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Incidence and prognosis of distant metastasis in malignant peripheral nerve sheath tumors

  • Original Article - Tumor - Other
  • Published:
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Abstract

Background

Malignant peripheral nerve sheath tumors (MPNSTs) are a type of soft tissue sarcomas (STS) with recurrence and metastatic potential. We aimed to investigate the risk factors for developing distant metastases (DM) and to identify the prognostic factors in patients with DM.

Methods

Based on the Surveillance, Epidemiology, and End Result (SEER) database, MPNST patients diagnosed between 2010 and 2016 were extracted in our study. The logistic regression model was performed for predicting DM development while the Cox proportional hazard regression model was conducted for revealing the prognostic factors.

Results

Eventually, 764 patients diagnosed with MPNSTs were included with 109 cases presenting with metastases at initial diagnosis. Larger tumor size and lymph node metastases were independent risk factors for developing DM. The median overall survival (OS) for patients with metastases was 8.0 (95% CI: 6.1–9.9) months. Multiple metastatic sites and no surgical treatment were prognostic factors for worse survival. Tumors located in non-head and neck region were related with better survival.

Conclusions

The incidence of DM was 14.3% with a dismal median OS of 8.0 months for metastatic MPNSTs. More evaluation should be applied for patients with large tumor size and lymph metastases. Tumors located in head and neck region and the presence of multiple metastases predicted worse survival outcome. Surgical treatment can significantly improve the survival of MPNST patients with distant metastasis.

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Funding

The present study was sponsored by the Natural Science Foundation of China (81702161, 81801781, 81802508, 81903398, 8191101553), the Natural Science Foundation of Tianjin Science and Technology Committee China (17JCQNJC11000), the Top Talent Training Program of the First Affiliated Hospital of PLA Army Medical University (SWH2018BJKJ-12), and the Chongqing Natural Science Foundation Program (cstc2019jcyj-msxmX0466). The sponsor had no role in the design or conduct of this research.

Author information

Author notes

  1. Yao Xu, Guijun Xu, and Zheng Liu contributed equally to the study

Authors and Affiliations

  1. Department of Bone and Soft Tissue Tumors, Key Laboratory of Cancer Prevention, Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, China

    Yao Xu, Guijun Xu, Zheng Liu, Jincai Duan, Yile Lin, Jiajia Zhu, Guowen Wang & Chao Zhang

  2. Department of Orthopedics, Tianjin Hospital, Tianjin, China

    Guijun Xu

  3. Department of Orthopedics, Heilongjiang Province Hospital, Harbin, China

    Zheng Liu

  4. Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of the Russian Federation, Moscow, Russian Federation

    Vladimir P. Baklaushev

  5. Department of Basic and Applied Neurobiology, Federal Medical Research Center for Psychiatry and Narcology, Moscow, Russian Federation

    Vladimir P. Chekhonin

  6. Department of Research and Innovation, University of Limpopo, Turfloop, South Africa

    Karl Peltzer

  7. Department of Epidemiology and Biostatistics, First Affiliated Hospital, Army Medical University, Chongqing, China

    Xin Wang

Authors
  1. Yao Xu
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  2. Guijun Xu
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  3. Zheng Liu
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  4. Jincai Duan
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  5. Yile Lin
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  6. Jiajia Zhu
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  7. Vladimir P. Baklaushev
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  8. Vladimir P. Chekhonin
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  9. Karl Peltzer
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  10. Guowen Wang
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  11. Xin Wang
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  12. Chao Zhang
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Contributions

Chao Zhang, Guowen Wang, and Xin Wang designed the experiments; Yao Xu extracted the initial data from public dataset; Yao Xu, Jincai Duan, Yile Lin, and Jiajia Zhu analyzed the data; Guijun Xu and Zheng Liu drafted the work; Vladimir P. Baklaushev, Karl Peltzer, and Vladimir P. Chekhonin revised the manuscript critically for important content. All the authors approved the submission of the final manuscript.

Corresponding author

Correspondence to Chao Zhang.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

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Not applicable.

