Skip to main content
Top
Published in: Acta Neurochirurgica 2/2015

01-02-2015 | Clinical Article - Brain Tumors

5-ALA-induced fluorescence behavior of reactive tissue changes following glioblastoma treatment with radiation and chemotherapy

Authors: Marcel A. Kamp, Jörg Felsberg, Hosai Sadat, Jamshid Kuzibaev, Hans-Jakob Steiger, Marion Rapp, Guido Reifenberger, Maxiné Dibué, Michael Sabel

Published in: Acta Neurochirurgica | Issue 2/2015

Login to get access

Abstract

Background

The 5-aminolevulinic acid (5-ALA) fluorescence-guided resection of recurrent malignant glioma is a standard surgical procedure at many neuro-oncological centers and is considered to be equally reliable as the primary resection of these tumors. 5-ALA induced fluorescence (5-AIF)-guided resection has been demonstrated to be highly predictive for tumor tissue. As pseudoprogression and radiation-induced necrosis are critical differential diagnoses of glioma recurrence, the purpose of the present analysis was to analyze 5-AIF behavior in resected tissue specimens histopathologically showing regressive and reactive changes but lacking active, that is, cellular recurrent tumor tissue after adjuvant treatment of malignant glioma.

Methods

A retrospective analysis was performed in patients suffering from malignant glioma who underwent surgical resection for suspected contrast-enhancing tumor recurrence (according to RANO criteria) at our institution between 2007 and 2013, but in whom histopathological analysis only revealed reactive changes. The presence of AIF in the resected tissue samples was intraoperatively assessed and classified by the surgeon, using the categories (1) no, (2) vague and (3) solid AIF.

Results

A total of 13 out of 313 patients who underwent AIF-guided surgical resection of tissue suspicious for recurrent glioma histologically demonstrated only reactive changes without active recurrent tumor tissue after adjuvant therapy. Pretreatment was chemotherapy with temozolomide in 1 patient and combined radio-/chemotherapy in 12 patients. Six patients had suffered previous tumor recurrence with a subsequently intensified adjuvant therapy. Seven of the 13 patients displayed solid, 5 patients vague and 1 patient no 5-AIF of the resected tissue specimens. However, all 5-AIF-positive lesions exhibited heterogeneous fluorescence patterns with vaguely or solidly fluorescent as well as nonfluorescent regions.

