Abstract
Background:
Few studies have focused on the efficacy of stereotactic body radiation therapy (SBRT) in treating early hepatocellular carcinoma (HCC) for curative intention. This study aims to determine the best option among resection, ablation, and SBRT in dealing with single HCC no more than 5 cm.
Materials and methods:
This multicenter retrospective cohort study included 985 patients from 3 hospitals: 495, 335, and 155 in the resection, ablation, and SBRT groups, respectively, between January 2014 and December 2021. Subgroup analysis and propensity score matching (PSM) were performed.
Results:
The SBRT group had unfavorable clinical features including larger tumor size, poorer liver function, and more relapsed tumors. The 1-year, 3-year, and 5-year recurrence-free survival (RFS) rates were 84.3%, 66.8%, and 56.2% with resection, 73.3%, 49.8%, and 37.2% with ablation and 73.2%, 56.4%, and 53.6% with SBRT, respectively (P<0.001). The 3-year overall survival (OS) rates were 89.0%, 89.2%, and 88.8% in the resection, ablation, and SBRT group, respectively (P=0.590). The three modalities resulted in similar RFS and OS after adjusting for clinical factors. Resection provided ideal local tumor control, successively followed by SBRT and ablation. SBRT led to comparable RFS time compared to resection for tumors <3 cm (HR=0.75, P=0.205), relapsed tumors (HR=0.83, P=0.420), and patients with poor liver function (HR=0.70, P=0.330). In addition, SBRT was superior to ablation regarding RFS when tumors were adjacent to intrahepatic vessels (HR=0.64, P=0.031). SBRT were more minimally invasive, however, gastrointestinal disorders, hepatic inflammation, and myelosuppression occurred more frequently.
Conclusion:
All three approaches could be applied as curative options. Resection remains the best choice for preventing tumor recurrence, and SBRT showed advantages in treating small, recurrent and vascular-type lesions as well as patients with relatively poor liver function.
Keywords: ablation, hepatocellular carcinoma, recurrence, resection, stereotactic body radiation therapy
Introduction
Highlights
Resection, ablation, and SBRT resulted in similar RFS and OS after adjusting for clinical factors.
SBRT led to comparable RFS time compared to resection for tumors <3 cm, relapsed tumors, and patients with poor liver function.
SBRT was superior to ablation regarding RFS when tumors were adjuvant to intrahepatic vessels.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for 75–85% of cases1. Surgical resection is the mainstay of HCC treatment and is recommended as the first choice for early-stage HCC with a 5-year survival rate of ~60–80%. However, for patients with severe cirrhosis and portal hypertension or lesions situated deeply within the liver, resection may be less appropriate, and thermal ablation would be a proper substitute2.
Radiotherapy was considered less effective in HCC treatment due to the limited ability of sufficient dose delivery without causing radiation-induced liver disease. Recently, several studies have demonstrated that stereotactic body radiation therapy (SBRT) leads to promising local tumor control with fair tolerance in advanced HCC patients3–6. Due to the lack of randomized controlled trials (RCT) comparing outcomes between SBRT and other curative treatments, the role of SBRT in early HCC, especially tumors no more than 5 cm, remains controversial. Hence, in this study, we aim to compare the outcomes of surgical resection, thermal ablation, and SBRT in treating early HCC patients with solitary nodule no more than 5 cm and discuss the best-suited populations for the three treatments.
Material and methods
Patients and data collection
Patients who were diagnosed with solitary HCC ≤5 cm and received either curative resection, percutaneous thermal ablation, or SBRT from 1st January 2014 to 31st December 2021, in three hospitals in China (Sun Yat-sen University Cancer Center, Guangdong Provincial People's Hospital and Hunan Provincial People's Hospital) were retrospectively reviewed. This study was approved by the ethics committees of the three hospitals (approval number: B2020-350-01). Signed informed consent for the use of data for research purposes was obtained from the patients before treatment. This study has been reported in line with the strengthening the reporting of cohort, cross-sectional, and case–control studies in surgery (STROCSS) criteria7 (Supplemental Digital Content 1, http://links.lww.com/JS9/D239).
The diagnosis of HCC in cirrhotic patients was based on typical dynamic change on multiphasic computed tomography (CT) or MRI (see details in the Supplementary Methods, Supplemental Digital Content 2, http://links.lww.com/JS9/D240). The detailed inclusion and exclusion criteria were presented in the Supplementary Methods (Supplemental Digital Content 2, http://links.lww.com/JS9/D240) as well.
