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Assessing the efficacy of repeat resections in recurrent glioblastoma: a systematic review

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Abstract

Background

The inevitable recurrence of glioblastoma (GBM) results in patients often undergoing multiple resections with questionable benefit to overall survival (OS).

Objective

To systematically review and analyze prior studies examining the potential added benefit of repeat resection (RR) in recurrent GBM.

Methods

We performed a PRISMA-compliant systematic review of literature published between 1969 to 2019 involving patients undergoing RR at GBM recurrence.

Results

The search yielded 3994 non-duplicate citations. Final abstraction included 43 articles, with 2 level II and 41 level III studies. The earliest paper we included was published in 1987 [1], and 35 identified papers (81.4%) were published within the last 10 years. The survival data of 9236 patients (55% male) were analyzed, with a median age of 56; 3726 patients underwent RR. In 31 studies with a comparable single-surgery-only cohort, 20 articles reported a statistically significant increase in OS with RR, 7 reported nonsignificant trends toward increased OS with RR, and 4 reported no significant increase in OS with RR. Twenty-two articles with multivariate analyses of Karnofsky performance scores and 17 articles with extent-of-resection reported these as significant prognostic factors of OS. In 26 studies, median OS among all patients was 17.85 months inclusive of median OS following RR totaling 9.6 months. Notably, in 10 studies with data on subsequent progressions (2+ recurrences), 6 studies reported significant increases in OS with subsequent repeat resection (sRR) compared to those not undergoing sRR.

Conclusions

Recurrent GBM presents a treatment challenge. There appears to be an OS benefit for RR upon first recurrence as well as sRR. Such findings warrant further investigation of the potential benefits of continued surgical intervention after subsequent progressions of GBM.

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References

  1. Ammirati M, Galicich JH, Arbit E, Liao Y (1987) Reoperation in the treatment of recurrent intracranial malignant gliomas. Neurosurgery. 21(5):607–614

    Article  CAS  PubMed  Google Scholar 

  2. DeAngelis LM (2001) Brain tumors. N Engl J Med 344(2):114–123

    Article  CAS  PubMed  Google Scholar 

  3. Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholtz-Sloan JS, Villano JL (2014) Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomark Prev 23(10):1985–1996

    Article  CAS  Google Scholar 

  4. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996

    Article  CAS  PubMed  Google Scholar 

  5. De la Garza-Ramos R, Kerezoudis P, Tamargo RJ, Brem H, Huang J, Bydon M (2016) Surgical complications following malignant brain tumor surgery: an analysis of 2002-2011 data. Clin Neurol Neurosurg 140:6–10

    Article  PubMed  Google Scholar 

  6. Solheim O, Selbekk T, Jakola AS, Unsgard G (2010) Ultrasound-guided operations in unselected high-grade gliomas--overall results, impact of image quality and patient selection. Acta Neurochir 152(11):1873–1886

    Article  PubMed  Google Scholar 

  7. Rutkowski M, Sankaran S (2019) Preoperative risk stratification of patient mortality following elective craniotomy; a comparative analysis of prediction algorithms. J Clin Neurosci 67:24–31

    Article  PubMed  Google Scholar 

  8. Chun S-J, Park S-H, Park C-K, Kim JW, Kim TM, Choi SH, Lee ST, Kim IH (2018) Survival gain with re-Op/RT for recurred high-grade gliomas depends upon risk groups. Radiother Oncol 128(2):254–259

    Article  PubMed  Google Scholar 

  9. Group OLoEW (2011) The Oxford 2011 Levels of Evidence. In: Oxford Centre for Evidence based Medicine

    Google Scholar 

  10. Daneyemez M, Gezen F, Canakci Z, Kahraman S (1999) Radical surgery and reoperation in supratentorial malignant glial tumors. Minim Invasive Neurosurg 41(4):209–213

    Article  Google Scholar 

  11. Barker FG II, Chang SM, Gutin PH, Malec MK, McDermott MW, Prados MD, Wilson CB (1998) Survival and functional status after resection of recurrent glioblastoma multiforme. Neurosurgery. 42(4):709–719

    Article  PubMed  Google Scholar 

  12. Boiardi A, Eoli M, Pozzi A, Salmaggi A, Broggi G, Silvani A (2000) Locally delivered chemotherapy and repeated surgery can improve survival in glioblastoma patients. Ital J Neurol Sci 20(1):43–48

