• Users Online: 189
  • Print this page
  • Email this page

Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 1-7

Role of surgery in recurrent high-grade glioma: Current evidence

Department of Neurosurgery, NIMHANS, Bengaluru, Karnataka, India

Date of Submission21-Apr-2020
Date of Acceptance04-Jun-2020
Date of Web Publication2-Jul-2020

Correspondence Address:
Dr. Arivazhagan Arimappamagan
Department of Neurosurgery, NIMHANS, Bengaluru - 560 038, Karnataka
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJNO.IJNO_7_20

Rights and Permissions

While the management protocol for de novo glioblastoma is well established, the role of surgery in recurrent high-grade glioma (HGG) is not yet clear. In the light of recent developments in radio and chemotherapy modalities, it has become essential to recognize true disease progression from its mimics. This article discusses the recent literature on the challenges in identifying recurrence in HGG, modalities to diagnose, indications for surgery, and the outcomes in contemporary studies. The factors identified in prognostication have been discussed.

Keywords: Glioblastoma, high grade, pseudoprogression, recurrence, surgery, treatment effect

How to cite this article:
Yeole U, Arimappamagan A. Role of surgery in recurrent high-grade glioma: Current evidence. Int J Neurooncol 2020;3:1-7

How to cite this URL:
Yeole U, Arimappamagan A. Role of surgery in recurrent high-grade glioma: Current evidence. Int J Neurooncol [serial online] 2020 [cited 2022 Dec 9];3:1-7. Available from: https://www.Internationaljneurooncology.com/text.asp?2020/3/1/1/288794

  Introduction Top

High-grade gliomas (HGGs) are the most common primary malignant tumors of the brain in adults.[1],[2],[3] With the evolution in the technology of neurosurgery, neuro-anesthesia and various adjuvant therapies, a significant improvement has occurred in the ways these tumors could be resected safely and completely. Awake surgery, intraoperative mapping of various functions, functional magnetic resonance imaging (MRI), and other investigations have improved the safety of resection. On the other hand, neuronavigation, use of intraoperative ultrasonography, intraoperative MRI and fluorescent guided resections have enabled the surgeon to push the extent of resection further. The standard of treatment currently practiced for primary HGG is very well established and includes maximal safe resection followed by radiotherapy (RT) 60 Gy (1.8 Gy/fraction for 33 fractions) with temozolomide 75 mg/m 2 followed by 6 cycles of Temozolomide at a dose of 150–200 mg/m 2 for 5 days every 28 days. Stupp et al. in 2002 achieved a median survival of 12–15 months with 2 years survival of 31%.[4] The ultimate aim of treatment is not only to improve overall survival but also to maintain the quality of life.

Unfortunately, recurrence is the rule in HGG. The time to recur may vary based on the grade of the tumor, molecular profile, etc. As mentioned above, the standard of care for de novo HGG is very well established and followed worldwide. The factors which influence survival in primary HGG are well studied, which include age, Karnofsky performance score, extent of resection, etc., Similarly, the molecular characteristics, namely O6-methyl guanine-methyl transferase methylation, isocitrate dehydrogenase (IDH) mutation status of HGG have been identified as prognostic factors in primary HGG. On the contrary, the clinical decision making in the setting of recurrent HGG is not clear.

The unfavorable outcomes in HGG are mainly due to a high propensity for recurrence. Most of the recurrences occur within 7–9 months after completion of treatment.[5],[6],[7] There are no standardized treatment strategies for recurrent HGG. The management of recurrent high-grade glioma raises two pertinent points, which will be discussed in this article. First, how is the recurrence defined or diagnosed in the current treatment scenario. Second, when and why surgery is indicated in these recurrent HGG? The article does not cover the literature on adjuvant RT/chemotherapy and alternate therapies, which are considered in the recurrent setting.

  How is a Recurrent Tumor Diagnosed? Top

The high-grade gliomas are most often contrast-enhancing lesions, and therefore, even the volume measurement of these tumors was performed by measuring the enhancing lesion in 2 or three dimensions. Similarly, recurrence or progression of disease was defined as an increase in the size of lesion, primarily contrast-enhancing component by 25% or more, as per McDonald's criteria. However, the introduction of RT resulted in the phenomenon of radiation necrosis, which can result in lesions, which enhance with contrast, incite perilesional edema and can cause mass effect. They occur usually 3–12 months after RT; however, it has been noted to occur up to several years following therapy. This resulted in the development of many techniques to differentiate tumor recurrence and radiation necrosis. To make the matters more complex, the last decade has witnessed two other phenomena.