Treatment and surveillance procedures
The patient’s treatment plan was decided by a multidisciplinary team (MDT). The detailed procedures of resection, ablation and SBRT, as well as the follow-up schedules were presented in the Supplementary Methods (Supplemental Digital Content 2, http://links.lww.com/JS9/D240).
Outcomes
The primary endpoints of this study were recurrence-free survival (RFS) time and overall survival (OS) time. The secondary endpoints were local tumor recurrence (LTR) rate and safety. LTR was defined as the appearance of new tumor foci at the surgical resection edge8, ablation region (after technical success was confirmed), or 95% isodose line for the SBRT (after technically success was confirmed as well)3,9. New recurrent lesions that emerged outside the local area but were limited inside the liver were classified as intrahepatic distant recurrence (IDR). To explore the corresponding suitable population for the three treatments, we divided tumor lesions into peripheral, central, and vascular types according to their intrahepatic locations (see details in the Supplementary Methods, Supplemental Digital Content 2, http://links.lww.com/JS9/D240).
Statistical analysis
Propensity score matching (PSM) was performed to balance the baseline characteristics among the three groups. Hazard ratios (HRs) and 95% CIs were estimated using the Cox proportional hazard model. A two-tailed P-value ≤0.05 was considered statistically significant, and the Benjamini and Hochberg false discovery rate (FDR) method was applied to adjust the P-value during multiple comparisons10. The detailed statistical methods were presented in the Supplementary Methods (Supplemental Digital Content 2, http://links.lww.com/JS9/D240).
Results
Patient characteristics
A total of 495 patients in the resection group, 335 patients in the ablation group, and 155 patients in the SBRT group were included in our study. The detailed inclusion flowchart is presented in Figure S1 (Supplemental Digital Content 3, http://links.lww.com/JS9/D241). The patient’s baseline characteristics are presented in Table 1. Patients in the resection group had the largest mean tumor size of 3.1 cm, followed by a mean diameter of 2.4 cm in the SBRT group, and the smallest size of 2.1 cm in the ablation group.
Table 1.
Baseline characteristics of the three group patients.
| Resection (n=495) | Ablation (n=335) | SBRT (n=155) | P | |
|---|---|---|---|---|
| Age, years (Mean, SD) | 54.8–11.5 | 53.9–12.0 | 55.7–11.8 | 0.250 |
| Sex | 0.957 | |||
| Male | 435 (87.9%) | 293 (87.5%) | 137 (88.4%) | |
| Female | 60 (12.1%) | 42 (12.5%) | 18 (11.6%) | |
| Etiology | 0.240 | |||
| Hepatitis B virus | 435 (87.9%) | 292 (87.2%) | 128 (82.6%) | |
| Hepatitis C virus | 8 (1.6%) | 10 (2.9%) | 3 (1.9%) | |
| Others | 52 (10.5%) | 33 (9.9%) | 24 (15.5%) | |
| Treatment historya | <0.001 | |||
| Naïve | 291 (77.6%) | 159 (47.5%) | 61 (39.4%) | |
| Recurrence | 84 (22.4%) | 176 (52.5%) | 94 (60.6%) | |
| Child-Pugh score | 0.358 | |||
| 5 | 462 (93.3%) | 317 (94.6%) | 140 (90.3%) | |
| 6 | 25 (5.1%) | 14 (4.3%) | 13 (8.4%) | |
| 7 | 7 (1.4%) | 4 (1.2%) | 1 (0.6%) | |
| 8 | 1 (0.2%) | 0 | 1 (0.6%) | |
| ALBI grade | <0.001 | |||
| I | 400 (80.8%) | 283 (84.5%) | 119 (76.8%) | |
| II | 92 (18.6%) | 52 (15.5%) | 36 (23.2%) | |
| III | 3 (0.6%) | 0 | 0 | |
| Cirrhosis | <0.001 | |||
| Yes | 332 (67.1%) | 202 (60.3%) | 123 (79.4%) | |
| No | 163 (32.9%) | 133 (39.7%) | 32 (20.6%) | |
| Tumor diameter, cm (Mean, SD) | 3.1–1.2 | 2.1–0.8 | 2.4–1.1 | <0.001 |
| >3 cm | 220 (44.4%) | 47 (14.0%) | 36 (23.2%) | <0.001 |
