Top

Published in:

01-02-2019 | Clinical Study

Is 5-ALA fluorescence of cerebral metastases a prognostic factor for local recurrence and overall survival?

Authors: Marcel A. Kamp, Christopher Munoz-Bendix, Hendrik-Jan Mijderwijk, Bernd Turowski, Maxine Dibué-Adjei, Christiane von Saß, Jan Frederick Cornelius, Hans-Jakob Steiger, Marion Rapp, Michael Sabel

Published in: Journal of Neuro-Oncology | Issue 3/2019

Abstract

Background

5-Aminolevulinic acid (5-ALA) fluorescence-guided resection technique was first introduced for malignant glioma. However, the impact of the 5-ALA fluorescence behaviour of cerebral metastases is still unclear. Aim of this study was to determine the impact of PpIX-fluorescence on the local progression-free and overall survival.

Materials and methods

A secondary analysis was performed and included an updated follow-up of 136 patients comprised in two previous studies. Additionally, 82 new patients were included. All patients underwent surgical resection of cerebral metastasis and intraoperative estimation of 5-ALA-induced fluorescence. The 5-ALA fluorescence behaviour of cerebral metastases was correlated with the rate of local recurrences, the local progression-free and overall survival.

Results

218 patients suffering from cerebral metastatic spread fulfilled the inclusion criteria and were analysed: complete surgical resection could be achieved in 123/218 patients (56.4%). Dichotomised degree of surgical resection (complete vs. incomplete or questionable complete resection) was not related to dichotomized 5-ALA fluorescence of cerebral metastases (p = 0.66). 51 patients (23.4%) developed a local in-brain progression within or at the border of the resection cavity. Of these, 8 patients showed a PpIX-fluorescent metastasis. There was a trend towards a correlation between a higher local in-brain progression in PpIX-non-fluorescent metastases (p = 0.03). Median time to local in-brain progression was 4 ± 11 months. PpIX-fluorescent and PpIX-non-fluorescent metastases showed a significantly different progression-free survival (p = 0.01). PpIX-positive and –negative metastases showed a significantly different overall survival (20 and 14 months respectively; p = 0.006).

Conclusion

The 5-ALA fluorescence behaviour was related to the local progression-free and the overall survival in the present retrospective series and might be considered a prognostic marker. Further studies are required to appreciate the oncological impact of the 5-ALA induced fluorescence behaviour of cerebral metastases.

Belloch JP, Rovira V, Llacer JL, Riesgo PA, Cremades A (2014) Fluorescence-guided surgery in high grade gliomas using an exoscope system. Acta Neurochir (Wien) 156:653–660CrossRef

Benveniste RJ, Ferraro N, Tsimpas A (2014) Yield and utility of routine postoperative imaging after resection of brain metastases. J Neurooncol 118:363–367CrossRefPubMed

Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, Greenspoon J, Parney IF, Laack NNI, Ashman JB, Bahary JP, Hadjipanayis CG, Urbanic JJ, Barker FG 2nd, Farace E, Khuntia D, Giannini C, Buckner JC, Galanis E, Roberge D (2017) Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 18:1049–1060CrossRefPubMedPubMedCentral

Coburger J, Engelke J, Scheuerle A, Thal DR, Hlavac M, Wirtz CR, Konig R (2014) Tumor detection with 5-aminolevulinic acid fluorescence and Gd-DTPA-enhanced intraoperative MRI at the border of contrast-enhancing lesions: a prospective study based on histopathological assessment. Neurosurg Focus 36:E3CrossRefPubMed

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, Santacroce A, Zella SM, Niemann L, Steiger HJ, Rapp M, Sabel M (2013) The tumour is not enough or is it? Problems and new concepts in the surgery of cerebral metastases. Ecancermedicalscience 7:306PubMedPubMedCentral

Kamp MA, Fischer I, Buhner J, Turowski B, Cornelius JF, Steiger HJ, Rapp M, Slotty PJ, Sabel M (2016) 5-ALA fluorescence of cerebral metastases and its impact for the local-in-brain progression. Oncotarget 7:66776–66789CrossRefPubMedPubMedCentral

Kamp MA, Fischer I, Dibue-Adjei M, Munoz-Bendix C, Cornelius JF, Steiger HJ, Slotty PJ, Turowski B, Rapp M, Sabel M (2017) Predictors for a further local in-brain progression after re-craniotomy of locally recurrent cerebral metastases. Neurosurg Rev 41:813–823CrossRefPubMed

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.