When patients with HGG are treated with temozolomide chemotherapy, the contrast-enhancing lesion sometimes increases in size during follow-up. Such changes are noted in 10-40% of patients in various series. In most cases, they may not be associated with clinical deterioration or mild symptoms, not reflecting the imaging features. This phenomenon has been called pseudoprogression. Most cases occur around three months of completing the chemoradiation therapy, while the exact mechanism for this phenomenon remains unclear.[8],[9]

Similarly, patients who have been treated with anti-angiogenic therapies like bevacizumab demonstrate that the contrast enhancement in the lesion decreases or disappears at follow-up. Such changes have been noted in 28–63% of patients treated with bevacizumab, while around 50% of patients treated with cediranib. However, this reduction in contrast-enhancing lesion does not translate to improvement in overall survival. This phenomenon is called pseudoresponse, which occurs more likely due to changes in vascular permeability following anti-angiogenic therapy.[10],[11],[12] Moreover, it has been noted that the non-enhancing component can increase significantly in patients on treatment with anti-angiogenic therapy.

All three processes, namely, radiation necrosis, pseudoprogression, and pseudoresponse can be collectively called as treatment effect, and this must be differentiated from true tumor recurrence.

Investigations to diagnose tumor recurrence

The modified RANO criteria for the assessment of tumor response in glioblastoma (GBM) in 2017 has proposed some important changes in the assessment. It proposed that post-radiation MRI imaging be taken as a baseline for the evaluation of disease progression, with the most important justification being the highly unpredictable, transient radiographic changes that often accompany the initial chemoradiation phase. In addition, the criteria have only considered the measured tumor volume in contrast-enhanced MRI scans to define the progression of the disease. A detailed description of modified RANO guidelines is out of the scope of this article and can be obtained in the publication.[13]

Notwithstanding the lack of utility of advanced imaging technologies in defining recurrence in RANO guidelines, significant research has occurred in the recent past, which helps us in this regard. The imaging technology can be broadly classified into advanced MRI sequences like MR spectroscopy, perfusion and diffusion studies, and metabolic imaging, which comprises positron emission tomography (PET) and single, photon emission computed tomography. Many authors have described the use of single/combined advanced MRI sequences in diagnosing recurrent tumor.[14] Proton magnetic resonance (MR) spectroscopy has been found to be useful in some studies,[15] while Steidl et al. noted that myoinositol could be a biomarker in recurrent GBM treated with bevacizumab.[16] However, Zhang et al., in their systematic review and meta-analysis of the available literature, emphasized clearly that MR spectroscopy alone can only be of moderate value in differentiating recurrence from treatment effect.[17] Many recent studies have noted that a combination of the techniques offers the highest accuracy in diagnosis. Liu et al. reported that arterial spin labeling (ASL) and amide proton transfer imaging techniques showed better diagnostic capability in distinguishing recurrent tumor from treatment effect compared to diffusion-weighted imaging (DWI) and Magnetic Resonance Spectroscopy sequences.[18]

Positron emission tomography has been used with various metabolites for differentiating tumor recurrence from radiation necrosis. The most common tracer used in PET imaging is fluorodeoxyglucose (FDG) PET. Recently, other tracers like O-(2-18 F-fluoroethyl)-L-tyrosine (FET) have been evaluated. Verger et al. noted that FET PET demonstrated a sensitivity of 80%, specificity 86%, accuracy 81% in differentiating recurrent disease from treatment-related effect. They also noted that 18F-FET PET was superior to perfusion-weighted imaging (PWI) in identifying recurrence.[19] In a systematic review to elucidate the diagnostic accuracy of various PET tracers, de Zwart et al. analyzed 39 studies involving 11 tracers. They showed that 18 F-FDG had sensitivity and specificity of 84%and 84%, respectively.8 F-FET had a sensitivity of 90% and specificity of 85%, respectively.11 C-MET demonstrated a sensitivity of 93% and specificity of 82%, respectively. They proposed that 18 F-FET and 11 C-MET should be preferred over FDG PET, as they demonstrated higher sensitivity and specificity in differentiating between tumor progression and treatment-related changes in HGG.[20] While metabolic imaging may be useful, it probably is not sufficient. Many authors have stressed the fact that multi-parametric imaging involving advanced MR sequences like DWI, PWI, ASL etc., in combination with metabolic imaging can provide the highest accuracy in diagnosing the recurrent glioma.[10],[21],[22]

