Skip to main content

Advertisement

SpringerLink
Log in

Hyperintense signal on diffusion-weighted imaging for monitoring the acute response and local recurrence after photodynamic therapy in malignant gliomas

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

Abstract

Purpose

Photodynamic therapy (PDT) subsequent to surgical tumor removal is a novel localized treatment for malignant glioma that provides effective local control. The acute response of malignant glioma to PDT can be detected as linear transient hyperintense signal on diffusion-weighted imaging (DWI) and a decline in apparent diffusion coefficient values without symptoms. However, their long-term clinical significance has not yet been examined. The aim of this study was to clarify the link between hyperintense signal on DWI as an acute response and recurrence after PDT in malignant glioma.

Methods

Thirty patients (16 men; median age, 60.5 years) underwent PDT for malignant glioma at our institution between 2017 and 2020. We analyzed the signal changes on DWI after PDT and the relationship between these findings and the recurrence pattern.

Results

All patients showed linear hyperintense signal on DWI at the surface of the resected cavity from day 1 after PDT. These changes disappeared in about 30 days without any neurological deterioration. During a mean post-PDT follow-up of 14.3 months, 19 patients (63%) exhibited recurrence: 10 local, 1 distant, and 8 disseminated. All of the local recurrences arose from areas that did not show hyperintense signal on DWI obtained on day 1 after PDT.

Conclusions

The local recurrence in malignant glioma after PDT occurs in an area without hyperintense signal on DWI as an acute response to PDT. This characteristic finding could aid in the monitoring of local recurrence after PDT.

Graphic abstract

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The data in this study are available from the corresponding author on reasonable request.

Code availability

No software application or custom code was used in this study.

Abbreviations

ADC:

Apparent diffusion coefficient

CE-T1WI:

Contrast-enhanced T1-weighted imaging

DWI:

Diffusion-weighted imaging

FLAIR:

Fluid-attenuated inversion recovery

FOV:

Field of view

IDH:

Isocitrate dehydrogenase

MGMT:

O6-methylguanine-DNA methyltransferase

MR:

Magnetic resonance

PDT:

Photodynamic therapy

TE:

Echo time

TI:

Inversion time

TR:

Repetition time

WHO:

World Health Organization

References

  1. Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS (2011) An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:3–8. https://doi.org/10.3171/2011.2.JNS10998

    Article  PubMed  Google Scholar 

  2. Marko NF, Weil RJ, Schroeder JL, Lang FF, Suki D, Sawaya RE (2014) Extent of resection of glioblastoma revisited: Personalized survival modeling facilitates more accurate survival prediction and supports a maximum-safe-resection approach to surgery. J Clin Oncol 32:774–782. https://doi.org/10.1200/JCO.2013.51.8886

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: Prognosis, extent of resection, and survival. J Neurosurg 95:190–198. https://doi.org/10.3171/jns.2001.95.2.0190

    Article  CAS  PubMed  Google Scholar 

  4. Grabowski MM, Recinos PF, Nowacki AS, Schroeder JL, Angelov L, Barnett GH, Vogelbaum MA (2014) Residual tumor volume versus extent of resection: Predictors of survival after surgery for glioblastoma. J Neurosurg 121:1115–1123. https://doi.org/10.3171/2014.7.JNS132449

    Article  PubMed  Google Scholar 

  5. Burger PC, Heinz ER, Shibata T, Kleihues P (1988) Topographic anatomy and CT correlations in the untreated glioblastoma multiforme. J Neurosurg 68:698–704. https://doi.org/10.3171/jns.1988.68.5.0698

    Article  CAS  PubMed  Google Scholar 

  6. Brandes AA, Tosoni A, Franceschi E, Sotti G, Frezza G, Amistà P, Morandi L, Spagnolli F, Ermani M (2009) Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: Correlation with MGMT promoter methylation status. J Clin Oncol 27:1275–1279. https://doi.org/10.1200/JCO.2008.19.4969

    Article  CAS  PubMed  Google Scholar 

  7. Dörner L, Mustafa A, Rohr A, Mehdorn HM, Nabavi A (2013) Growth pattern of tumor recurrence following bis-chloroethylnitrosourea (BCNU) wafer implantation in malignant glioma. J Clin Neurosci 20:429–434. https://doi.org/10.1016/j.jocn.2012.01.060

    Article  CAS  PubMed  Google Scholar 

  8. Rapp M, Baernreuther J, Turowski B, Steiger H-J, Sabel M, Kamp MA (2017) Recurrence pattern analysis of primary glioblastoma. World Neurosurg 103:733–740. https://doi.org/10.1016/j.wneu.2017.04.053