    Article  Google Scholar 

  13. Azizi A, Black P, Miyamoto C, Croul SE (2001) Treatment of malignant astrocytomas with repetitive resections: a longitudinal study. Isr Med Assoc J 3(4):254–257

    CAS  PubMed  Google Scholar 

  14. Pinsker M, Lumenta C (2002) Experiences with reoperation on recurrent glioblastoma multiforme. Zentralbl Neurochir 62(2):43–47

    Article  Google Scholar 

  15. Terasaki M, Ogo E, Fukushima S, Sakata K, Miyagi N, Abe T, Shigemori M (2007) Impact of combination therapy with repeat surgery and temozolomide for recurrent or progressive glioblastoma multiforme: a prospective trial. Surg Neurol 68(3):250–254

    Article  PubMed  Google Scholar 

  16. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 339:b2700

    Article  PubMed  PubMed Central  Google Scholar 

  17. Helseth R, Helseth E, Johannesen TB, Langberg CW, Lote K, Rønning P, Scheie D, Vik A, Meling TR (2010) Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme. Acta Neurol Scand 122(3):159–167

    Article  CAS  PubMed  Google Scholar 

  18. Bloch O, Han S, Kaur G et al (2012) Extent of resection at repeat craniotomy for recurrent glioblastoma predicts overall survival. J Neurosurg 117(2):A426

    Google Scholar 

  19. De Bonis P, Fiorentino A, Anile C et al (2012) The impact of repeated surgery and adjuvant therapy on survival for patients with recurrent glioblastoma. Clin Neurol Neurosurg 115(7):883–886

    Article  PubMed  Google Scholar 

  20. Bekar A, Ozgur Taskapilioglu M, Morali Güler T, Aktas U, Tolunay S (2012) Effect of reoperation on survival of patients with glioblastoma. J Neurol Sci 29(1):110–116

    Google Scholar 

  21. Skeie BS, Enger PO, Brogger J et al (2012) gamma knife surgery versus reoperation for recurrent glioblastoma multiforme. World Neurosurg 78(6):658–669

    Article  PubMed  Google Scholar 

  22. Chaichana KL, Zadnik P, Weingart JD, Olivi A, Gallia GL, Blakeley J, Lim M, Brem H, Quiñones-Hinojosa A (2013) Multiple resections for patients with glioblastoma: prolonging survival clinical article. J Neurosurg 118(4):812–820

    Article  PubMed  Google Scholar 

  23. Hong B, Wiese B, Bremer M et al (2012) Multiple microsurgical resections for repeated recurrence of glioblastoma multiforme. Am J Clin Oncol 36(3):261–268

    Article  Google Scholar 

  24. Archavlis E, Tselis N, Birn G, Ulrich P, Baltas D, Zamboglou N (2013) Survival analysis of HDR brachytherapy versus reoperation versus temozolomide alone: a retrospective cohort analysis of recurrent glioblastoma multiforme. BMJ Open 3(3)

  25. De Cock L, Sala Q, Barrie M et al (2014) Patterns of care and outcome for patients with recurrent glioblastoma (GB). J Clin Oncol 32(15)

  26. McNamara MG, Lwin Z, Jiang H et al (2014) Factors impacting survival following second surgery in patients with glioblastoma in the temozolomide treatment era, incorporating neutrophil/lymphocyte ratio and time to first progression. J Neuro-Oncol 117(1):147–152

    Article  CAS  Google Scholar 

  27. Oppenlander ME, Wolf AB, Snyder LA, Bina R, Wilson JR, Coons SW, Ashby LS, Brachman D, Nakaji P, Porter RW, Smith KA, Spetzler RF, Sanai N (2014) An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity: Clinical article. J Neurosurg 120(4):846–853

    Article  PubMed  Google Scholar 

  28. Yong RL, Wu T, Mihatov N et al (2013) Re-operation for recurrent glioblastoma multiforme. Neuro-Oncology 15:iii224–iii225

    Article  CAS  Google Scholar 

  29. Quick J, Gessler F, Dutzmann S et al (2014) Benefit of tumor resection for recurrent glioblastoma. J Neuro-Oncol 117(2):365–372

    Article  CAS  Google Scholar 

  30. Ening G, Huynh MT, Schmieder K, Brenke C (2015) Repeat-surgery at glioblastoma recurrence, when and why to operate? Clin Neurol Neurosurg 136:89–94