Surgery for recurrent high grade glioma

Unlike de novo HGG, wherein surgical resection is the first management option, the role and need for surgery in recurrent setting are less clear. Once the dilemma of true progression of the disease versus treatment effect is settled based on the above discussion, the clinician is faced with the tough act of deciding the next course of action. The next step of management is dependent on a multitude of factors, some patient-related, and some treatment related. The management plan must be made with complete involvement of the patient and relatives, after carefully weighing the risk/benefits of each option, gains in overall survival and quality of life for the patient.

The decision for treatment after recurrence mostly depends on the expectation of the patient and family, because recurrence and the possible treatment is associated with greater morbidity and mortality.[23] The outcome in recurrent HGG depends on the type of treatment strategy adopted, and median survival varies from as low as a month [24] to >9 months [24],[25],[26] Various treatment options are considered for recurrent HGG based on the clinical and imaging conditions, namely re-surgery, RT, chemotherapy with TMZ or alternate combinations, anti-angiogenic therapy, etc., Various studies have noted that the incidence of re-surgery in patients with recurrent HGG ranges from 13 to 37%.[27],[28],[29]

  When is Surgery Considered? Top

Surgery can be considered when (1) the procedure can reasonably improve the quality of life of the patient (2) the procedure can reduce the raised intracranial pressure (3) the patient is in a better functional status (4) the procedure would not cause significant new neurological deficit or morbidity, precluding further adjuvant therapy. Furthermore, surgery is considered when the disease is focal and not involving deep structures or both hemispheres. The factors that improve the outcome after surgery have been identified in studies as younger age, better performance status, recurrence in non-eloquent region, WHO grade III tumors, extent of resection, and the interval between operations ≥6 months. The surgery can be effective if all of the above-mentioned factors co-exist, which rarely occurs.[25],[30],[31],[32]

The outcome is often variable and re-surgery involves additional morbidities like wound infection and dehiscence after immune-suppressing adjuvant therapies.[33] Hence, it becomes even more essential to establish the goal of treatment. The goals of surgery should be to relieve the mass effect due to recurrent tumor, to achieve radical resection,[34],[35],[36] which improves survival and also the overall effect of adjuvant therapy. It can also help establish further molecular markers for novel adjuvant therapies, immunotherapies, and prognostication.

Outcomes following surgery

Many retrospective studies have reported overall survival and PFS in cohorts of patients with recurrent HGG [25],[36],[37],[38],[39],[40] [Table 1].
Table 1: Studies showing the benefit of reoperation in recurrent high-grade gliomas

Click here to view

While many studies demonstrated the benefit of re-surgery in recurrent setting, some differed. Franceschi et al. noted that no significant effect of re-surgery was found, with age (P = 0.001), MGMT methylation (P = 0.002) and PFS at 6 months (P = 0.0001) being significant prognostic factors on multivariate analysis.[39] Two meta-analyses analyzed all the studies in contemporary literature to provide meaningful insight into the utility of surgery and the effect of other factors. Montemurro et al. reported the analyses of data from 19 studies on recurrent GBM. The data revealed that the median time from the second surgery until death from any cause was 9.7 months, and the median OS (duration from the time of diagnosis to death) was 18.5 months, respectively. Furthermore, they noted that 13 studies, which included 1017 patients, reported data regarding PFS, which was 9.2 months.[56] In a more recent analysis, Lu et al. analyzed eight observational studies and noted that re-surgery conferred a statistically significant survival compared with no surgery at recurrence in the pooled cohort (HR, 0.722; P < 0.001). Furthermore, newer studies trended toward a more superior prognostic advantage of repeat surgery compared with earlier studies (P = 0.012). The median PFS of the cohorts ranged from 5.6 to 11.2 months after primary treatment. From the available data, the median OS from primary diagnosis and recurrence ranged from 8.4 to 29 months and 4.7–11.4 months, respectively.[27]

