The importance of considering competing risks in recurrence analysis of intracranial meningioma

Christian Mirian¹, Lasse Rehné Jensen², Tareq A Juratli^{3

4}, Andrea Daniela Maier^{2

5}, Sverre H Torp^{6

7}, Helen A Shih⁸, Ramin A Morshed⁹, Jacob S Young⁹, Stephen T Magill^{9

10}, Luca Bertero¹¹, Walter Stummer¹², Dorothee Cäcilia Spille¹², Benjamin Brokinkel^{12

13}, Soichi Oya¹⁴, Satoru Miyawaki¹⁵, Nobuhito Saito¹⁵, Martin Proescholdt¹⁶, Yasuhiro Kuroi¹⁷, Konstantinos Gousias¹⁸, Matthias Simon¹⁹, Jennifer Moliterno²⁰, Ricardo Prat-Acin²¹, Stéphane Goutagny²², Vikram C Prabhu²³, John T Tsiang²³, Johannes Wach²⁴, Erdem Güresir²⁴, Junkoh Yamamoto²⁵, Young Zoon Kim²⁶, Joo Ho Lee²⁷, Matthew Koshy²⁸, Karthikeyan Perumal²⁹, Mustafa K Baskaya²⁹, Donald M Cannon³⁰, Dennis C Shrieve³⁰, Chang-Ok Suh³¹, Jong Hee Chang³², Maria Kamenova³³, Sven Straumann³³, Jehuda Soleman³³, Ilker Y Eyüpoglu³, Tony Catalan⁹, Austin Lui⁹, Philip V Theodosopoulos⁹, Michael W McDermott^{9

34}, Fang Wang³⁵, Fuyou Guo³⁵, Pedro Góes³⁶, Manoel Antonio de Paiva Neto³⁶, Aria Jamshidi³⁷, Ricardo Komotar³⁷, Michael Ivan³⁷, Evan Luther³⁷, Luis Souhami³⁸, Marie-Christine Guiot³⁹, Tamás Csonka⁴⁰, Toshiki Endo⁴¹, Olivia Claire Barrett⁴², Randy Jensen⁴³, Tejpal Gupta⁴⁴, Akash J Patel^{45

46

47}, Tiemo J Klisch^{47

48}, Jun Won Kim⁴⁹, Francesco Maiuri⁵⁰, Valeria Barresi⁵¹, María Dolores Tabernero⁵², Simon Skyrman⁵³, Anders Broechner², Mathias Jacobsen Bach², Ian Law^{54