    Article  PubMed  Google Scholar 

  9. Gaspar LE, Fisher BJ, Macdonald DR, LeBer DV, Halperin EC, Schold SC Jr, Cairncross JG (1992) Supratentorial malignant glioma: Patterns of recurrence and implications for external beam local treatment. Int J Radiat Oncol Biol Phys 24:55–57. https://doi.org/10.1016/0360-3016(92)91021-E

    Article  CAS  PubMed  Google Scholar 

  10. Konishi Y, Muragaki Y, Iseki H, Mitsuhashi N, Okada Y (2012) Patterns of intracranial glioblastoma recurrence after aggressive surgical resection and adjuvant management: retrospective analysis of 43 cases. Neurol Med Chir (Tokyo) 52:577–586. https://doi.org/10.2176/nmc.52.577

    Article  Google Scholar 

  11. Nitta M, Muragaki Y, Maruyama T, Iseki H, Komori T, Ikuta S, Saito T, Yasuda T, Hosono J, Okamoto S, Koriyama S, Kawamata T (2018) Role of photodynamic therapy using talaporfin sodium and a semiconductor laser in patients with newly diagnosed glioblastoma. J Neurosurg 131:1361–1368. https://doi.org/10.3171/2018.7.JNS18422

    Article  Google Scholar 

  12. Muragaki Y, Akimoto J, Maruyama T, Iseki H, Ikuta S, Nitta M, Maebayashi K, Saito T, Okada Y, Kaneko S, Matsumura A, Kuroiwa T, Karasawa K, Nakazato Y, Kayama T (2013) Phase II clinical study on intraoperative photodynamic therapy with talaporfin sodium and semiconductor laser in patients with malignant brain tumors. J Neurosurg 119:845–852. https://doi.org/10.3171/2013.7.JNS13415

    Article  CAS  PubMed  Google Scholar 

  13. Akimoto J (2016) Photodynamic therapy for malignant brain tumors. Neurol Med Chir (Tokyo) 56:151–157. https://doi.org/10.2176/nmc.ra.2015-0296

    Article  Google Scholar 

  14. Henderson BW, Dougherty TJ (1992) How does photodynamic therapy work? Photochem Photobiol 55:145–157. https://doi.org/10.1111/j.1751-1097.1992.tb04222.x

    Article  CAS  PubMed  Google Scholar 

  15. Dolmans EJGJ, Fukumura D, Jain RK (2003) Photodynamic therapy for cancer. Nat Rev Cancer 3:380–387. https://doi.org/10.1038/nrc1071

    Article  CAS  PubMed  Google Scholar 

  16. Castano AP, Mroz P, Hamblin MR (2006) Photodynamic therapy and anti-tumour immunity. Nat Rev Cancer 6:535–545. https://doi.org/10.1038/nrc1894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, 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 Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. https://doi.org/10.1056/NEJMoa043330

  18. Azoulay M, Santos F, Shenouda G, Petrecca K, Oweida A, Guiot MC, Owen S, Panet-Raymond V, Souhami L, Abdulkarim BS (2017) Benefit of re-operation and salvage therapies for recurrent glioblastoma multiforme: results from a single institution. J Neurooncol 132:419–426. https://doi.org/10.1007/s11060-017-2383-2

    Article  CAS  PubMed  Google Scholar 

  19. Tully PA, Gogos AJ, Love C, Liew D, Drummond KJ, Morokoff AP (2016) Reoperation for recurrent glioblastoma and its association with survival benefit. Neurosurgery 79:678–689. https://doi.org/10.1227/NEU.0000000000001338

    Article  PubMed  Google Scholar 

  20. Suchorska B, Weller M, Tabatabai G, Senft C, Hau P, Sabel MC, Herrlinger U, Ketter R, Schlegel U, Marosi C, Reifenberger G, Wick W, Tonn JC, Wirsching H-G (2016) Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma - Results from the DIRECTOR trial. Neuro Oncol 18:549–556. https://doi.org/10.1093/neuonc/nov326

    Article  PubMed  PubMed Central  Google Scholar 

  21. Montemurro N, Perrini P, Blanco MO, Vannozzi R (2016) Second surgery for recurrent glioblastoma: a concise overview of the current literature. Clin Neurol Neurosurg 142:60–64. https://doi.org/10.1016/j.clineuro.2016.01.010

    Article  PubMed  Google Scholar 

  22. Wann A, Tully PA, Barnes EH, Lwin Z, Jeffree R, Drummond KJ, Gan H, Khasraw M (2018) Outcomes after second surgery for recurrent glioblastoma: a retrospective case–control study. J Neurooncol 137:409–415. https://doi.org/10.1007/s11060-017-2731-2