Kamp MA, Rapp M, Buhner J, Slotty PJ, Reichelt D, Sadat H, Dibue-Adjei M, Steiger HJ, Turowski B, Sabel M (2015) Early postoperative magnet resonance tomography after resection of cerebral metastases. Acta Neurochir (Wien) 157:1573–1580CrossRef

11.

Kamp MA, Rapp M, Slotty PJ, Turowski B, Sadat H, Smuga M, Dibue-Adjei M, Steiger HJ, Szelenyi A, Sabel M (2015) Incidence of local in-brain progression after supramarginal resection of cerebral metastases. Acta Neurochir (Wien) 157:905–910; discussion 910–901CrossRef

12.

Kamp MA, Slotty PJ, Cornelius JF, Steiger HJ, Rapp M, Sabel M (2016) The impact of cerebral metastases growth pattern on neurosurgical treatment. Neurosurg Rev 41:77–86CrossRefPubMed

13.

Kamp MA, Cornelius JF, Steiger HJ, Sabel M (2018) 5-Aminolevulinic acid and brain metastases. In: Hadjipanayis CS, W. (ed) Fluorescence-guided neurosurgery: neuro-oncology and cerebrovascular application. Thieme, New York

14.

Kemmner W, Wan K, Ruttinger S, Ebert B, Macdonald R, Klamm U, Moesta KT (2008) Silencing of human ferrochelatase causes abundant protoporphyrin-IX accumulation in colon cancer. FASEB J 22:500–509CrossRefPubMed

15.

Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann RD, Carrie C, Ben Hassel M, Kouri M, Valeinis E, van den Berge D, Collette S, Collette L, Mueller RP (2011) Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 29:134–141CrossRefPubMed

16.

Kong XTA, Bota D, D.A (2014) Epidemiology of central nervous system metastases. In: Hayat MA (ed) Brain metastases from primary tumors. epidemiology, biology, and therapy, vol 1. Academic Press, London, pp 11–23CrossRef

17.

Lin NU, Lee EQ, Aoyama H, Barani IJ, Barboriak DP, Baumert BG, Bendszus M, Brown PD, Camidge DR, Chang SM, Dancey J, de Vries EG, Gaspar LE, Harris GJ, Hodi FS, Kalkanis SN, Linskey ME, Macdonald DR, Margolin K, Mehta MP, Schiff D, Soffietti R, Suh JH, van den Bent MJ, Vogelbaum MA, Wen PY, Response Assessment in Neuro-Oncology Group (2015) Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol 16:e270–e278CrossRefPubMed

18.

Mahajan A, Ahmed S, McAleer MF, Weinberg JS, Li J, Brown P, Settle S, Prabhu SS, Lang FF, Levine N, McGovern S, Sulman E, McCutcheon IE, Azeem S, Cahill D, Tatsui C, Heimberger AB, Ferguson S, Ghia A, Demonte F, Raza S, Guha-Thakurta N, Yang J, Sawaya R, Hess KR, Rao G (2017) Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 18:1040–1048CrossRefPubMedPubMedCentral

19.

Marbacher S, Klinger E, Schwyzer L, Fischer I, Nevzati E, Diepers M, Roelcke U, Fathi AR, Coluccia D, Fandino J (2014) Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases. Neurosurg Focus 36:E10CrossRefPubMed

20.

Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, Markesbery WR, Foon KA, Young B (1998) Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 280:1485–1489CrossRefPubMed

21.

Patel AJ, Suki D, Hatiboglu MA, Abouassi H, Shi W, Wildrick DM, Lang FF, Sawaya R (2010) Factors influencing the risk of local recurrence after resection of a single brain metastasis. J Neurosurg 113:181–189CrossRefPubMed

22.

Patel AJ, Suki D, Hatiboglu MA, Rao VY, Fox BD, Sawaya R (2015) Impact of surgical methodology on the complication rate and functional outcome of patients with a single brain metastasis. J Neurosurg 122:1132–1143CrossRefPubMed

23.

Piquer J, Llacer JL, Rovira V, Riesgo P, Rodriguez R, Cremades A (2014) Fluorescence-guided surgery and biopsy in gliomas with an exoscope system. Biomed Res Int. https://doi.org/10.1155/2014/207974 CrossRefPubMedPubMedCentral

24.

Roos DE, Smith JG, Stephens SW (2011) Radiosurgery versus surgery, both with adjuvant whole brain radiotherapy, for solitary brain metastases: a randomised controlled trial. Clin Oncol (R Coll Radiol) 23:646–651CrossRef

25.