    Article  PubMed  Google Scholar 

  31. Franceschi E, Bartolotti M, Tosoni A, Bartolini S, Sturiale C, Fioravanti A, Pozzati E, Galzio R, Talacchi A, Volpin L, Morandi L, Danieli D, Ermani M, Brandes AA (2015) The effect of re-operation on survival in patients with recurrent glioblastoma. Anticancer Res 35(3):1743–1748

    PubMed  Google Scholar 

  32. Kim HR, Kim KH, Kong DS, Seol HJ, Nam DH, Lim DH, Lee JI (2015) Outcome of salvage treatment for recurrent glioblastoma. J Clin Neurosci 22(3):468–473

    Article  PubMed  Google Scholar 

  33. Amini A, Altoos B, Karam SD, Waxweiler TV, Rusthoven CG, Gaspar LE, Honce JM, Damek DM, Ney DE, Ormond DR, Lillehei KO, Chen C, Kavanagh BD, Liu AK (2016) Outcomes of symptomatic compared to asymptomatic recurrences in patients with glioblastoma multiforme (GBM). J Radiat Oncol 5(1):33–39

    Article  Google Scholar 

  34. Sughrue ME, Sheean T, Bonney PA, Maurer AJ, Teo C (2015) Aggressive repeat surgery for focally recurrent primary glioblastoma: outcomes and theoretical framework. Neurosurg Focus 38(3):E11

    Article  PubMed  Google Scholar 

  35. Ortega A, Sarmiento JM, Ly D, Nuño M, Mukherjee D, Black KL, Patil CG (2016) Multiple resections and survival of recurrent glioblastoma patients in the temozolomide era. J Clin Neurosci 24:105–111

    Article  PubMed  Google Scholar 

  36. Woernle CM, Peus D, Hofer S et al (2015) Efficacy of surgery and further treatment of progressive glioblastoma. World Neurosurg 84(2):301–307

    Article  PubMed  Google Scholar 

  37. Perrini P, Gambacciani C, Weiss A et al (2016) Survival outcomes following repeat surgery for recurrent glioblastoma: a single-center retrospective analysis. J Neuro-Oncol 131(3):585–591

    Article  CAS  Google Scholar 

  38. Chen MW, Morsy AA, Liang S, Ng WH (2015) Re-do craniotomy for recurrent grade IV glioblastomas: impact and outcomes from the National Neuroscience Institute Singapore. World Neurosurg 87:439–445

    Article  PubMed  Google Scholar 

  39. Brandes AA, Bartolotti M, Tosoni A et al (2016) Patient outcomes following second surgery for recurrent glioblastoma. Future Oncol 12(8):1039–1044

    Article  CAS  PubMed  Google Scholar 

  40. Parakh S, Thursfield V, Cher L et al (2015) Recurrent glioblastoma: current patterns of care in an Australian population. J Clin Neurosci 24:78–82

    Article  PubMed  Google Scholar 

  41. Ringel F, Pape H, Sabel M, Krex D, Bock HC, Misch M, Weyerbrock A, Westermaier T, Senft C, Schucht P, Meyer B, Simon M, SN1 study group (2015) Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection. Neuro-Oncology 18(1):96–104

    Article  PubMed  PubMed Central  Google Scholar 

  42. 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(5):678–689

    Article  PubMed  Google Scholar 

  43. Gately L, McLachlan SA, Philip J, Ruben J, Dowling A (2017) Long-term survivors of glioblastoma: a closer look. J Neuro-Oncol 136(1):155–162

    Article  Google Scholar 

  44. Coburger J, Wirtz CR, Konig RW (2015) Impact of extent of resection and recurrent surgery on clinical outcome and overall survival in a consecutive series of 170 patients for glioblastoma in intraoperative high field magnetic resonance imaging. J Neurosurg Sci 61(3):233–244

    PubMed  Google Scholar 

  45. Delgado-Fernandez J, Garcia-Pallero MA, Blasco G, Penanes JR, Gil-Simoes R, Pulido P, Sola RG (2017) Usefulness of reintervention in recurrent glioblastoma: An Indispensable Weapon for Increasing Survival. World Neurosurg 108:610–617

    Article  PubMed  Google Scholar 

  46. 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 Neuro-Oncol 132(3):419–426

    Article  CAS  Google Scholar 

  47. van Linde ME, Brahm CG, de Witt Hamer PC, Reijneveld JC, Bruynzeel AME, Vandertop WP, van de Ven PM, Wagemakers M, van der Weide HL, Enting RH, Walenkamp AME, Verheul HMW (2017) Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis. J Neuro-Oncol 135(1):183–192