55}, David Scheie⁵, Bjarne Winther Kristensen^{5

56}, Tina Nørgaard Munch^{2

55

57}, Torstein Meling^{2

58}, Kåre Fugleholm^{2

55}, Paul Blanche⁵⁹, Tiit Mathiesen^{2

53

55}

Affiliations

¹ Department of Neurosurgery, Copenhagen University Hospital, Copenhagen, Denmark. Christian.mirian.larsen@regionh.dk.
² Department of Neurosurgery, Copenhagen University Hospital, Copenhagen, Denmark.
³ Department of Neurosurgery, Division of Neuro-Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany.
⁴ Department of Neurosurgery, Laboratory of Translational Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA.
⁵ Department of Pathology, Bartholin Institute, Rigshospitalet, Copenhagen University Hospital , Copenhagen, Denmark.
⁶ Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian, University of Science and Technology (NTNU), Laboratory Centre, St. Olavs Hospital, NO-7491, Trondheim, Norway.
⁷ Department of Pathology, Laboratory Centre, St. Olavs Hospital, NO-7030, Trondheim, Norway.
⁸ Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine, Illinois, USA.
¹¹ Pathology Unit, Department of Medical Sciences, University and Città Della Salute E Della Scienza University Hospital of Turin, Turin, Italy.
¹² Department of Neurosurgery, University of Münster, Münster, Germany.
¹³ Institute for Neuropathology, University of Münster, Münster, Germany.
¹⁴ Department of Neurosurgery, Saitama Medical Center/University, Saitama, Japan.
¹⁵ Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan.
¹⁶ Department of Neurosurgery, University Regensburg Medical Center, Regensburg, Germany.
¹⁷ Department of Neurosurgery, Adachi Medical Center, Tokyo Women's Medical University, Tokyo, Japan.
¹⁸ Department of Neurosurgery, Athens Medical Center, Athens, Greece.
¹⁹ Department of Neurosurgery, Bethel Clinic University of Bielefeld Medical Center, Bielefeld, Germany.
²⁰ Department of Neurosurgery, Yale School of Medicine Yale New Haven Hospital, Smilow Cancer Hospital, New Haven, USA.
²¹ Department of Neurosurgery, Hospital La Fe, Valencia, Spain.
²² Department of Neurosurgery, Université Paris Cité, Beaujon Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
²³ Department of Neurological Surgery, Loyola University Medical Center, Stritch School of Medicine, Illinois, USA.
²⁴ Department of Neurosurgery, University Hospital Leipzig, Leipzig, Germany.
²⁵ Department of Neurosurgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
²⁶ Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
²⁷ Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
²⁸ Department of Radiation Oncology, University of Illinois Hospital and Health Sciences System, Illinois, USA.
²⁹ Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
³⁰ Department of Radiation Oncology Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT, USA.
³¹ Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
³² Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
³³ Department of Neurosurgery, University Hospital Basel, Basel, Switzerland.
³⁴ Division of Neurosurgery, Miami Neuroscience Institute, Miami, FL, USA.
³⁵ Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
³⁶ Department of Neurosurgery, Federal University of São Paulo, São Paulo, Brazil.
³⁷ Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
³⁸ Division of Radiation Oncology, McGill University Health Centre, McGill University, Montreal, QC, Canada.
³⁹ Department of Pathology, McGill University Health Centre, Montreal, QC, Canada.
⁴⁰ Department of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁴¹ Division of Neurosurgery, Tohoku Medical and Pharmaceutical University, Tohoku, Japan.
⁴² Infirmary Cancer Care, Montgomery, AL, USA.
⁴³ Department of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
⁴⁴ Department of Radiation Oncology ACTREC, Tata Memorial Centre, HBNI Kharghar, Navi Mumbai, 410210, India.
⁴⁵ Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
⁴⁶ Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX , USA.
⁴⁷ Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX , USA.
⁴⁸ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
⁴⁹ Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁵⁰ Department of Neurosurgery, University of Naples Federico II, Naples, Italy.
⁵¹ Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
⁵² Instituto de Investigación Biomédica de Salamanca (IBSAL), University Hospital of Salamanca, Salamanca, Spain.
⁵³ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁵⁴ Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
⁵⁵ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁵⁶ Department of Clinical Medicine and Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.
⁵⁷ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
⁵⁸ Department of Neurological Surgery, Istituto Nazionale Neurologico "C.Besta", Milan, Italy.
⁵⁹ Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

PMID: 38336917
PMCID: PMC10876814
DOI: 10.1007/s11060-024-04572-y

The importance of considering competing risks in recurrence analysis of intracranial meningioma

Christian Mirian et al. J Neurooncol. 2024 Feb.

. 2024 Feb;166(3):503-511.

doi: 10.1007/s11060-024-04572-y. Epub 2024 Feb 10.