Sabel M, Knipps J, Neumann LM, Kieslich M, Steiger HJ, Rapp M, Kamp MA (2018) Quantification of ALA-fluorescence induced by a modified commercially available head lamp and a surgical microscope. Neurosurg Rev 41:1079–1083CrossRefPubMed

26.

Salas S, Brulard C, Terrier P, Ranchere-Vince D, Neuville A, Guillou L, Lae M, Leroux A, Verola O, Jean-Emmanuel K, Bonvalot S, Blay JY, Le Cesne A, Aurias A, Coindre JM, Chibon F (2015) Gene expression profiling of desmoid tumors by cDNA microarrays and correlation with progression-free survival. Clin Cancer Res 21:4194–4200CrossRefPubMed

27.

Sawaya R (2001) Considerations in the diagnosis and management of brain metastases. Oncology 15:1144–1154, 1157 – 1148; discussion 1158, 1163 – 1145PubMed

28.

Schucht P, Beck J, Vajtai I, Raabe A (2011) Paradoxical fluorescence after administration of 5-aminolevulinic acid for resection of a cerebral melanoma metastasis. Acta Neurochir 153:1497–1499CrossRefPubMed

29.

Stummer W, Kamp MA (2009) The importance of surgical resection in malignant glioma. Curr Opin Neurol 22:645–649CrossRefPubMed

30.

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 7:392–401CrossRefPubMed

31.

Stummer W, Stocker S, Novotny A, Heimann A, Sauer O, Kempski O, Plesnila N, Wietzorrek J, Reulen HJ (1998) In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid. J Photochem Photobiol B 45:160–169CrossRefPubMed

32.

Suki D, Abouassi H, Patel AJ, Sawaya R, Weinberg JS, Groves MD (2008) Comparative risk of leptomeningeal disease after resection or stereotactic radiosurgery for solid tumor metastasis to the posterior fossa. J Neurosurg 108:248–257CrossRefPubMed

33.

Utsuki S, Miyoshi N, Oka H, Miyajima Y, Shimizu S, Suzuki S, Fujii K (2007) Fluorescence-guided resection of metastatic brain tumors using a 5-aminolevulinic acid-induced protoporphyrin IX: pathological study. Brain Tumor Pathol 24:53–55CrossRefPubMed

34.

Valdes PA, Leblond F, Kim A, Harris BT, Wilson BC, Fan X, Tosteson TD, Hartov A, Ji S, Erkmen K, Simmons NE, Paulsen KD, Roberts DW (2011) Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker. J Neurosurg 115:11–17CrossRefPubMedPubMedCentral

35.

Widhalm G, Minchev G, Woehrer A, Preusser M, Kiesel B, Furtner J, Mert A, Di Ieva A, Tomanek B, Prayer D, Marosi C, Hainfellner JA, Knosp E, Wolfsberger S (2012) Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies. Neurosurg Rev 35:381–391; discussion 391CrossRefPubMed

36.

Yoo H, Kim YZ, Nam BH, Shin SH, Yang HS, Lee JS, Zo JI, Lee SH (2009) Reduced local recurrence of a single brain metastasis through microscopic total resection. J Neurosurg 110:730–736CrossRefPubMed

Title: Is 5-ALA fluorescence of cerebral metastases a prognostic factor for local recurrence and overall survival?
Authors: Marcel A. Kamp
Christopher Munoz-Bendix
Hendrik-Jan Mijderwijk
Bernd Turowski
Maxine Dibué-Adjei
Christiane von Saß
Jan Frederick Cornelius
Hans-Jakob Steiger
Marion Rapp
Michael Sabel
Publication date: 01-02-2019
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 3/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-03066-y

ACC 2024 Congress

Springer Medicine

Is 5-ALA fluorescence of cerebral metastases a prognostic factor for local recurrence and overall survival?

Abstract

Background

Materials and methods

Results

Conclusion

ACC 2024 Congress

Springer Medicine

Abstract

Background

Materials and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2019

The use of 5-aminolevulinic acid in resection of pediatric brain tumors: a critical review

Visualization technologies for 5-ALA-based fluorescence-guided surgeries

5-ALA fluorescence-guided surgery of CNS tumors

Established and emerging uses of 5-ALA in the brain: an overview

5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas

The role of 5-aminolevulinic acid in spinal tumor surgery: a review