Incidence, molecular characteristics, and imaging features of "clinically-defined pseudoprogression" in newly diagnosed glioblastoma treated with chemoradiation

Akifumi Hagiwara^{1

2

3}, Jacob Schlossman¹, Soroush Shabani¹, Catalina Raymond^{1

2}, Hiroyuki Tatekawa^{1

2

4}, Lauren E Abrey⁵, Josep Garcia⁵, Olivier Chinot⁶, Frank Saran⁷, Ryo Nishikawa⁸, Roger Henriksson^{9

10}, Warren P Mason¹¹, Wolfgang Wick¹², Timothy F Cloughesy^{13

14

15}, Benjamin M Ellingson^{16

17

18

19

20

21

22}

Affiliations

¹ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
² Deptartment of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
³ Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan.
⁴ Department of Diagnostic and Interventional Radiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
⁵ F. Hoffman-La Roche, Ltd., Basel, Switzerland.
⁶ Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France.
⁷ The Royal Marsden NHS Foundation Trust, Sutton, UK.
⁸ Saitama Medical University, Saitama, Japan.
⁹ Regional Cancer Center Stockholm, Stockholm, Sweden.
¹⁰ Umeå University, Umeå, Sweden.
¹¹ Princess Margaret Hospital, Toronto, Canada.
¹² Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹³ UCLA Brain Research Institute (BRI), David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁴ UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁵ Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁶ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
¹⁷ Deptartment of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
¹⁸ UCLA Brain Research Institute (BRI), David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
¹⁹ UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
²⁰ Department of Physics and Biology in Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
²¹ Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
²² Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.

PMID: 35842871
DOI: 10.1007/s11060-022-04088-3

Incidence, molecular characteristics, and imaging features of "clinically-defined pseudoprogression" in newly diagnosed glioblastoma treated with chemoradiation

Akifumi Hagiwara et al. J Neurooncol. 2022 Sep.

. 2022 Sep;159(3):509-518.

doi: 10.1007/s11060-022-04088-3. Epub 2022 Jul 17.

Authors

Affiliations

¹ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
² Deptartment of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
³ Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan.
⁴ Department of Diagnostic and Interventional Radiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
⁵ F. Hoffman-La Roche, Ltd., Basel, Switzerland.
⁶ Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France.
⁷ The Royal Marsden NHS Foundation Trust, Sutton, UK.
⁸ Saitama Medical University, Saitama, Japan.
⁹ Regional Cancer Center Stockholm, Stockholm, Sweden.
¹⁰ Umeå University, Umeå, Sweden.
¹¹ Princess Margaret Hospital, Toronto, Canada.
¹² Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹³ UCLA Brain Research Institute (BRI), David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁴ UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁵ Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁶ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
¹⁷ Deptartment of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
¹⁸ UCLA Brain Research Institute (BRI), David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
¹⁹ UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
²⁰ Department of Physics and Biology in Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
²¹ Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
²² Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.

PMID: 35842871
DOI: 10.1007/s11060-022-04088-3

Abstract

Purpose: Pseudoprogression (PsP) remains an elusive and clinically important, yet ill-defined, phenomena that, generally, involves a period of early radiographic progression (enhancement) followed by a period of radiographic stability or regression. In the current study, we utilized data from the control arm of a phase III clinical trial in newly-diagnosed glioblastoma to explore imaging characteristics of "clinically-defined PsP", or early radiographic progression (PFS < 6 months from chemoradiation) followed by a long post-progression residual overall survival (ROS > 12 months).

Methods: One hundred sixty-nine patients with newly-diagnosed GBM from the control arm of the AVAglio trial (NCT00943826) who presented with early radiographic progressive disease (PD) (< 6 months) were included. Clinical characteristics, topographical patterns, and radiomic features were compared between newly-diagnosed GBM exhibiting early PD and early death (< 12-month ROS, "true PD") with those exhibiting early PD and a long residual survival (> 12-month ROS, "clinically-defined PsP").

Results: "Clinically-defined PsP" occurred to 38.5% of patients with early PD, and was more associated with MGMT methylation (P = 0.02), younger age (P = 0.003), better neurological performance (P = 0.01), and lower contrast-enhancing tumor volume (P = 0.002) at baseline. GBM showing "true PD" occurred more frequently in the right internal capsule, thalamus, lentiform nucleus, and temporal lobe than those with "clinical PsP". Radiomic analysis predicted "clinical PsP" with > 70% accuracy on the validation dataset.

Conclusion: Patients with early PD that eventually exhibit "clinically-defined PsP" have distinct clinical, molecular, and MRI characteristics. This information may be useful for treating clinicians to better understand the potential risks and outcome in patients exhibiting early radiographic changes following chemoradiation.

Keywords: Chemoradiation; Clinical trial; Newly diagnosed glioblastoma; Pseudoprogression; Radiomics.

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References

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Incidence, molecular characteristics, and imaging features of "clinically-defined pseudoprogression" in newly diagnosed glioblastoma treated with chemoradiation

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Incidence, molecular characteristics, and imaging features of "clinically-defined pseudoprogression" in newly diagnosed glioblastoma treated with chemoradiation

Authors

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Abstract

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