| ≤3 cm | 275 (55.6%) | 288 (86.0%) | 119 (76.8%) | |
| Tumor location typea | ||||
| Peripheral | 326 (86.9%) | 131 (39.2%) | 35 (22.6%) | <0.001 |
| Central | 49 (13.1%) | 204 (60.8%) | 120 (77.4%) | |
| Vascular | 163 (43.5%) | 177 (52.8%) | 91 (58.7%) | 0.002 |
| Nonvascular | 212 (56.5%) | 158 (47.2%) | 64 (41.3%) | |
| AFP, ng/ml (Mean) | 1395.1 | 296.3 | 441.6 | <0.001 |
| ≥400 ng/ml | 117 (23.6%) | 42 (12.5%) | 27 (17.4%) | <0.001 |
| <400 ng/ml | 378 (76.4%) | 293 (87.5%) | 128 (82.6%) | |
| Laboratory tests | ||||
| Albumin, g/l (Mean, SD) | 42.7–4.6 | 43.3–3.8 | 42.7–4.3 | 0.109 |
| TBil, μmol/l (Mean, SD) | 14.2–5.9 | 15.7–9.1 | 15.6–8.3 | 0.009 |
| PT, seconds (Mean, SD) | 12.3–1.2 | 12.0–1.0 | 12.1–0.9 | <0.001 |
| Lg (HBV-DNA+1) (Mean, SD) | 1.4–2.0 | 1.1–1.9 | 0.7–1.5 | 0.004 |
AFP, alpha-fetoprotein; ALBI grade, Albumin-Bilirubin grade; Lg (HBV-DNA+1), log10 (Hepatitis B virus DNA copies plus 1); PT, prothrombin time; TBil, total bilirubin.
Among patients who underwent liver resection, only patients from SYSUCC cohort (n=375) contained the information of treatment history and tumor location.
Tumor recurrence and survival
As of 1st October 2023, the median follow-up time was 55.6 months, 67.7 months, and 30.5 months in the resection, ablation, and SBRT groups, respectively. During the follow-up time, a total of 195 (39.4%) patients in the resection group, 217 (64.8%) patients in the ablation group and 60 (38.7%) patients in the SBRT group had experienced tumor recurrence. The median RFS times were 81.7 months, 35.7 months, and unreached in the resection, ablation and SBRT groups, respectively (Fig. 1A). Hepatectomy remained the best curative approach for preventing tumor recurrence, with 1-year, 3-year, and 5-year RFS rates of 84.3%, 66.8%, and 56.2% (HR=0.57, P<0.001 for resection vs. ablation, and HR=0.70, P=0.025 for resection vs. SBRT, respectively). SBRT resulted in comparable long-term outcomes as thermal ablation; the 1-year, 3-year, and 5-year RFS rates were 73.3%, 49.8%, and 37.2%, respectively, in the ablation group and 73.2%, 56.4%, and 53.6%, respectively, in the SBRT group (HR=0.82, 95% CI: 0.61–1.10, P=0.182).
Figure 1.
The recurrence-free survival and overall survival of the three groups of patients. Kaplan–Meier curves of (A) recurrence-free survival and (B) overall survival before PSM and after PSM (C and D). The overall P-value is presented in the middle of the figure, and P-values (lower left) and hazard ratios (upper right) of multiple comparisons (resection versus ablation, resection versus SBRT, and SBRT versus ablation) are presented in the mini-dotted box on each figure. The P-value is adjusted by the Benjamini and Hochberg false discovery rate (FDR) method. AB, ablation; OS, overall survival; PSM, propensity score matching; RE, resection; RFS, recurrence-free survival; SBRT, stereotactic body radiation therapy.
Due to all included patients were early-stage HCC, the OS times were nearly the same among three groups (Fig. 1B). The median OS time was not reached, the 3-year OS rates were 89.0%, 89.2% and 88.8% in the resection, ablation and SBRT groups, respectively. The 5-year OS rate of resection was 81.4% and that of ablation was 84.7%.
PSM was further applied to minimize the selection bias at a caliper score of 0.1 and match ratio of 1:1:1. There was no difference in the baseline characteristics after PSM among the three groups (Table S1, Supplemental Digital Content 3, http://links.lww.com/JS9/D241), and the RFS and OS times were similar among the three treatments (Fig. 1C and D).
Subgroup analysis
Subgroup analyses were conducted based on tumor size, tumor location, treatment history, and liver function (Figure S2, Supplemental Digital Content 3, http://links.lww.com/JS9/D241). We found that SBRT led to similar outcomes compared to ablation regardless of tumor size and even comparable to resection when the tumor size <3 cm (HR=1.21, P=0.205, versus resection). For recurrent HCCs or patients with relatively poor liver function (ALBL grade II), the three modalities resulted in analogous RFS times (P=0.110 and 0.140, respectively), and both ablation and SBRT could be substitutes for resection in those patients.
The recurrence patterns of the three groups were shown in Figure S3 (Supplemental Digital Content 3, http://links.lww.com/JS9/D241), the majority of patients in the resection and SBRT groups developed intrahepatic distant recurrence during the follow-up time, while nearly half of the patients in the ablation group experienced local tumor recurrence. The LTR-free survival and IDR-free survival before and after PSM are presented in Figure S4 (Supplemental Digital Content 3, http://links.lww.com/JS9/D241), the similar conclusion could be drawn that curative resection provided ideal local tumor control, successively followed by SBRT and ablation, with no difference in preventing intrahepatic recurrence for all three treatments.
Cox regression was conducted to identify the risk factors for RFS and OS (Table S2, Supplemental Digital Content 3, http://links.lww.com/JS9/D241), multiple variable analysis revealed that cirrhosis, ALBI grade, tumor size, treatment-naïve status, and the three treatment modalities were significantly associated with RFS, while Child-Pugh score, ALBI grade, tumor size, and treatment-naïve status were independently related to OS.
Safety and adverse events
The mean post-treatment hospital stay was 5.6 days in the resection group versus 2.1 days in the ablation group (P<0.001), ablation was a much minimal invasive and rapid-recovered option for HCC patients when compared with resection. SBRT was performed at the outpatient department every other day with a total of three radiation times.
Adverse events were evaluated at 1 month after treatment completion (Table 2). Generally, the adverse events were mild and controllable; most were grades 1 and 2, and no grades 4 or 5 events occurred. There was no difference in the impact of the three treatments on liver function, only less than 5% of patients had experienced deterioration of liver function after treatments. Because the liver function of the ablation and radiotherapy groups was poorer before treatment, more patients developed hyperbilirubinemia and hypoalbuminemia after treatment. In addition, SBRT showed obvious myelosuppression, which was reflected in the fact that significantly more patients had grade 3 anemia and thrombocytopenia than the other two groups.
Table 2.
Treatment-related adverse events of the three treatments.
| Grade 1–2 | Grade 3 | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse events | Resection | Ablation | SBRT | P | Resection | Ablation | SBRT | P |
| Abdominal pain | 44 (8.9%) | 38 (11.3%) | 2 (1.3%) | 0.001 | 17 (3.4%) | 8 (2.4%) | 0 | 0.059 |
| Decreased appetite | 26 (5.3%) | 4 (1.2%) | 8 (5.2%) | 0.008 | NA | NA | NA | NA |
| Nausea | 18 (3.6%) | 12 (3.6%) | 15 (9.7%) | 0.004 | NA | NA | NA | NA |
| Vomiting | 22 (4.4%) | 8 (2.4%) | 1 (0.6%) | 0.038 | NA | NA | NA | NA |
| Fever | 15 (3.0%) | 13 (3.9%) | 2 (1.3%) | 0.300 | NA | NA | NA | NA |
| Bile leakage | 5 (1.0%) | 0 | 0 | 0.032 | NA | NA | NA | NA |
| Bowel obstruction | 6 (1.2%) | 0 | 0 | 0.016 | NA | NA | NA | NA |
| Pleural effusion | 4 (0.8%) | 1 (0.3%) | 1 (0.6%) | 0.620 | NA | NA | NA | NA |
| Pneumothorax | 0 | 1 (0.3%) | 0 | 0.340 | NA | NA | NA | NA |
| Anemia | 19 (3.8%) | 16 (4.8%) | 6 (3.9%) | 0.787 | 0 | 0 | 1 (0.6%) | 0.157 |
| Neutropenia | 23 (4.6%) | 21 (3.6%) | 9 (5.8%) | 0.577 | 0 | 0 | 1 (0.6%) | 0.157 |