Through their study, Park et al. tried establishing guidelines for considering reoperation. By using a set of prognostic factors, an NIH recurrent GBM Scale was developed. They considered a KPS of ≥70 and ependymal involvement and devised a scale with a total sum score of 0–2. Although this scoring system is not universally accepted because of the distinction of presumed eloquence based on tumor location. However, it can be useful objective criteria for counseling patients for reoperation.[43]

The major limitations of these studies are due to their retrospective nature, leading to selection bias. Patients who underwent reoperation for recurrent WHO grade III or IV gliomas may have had a survival benefit resulting from younger age, better neurological function, lack of medical comorbidities, and more aggressive adjuvant therapies.

Some authors analyzed the utility of re-surgery in the elderly at the time of recurrence.[38],[57] D' Amico RS et al. reported a cohort of pts with GBM >65 years. They either underwent biopsy, single surgery or resurgery when required, followed by adjuvant therapy. The median survival for the reoperation group, single-surgery group, and biopsy only group was 18.4, 8.9, and 3.4 months, respectively. The reoperation group had greater total survival than the single surgery group as a whole (log-rank P < 0.05; hazard ratio 2.078;95% confidence interval [CI] 1.348–3.203), and the single-surgery group had greater total survival than the biopsy group (log-rank P < 0.05; hazard ratio 2.626; 95% CI 1.941–3.552). However, the incidence of complications was noted to be 21.9%. The authors concluded that age alone need not be criteria for denying re-surgery.[57]

As can be seen, most of the data are retrospective, therefore the strength of inferences are modest. The effect of extent of resection in recurrent HGG is yet unclear. Montemurro et al. concluded that extent of resection at reoperation improves overall survival, even in patients with subtotal resection at the initial operation.[56] On the contrary, De Bonis et al. noted in their series that survival analysis showed no significant differences between patients receiving gross total (11 patients) or partial (22 patients) tumor resection (Breslow test, P = 0.20; log-rank test, P = 0.27; respective median OS, 10 months [CI 95%, 1–20] and 9 months [CI 95%, 4–14]).[44] Notwithstanding a randomized prospective data, it might be difficult to emphasize the influence of extent of resection. The analysis of the role of surgery and extent of resection of recurrent GBM, in DIRECTOR trial, which is a prospective trial analysing different dose regimes of TMZ, sheds some light on this issue.[58] Suchorska et al. published the role of re-surgery in patients who were a part of DIRECTOR trial recruited prospectively and followed up.[28] The analysis was performed on recurrent GBM patients who underwent complete resection (n = 40), incomplete resection (n = 19) or no surgery (n = 34). Though they belonged to one of the two arms of TMZ dose, since the original DIRECTOR trial demonstrated similar outcomes in both arms, this provided a good possibility to evaluate the role of other variables like re-surgery. Also, the incidence of re-surgery was 68% in this trial, as opposed to the range of 13%–37% in standard practice. The authors noted that patients, complete resection of contrast-enhancing tumor (n = 40) versus incomplete resection (n = 19) was associated with improved post recurrence survival (PRS) (12.9 months [95% CI: 11.5–18.2] vs. 6.5 months [95% CI: 3.6–9.9], P,.001) and better quality of life. Incomplete tumor resection was associated with inferior PRS compared with patients who did not undergo surgery (6.5 vs. 9.8 months, P = 0.052). However, it has to be noted that preoperative tumor volumes at recurrence were larger in patients with incomplete resection (P = 0.004), and tumors with incomplete resection were more often localized in eloquent regions (P = 0.178).[28]

Molecular markers like MGMT, 1p19q deletion, IDH mutation have been well established as prognostic factors in HGG. However, in the recurrent setting, their utility has not been demonstrated satisfactorily. Various studies have addressed this issue with mixed results.[39],[56],[59] Brandes et al. noted in their study that MGMT methylation status determined at first surgery had prognostic value; however, it was not predictive of outcome following the second surgery. They also noted that MGMT status at the time of the second surgery in patients with GBM is neither prognostic for OS nor for RFS after second surgery.[60]

