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Clinicopathologic Characteristics and Prognosis of PDGFRA-Mutant Gastrointestinal Stromal Tumors: A Large-Scale, Multi-Institutional, Observational Study in China

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Abstract

Introduction

To evaluate clinicopathologic features and prognosis of post-complete resection in patients with PDGFRA-mutant gastrointestinal stromal tumor (GIST), and even to establish a relapse-free survival (RFS) prognostic model for this subgroup.

Methods

This retrospective study used data from patients with primary PDGFRA-mutant GIST who underwent complete resection (2005–2019) at 16 large-scale medical centers in China. Stepwise multivariate Cox regression models were performed to build the prediction model, in which the potential predictors were available in routine clinical practice and using the risk score functions. The prediction model was cross-validated by calibration histogram and time-dependent receiver operating characteristic curves.

Results

A total of 280 patients with PDGFRA-mutant (172 D842V-mutant and 108 non-D842V-mutant) GIST after complete resection were enrolled. Most tumors originated in the stomach (89.6%). The 1-, 3-, and 5-year RFS rates were 95.9%, 91.2%, and 89.5%, respectively. The RFS of the non-D842V-mutant group was superior to that of the D842V group (P = 0.033). Multivariate analysis demonstrated that D842V mutation (P = 0.017), non-gastric tumor (P < 0.001), and Ki-67 > 5% (P = 0.005) were the independent variables influencing the prognosis of patients with PDGFRA-mutant GIST. The scoring model showed the predicted and actual cumulative 1-, 3- and 5-year follow-up relapse rates fit well.

Conclusions

PDGFRA-mutant GIST mostly originated in the stomach and had a favorable prognosis after surgery. Non-D842V-mutant patients might have better prognoses than D842V-mutant patients. The prognostic model demonstrated favorable prediction accuracy, suggesting its clinical utility.

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Acknowledgements

Funding

The National Natural Science Foundation of China (No.81874184) funded this study, and the journal’s Rapid Service fees.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

Concept and Design: Drs. Tao, Cao, Shen. Acquisition, Analysis, and Interpretation of Data: Drs. P. Zhang, Wang, Gao, Li, B. Zhang, Liang, Y. Zhou, Liao, Feng, Y.B. Zhou, Yu, J. Zhang, Y.J. Zhou, Ye, Chen, Zhao. Drafting of the Manuscript: Drs. P. Zhang, Wang, Li. Critical Revision of the Manuscript for Important Intellectual Content: Drs. Liao, Feng, Y.B. Zhou, Yu, J. Zhang, Y.J. Zhou, Ye, Chen, Y. Zhao.

Disclosures

All named authors confirm that they have no conflicts of interest to declare.

Compliance with Ethics Guidelines

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. And this is a retrospective study and does not contain any new studies with human or animal subjects by any of the authors; as such, informed consent of individuals was not required.

Data Availability

The data presented in this study are available on request from the corresponding author.

Author information

Author notes

  1. Peng Zhang, Ming Wang, and Jian Li contributed equally to this paper.

  2. Kuntang Shen, Hui Cao, and Kaixiong Tao are co-corresponding authors.

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China

    Peng Zhang & Kaixiong Tao

  2. Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160 Pujian Road, Shanghai, 200127, China

    Ming Wang & Hui Cao

  3. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China

    Jian Li

  4. Department of General Surgery, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China

    Xiaodong Gao & Kuntang Shen

  5. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China

    Bo Zhang

  6. Department of Gastric Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China

    Han Liang

  7. Department of Gastric Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China

    Ye Zhou

  8. Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China

    Guoqing Liao

  9. Department of Digestive Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China

    Fan Feng

  10. Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China

    Yanbing Zhou

  11. Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Jiren Yu

  12. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Jun Zhang

  13. Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China

    Yongjian Zhou

  14. Department of Gastrointestinal Surgery, Peking University People’s Hospital, Beijing, China

    Yingjiang Ye

  15. Department of Medical Image Center, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China

    Jiansi Chen

  16. Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China

    Qun Zhao

  17. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Ye Zhou

Authors
  1. Peng Zhang
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  2. Ming Wang
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  3. Jian Li
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  4. Xiaodong Gao
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  5. Bo Zhang
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  6. Han Liang
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  7. Ye Zhou
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  8. Guoqing Liao
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  9. Fan Feng
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  10. Yanbing Zhou
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  11. Jiren Yu
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  12. Jun Zhang
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  13. Yongjian Zhou
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  14. Yingjiang Ye
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  15. Jiansi Chen
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  16. Qun Zhao
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  17. Kuntang Shen
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  18. Hui Cao
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  19. Kaixiong Tao
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Corresponding authors

Correspondence to Kuntang Shen, Hui Cao or Kaixiong Tao.

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Zhang, P., Wang, M., Li, J. et al. Clinicopathologic Characteristics and Prognosis of PDGFRA-Mutant Gastrointestinal Stromal Tumors: A Large-Scale, Multi-Institutional, Observational Study in China. Adv Ther 39, 2920–2931 (2022). https://doi.org/10.1007/s12325-022-02115-3

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  • DOI: https://doi.org/10.1007/s12325-022-02115-3

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