Additional information

Comments

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas with particularly poor prognosis owning to their propensity to metastasize, challenges at identifying metastatic disease, and current limited treatment options particularly in advanced stage disease. We read with interest the article by Yao Xu and colleagues [10] who used the Surveillance, Epidemiology, and End Results (SEER) database to analyze factors associated with the development of distant MPNST metastases. Their findings concluded that tumor size larger than 5 cm and lymph node involvement were associated with the development of distant metastasis. Similar to other published reports, patients with MPNST in the head or neck region had worse outcomes compared to other sites [2]. We commend the authors on a well-designed study that analyzes one of the larger patient populations to date. This study contributes to our understanding of important factors associated with the development of metastatic disease from MPNSTs.

While database studies allow for evaluation of various factors across a large population, they are not without certain limitations. One key limitation to this study and use of the SEER database is the patients with distant metastases had evidence of metastatic disease only at the time of initial diagnosis. Unfortunately, patients with MPNSTs that then went on to develop metastases throughout the course of the disease were not captured or analyzed. Thus, the conclusions the study provides need to be taken into careful consideration when determining prognostic factors for specific patient populations. The same factors associated with distant metastases at the time of diagnosis may not be able to be extrapolated to the patient population that develops metastatic disease later during the course of treatment. Accordingly, it would be beneficial to develop biomarker testing that allows for early detection of distant metastases and aids in monitoring disease progression of MPNSTs.

Molecular techniques that have recently been developed enable monitoring of disease progression in many cancers [1,5]. Liquid biopsy is a noninvasive but highly specialized blood or other fluid-based test used to measure circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) [3,9]. ctDNA is hypothesized to enter the blood stream via two main mechanisms either through apoptosis/necrosis or through active shedding from the primary tumor [7]. These biomarkers contain the various tumor-specific genetic alterations that allow for characterization of different tumor pathologies [6]. While the detection ranges differ depending on tumor type and stage, studies have suggested a linear relationship exists between the presence and amount of ctDNA and progression of the primary cancer [9]. These molecular techniques have shown promise in diagnosis and disease monitoring of other soft tissue sarcomas, but have only been investigated in a limited fashion in MPNSTs [8,9].

The use of liquid biopsies can improve the care of patients with peripheral nerve tumors in multiple ways. Currently, there are not definitive imaging characteristics or clinical findings that predict the malignant potential of peripheral nerve tumors with a high degree of accuracy; therefore, the diagnosis of MPNSTs can often be difficult to predict pre-operatively. Molecular evaluation with liquid biopsies could determine the diagnosis prior to surgical intervention to aid with patient counseling and operative planning. Liquid biopsies could also be utilized as a screening tool for early detection of peripheral nerve tumors that have undergone malignant transformation in high risk patient groups, such as those with NF1. Biomarkers can also be used in the detection of early metastatic disease from MPNSTs, which can be challenging with conventional imaging techniques. ctDNA or other similar biomarkers have the potential to determine local recurrence or metastatic disease prior to their radiographic diagnosis. This is particularly important as the metastatic tumor burden has been linked with overall prognosis, so early detection could improve patient outcomes [4]. Finally, liquid biopsies may be used to monitor response to treatment with conventional algorithms and future clinical trials.In conclusion, factors that predict outcomes and metastatic potential of MPNSTs are important for better understanding this challenging disease entity. The findings in the study by Xu et al. [10] investigated the factors that influence the development of distant metastatic disease and impact prognosis. To ultimately impact the outcomes for patients, better diagnostic tools, imaging techniques, and therapeutic treatments are necessary. Personalized molecular medicine, such as liquid biopsies, has the potential to do just that.

Megan M. Jack, Robert J. Spinner

Rochester, MN

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10. Xu Y, Xu G, Liu Z, Duan J, Lin Y, Zhu J, Baklaushev VP, Chekhonin VP, Peltzer K, Wang G, Wang X, Zhang C (2020). Incidence and prognosis of distant metastasis in malignant peripheral nerve sheath tumors. Acta Neurochir.

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Xu, Y., Xu, G., Liu, Z. et al. Incidence and prognosis of distant metastasis in malignant peripheral nerve sheath tumors. Acta Neurochir 163, 521–529 (2021). https://doi.org/10.1007/s00701-020-04647-5

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