  Conclusion Top

The present evidence suggests that surgery has a definite role in the setting of recurrence in HGG. Identification of true progression and differentiation from treatment-related changes is very important before considering surgical treatment. Multiparametric imaging, including molecular imaging, should be utilized in decision making routinely. The patient selection should be based on clinical factors, resectability of lesion, and the quality of life gains. Complete resection would significantly improve survival in recurrent GBM, when feasible and should be considered.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Surawicz TS, Davis F, Freels S, Laws ER Jr., Menck HR. Brain tumor survival: Results from the national cancer data base. J Neurooncol 1998;40:151-60.  Back to cited text no. 1
Deorah S, Lynch CF, Sibenaller ZA, Ryken TC. Trends in brain cancer incidence and survival in the United States: Surveillance, Epidemiology, and End Results Program, 1973 to 2001. Neurosurg Focus 2006;20:E1.  Back to cited text no. 2
DeAngelis LM. Brain tumors. N Engl J Med 2001;344:114-23.  Back to cited text no. 3
Stupp R, Dietrich PY, Kraljevic SO, Pica A, Maillard I, Maeder P, et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 2002;20:1375-82.  Back to cited text no. 4
Ammirati M, Galicich JH, Arbit E, Liao Y. Reoperation in the treatment of recurrent intracranial malignant gliomas. Neurosurgery 1987;21:607-14.  Back to cited text no. 5
Choucair AK, Levin VA, Gutin PH, Davis RL, Silver P, Edwards MS, et al. Development of multiple lesions during radiation therapy and chemotherapy in patients with gliomas. J Neurosurg 1986;65:654-8.  Back to cited text no. 6
Hou LC, Veeravagu A, Hsu AR, Tse VC. Recurrent glioblastoma multiforme: A review of natural history and management options. Neurosurg Focus 2006;20:E5.  Back to cited text no. 7
Knudsen-Baas KM, Moen G, Fluge Ø, Storstein A. Pseudoprogression in high-grade glioma. Acta Neurol Scand Suppl 2013;127:31-7.  Back to cited text no. 8
Kucharczyk MJ, Parpia S, Whitton A, Greenspoon JN. Evaluation of pseudoprogression in patients with glioblastoma. Neurooncol Pract 2017;4:120-34.  Back to cited text no. 9
Zikou A, Sioka C, Alexiou GA, Fotopoulos A, Voulgaris S, Argyropoulou MI. Radiation necrosis, pseudoprogression, pseudoresponse, and tumor recurrence: Imaging challenges for the evaluation of treated gliomas. Contrast Media Mol Imaging 2018;2018:1-6.  Back to cited text no. 10
Strauss SB, Meng A, Ebani EJ, Chiang GC. Imaging glioblastoma posttreatment: Progression, pseudoprogression, pseudoresponse, radiation necrosis. Radiol Clin North Am 2019;57:1199-216.  Back to cited text no. 11
Delgado-López PD, Riñones-Mena E, Corrales-García EM. Treatment-related changes in glioblastoma: A review on the controversies in response assessment criteria and the concepts of true progression, pseudoprogression, pseudoresponse and radionecrosis. Clin Transl Oncol 2018;20:939-53.  Back to cited text no. 12
Ellingson BM, Wen PY, Cloughesy TF. Modified criteria for radiographic response assessment in glioblastoma clinical trials. Neurotherapeutics 2017;14:307-20.  Back to cited text no. 13
Kazda T, Bulik M, Pospisil P, Lakomy R, Smrcka M, Slampa P, et al. Advanced MRI increases the diagnostic accuracy of recurrent glioblastoma: Single institution thresholds and validation of MR spectroscopy and diffusion weighted MR imaging. Neuroimage Clin 2016;11:316-21.  Back to cited text no. 14
Crain ID, Elias PS, Chapple K, Scheck AC, Karis JP, Preul MC. Improving the utility of 1 H-MRS for the differentiation of glioma recurrence from radiation necrosis. J Neurooncol 2017;133:97-105.  Back to cited text no. 15