| Thrombocytopenia | 31 (3.6%) | 53 (15.8%) | 19 (12.3%) | <0.001 | 2 (0.4%) | 5 (1.5%) | 8 (5.2%) | 0.001 |
| Elevated ALT | 29 (5.9%) | 40 (11.9%) | 18 (11.6%) | 0.004 | 1 (0.2%) | 2 (0.6%) | 0 | 0.391 |
| Elevated AST | 46 (9.3%) | 62 (18.5%) | 36 (23.2%) | <0.001 | 2 (0.4%) | 1 (0.3%) | 0 | 0.579 |
| Hyperbilirubinemia | 28 (5.7%) | 36 (10.7%) | 21 (13.5%) | 0.002 | 0 | 0 | 0 | NA |
| Hypoalbuminemia | 37 (7.5%) | 51 (15.2%) | 23 (14.8%) | <0.001 | 0 | 0 | 0 | NA |
| Elevated Creatinine | 13 (2.6%) | 8 (2.4%) | 4 (2.6%) | 0.976 | 0 | 1 (0.3%) | 0 | 0.340 |
| Deterioration in CPSa | 7 (1.4%) | 5 (1.5%) | 5 (3.2%) | 0.358 | NA | NA | NA | NA |
| Deterioration in ALBIa | 12 (2.4%) | 13 (3.9%) | 2 (1.3%) | 0.206 | NA | NA | NA | NA |
| Blood Transfusion | 10 (2.0%) | 0 | 0 | 0.001 | NA | NA | NA | NA |
| Post-treat hospital stayb | 5.6 | 2.1 | NA | <0.001 | NA | NA | NA | NA |
| 180-day mortality | 3 (0.6%) | 0 | 0 | <0.001 | NA | NA | NA | NA |
Deterioration of Child-Pugh score or ALBI grade after treatments.
The post-treat hospital stay (days) was presented as mean (SD) and compared by the t-test. Patients received SBRT at outpatient department without hospitalization.
ALBI, Albumin-Bilirubin grade; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPS, Child-Pugh score; NA, not applicable.
Discussion
To the best of our knowledge, in this study, we reported the largest real-world efficacy comparison among surgical resection, percutaneous thermal ablation, and SBRT in curatively treating patients with single HCC ≤5 cm. We found that curative resection remained the best approach for early-stage HCC, and SBRT was comparable to ablation in general. However, when dealing with recurrent tumors or patients with poor liver function, surgery would lose its superiority, and the outcomes of the three treatments tended to be similar. Regarding treatment-related side effects, resection also resulted in more adverse events than both ablation and SBRT; SBRT was proven to be safe and tolerable in treating HCC patients.
The long-term oncological benefits of SBRT in treating HCC patients remain controversial due to the lack of prospective, randomized studies. In this study, we only enrolled patients with solitary HCC ≤5 cm and receiving SBRT and ablation for curative intent to reduce the potential bias. Our results again verified that both overall tumor control and survival rate of SBRT were equal to those of ablation before and after PSM (HR=0.82, P=0.182, and HR=0.90, P=0.57 for RFS; HR=1.05, P=0.880, and HR=0.77, P=0.97 for OS, respectively). According to our findings, SBRT could be recommended as an alternative curative option for early-stage HCC patients who are not candidates for ablation. Subgroup analysis demonstrated that the efficacy of SBRT was less influenced by tumor location, especially the relationship between the lesions and adjacent vessels (HR=0.72, P=0.031, SBRT vs. ablation). Therefore, SBRT might be a better choice for tumors located both deeply within the liver parenchyma and close to intrahepatic vessels.
Studies comparing surgical resection and SBRT in treating HCC patients are rare, in our study, we found that the OS time of patients who underwent resection and SBRT were nearly the same both before and after PSM, but resection indeed provided better RFS time for most patients compared to SBRT except when dealing with patients with poor liver function (ALBI Grade II), lesions less than 3 cm, or recurrent tumors (HR=0.70, P=0.330; HR=0.75, P=0.205; HR=0.83, P=0.420, respectively). When treating the above three types of tumors, surgical resection would not result in better outcomes, but increase the treatment-related damage to the patient on the contrary. Hence, we recommend that for early-stage HCC patients not suitable for resection regardless of the reasons, SBRT is an effective alternative, and especially for patients with single lesions less than 3 cm.