Conclusions

Resection of reactive tissue without active recurrent tumor after multimodal treatment for glioblastoma is frequently associated with solid or vague 5-AIF. Therefore, neurosurgeons should remain cautious when attempting to employ intraoperative 5-AIF to discriminate radiation- and chemotherapy-induced tissue changes from true disease progression. Nevertheless, 5-AIF-guided resection remains a valid tool in the neurosurgical treatment of recurrent gliomas.
Literature
1.
go back to reference 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 Oncol 10:361–367PubMedCentralPubMedCrossRef 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 Oncol 10:361–367PubMedCentralPubMedCrossRef
2.
go back to reference 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 9:453–461PubMedCrossRef 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 9:453–461PubMedCrossRef
3.
go back to reference 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 82:81–83PubMedCrossRef 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 82:81–83PubMedCrossRef
4.
go back to reference Chaskis C, Neyns B, Michotte A, De Ridder M, Everaert H (2009) Pseudoprogression after radiotherapy with concurrent temozolomide for high-grade glioma: Clinical observations and working recommendations. Surg Neurol 72:423–428PubMedCrossRef Chaskis C, Neyns B, Michotte A, De Ridder M, Everaert H (2009) Pseudoprogression after radiotherapy with concurrent temozolomide for high-grade glioma: Clinical observations and working recommendations. Surg Neurol 72:423–428PubMedCrossRef
5.
go back to reference 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 63:535–537PubMedCrossRef 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 63:535–537PubMedCrossRef
7.
go back to reference Gunjur A, Lau E, Taouk Y, Ryan G (2011) Early post-treatment pseudo-progression amongst glioblastoma multiforme patients treated with radiotherapy and temozolomide: A retrospective analysis. J Med Imaging Radiat Oncol 55:603–610PubMedCrossRef Gunjur A, Lau E, Taouk Y, Ryan G (2011) Early post-treatment pseudo-progression amongst glioblastoma multiforme patients treated with radiotherapy and temozolomide: A retrospective analysis. J Med Imaging Radiat Oncol 55:603–610PubMedCrossRef
8.
go back to reference Kamp MA, Dibue M, Niemann L, Reichelt DC, Felsberg J, Steiger HJ, Szelenyi A, Rapp M, Sabel M (2012) Proof of principle: Supramarginal resection of cerebral metastases in eloquent brain areas. Acta Neurochir (Wien) 154:1981–1986CrossRef Kamp MA, Dibue M, Niemann L, Reichelt DC, Felsberg J, Steiger HJ, Szelenyi A, Rapp M, Sabel M (2012) Proof of principle: Supramarginal resection of cerebral metastases in eloquent brain areas. Acta Neurochir (Wien) 154:1981–1986CrossRef
9.
go back to reference Kamp MA, Grosser P, Felsberg J, Slotty PJ, Steiger HJ, Reifenberger G, Sabel M (2012) 5-aminolevulinic acid (5-ALA)-induced fluorescence in intracerebral metastases: A retrospective study. Acta Neurochir (Wien) 154:223–228, discussion 228CrossRef Kamp MA, Grosser P, Felsberg J, Slotty PJ, Steiger HJ, Reifenberger G, Sabel M (2012) 5-aminolevulinic acid (5-ALA)-induced fluorescence in intracerebral metastases: A retrospective study. Acta Neurochir (Wien) 154:223–228, discussion 228CrossRef
10.
go back to reference 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 217:377–384PubMedCrossRef 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 217:377–384PubMedCrossRef
11.
12.
go back to reference Nabavi A, Thurm H, Zountsas B, Pietsch T, Lanfermann H, Pichlmeier U, Mehdorn M, Group ALA-RGS (2009) Five-aminolevulinic acid for fluorescence-guided resection of recurrent malignant gliomas: A phase II study. Neurosurgery 65:1070–1076, discussion 1076-1077PubMedCrossRef Nabavi A, Thurm H, Zountsas B, Pietsch T, Lanfermann H, Pichlmeier U, Mehdorn M, Group ALA-RGS (2009) Five-aminolevulinic acid for fluorescence-guided resection of recurrent malignant gliomas: A phase II study. Neurosurgery 65:1070–1076, discussion 1076-1077PubMedCrossRef
13.
go back to reference Perry A, Schmidt RE (2006) Cancer therapy-associated CNS neuropathology: An update and review of the literature. Acta Neuropathol 111:197–212PubMedCrossRef Perry A, Schmidt RE (2006) Cancer therapy-associated CNS neuropathology: An update and review of the literature. Acta Neuropathol 111:197–212PubMedCrossRef
14.
go back to reference Stummer W, Kamp MA (2009) The importance of surgical resection in malignant glioma. Curr Opin Neurol 22:645–649PubMedCrossRef Stummer W, Kamp MA (2009) The importance of surgical resection in malignant glioma. Curr Opin Neurol 22:645–649PubMedCrossRef
15.
go back to reference Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ (2000) Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. J Neurosurg 93:1003–1013PubMedCrossRef Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ (2000) Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. J Neurosurg 93:1003–1013PubMedCrossRef
16.
go back to reference Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, Group AL-GS (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401PubMedCrossRef Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, Group AL-GS (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401PubMedCrossRef
17.
go back to reference Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. NEJM 352:987-996 Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. NEJM 352:987-996
18.
go back to reference Taal W, Brandsma D, de Bruin HG, Bromberg JE, Swaak-Kragten AT, Smitt PA, van Es CA, van den Bent MJ (2008) Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide. Cancer 113:405–410PubMedCrossRef Taal W, Brandsma D, de Bruin HG, Bromberg JE, Swaak-Kragten AT, Smitt PA, van Es CA, van den Bent MJ (2008) Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide. Cancer 113:405–410PubMedCrossRef
19.
go back to reference Utsuki S, Oka H, Sato S, Shimizu S, Suzuki S, Tanizaki Y, Kondo K, Miyajima Y, Fujii K (2007) Histological examination of false positive tissue resection using 5-aminolevulinic acid-induced fluorescence guidance. Neurol Med Chir (Tokyo) 47:210–213, discussion 213-214CrossRef Utsuki S, Oka H, Sato S, Shimizu S, Suzuki S, Tanizaki Y, Kondo K, Miyajima Y, Fujii K (2007) Histological examination of false positive tissue resection using 5-aminolevulinic acid-induced fluorescence guidance. Neurol Med Chir (Tokyo) 47:210–213, discussion 213-214CrossRef
20.
go back to reference 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 28:1963–1972PubMedCrossRef 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 28:1963–1972PubMedCrossRef
21.
go back to reference Wong CS, Van der Kogel AJ (2004) Mechanisms of radiation injury to the central nervous system: Implications for neuroprotection. Mol Interv 4:273–284PubMedCrossRef Wong CS, Van der Kogel AJ (2004) Mechanisms of radiation injury to the central nervous system: Implications for neuroprotection. Mol Interv 4:273–284PubMedCrossRef
22.
go back to reference Woodworth GF, Garzon-Muvdi T, Ye X, Blakeley JO, Weingart JD, Burger PC (2013) Histopathological correlates with survival in reoperated glioblastomas. J Neurooncol 113:485–493PubMedCentralPubMedCrossRef Woodworth GF, Garzon-Muvdi T, Ye X, Blakeley JO, Weingart JD, Burger PC (2013) Histopathological correlates with survival in reoperated glioblastomas. J Neurooncol 113:485–493PubMedCentralPubMedCrossRef
Metadata
Title
5-ALA-induced fluorescence behavior of reactive tissue changes following glioblastoma treatment with radiation and chemotherapy
Authors
Marcel A. Kamp
Jörg Felsberg
Hosai Sadat
Jamshid Kuzibaev
Hans-Jakob Steiger
Marion Rapp
Guido Reifenberger
Maxiné Dibué
Michael Sabel
Publication date
01-02-2015
Publisher
Springer Vienna
Published in
Acta Neurochirurgica / Issue 2/2015
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-014-2313-4

Other articles of this Issue 2/2015

Acta Neurochirurgica 2/2015 Go to the issue