Steidl E, Pilatus U, Hattingen E, Steinbach JP, Zanella F, Ronellenfitsch MW, et al. Myoinositol as a biomarker in recurrent glioblastoma treated with bevacizumab: A 1H-magnetic resonance spectroscopy study. PLoS One 2016;11:e0168113.  Back to cited text no. 16
Zhang H, Ma L, Wang Q, Zheng X, Wu C, Xu BN. Role of magnetic resonance spectroscopy for the differentiation of recurrent glioma from radiation necrosis: A systematic review and meta-analysis. Eur J Radiol 2014;83:2181-9.  Back to cited text no. 17
Liu J, Li C, Chen Y, Lv X, Lv Y, Zhou J, et al. Diagnostic performance of multiparametric MRI in the evaluation of treatment response in glioma patients at 3T. J Magn Reson Imaging 2020;51:1154-61.  Back to cited text no. 18
Verger A, Filss CP, Lohmann P, Stoffels G, Sabel M, Wittsack HJ, et al. Comparison of O-(2-18F-Fluoroethyl)-L-tyrosine positron emission tomography and perfusion-weighted magnetic resonance imaging in the diagnosis of patients with progressive and recurrent glioma: A hybrid positron emission tomography/magnetic resonance stud. World Neurosurg 2018;113:e727-37.  Back to cited text no. 19
de Zwart PL, van Dijken BRJ, Holtman GA, Stormezand GN, Dierckx RA, Jan van Laar P, et al. Diagnostic accuracy of PET tracers for the differentiation of tumor progression from treatment-related changes in high-grade glioma: A systematic review and metaanalysis. J Nucl Med 2020;61:498-504.  Back to cited text no. 20
Jena A, Taneja S, Jha A, Damesha NK, Negi P, Jadhav GK, et al. Multiparametric evaluation in differentiating glioma recurrence from treatment-induced necrosis using simultaneous 18 F-FDG-PET/MRI: A single-institution retrospective study. AJNR Am J Neuroradiol 2017;38:899-907.  Back to cited text no. 21
Pyka T, Hiob D, Preibisch C, Gempt J, Wiestler B, Schlegel J, et al. Diagnosis of glioma recurrence using multiparametric dynamic 18F-fluoroethyl-tyrosine PET-MRI. Eur J Radiol 2018;103:32-7.  Back to cited text no. 22
Nieder C, Grosu AL, Molls M. A comparison of treatment results for recurrent malignant gliomas. Cancer Treat Rev 2000;26:397-409.  Back to cited text no. 23
Park JK, Hodges T, Arko L, Shen M, Dello Iacono D, McNabb A, et al. Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol 2010;28:3838-43.  Back to cited text no. 24
Rusthoven KE, Olsen C, Franklin W, Kleinschmidt-DeMasters BK, Kavanagh BD, Gaspar LE, et al. Favorable prognosis in patients with high-grade glioma with radiation necrosis: The University of Colorado reoperation series. Int J Radiat Oncol Biol Phys 2011;81:211-7.  Back to cited text no. 25
Clark AJ, Lamborn KR, Butowski NA, Chang SM, Prados MD, Clarke JL, et al. Neurosurgical management and prognosis of patients with glioblastoma that progresses during bevacizumab treatment. Neurosurgery 2012;70:361-70.  Back to cited text no. 26
Lu VM, Jue TR, McDonald KL, Rovin RA. The survival effect of repeat surgery at glioblastoma recurrence and its trend: A systematic review and meta-analysis. World Neurosurg 2018;115:453-459.e3.  Back to cited text no. 27
Suchorska B, Weller M, Tabatabai G, Senft C, Hau P, Sabel MC, et al. Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma-results from the DIRECTOR trial. Neuro Oncol 2016;18:549-56.  Back to cited text no. 28
Nava F, Tramacere I, Fittipaldo A, Bruzzone MG, Dimeco F, Fariselli L, et al. Survival effect of first- and second-line treatments for patients with primary glioblastoma: A cohort study from a prospective registry, 1997-2010. Neuro Oncol 2014;16:719-27.  Back to cited text no. 29