Compared to resection and ablation, SBRT was more minimally invasive, as patients could receive treatment without hospitalization and anesthesia. In our study, SBRT was proven to be safe and tolerable, and the most common subjective adverse events were decreased appetite and nausea. Treatment-related abdominal pain was much unusual, and impairment of liver function was mild and comparable to resection and ablation. However, SBRT resulted in distinct persistent hepatic inflammation and systematic myelosuppression, thus, regular surveillance as well as liver protection and supplementary treatment are indispensable.
There are several limitations of the current study. First, most of the included patients were HBV-related HCCs, the differences in efficacy of these three treatment modalities among patients with different HBV genotypes and with other etiologies of HCCs require further investigation. Second, although we enrolled patients from multiple centers and performed PSM analysis, potential bias was unavoidable, as propensity-matching techniques do not account for unobserved factors that influence treatment allocation. Additionally, the relatively short follow-up time of the SBRT group might overestimate the long-term outcomes. Hence, prospective randomized controlled trials are still needed.
In summary, we revealed that surgical resection, thermal ablation, and SBRT provided equivalent overall survival in treating patients with single HCC ≤5 cm. Resection remained the best choice for preventing tumor recurrence, while SBRT was comparable to resection when treating relapsed tumors or patients with relatively poor liver function. In addition, SBRT was superior to ablation in terms of local tumor control, especially for tumors adjacent to intrahepatic vessels. SBRT could be an effective alternative to both resection and ablation for early-stage HCC.
Ethical approval
This study was conducted according to the ethical guidelines of the 1975 Declaration of Helsinki. This study was approved by the ethics committees of the Sun Yat-sen University Cancer Center, Guangdong Provincial People’s Hospital and Hunan Provincial People’s Hospital (judgement number: B2020-350-01).
Consent
Signed informed consent for the use of data for research purposes was obtained from the patients before treatment.
Source of funding
This work is funded by the ‘5010 program’ of Sun Yat-Sen University (No. 2019013), the China Postdoctoral Science Foundation (No: 2023M744018), the Postdoctoral Fellowship Program of CPSF (No. GZC20233219), and the National Natural Science Foundation of China (No: 82372744).
Author contribution
Y.F., Z.Y., S.L., M.X., and Y.Z.: study concept and design; Y.F., Z.Y., R.G., and X.W.: acquisition of data; Y.F., Z.Y., and S.L.: analysis and interpretation of data; J.C., J.W., Y.P., M.L., and M.C.: administrative and technical support; Y.F., Z.Y., and S.L.: drafting of the manuscript; M.X. and Y.Z.: revision of the manuscript; Y.F., M.X., and Y.Z.: obtained funding.
Conflicts of interest disclosure
The authors declare no conflict of interest.
Research registration unique identifying number (UIN)
Name of the registry: Research Registry. Unique identifying number or registration ID: researchregistry10064. Hyperlink to the registration: https://www.researchregistry.com.
Guarantor
Yaojun Zhang and Yizhen Fu.
Data availability statement
All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.
Provenance and peer review
None.
Assistance with the study
None.
Presentation
The abstract of this study has been accepted by the 33rd Annual Meeting of Asian Pacific Association for the Study of the Liver (APASL 2024).
Supplementary Material
Footnotes
Yizhen Fu, Zhoutian Yang, and Shiliang Liu are co-first authors.
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.lww.com/international-journal-of-surgery.
Contributor Information
Yizhen Fu, Email: fuyz@sysucc.org.cn.
Zhoutian Yang, Email: yangzt@sysucc.org.cn.
Shiliang Liu, Email: liushil@sysucc.org.cn.
Renguo Guan, Email: guanrenguo@gdph.org.cn.
Xiaohui Wang, Email: xiaohuiwang21@163.com.
Jinbin Chen, Email: chenjb@sysucc.org.cn.
Juncheng Wang, Email: wangjch@sysucc.org.cn.
Yangxun Pan, Email: panyx@sysucc.org.cn.
Mengzhong Liu, Email: liumzh@sysucc.org.cn.
Minshan Chen, Email: chenmsh@sysucc.org.cn.
Mian Xi, Email: ximian@sysucc.org.cn.
Yaojun Zhang, Email: zhangyuj@sysucc.org.cn.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.