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Standard or extended STUPP? Optimal duration of temozolomide for patients with high-grade gliomas: a retrospective analysis

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Abstract

Purpose

Brain radiotherapy combined with concomitant and six cycles of adjuvant temozolomide (TMZ) is the standard treatment for newly diagnosed high-grade gliomas (HGGs). However, the optimal number of cycles of TMZ is still controversial. We conducted this retrospective cohort study to evaluate whether prolonging adjuvant TMZ beyond six cycles resulted in better survival outcomes.

Methods

Patients with high-grade gliomas treated with standard brain radiotherapy combined with TMZ were retrospectively analysed. The duration of adjuvant TMZ ranged from 6 to 12 cycles. Those with 6 cycles of adjuvant TMZ were defined as the standard STUPP group, and those with 7–12 cycles were called the extended STUPP group. Median progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The Cox proportional hazards model was adopted to estimate the Hazard ratio (HR) associated with PFS and OS.

Results

From September 2011 to May 2021, 372 patients were eligible (143 in the standard group, 229 in the extended group). Patients who received extended STUPP had better PFS and OS compared with standard STUPP. The median PFS for the standard STUPP group was 12 months and for the extended STUPP group 22 months (log-rank P < 0.001). The median OS for the standard STUPP group and extended STUPP group were 12 months and 36 months, respectively (log-rank P < 0.001). In the subgroup analysis, the two treatments did not differ in IDH-mutated patients, while patients with IDH wild-type had a significantly better response to extended treatment than to standard treatment (PFS: log-rank P = 0.004; OS log-rank P = 0.001). Patients with MGMT promoter methylation treated with extended STUPP obtained longer PFS and OS than those treated with standard STUPP (PFS: log-rank P = 0.015; OS log-rank P = 0.010). Adverse events including leukopenia (P < 0.001), thrombocytopenia (P = 0.090), fatigue (P < 0.001) and nausea/vomiting (P = 0.004) were more frequent in the extended group.

Conclusion

Extended TMZ treatment was superior to standard 6-cycle TMZ for both PFS and OS. The incidence of toxicities in extended group was higher but tolerable.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We acknowledge Dr. Ye Hong of Sun Yat-sen University Cancer Center for her valuable advice on the data analysis in our study.

Funding

The study was supported by National Natural Science Foundation of China (Grant Nos. 82172842, and 81803104 and 81672386), the Sichuan Province Science and Technology Support Program (Grant Nos. 2021YFSY008, 2020YFS0276), West China Nursing Discipline Development Special Fund Project (Grant No. HXHL21008), the Technology Innovation Project of Chengdu Science and Technology Bureau (Grant No. 2019-YF05-00459-SN), Postdoctoral research and Development Fund and Translational medicine fund of West China Hospital (Grant Nos. 2020HXBH119 and CGZH19002), National Key R&D Program of China (2018YFA0108604), the 1·3·5 project for disciplines of excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University (21HXFH046), the project of Sichuan Science and Technology Bureau (22ZDYF0798), and Clinical Incubation Program of West China Hospital, SCU(2018HXFU008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    Authors and Affiliations

    1. Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China

      Jingjing Wang, Yan Huang, Ling He, Zheran Liu, Yiyan Pei, Zhigong Wei, Ruidan Li & Xingchen Peng

    2. Oncology Clinical Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China

      Feng Zhao

    3. West China School of Basic Medical Science & Forensic Medicine, Sichuan University, Chengdu, Sichuan, China

      Jianhui Chen

    4. Department of Radiation Oncology and Department of Head & Neck Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China

      Ping Ai

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    Contributions

    Xingchen Peng, Ping Ai, and Jingjing Wang contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jingjing Wang, Yan Huang, Feng Zhao, Jianhui Chen, Ling He, Zheran Liu and Yiyan Pei. The first draft of the manuscript was written by Jingjing Wang and Yan Huang. Xingchen Peng and Ping Ai reviewed the manuscript and provided intellectual contributions. Jingjing Wang, Yan Huang, Zhigong Wei, and Ruidan Li edited the manuscript. All authors read and approved the final manuscript.

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    Correspondence to Ping Ai or Xingchen Peng.

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    The authors declare that they have no competing interests.

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    This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University.

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    The Ethics Committee on Biomedical Research, West China Hospital of Sichuan University agreed to exempt the informed consent form for this study.

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    Our manuscript did not contain any individual person’s data.

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    Jingjing Wang and Yan Huang contributed equally to this article.

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    Wang, J., Huang, Y., Zhao, F. et al. Standard or extended STUPP? Optimal duration of temozolomide for patients with high-grade gliomas: a retrospective analysis. J Neurooncol 160, 433–443 (2022). https://doi.org/10.1007/s11060-022-04162-w

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