Chang SM, Parney IF, McDermott M, Barker FG 2nd, Schmidt MH, Huang W, et al. Perioperative complications and neurological outcomes of first and second craniotomies among patients enrolled in the Glioma Outcome Project. J Neurosurg 2003;98:1175-81.  Back to cited text no. 30
Helseth R, Helseth E, Johannesen TB, Langberg CW, Lote K, Rønning P, et al. Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme. Acta Neurol Scand 2010;122:159-67.  Back to cited text no. 31
Terasaki M, Ogo E, Fukushima S, Sakata K, Miyagi N, Abe T, et al. Impact of combination therapy with repeat surgery and temozolomide for recurrent or progressive glioblastoma multiforme: A prospective trial. Surg Neurol 2007;68:250-4.  Back to cited text no. 32
Grossman SA, Ye X, Piantadosi S, Desideri S, Nabors LB, Rosenfeld M, et al. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res 2010;16:2443-9.  Back to cited text no. 33
McGirt MJ, Chaichana KL, Gathinji M, Attenello FJ, Than K, Olivi A, et al. Independent association of extent of resection with survival in patients with malignant brain astrocytoma: Clinical article. J Neurosurg 2009;110:156-62.  Back to cited text no. 34
Chaichana KL, Zadnik P, Weingart JD, Olivi A, Gallia GL, Blakeley J, et al. Multiple resections for patients with glioblastoma: Prolonging survival. J Neurosurg 2013;118:812-20.  Back to cited text no. 35
Woodworth GF, Garzon-Muvdi T, Ye X, Blakeley JO, Weingart JD, Burger PC. Histopathological correlates with survival in reoperated glioblastomas. J Neurooncol 2013;113:485-93.  Back to cited text no. 36
Pessina F, Navarria P, Cozzi L, Tomatis S, Riva M, Ascolese AM, et al. Role of surgical resection in recurrent glioblastoma: Prognostic factors and outcome evaluation in an observational study. J Neurooncol 2017;131:377-84.  Back to cited text no. 37
Hager J, Herrmann E, Kammerer S, Dinc N, Won SY, Senft C, et al. Impact of resection on overall survival of recurrent Glioblastoma in elderly patients. Clin Neurol Neurosurg 2018;174:21-5.  Back to cited text no. 38
Franceschi E, Bartolotti M, Tosoni A, Bartolini S, Sturiale C, Fioravanti A, et al. The effect of re-operation on survival in patients with recurrent glioblastoma. Anticancer Res 2015;35:1743-8.  Back to cited text no. 39
Azoulay M, Santos F, Shenouda G, Petrecca K, Oweida A, Guiot MC, et al. Benefit of re-operation and salvage therapies for recurrent glioblastoma multiforme: Results from a single institution. J Neurooncol 2017;132:419-26.  Back to cited text no. 40
Tugcu B, Postalci LS, Gunaldi O, Tanriverdi O, Akdemir H. Efficacy of clinical prognostic factors on survival in patients with glioblastoma. Turk Neurosurg 2010;20:117-25.  Back to cited text no. 41
Bloch O, Han SJ, Cha S, Sun MZ, Aghi MK, McDermott MW, et al. Impact of extent of resection for recurrent glioblastoma on overall survival: Clinical article. J Neurosurg 2012;117:1032-8.  Back to cited text no. 42
Park CK, Kim JH, Nam DH, Kim CY, Chung SB, Kim YH, et al. A practical scoring system to determine whether to proceed with surgical resection in recurrent glioblastoma. Neuro Oncol 2013;15:1096-101.  Back to cited text no. 43
De Bonis P, Fiorentino A, Anile C, Balducci M, Pompucci A, Chiesa S, et al. The impact of repeated surgery and adjuvant therapy on survival for patients with recurrent glioblastoma. Clin Neurol Neurosurg 2013;115:883-6.  Back to cited text no. 44
McNamara MG, Lwin Z, Jiang H, Templeton AJ, Zadeh G, Bernstein M, et al. 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 Neurooncol 2014;117:147-52.  Back to cited text no. 45
Oppenlander ME, Wolf AB, Snyder LA, Bina R, Wilson JR, Coons SW, et al. An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. J Neurosurg 2014;120:846-53.  Back to cited text no. 46