    Article  PubMed  Google Scholar 

  23. Fujita Y, Sasayama T, Tanaka K, Kyotani K, Nagashima H, Kohta M, Kimura H, Fujita A, Kohmura E (2019) DWI for monitoring the acute response of malignant gliomas to photodynamic therapy. Am J Neuroradiol 40:2045–2051. https://doi.org/10.3174/ajnr.A6300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 48:452–458. https://doi.org/10.1038/bmt.2012.244

    Article  CAS  PubMed  Google Scholar 

  25. Moan J, Berg K (1991) The photodegredation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen. Photochem Photobiol 53:549–553. https://doi.org/10.1111/j.1751-1097.1991.tb03669.x

    Article  CAS  PubMed  Google Scholar 

  26. Stylli SS, Kaye AH (2006) Photodynamic therapy of cerebral glioma: a review part I—a biological basis. J Clin Neurosci 13:615–625. https://doi.org/10.1016/J.JOCN.2005.11.014

    Article  CAS  PubMed  Google Scholar 

  27. Henderson BW, Waldow SM, Mang TS, Potter WR, Malone PB, Dougherty TJ (1985) Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. Cancer Res 45:572–576

    CAS  PubMed  Google Scholar 

  28. Fingar VH, Wieman TJ, Haydon PS (1997) The effects of thrombocytopenia on vessel stasis and macromolecular leakage after photodynamic therapy using photofrin. Photochem Photobiol 66:513–517. https://doi.org/10.1111/j.1751-1097.1997.tb03182.x

    Article  CAS  PubMed  Google Scholar 

  29. Ferrario A, von Tiehl KF, Rucker N, Schwarz MA, Gill PS, Gomer CJ (2000) Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. Cancer Res 60:4066–4069

    CAS  PubMed  Google Scholar 

  30. Shumaker BP, Hetzel FW (1987) Clinical laser photodynamic therapy in the treatment of bladder carcinoma. Photochem Photobiol 46:899–901. https://doi.org/10.1111/j.1751-1097.1987.tb04866.x

    Article  CAS  PubMed  Google Scholar 

  31. de Vree WJ, Essers MC, de Bruijn HS, Star WM, Foster JF, Sluiter W (1996) Evidence for an important role of neutrophils in the efficacy of photodynamic therapy in vivo. Cancer Res 56:2908–2911

    PubMed  Google Scholar 

  32. Gollnick SO, Liu X, Owczarczak B, Musser DA, Henderson BW (1997) Altered expression of interleukin 6 and interleukin 10 as a result of photodynamic therapy in vivo. Cancer Res 57:3904–3909

    CAS  PubMed  Google Scholar 

  33. Moseley ME, Cohen Y, Mintorovitch J, Chileuitt L, Shimizu H, Kucharczyk J, Wendland MF, Weinstein PR (1990) Early detection of regional cerebral ischemia in cats: Comparison of diffusion- and T2-weighted MRI and spectroscopy. Magn Reson Med 14:330–346. https://doi.org/10.1002/mrm.1910140218

    Article  CAS  PubMed  Google Scholar 

  34. Ellingson BM, Abrey LE, Nelson SJ, Kaufmann TJ, Garcia J, Chinot O, Saran F, Nishikawa R, Henriksson R, Mason WP, Wick W, Butowski N, Ligon KL, Gerstner ER, Colman H, de Groot J, Chang S, Mellinghoff I, Young RJ, Alexander BM, Colen R, Taylor JW, Arrillaga-Romany I, Mehta A, Huang RY, Pope WB, Reardon D, Batchelor T, Prados M, Galanis E, Wen PY, Cloughesy TF (2018) Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma. Neuro Oncol 20:1240–1250. https://doi.org/10.1093/neuonc/noy053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Huang Z, Hsu YC, Li LB, Wang LW, Song XD, Yow CMN, Lei X, Musani AI, Luo RC, Day BJ (2015) Photodynamic therapy of cancer - Challenges of multidrug resistance. J Innov Opt Health Sci 8:1530002. https://doi.org/10.1142/S1793545815300025

    Article  CAS  Google Scholar 

  36. Gołab J, Nowis D, Skrzycki M, Czeczot H, Baranczyk-Kuzma A, Wilczynski GM, Makowski M, Mroz P, Kozar K, Kaminski R, Jalili A, Kopec’ M, Grzela T, Jakobisiak M (2003) Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol: a superoxide dismutase inhibitor. J Biol Chem 278:407–414. https://doi.org/10.1074/jbc.M209125200

