Skip to main content

Advertisement

SpringerLink
Log in

Pseudoprogression in glioblastoma patients: the impact of extent of resection

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Pseudoprogression (psPD) is a radiation-induced toxicity that has substantial neurological consequence in glioblastoma (GBM) patients. MGMT promoter methylation has been shown to be an important prognostic factor of psPD, but the significance of extent of resection (EOR) remains unclear. We performed a retrospective analysis on newly diagnosed GBM patients with assessable MGMT promoter status who underwent the Stupp protocol. EOR was grouped into gross total resection (GTR), subtotal resection (STR), partial resection (PR) and stereotactic biopsy. Contrast enhancing lesion enlargement was classified as psPD or non-psPD. Among a total of 101 patients, GTR, STR, PR and stereotactic biopsy was performed in 57 (56.4 %), 34 (33.7 %), 9 (8.9 %) and 1 patient (1 %), respectively. Follow-up imaging at the end of Stupp protocol classified 45 patients (44.6 %) as psPD and 56 (55.4 %) as non-psPD. psPD was observed in 24 (61.5 %) of 39 patients with methylated MGMT promoter and 21 (33.9 %) of 62 patients with unmethylated MGMT promoter (p < 0.01). psPD was documented in 17 (29.8 %), 19 (55.9 %), 8 (88.9 %) and 1 (100 %) patient with GTR, STR, PR and stereotactic biopsy (p < 0.01), respectively. On multivariate analysis MGMT promoter status (OR 3.36, 95 % CI 1.36–8.34) and EOR (OR 4.12, 95 % CI 1.71–9.91) were independent predictors of psPD. A Cox proportional hazards model showed that MGMT status (HR 2.51, p < 0.01) and EOR (HR 2.99, p < 0.01) significantly influenced survival. MGMT status and EOR have a significant impact on psPD. GTR can reduce the side effects of psPD and prolong survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Deorah S, Lynch CF, Sibenaller ZA, Ryken TC (2006) Trends in brain cancer incidence and survival in the United States: surveillance, epidemiology, and end results program, 1973 to 2001. Neurosurg Focus 20(4):E1

    Article  PubMed  Google Scholar 

  2. Surawicz TS, Davis F, Freels S, Laws ER Jr, Menck HR (1998) Brain tumor survival: results from the National Cancer Data Base. J Neurooncol 40:151–160

    Article  PubMed  CAS  Google Scholar 

  3. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  PubMed  CAS  Google Scholar 

  4. Chamberlain MC, Glantz MJ, Chalmers L, Van Horn A, Sloan AE (2007) Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. J Neurooncol 82:81–83

    Article  PubMed  Google Scholar 

  5. Taal W, Brandsma D, de Bruin HG et al (2007) The incidence of pseudo-progression in a cohort of malignant glioma patients treated with chemo-radiation with temozolomide. Cancer 113:405–410

    Article  Google Scholar 

  6. Brandes AA, Franceschi E, Tosoni A et al (2008) MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol 26:2192–2197

    Article  PubMed  Google Scholar 

  7. Peca C, Pacelli R, Elefante A et al (2009) Early clinical and neuroradiological worsening after radiotherapy and concomitant temozolomide in patients with glioblastoma: tumour progression or radionecrosis? Clin Neurol Neurosurg 111:331–334

    Article  PubMed  CAS  Google Scholar 

  8. Yaman E, Buyukberber S, Benekli M et al (2010) Radiation induced early necrosis in patients with malignant gliomas receiving temozolomide. Clin Neurol Neurosurg 112:662–667

    Article  PubMed  Google Scholar 

  9. Ruben JD, Dally M, Bailey M, Smith R, McLean CA, Fedele P (2006) Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int J Radiat Oncol Biol Phys 65:499–508

    Article  PubMed  Google Scholar 

  10. Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9:453–461

    Article  PubMed  Google Scholar 

  11. Floyd NS, Woo SY, Teh BS et al (2004) Hypofractionated intensity-modulated radiotherapy for primary glioblastoma multiforme. Int J Radiat Oncol Biol Phys 58:721–726

    Article  PubMed  Google Scholar 

  12. Nieder C, Andratschke N, Wiedenmann N, Busch R, Grosu AL, Molls M (2004) Radiotherapy for high-grade gliomas. Does altered fractionation improve the outcome? Strahlenther Onkol 180:401–407

    Article  PubMed  Google Scholar 

  13. Hara W, Tran P, Li G et al (2009) Cyberknife for brain metastases of malignant melanoma and renal cell carcinoma. Neurosurgery 64:A26–A32

    Article  PubMed  Google Scholar 

  14. Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG (1999) Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 59:793–797