Sughrue ME, Sheean T, Bonney PA, Maurer AJ, Teo C. Aggressive repeat surgery for focally recurrent primary glioblastoma: Outcomes and theoretical framework. Neurosurg Focus 2015;38:E11.  Back to cited text no. 47
Ortega A, Sarmiento JM, Ly D, Nuño M, Mukherjee D, Black KL, et al. Multiple resections and survival of recurrent glioblastoma patients in the temozolomide era. J Clin Neurosci 2016;24:105-11.  Back to cited text no. 48
Brandes AA, Bartolotti M, Tosoni A, Poggi R, Bartolini S, Paccapelo A, et al. Patient outcomes following second surgery for recurrent glioblastoma. Future Oncol 2016;12:1039-44.  Back to cited text no. 49
Chen MW, Morsy AA, Liang S, Ng WH. Re-do craniotomy for recurrent grade IV glioblastomas: Impact and outcomes from the national neuroscience institute singapore. World Neurosurg 2016;87:439-45.  Back to cited text no. 50
Delgado-Fernandez J, Garcia-Pallero MÁ, Blasco G, Penanes JR, Gil-Simoes R, Pulido P, et al. Usefulness of reintervention in recurrent glioblastoma: An Indispensable Weapon for Increasing Survival. World Neurosurg 2017;108:610-7.  Back to cited text no. 51
Zanello M, Roux A, Ursu R, Peeters S, Bauchet L, Noel G, et al. Recurrent glioblastomas in the elderly after maximal first-line treatment: Does preserved overall condition warrant a maximal second-line treatment? J Neurooncol 2017;135:285-97.  Back to cited text no. 52
Wann A, Tully PA, Barnes EH, Lwin Z, Jeffree R, Drummond KJ, et al. Outcomes after second surgery for recurrent glioblastoma: A retrospective case-control study. J Neurooncol 2018;137:409-15.  Back to cited text no. 53
Salvati M, Pesce A, Palmieri M, Floriana Brunetto GM, Santoro A, Frati A. The role and real effect of an iterative surgical approach for the management of recurrent high-grade glioma: An observational analytic cohort study. World Neurosurg 2019;124:e480-8.  Back to cited text no. 54
Fariña Nuñez MT, Franco P, Cipriani D, Neidert N, Behringer SP, Mader I, et al. Resection of recurrent glioblastoma multiforme in elderly patients: a pseudo-randomized analysis revealed clinical benefit. J Neurooncol 2020;146:381-7.  Back to cited text no. 55
Montemurro N, Perrini P, Blanco MO, Vannozzi R. Second surgery for recurrent glioblastoma: A concise overview of the current literature. Clin Neurol Neurosurg 2016;142:60-4.  Back to cited text no. 56
D'Amico RS, Cloney MB, Sonabend AM, Zacharia B, Nazarian MN, Iwamoto FM, et al. The safety of surgery in elderly patients with primary and recurrent glioblastoma. World Neurosurg 2015;84:913-9.  Back to cited text no. 57
Weller M, Tabatabai G, Kästner B, Felsberg J, Steinbach JP, Wick A, et al. MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: The DIRECTOR trial. Clin Cancer Res 2015;21:2057-64.  Back to cited text no. 58
Quick J, Gessler F, Dützmann S, Hattingen E, Harter PN, Weise LM, et al. Benefit of tumor resection for recurrent glioblastoma. J Neurooncol 2014;117:365-72.  Back to cited text no. 59
Brandes AA, Franceschi E, Tosoni A, Bartolini S, Bacci A, Agati R, et al. O (6)-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: Clinical implications. Neuro Oncol 2010;12:283-8.  Back to cited text no. 60


  [Table 1]

This article has been cited by
1 High-dose salvage re-irradiation for recurrent/progressive adult diffuse glioma: healing or hurting?
T. Gupta,M. Maitre,P. Maitre,J. S. Goda,R. Krishnatry,A. Chatterjee,A. Moiyadi,P. Shetty,S. Epari,A. Sahay,V. Patil,R. Jalali
Clinical and Translational Oncology. 2021;
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
How is a Recurre...
When is Surgery ...
Article Tables

 Article Access Statistics
    PDF Downloaded358    
    Comments [Add]    
    Cited by others 1    

Recommend this journal