of treatment can be 
estimated using worst-case scenarios.  
(4) The missing values of qualitative secondary effectiveness evaluation 
indicators ORR, DCR and long-term follow-up effectiveness evaluation 
indicators can be estimated using worst-case scenarios;  
(5) The missing values of quantitative secondary efficacy evaluation 
indicators DOR, tumor markers, product ease assessment and long-term 
follow-up effectiveness evaluation indicators were not estimated.  
(6) Erroneous, unreasonable data (out-of-range data and data that 
contradicts other data or indicators of the study protocol) can be treated 
as missing values; 
(7) Worst-case estimates are used for missing values for all minor safety 
indicators; 

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(8) The sensitivity analysis of the main effectiveness evaluation indicators 
and main safety evaluation indicators after treatment was carried out in 
the whole analysis center. 
(9) The sensitivity analysis of all secondary effectiveness evaluation 
indicators after treatment was carried out in the whole analysis center. 
(10) For all secondary safety evaluation indicators after treatment, 
sensitivity analysis was carried out in the security dataset. 
4.8 Procedures for reporting deviations from the original statistical plan 
Under normal circumstances, only the statistical analysis content agreed in 
advance included in the statistical analysis plan can be presented in the clinical 
trial report of this trial. The increased demand for statistical analysis for various 
uncertain reasons is only exploratory analysis. 
4.9 Selection criteria and rationale for participants included in the analysis 
Full Analysis Set (FAS): All subjects who received at least 1 investigational 
device treatment and at least one post-baseline observation data will be enrolled 
in FAS, according to the basic principles of intention-to-heart analysis. FAS will 
be used as the primary population for baseline data and sensitivity analysis for 
validity evaluation. Participants may only be excluded in very limited 
circumstances, including when important inclusion criteria are violated and no 
observational data are available after enrollment.  

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Compliant protocol set (PPS): is a subset of FAS, defined as subjects who 
have measurable lesions at baseline and have completed at least one assessment 
of primary efficacy indicators after baseline. PPS will be the primary population 
for the effectiveness evaluation of this study.  
Safety dataset (SS): all participants who received at least 1 study device 
treatment and at least one safety assessment. SS will be the primary population 
for safety analysis in this study.  
The assessment of baseline characteristics will use the full set of analyses; 
The evaluation of effectiveness will use both the full analysis set and the 
conforming protocol set; Security analysis uses security datasets. 
4.10 Covariate and subgroup analysis 
Subgroup analysis as necessary was not precluded. Subgroups include, but 
are not limited to: 
(1) Tumor sites (tumors of the nervous system, head and neck, chest, 
abdomen, spine, pelvis, extremities, etc.).