    Article  CAS  PubMed  Google Scholar 

  37. Broekgaarden M, Weijer R, van Gulik TM, Hamblin MR, Heger M (2015) Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies. Cancer Metastasis Rev 34:643–690. https://doi.org/10.1007/s10555-015-9588-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, Hahn SM, Hamblin MR, Juzeniene A, Kessel D, Korbelik M, Moan J, Mroz P, Nowis D, Piette J, Wilson BC, Golab J (2011) Photodynamic therapy of cancer: an update. CA Cancer J Clin 61:250–281. https://doi.org/10.3322/caac.20114

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ghahe SS, Kosicki K, Wojewódzka M, Majchrzak BA, Fogtman A, Iwanicka-Nowicka R, Ciuba A, Koblowska M, Kruszewski M, Tudek B, Speina E (2021) Increased DNA repair capacity augments resistance of glioblastoma cells to photodynamic therapy. DNA Repair 104:103136. https://doi.org/10.1016/j.dnarep.2021.103136

    Article  CAS  Google Scholar 

  40. Thompson EM, Frenkel EP, Neuwelt EA (2011) The paradoxical effect of bevacizumab in the therapy of malignant gliomas. Neurology 76:87–93. https://doi.org/10.1212/WNL.0b013e318204a3af

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. van Dijken BRJ, van Laar PJ, Li C, Yan JL, Boonzaier NR, Price SJ, van der Hoorn FCRS A (2019) Ventricle contact is associated with lower survival and increased peritumoral perfusion in glioblastoma. J Neurosurg 131:717–723. https://doi.org/10.3171/2018.5.JNS18340

    Article  Google Scholar 

  42. Mistry AM, Kelly PD, Gallant JN, Mummareddy N, Mobley BC, Thompson RC, Chambless LB (2019) Comparative analysis of subventricular zone glioblastoma contact and ventricular entry during resection in predicting dissemination, hydrocephalus, and survival. Neurosurgery 85:E924–E932. https://doi.org/10.1093/neuros/nyz144

    Article  PubMed  PubMed Central  Google Scholar 

  43. Mistry AM, Kelly PD, Thompson RC, Chambless LB (2018) Cancer dissemination, hydrocephalus, and survival after cerebral ventricular entry during high-grade glioma surgery: a meta-analysis. Neurosurgery 83:1119–1127. https://doi.org/10.1093/neuros/nyy202

    Article  PubMed  Google Scholar 

  44. Young JS, Gogos AJ, Pereira MP, Morshed RA, Li J, Barkovich MJ, Hervey-Jumper SL, Berger MS (2021) Effects of ventricular entry on patient outcome during glioblastoma resection. J Neurosurg. https://doi.org/10.3171/2020.7.jns201362

    Article  PubMed  Google Scholar 

  45. Elliott JP, Keles GE, Waite M, Temkin N, Berger MS (1994) Ventricular entry during resection of malignant gliomas: effect on intracranial cerebrospinal fluid tumor dissemination. J Neurosurg 80:834–839. https://doi.org/10.3171/jns.1994.80.5.0834

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Ms. Takiko Uno for molecular analysis of the IDH mutation status of the patients included in this study.

Funding

This work was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology [grant number: 20K09369 to Takashi Sasayama and 20K09389 to Kazuhiro Tanaka]. The sponsor had no role in the study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan

    Yuichi Fujita, Hiroaki Nagashima, Kazuhiro Tanaka, Mitsuru Hashiguchi & Takashi Sasayama

  2. Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

    Tomoo Itoh

Authors
  1. Yuichi Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroaki Nagashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuhiro Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mitsuru Hashiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tomoo Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takashi Sasayama
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: YF, TS. Collection and assembly of data: YF, HN, KT, MH, TI, TS. Analysis and interpretation of data: YF, HN, KT, TS. Drafting the article: YF. Reviewed submitted version of manuscript: all authors. Approved the final version of manuscript: all authors.

Corresponding author

Correspondence to Yuichi Fujita.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the institutional review board (protocol number B190100) and conducted according to institutional and national ethical guidelines and in accordance with the Helsinki Declaration.

Consent to participate

Patient informed consents were waived by the institutional review board due to the retrospective nature of the study and use of anonymized data.

Consent for publication

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1989.1 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fujita, Y., Nagashima, H., Tanaka, K. et al. Hyperintense signal on diffusion-weighted imaging for monitoring the acute response and local recurrence after photodynamic therapy in malignant gliomas. J Neurooncol 155, 81–92 (2021). https://doi.org/10.1007/s11060-021-03845-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-021-03845-0

Keywords

Search

Navigation