    PubMed  CAS  Google Scholar 

  15. Esteller M, Garcia-Foncillas J, Andion E et al (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354

    Article  PubMed  CAS  Google Scholar 

  16. Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. NEJM 352:997–1003

    Article  PubMed  CAS  Google Scholar 

  17. Chang EF, Smith JS, Chang SM et al (2008) Preoperative prognostic classification system for hemispheric low-grade gliomas in adults. J Neurosurg 109:817–824

    Article  PubMed  Google Scholar 

  18. Wen PY, Macdonald DR, Reardon DA et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972

    Article  PubMed  Google Scholar 

  19. Ellika SK, Jain R, Patel SC et al (2007) Role of perfusion CT in glioma grading and comparison with conventional MR imaging features. Am J Neuroradiol 28:1981–1987

    Article  PubMed  CAS  Google Scholar 

  20. Kamada K, Houkin K, Abe H, Sawamura Y, Kashiwaba T (1997) Differentiation of cerebral radiation necrosis from tumor recurrence by proton magnetic resonance spectroscopy. Neurol Med-Chir 37:250–256

    Article  CAS  Google Scholar 

  21. Chao ST, Suh JH, Raja S, Lee SY, Barnett G (2001) The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery. Int J Cancer 96:191–197

    Article  PubMed  CAS  Google Scholar 

  22. de Wit MC, de Bruin HG, Eijkenboom W, Sillevis Smitt PA, van den Bent MJ (2004) Immediate post-radiotherapy changes in malignant glioma can mimic tumor progression. Neurology 63:535–537

    Article  PubMed  Google Scholar 

  23. Brandsma D, van den Bent MJAN (2009) Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol 22:633–638

    Article  PubMed  Google Scholar 

  24. Shah AH, Snelling B, Bregy A et al (2013) Discriminating radiation necrosis from tumor progression in gliomas: a systematic review what is the best imaging modality? J Neurooncol 112:141–152

    Article  PubMed  CAS  Google Scholar 

  25. Siu A, Wind JJ, Iorgulescu JB, Chan TA, Yamada Y, Sherman JH (2012) Radiation necrosis following treatment of high grade glioma—a review of the literature and current understanding. Acta Neurochir (Wien) 154:191–201

    Article  Google Scholar 

  26. Liu L, Markowitz S, Gerson SL (1996) Mismatch repair mutations override alkyltransferase in conferring resistance to temozolomide, but not to 1,3-bis (2-chloroethyl) nitrosourea. Cancer Res 56:5375–5379

    PubMed  CAS  Google Scholar 

  27. Ochs K, Kaina B (2000) Apoptosis induced by DNA damage O6-methylguanine is Bcl-2 and caspase-9/3 regulated and Fas/caspase-8 independent. Cancer Res 60:5815–5824

    PubMed  CAS  Google Scholar 

  28. Olson RA, Brastianos PK, Palma DA (2011) Prognostic and predictive value of epigenetic silencing of MGMT in patients with high grade gliomas: a systematic review and meta-analysis. J Neurooncol 105:325–335

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2014R1A1A2058058).

Author information

Authors and Affiliations

  1. Departments of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea

    Hun Ho Park, Tae Hoon Roh, Seok Gu Kang, Eui Hyun Kim, Chang-Ki Hong, Sun Ho Kim, Kyu-Sung Lee & Jong Hee Chang

  2. Departments of Pathology, Yonsei University College of Medicine, Seoul, Korea

    Se Hoon Kim

  3. Departments of Radiology, Yonsei University College of Medicine, Seoul, Korea

    Sung Soo Ahn & Seung Koo Lee

  4. Departments of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea

    Hye Jin Choi

  5. Departments of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea

    Jaeho Cho & Chang-Ok Suh

  6. Brain Tumor Center, Yonsei University College of Medicine, Seoul, Korea

    Hun Ho Park, Tae Hoon Roh, Seok Gu Kang, Eui Hyun Kim, Se Hoon Kim, Sung Soo Ahn, Seung Koo Lee, Hye Jin Choi, Jaeho Cho, Sun Ho Kim, Kyu-Sung Lee, Chang-Ok Suh & Jong Hee Chang

  7. Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea

    Seok Gu Kang, Eui Hyun Kim, Se Hoon Kim, Sun Ho Kim, Kyu-Sung Lee & Jong Hee Chang

  8. Department of Radiation Oncology, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea

    Chang-Ok Suh

  9. Department of Neurosurgery, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korean

    Jong Hee Chang

Authors
  1. Hun Ho Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tae Hoon Roh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seok Gu Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eui Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chang-Ki Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Se Hoon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sung Soo Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Seung Koo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hye Jin Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jaeho Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sun Ho Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kyu-Sung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Chang-Ok Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jong Hee Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Chang-Ok Suh or Jong Hee Chang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, H.H., Roh, T.H., Kang, S.G. et al. Pseudoprogression in glioblastoma patients: the impact of extent of resection. J Neurooncol 126, 559–566 (2016). https://doi.org/10.1007/s11060-015-2001-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-015-2001-0

Keywords

Search

Navigation