Authors

Affiliations

¹ Department of Neurosurgery, Copenhagen University Hospital, Copenhagen, Denmark. Christian.mirian.larsen@regionh.dk.
² Department of Neurosurgery, Copenhagen University Hospital, Copenhagen, Denmark.
³ Department of Neurosurgery, Division of Neuro-Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany.
⁴ Department of Neurosurgery, Laboratory of Translational Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA.
⁵ Department of Pathology, Bartholin Institute, Rigshospitalet, Copenhagen University Hospital , Copenhagen, Denmark.
⁶ Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian, University of Science and Technology (NTNU), Laboratory Centre, St. Olavs Hospital, NO-7491, Trondheim, Norway.
⁷ Department of Pathology, Laboratory Centre, St. Olavs Hospital, NO-7030, Trondheim, Norway.
⁸ Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine, Illinois, USA.
¹¹ Pathology Unit, Department of Medical Sciences, University and Città Della Salute E Della Scienza University Hospital of Turin, Turin, Italy.
¹² Department of Neurosurgery, University of Münster, Münster, Germany.
¹³ Institute for Neuropathology, University of Münster, Münster, Germany.
¹⁴ Department of Neurosurgery, Saitama Medical Center/University, Saitama, Japan.
¹⁵ Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan.
¹⁶ Department of Neurosurgery, University Regensburg Medical Center, Regensburg, Germany.
¹⁷ Department of Neurosurgery, Adachi Medical Center, Tokyo Women's Medical University, Tokyo, Japan.
¹⁸ Department of Neurosurgery, Athens Medical Center, Athens, Greece.
¹⁹ Department of Neurosurgery, Bethel Clinic University of Bielefeld Medical Center, Bielefeld, Germany.
²⁰ Department of Neurosurgery, Yale School of Medicine Yale New Haven Hospital, Smilow Cancer Hospital, New Haven, USA.
²¹ Department of Neurosurgery, Hospital La Fe, Valencia, Spain.
²² Department of Neurosurgery, Université Paris Cité, Beaujon Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
²³ Department of Neurological Surgery, Loyola University Medical Center, Stritch School of Medicine, Illinois, USA.
²⁴ Department of Neurosurgery, University Hospital Leipzig, Leipzig, Germany.
²⁵ Department of Neurosurgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
²⁶ Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
²⁷ Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
²⁸ Department of Radiation Oncology, University of Illinois Hospital and Health Sciences System, Illinois, USA.
²⁹ Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
³⁰ Department of Radiation Oncology Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT, USA.
³¹ Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
³² Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
³³ Department of Neurosurgery, University Hospital Basel, Basel, Switzerland.
³⁴ Division of Neurosurgery, Miami Neuroscience Institute, Miami, FL, USA.
³⁵ Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
³⁶ Department of Neurosurgery, Federal University of São Paulo, São Paulo, Brazil.
³⁷ Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
³⁸ Division of Radiation Oncology, McGill University Health Centre, McGill University, Montreal, QC, Canada.
³⁹ Department of Pathology, McGill University Health Centre, Montreal, QC, Canada.
⁴⁰ Department of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁴¹ Division of Neurosurgery, Tohoku Medical and Pharmaceutical University, Tohoku, Japan.
⁴² Infirmary Cancer Care, Montgomery, AL, USA.
⁴³ Department of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
⁴⁴ Department of Radiation Oncology ACTREC, Tata Memorial Centre, HBNI Kharghar, Navi Mumbai, 410210, India.
⁴⁵ Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
⁴⁶ Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX , USA.
⁴⁷ Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX , USA.
⁴⁸ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
⁴⁹ Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁵⁰ Department of Neurosurgery, University of Naples Federico II, Naples, Italy.
⁵¹ Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
⁵² Instituto de Investigación Biomédica de Salamanca (IBSAL), University Hospital of Salamanca, Salamanca, Spain.
⁵³ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁵⁴ Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
⁵⁵ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁵⁶ Department of Clinical Medicine and Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.
⁵⁷ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
⁵⁸ Department of Neurological Surgery, Istituto Nazionale Neurologico "C.Besta", Milan, Italy.
⁵⁹ Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

PMID: 38336917
PMCID: PMC10876814
DOI: 10.1007/s11060-024-04572-y

Abstract

Background: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated.

Methods: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions.

Results: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions).

Conclusion: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Keywords: Competing risk; Meningioma; Neuro-oncology; Recurrence.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
Flowchart of patients included from the PERNS database

**Fig. 2**
The risk of recurrence when estimated with the Kaplan–Meier *vs.* Aalen-Johansen method while stratified for age group and WHO grade

See this image and copyright information in PMC

References

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The importance of considering competing risks in recurrence analysis of intracranial meningioma

Affiliations

The importance of considering competing risks in recurrence analysis of intracranial meningioma

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources