Skip to main content
SpringerLink
Log in

Discriminating radiation necrosis from tumor progression in gliomas: a systematic review what is the best imaging modality?

  • Topic Review
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Differentiating post radiation necrosis from progression of glioma and pseudoprogression poses a diagnostic conundrum for many clinicians. As radiation therapy and temozolomide chemotherapy have become the mainstay of treatment for higher-grade gliomas, radiation necrosis and post treatment changes such as pseudoprogression have become a more relevant clinical problem for neurosurgeons and neurooncologists. Due to their radiological similarity to tumor progression, accurate recognition of these findings remains paramount given their vastly different treatment regimens and prognoses. However, no consensus has been reached on the optimal technique to discriminate between these two lesions. In order to clarify the types of imaging modalities for recurrent enhancing lesions, we conducted a systematic review of case reports, case series, and prospective studies to increase our current understanding of the imaging options for these common lesions and their efficacy. In particular, we were interested in distinguishing radiation necrosis from true tumor progression. A PubMed search was performed to include all relevant studies where the imaging was used to differentiate between radiation necrosis and recurrent gliomas with post-radiation enhancing lesions. After screening for certain parameters in our study, seventeen articles with 435 patients were included in our analysis including 10 retrospective and 7 prospective studies. The average time from the end of radiation therapy to the onset of a recurrent enhancing lesion was 13.2 months. The most sensitive and specific imaging modality was SPECT with a sensitivity of 87.6 % and specificity of 97.8 %. Based on our review, we conclude that certain imaging modalities may be preferred over other less sensitive/specific techniques. Overall, tests such as SPECT may be preferable in differentiating TP (tumor progression) from RN (radiation necrosis) due to its high specificity, while nonspecific imaging such as conventional MRI is not ideal.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Burger PC, Mahley MS Jr, Dudka L, Vogel FS (1979) The morphologic effects of radiation administered therapeutically for intracranial gliomas: a postmortem study of 25 cases. Cancer 44:1256–1272

    Article  CAS  PubMed  Google Scholar 

  2. Kumar AJ, Leeds NE, Fuller GN, Van Tassel P, Maor MH, Sawaya RE, Levin VA (2000) Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 217:377–384

    Article  CAS  PubMed  Google Scholar 

  3. Marks JE, Baglan RJ, Prassad SC, Blank WF (1981) Cerebral radionecrosis: incidence and risk in relation to dose, time, fractionation and volume. Int J Radiat Oncol Biol Phys 7:243–252

    Article  CAS  PubMed  Google Scholar 

  4. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280

    Article  CAS  PubMed  Google Scholar 

  5. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972. doi:10.1200/JCO.2009.26.3541

    Article  PubMed  Google Scholar 

  6. Glantz MJ, Burger PC, Friedman AH, Radtke RA, Massey EW, Schold SC Jr (1994) Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology 44:2020–2027

    Article  CAS  PubMed  Google Scholar 

  7. Chuba PJ, Aronin P, Bhambhani K, Eichenhorn M, Zamarano L, Cianci P, Muhlbauer M, Porter AT, Fontanesi J (1997) Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer 80:2005–2012

    Article  CAS  PubMed  Google Scholar 

  8. Brandes AA, Tosoni A, Spagnolli F, Frezza G, Leonardi M, Calbucci F, Franceschi E (2008) Disease progression or pseudoprogression after concomitant radiochemotherapy treatment: pitfalls in neurooncology. Neuro-oncology 10:361–367. doi:10.1215/15228517-2008-008

    Article  PubMed  PubMed Central  Google Scholar 

  9. Alexiou GA, Tsiouris S, Kyritsis AP, Voulgaris S, Argyropoulou MI, Fotopoulos AD (2009) Glioma recurrence versus radiation necrosis: accuracy of current imaging modalities. J Neurooncol 95:1–11. doi:10.1007/s11060-009-9897-1

    Article  PubMed  Google Scholar 

  10. Czernicki T, Szeszkowski W, Marchel A, Golebiowski M (2009) Spectral changes in postoperative MRS in high-grade gliomas and their effect on patient prognosis. Folia Neuropathol 47:43–49

    CAS  PubMed  Google Scholar 

  11. Hu X, Wong KK, Young GS, Guo L, Wong ST (2011) Support vector machine multiparametric MRI identification of pseudoprogression from tumor recurrence in patients with resected glioblastoma. J Magn Reson Imaging 33:296–305. doi:10.1002/jmri.22432

    Article  PubMed  PubMed Central  Google Scholar 

  12. Santra A, Sharma P, Kumar R, Bal C, Kumar A, Julka PK, Malhotra A (2011) Comparison of glucoheptonate single photon emission computed tomography and contrast-enhanced MRI in detection of recurrent glioma. Nucl Med Commun 32:206–211. doi:10.1097/MNM.0b013e328341c3e9

    Article  PubMed  Google Scholar 

  13. Barajas RF Jr, Chang JS, Segal MR, Parsa AT, McDermott MW, Berger MS, Cha S (2009) Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology 253:486–496. doi:10.1148/radiol.2532090007

    Article  PubMed  PubMed Central  Google Scholar 

  14. Narang J, Jain R, Arbab AS, Mikkelsen T, Scarpace L, Rosenblum ML, Hearshen D, Babajani-Feremi A (2011) Differentiating treatment-induced necrosis from recurrent/progressive brain tumor using nonmodel-based semiquantitative indices derived from dynamic contrast-enhanced T1-weighted MR perfusion. Neuro-oncology 13:1037–1046. doi:10.1093/neuonc/nor075

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ozsunar Y, Mullins ME, Kwong K, Hochberg FH, Ament C, Schaefer PW, Gonzalez RG, Lev MH (2010) Glioma recurrence versus radiation necrosis? A pilot comparison of arterial spin-labeled, dynamic susceptibility contrast enhanced MRI, and FDG-PET imaging. Acad Radiol 17:282–290. doi:10.1016/j.acra.2009.10.024

    Article  PubMed  Google Scholar 

  16. Tie J, Gunawardana DH, Rosenthal MA (2008) Differentiation of tumor recurrence from radiation necrosis in high-grade gliomas using 201Tl-SPECT. J Clin Neurosci 15:1327–1334. doi:10.1016/j.jocn.2007.12.008

    Article  PubMed  Google Scholar 

  17. Kim YH, Oh SW, Lim YJ, Park CK, Lee SH, Kang KW, Jung HW, Chang KH (2010) Differentiating radiation necrosis from tumor recurrence in high-grade gliomas: assessing the efficacy of 18F-FDG PET, 11C-methionine PET and perfusion MRI. Clin Neurol Neurosurg 112:758–765. doi:10.1016/j.clineuro.2010.06.005

    Article  PubMed  Google Scholar 

  18. Amin A, Moustafa H, Ahmed E, El-Toukhy M (2012) Glioma residual or recurrence versus radiation necrosis: accuracy of pentavalent technetium-99m-dimercaptosuccinic acid [Tc-99m (V) DMSA] brain SPECT compared to proton magnetic resonance spectroscopy (1H-MRS): initial results. J Neurooncol 106:579–587. doi:10.1007/s11060-011-0694-2

    Article  CAS  PubMed  Google Scholar 

  19. Nakajima T, Kumabe T, Kanamori M, Saito R, Tashiro M, Watanabe M, Tominaga T (2009) Differential diagnosis between radiation necrosis and glioma progression using sequential proton magnetic resonance spectroscopy and methionine positron emission tomography. Neurol Med Chir 49:394–401

    Article  Google Scholar 

  20. Peca C, Pacelli R, Elefante A, Del Basso De Caro ML, Vergara P, Mariniello G, Giamundo A, Maiuri F (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 doi:10.1016/j.clineuro.2008.11.003

  21. Prat R, Galeano I, Lucas A, Martinez JC, Martin M, Amador R, Reynes G (2010) Relative value of magnetic resonance spectroscopy, magnetic resonance perfusion, and 2-(18F) fluoro-2-deoxy-d-glucose positron emission tomography for detection of recurrence or grade increase in gliomas. J Clin Neurosci 17:50–53. doi:10.1016/j.jocn.2009.02.035

    Article  CAS  PubMed  Google Scholar 

  22. Jain R, Narang J, Schultz L, Scarpace L, Saksena S, Brown S, Rock JP, Rosenblum M, Gutierrez J, Mikkelsen T (2011) Permeability estimates in histopathology-proved treatment-induced necrosis using perfusion CT: can these add to other perfusion parameters in differentiating from recurrent/progressive tumors? AJNR Am J Neuroradiol 32:658–663. doi:10.3174/ajnr.A2378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Koot RW, Habraken JB, Hulshof MC, Paans AM, Bosch DA, Pruim J (2008) What is the value of emission tomography studies in patients with a primary glioblastoma multiforme treated by 192Ir brachytherapy? Acta Neurochir 150:345–349. doi:10.1007/s00701-007-1494-5

    Article  CAS  PubMed  Google Scholar 

  24. Terakawa Y, Tsuyuguchi N, Iwai Y, Yamanaka K, Higashiyama S, Takami T, Ohata K (2008) Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med 49:694–699. doi:10.2967/jnumed.107.048082

    Article  PubMed  Google Scholar 

  25. Xiangsong Z, Weian C (2007) Differentiation of recurrent astrocytoma from radiation necrosis: a pilot study with 13N-NH3 PET. J Neurooncol 82:305–311. doi:10.1007/s11060-006-9286-y

    Article  CAS  PubMed  Google Scholar 

  26. Yamane T, Sakamoto S, Senda M (2010) Clinical impact of (11)C-methionine PET on expected management of patients with brain neoplasm. Eur J Nucl Med Mol imaging 37:685–690. doi:10.1007/s00259-009-1302-y

    Article  PubMed  Google Scholar 

  27. Minniti G, Clarke E, Lanzetta G, Osti MF, Trasimeni G, Bozzao A, Romano A, Enrici RM (2011) Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol 6:48. doi:10.1186/1748-717X-6-48

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kim YZ, Kim DY, Yoo H, Yang HS, Shin SH, Hong EK, Cho KH, Lee SH (2007) Radiation-induced necrosis deteriorating neurological symptoms and mimicking progression of brain metastasis after stereotactic-guided radiotherapy. Cancer Res Treat 39:16–21. doi:10.4143/crt.2007.39.1.16

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mullins ME, Barest GD, Schaefer PW, Hochberg FH, Gonzalez RG, Lev MH (2005) Radiation necrosis versus glioma recurrence: conventional MR imaging clues to diagnosis. AJNR Am J Neuroradiol 26:1967–1972

    PubMed  PubMed Central  Google Scholar 

  30. Byrne TN (1994) Imaging of gliomas. Semin Oncol 21:162–171

    CAS  PubMed  Google Scholar 

  31. Yoshii Y, Satou M, Yamamoto T, Yamada Y, Hyodo A, Nose T, Ishikawa H, Hatakeyama R (1993) The role of thallium-201 single photon emission tomography in the investigation and characterisation of brain tumours in man and their response to treatment. Eur J Nucl Med 20:39–45

    Article  CAS  PubMed  Google Scholar 

  32. Kosuda S, Fujii H, Aoki S, Suzuki K, Tanaka Y, Nakamura O, Shidara N (1993) Reassessment of quantitative thallium-201 brain SPECT for miscellaneous brain tumors. Ann Nucl Med 7:257–263

    Article  CAS  PubMed  Google Scholar 

  33. Yoshii Y, Moritake T, Suzuki K, Fujita K, Nose T, Satou M (1996) Cerebral radiation necrosis with accumulation of thallium 201 on single-photon emission CT. AJNR Am J Neuroradiol 17:1773–1776

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Yoshii Y, Moritake T, Yamamoto T, Takano S, Tsuboi K, Hyodo A, Nose T, Satou M (1996) Correlation of histopathological factor of brain tumor and high thallium-201 uptake in single photon emission computed tomography. Noshuyo byori 13:61–65

    CAS  PubMed  Google Scholar 

  35. Fatterpekar GM, Galheigo D, Narayana A, Johnson G, Knopp E (2012) Treatment-related change versus tumor recurrence in high-grade gliomas: a diagnostic conundrum-use of dynamic susceptibility contrast-enhanced (DSC) perfusion MRI. AJR Am J Roentgenol 198:19–26. doi:10.2214/AJR.11.7417

    Article  PubMed  Google Scholar 

  36. Boxerman JL, Schmainda KM, Weisskoff RM (2006) Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade, whereas uncorrected maps do not. AJNR Am J Neuroradiol 27:859–867

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Paulson ES, Schmainda KM (2008) Comparison of dynamic susceptibility-weighted contrast-enhanced MR methods: recommendations for measuring relative cerebral blood volume in brain tumors. Radiology 249:601–613. doi:10.1148/radiol.2492071659

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kang Y, Choi SH, Kim YJ, Kim KG, Sohn CH, Kim JH, Yun TJ, Chang KH (2011) Gliomas: histogram analysis of apparent diffusion coefficient maps with standard- or high-b-value diffusion-weighted MR imaging—correlation with tumor grade. Radiology 261:882–890. doi:10.1148/radiol.11110686

    Article  PubMed  Google Scholar 

  39. Arvinda HR, Kesavadas C, Sarma PS, Thomas B, Radhakrishnan VV, Gupta AK, Kapilamoorthy TR, Nair S (2009) Glioma grading: sensitivity, specificity, positive and negative predictive values of diffusion and perfusion imaging. J Neurooncol 94:87–96. doi:10.1007/s11060-009-9807-6

    Article  CAS  PubMed  Google Scholar 

  40. Law M, Yang S, Wang H, Babb JS, Johnson G, Cha S, Knopp EA, Zagzag D (2003) Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol 24:1989–1998

    PubMed  PubMed Central  Google Scholar 

  41. Lev MH, Ozsunar Y, Henson JW, Rasheed AA, Barest GD, Harsh GRt, Fitzek MM, Chiocca EA, Rabinov JD, Csavoy AN, Rosen BR, Hochberg FH, Schaefer PW, Gonzalez RG (2004) Glial tumor grading and outcome prediction using dynamic spin-echo MR susceptibility mapping compared with conventional contrast-enhanced MR: confounding effect of elevated rCBV of oligodendrogliomas [corrected]. AJNR Am J Neuroradiol 25:214–221

  42. Morita N, Wang S, Chawla S, Poptani H, Melhem ER (2010) Dynamic susceptibility contrast perfusion weighted imaging in grading of nonenhancing astrocytomas. J Magn Reson Imaging 32:803–808. doi:10.1002/jmri.22324

    Article  PubMed  Google Scholar 

  43. 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 154:191–201; discussion 201. doi:10.1007/s00701-011-1228-6

    Article  PubMed  Google Scholar 

  44. 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. doi:10.1016/S1470-2045(08)70125-6

    Article  PubMed  Google Scholar 

  45. Zeng QS, Li CF, Zhang K, Liu H, Kang XS, Zhen JH (2007) Multivoxel 3D proton MR spectroscopy in the distinction of recurrent glioma from radiation injury. J Neurooncol 84:63–69. doi:10.1007/s11060-007-9341-3

    Article  CAS  PubMed  Google Scholar 

  46. Gomez-Rio M, Rodriguez-Fernandez A, Ramos-Font C, Lopez-Ramirez E, Llamas-Elvira JM (2008) Diagnostic accuracy of 201Thallium-SPECT and 18F-FDG-PET in the clinical assessment of glioma recurrence. Eur J Nucl Med Mol imaging 35:966–975. doi:10.1007/s00259-007-0661-5

    Article  PubMed  Google Scholar 

  47. Kahn D, Follett KA, Bushnell DL, Nathan MA, Piper JG, Madsen M, Kirchner PT (1994) Diagnosis of recurrent brain tumor: value of 201Tl SPECT vs 18F-fluorodeoxyglucose PET. AJR Am J Roentgenol 163:1459–1465

    Article  CAS  PubMed  Google Scholar 

  48. Olivero WC, Dulebohn SC, Lister JR (1995) The use of PET in evaluating patients with primary brain tumours: is it useful? J Neurol Neurosurg Psychiatry 58:250–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ricci PE, Karis JP, Heiserman JE, Fram EK, Bice AN, Drayer BP (1998) Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography? AJNR Am J Neuroradiol 19:407–413

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Stokkel M, Stevens H, Taphoorn M, Van Rijk P (1999) Differentiation between recurrent brain tumour and post-radiation necrosis: the value of 201Tl SPET versus 18F-FDG PET using a dual-headed coincidence camera—a pilot study. Nucl Med Commun 20:411–417

    Article  CAS  PubMed  Google Scholar 

  51. Thompson TP, Lunsford LD, Kondziolka D (1999) Distinguishing recurrent tumor and radiation necrosis with positron emission tomography versus stereotactic biopsy. Stereotact Funct Neurosurg 73:9–14

    Article  CAS  PubMed  Google Scholar 

  52. Kong DS, Kim ST, Kim EH, Lim DH, Kim WS, Suh YL, Lee JI, Park K, Kim JH, Nam DH (2011) Diagnostic dilemma of pseudoprogression in the treatment of newly diagnosed glioblastomas: the role of assessing relative cerebral blood flow volume and oxygen-6-methylguanine-DNA methyltransferase promoter methylation status. AJNR Am J Neuroradiol 32:382–387. doi:10.3174/ajnr.A2286

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kim CK et al (1991) New grading system of cerebral gliomas using positron emission tomography with F-18 fluorodeoxyglucose. J Neurooncol 10(1):85–91

    Article  CAS  PubMed  Google Scholar 

  54. Bobek-Billewicz B et al (2010) Differentiation between brain tumor recurrence and radiation injury using perfusion, diffusion-weighted imaging and MR spectroscopy. Folia Neuropathol 48(2):81–92

    PubMed  Google Scholar 

  55. Bisdas S et al (2011) Distinguishing recurrent high-grade gliomas from radiation injury: a pilot study using dynamic contrast-enhanced MR imaging. Acad Radiol 18(5):575–583

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurological Surgery, University of Miami, West Building, Suite 306, Miami, FL, 33125, USA

    Ashish H. Shah, Brian Snelling, Amade Bregy, Danoushka Tememe & Ricardo J. Komotar

  2. Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, FI, USA

    Payal R. Patel

  3. Department of Neuroradiology, University of Miami, Miami, FL, USA

    Rita Bhatia & Evelyn Sklar

Authors
  1. Ashish H. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian Snelling
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amade Bregy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Payal R. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Danoushka Tememe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rita Bhatia
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Evelyn Sklar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ricardo J. Komotar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ricardo J. Komotar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shah, A.H., Snelling, B., Bregy, A. et al. Discriminating radiation necrosis from tumor progression in gliomas: a systematic review what is the best imaging modality?. J Neurooncol 112, 141–152 (2013). https://doi.org/10.1007/s11060-013-1059-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-013-1059-9

Keywords

Search

Navigation