    Article  CAS  Google Scholar 

  48. Zanello M, Roux A, Ursu R et al (2017) Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment? J Neuro-Oncol 135(2):285–297

    Article  CAS  Google Scholar 

  49. Hager J, Herrmann E, Kammerer S, Dinc N, Won SY, Senft C, Seifert V, Marquardt G, Quick-Weller J (2018) Impact of resection on overall survival of recurrent glioblastoma in elderly patients. Clin Neurol Neurosurg 174:21–25

    Article  PubMed  Google Scholar 

  50. Goldman DA, Hovinga K, Reiner AS, Esquenazi Y, Tabar V, Panageas KS (2018) The relationship between repeat resection and overall survival in patients with glioblastoma: a time-dependent analysis. J Neurosurg 129(5):1231–1239

    Article  PubMed  PubMed Central  Google Scholar 

  51. Wann A, Tully P, Barnes L et al (2016) Outcomes of second surgery for recurrent glioblastoma multiforme: a retrospective case control study. Neuro-Oncology 18:vi192

    Article  Google Scholar 

  52. McGirt MJ, Chaichana KL, Gathinji M et al (2009) Independent association of extent of resection with survival in patients with malignant brain astrocytoma: Clinical article. J Neurosurg 110(1):156–162

    Article  PubMed  Google Scholar 

  53. Sastry RA, Shankar GM, Gerstner ER, Curry WT (2018) The impact of surgery on survival after progression of glioblastoma: A retrospective cohort analysis of a contemporary patient population. J Clin Neurosci 53:41–47

    Article  PubMed  Google Scholar 

  54. Harsh GR, Levin VA, Gutin PH, Seager M, Silver P, Wilson CB (1987) Reoperation for recurrent glioblastoma and anaplastic astrocytoma. Neurosurgery. 21(5):615–621

    Article  PubMed  Google Scholar 

  55. Lu VM, Jue TR, McDonald KL, Rovin RA (2018) The survival effect of repeat surgery at glioblastoma recurrence and its trend: a systematic review and meta-analysis. World Neurosurg 115:453–459.e453

    Article  PubMed  Google Scholar 

  56. 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 HG (2016) Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma-results from the DIRECTOR trial. Neuro-Oncology 18(4):549–556

    Article  PubMed  PubMed Central  Google Scholar 

  57. Nava F, Tramacere I, Fittipaldo A, Bruzzone MG, DiMeco F, Fariselli L, Finocchiaro G, Pollo B, Salmaggi A, Silvani A, Farinotti M, Filippini G (2014) Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 19972010. Neuro-Oncology. 16(5):719–727

    Article  PubMed  PubMed Central  Google Scholar 

  58. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131(6):803–820

    Article  PubMed  Google Scholar 

  59. Scheithauer BW, Fuller GN, VandenBerg SR (2008) The 2007 WHO classification of tumors of the nervous system: controversies in surgical neuropathology. Brain Pathol 18(3):307–316

    Article  PubMed  PubMed Central  Google Scholar 

  60. 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(2):190–198

    Article  CAS  PubMed  Google Scholar 

  61. Crooks V, Waller S, Smith T, Hahn T (1991) The use of Karnofsky performance scale in determining outcomes and risk in geriatric outpatients. J Gerontol 46(4):M139–M144

    Article  CAS  PubMed  Google Scholar 

  62. Schag CC, Heinrich RL, Ganz PA (1984) Karnofsky performance status revisited: reliability, validity, and guidelines. J Clin Oncol 2(3):187–193

    Article  CAS  PubMed  Google Scholar 

  63. Mariniello G, Peca C, De Caro MB, Giamundo A, Donzelli R, Maiuri F (2014) Glioblastoma in the elderly: the impact of advanced age on treatment and survival. J Neurol Surg A Central Eur Neurosurg 75(4):276–281

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, USA

    David Botros, Hayden Dux, Adham M. Khalafallah & Debraj Mukherjee

  2. Welch Medical Library, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Carrie Price

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  1. David Botros
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Correspondence to Debraj Mukherjee.

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Hayden Dux is currently seeking a B.S. degree

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Botros, D., Dux, H., Price, C. et al. Assessing the efficacy of repeat resections in recurrent glioblastoma: a systematic review. Neurosurg Rev 44, 1259–1271 (2021). https://doi.org/10.1007/s10143-020-01331-1

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