Recurrence Pattern After Temozolomide Concomitant With and Adjuvant to Radiotherapy in Newly Diagnosed Patients With Glioblastoma: Correlation With <i>MGMT</i> Promoter Methylation Status

Brandes, Alba A.; Tosoni, Alicia; Franceschi, Enrico; Sotti, Guido; Frezza, G.; Amistà, Pietro; Morandi, Luca; Spagnolli, F.; Ermani, Mario

doi:10.1200/jco.2008.19.4969

Cited by 347 publications

(303 citation statements)

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“…In several studies analyzing patients treated with radiation and temozolomide, 72% to 92% of recurrence was revealed as local relapse, 25,26 the most frequent pattern of glioblastoma recurrence. 6 Local control is also important for recurrent lesions, but treatment with SRS led to local progression in 65% to 90%, 14,[27][28][29] which was in line with our result with conventional SRS targeting only the gadolinium-enhanced area.…”

Section: Discussionmentioning

confidence: 99%

Extended field stereotactic radiosurgery for recurrent glioblastoma

Koga

Maruyama

Tanaka

et al. 2011

Cancer

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BACKGROUND: Stereotactic radiosurgery (SRS) is among the few therapeutic options for glioblastoma that recurs after standard radiation and chemotherapy, but its efficacy has been limited. METHODS: Since November 2007, the authors have modified the clinical target volume by adding a 0.5-to 1-cm margin to the gadolinium-enhanced area (extended field SRS), in contrast to conventional SRS using no margin to set the clinical target volume. A total of 35 recurred glioblastoma lesions in 9 patients were treated with conventional SRS between December 1990 and January 2007, and 14 lesions in 9 patients were treated with extended field SRS. RESULTS: The median follow-up periods were 7 months (range, 3-29 months) and 8 months (range, 6-27 months), respectively. The local control rate was 47% for conventional SRS and 93% for extended field SRS (P ¼ .0035), and the numbers of radiation necrosis observed in SRS-treated lesions were 2 and 4, respectively. The median overall survival from the diagnosis was 24 months (range, 14-57 months) for conventional SRS and 21 months (range, 15-51 months) for extended field SRS (statistically not significant). Seven patients treated with conventional SRS died during follow-up, 6 from progression of the SRS-treated tumor, whereas 7 patients treated with extended field SRS died during follow-up, 6 from remote intracerebral dissemination. CONCLUSIONS: Extended field SRS was superior to conventional SRS in the local control of small recurrent lesions of glioblastoma, although a further device to suppress remote dissemination may be necessary to increase survival. KEYWORDS: glioblastoma, glioma, gamma knife, stereotactic radiosurgery, radiation therapy, recurrence. INTRODUCTIONGlioblastoma is a highly malignant and aggressive tumor of the central nervous system that corresponds to grade IV of the World Health Organization histological classification. 1 The current standard treatment for glioblastoma is a maximal resection with functional preservation, followed by radiation and chemotherapy. When temozolomide is used for chemotherapy, the median survival is 14.6 months after initial presentation, 2 and ranges from 5 to 13 months after recurrence. 3,4 Because of the aggressive and invasive nature of the tumor, recurrence is seen in >90% of patients. 5 The most common pattern of recurrence is local regrowth 6 ; therefore, successful local control should lead to prolongation of patients' survival. Various local treatment strategies have been attempted, including repeated operations, conformal radiotherapy, brachytherapy, and local chemotherapy. 7 Although stereotactic radiosurgery (SRS) is an option as salvage treatment for recurrent glioblastoma in clinical settings, the role of SRS is still limited for glioma. SRS is useful in controlling relatively well-demarcated glioma such as ependymoma, pilocytic astrocytoma, and pleomorphic xanthoastrocytoma. [8][9][10][11][12][13] However, the majority of glioma is infiltrative to brain parenchyma and is difficult to target with SRS. A randomized controlle...

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Section: Discussionmentioning

confidence: 99%

Extended field stereotactic radiosurgery for recurrent glioblastoma

Koga

Maruyama

Tanaka

et al. 2011

Cancer

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“…In another series, MGMT promoter methylation was associated with an increased frequency of distant recurrences, defined as recurrences with ≤20% enhancing tumor residing inside the 95% isodose of the radiation field. 67 The best methodology to determine this clinically relevant point needs to be confirmed prospectively.…”

Section: Pseudoprogression Relapse Patterns and Mgmtmentioning

confidence: 99%

MGMT promoter methylation in malignant gliomas: ready for personalized medicine?

et al. 2009

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The DNA repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) antagonizes the genotoxic effects of alkylating agents. MGMT promoter methylation is the key mechanism of MGMT gene silencing and predicts a favorable outcome in patients with glioblastoma who are exposed to alkylating agent chemotherapy. This biomarker is on the verge of entering clinical decision-making and is currently used to stratify or even select glioblastoma patients for clinical trials. In other subtypes of glioma, such as anaplastic gliomas, the relevance of MGMT promoter methylation might extend beyond the prediction of chemosensitivity, and could reflect a distinct molecular profile.Here, we review the most commonly used assays for evaluation of MGMT status, outline the prerequisites for standardized tests, and evaluate reasons for difficulties in reproducibility. We critically discuss the prognostic and predictive value of MGMT silencing, reviewing trials in which patients with different types of glioma were treated with various chemotherapy schedules, either upfront or at recurrence. Standardization of MGMT testing requires comparison of different technologies across laboratories, and prospectively validated cut-off values for prognostic or predictive effects. Moreover, future clinical trials will need to determine, for each subtype of glioma, the degree to which MGMT promoter methylation is predictive or prognostic, and whether testing should become routine clinical practice.

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“…4,20,33,37,48) The progression of glioblastoma after treatment in up to 97% of cases occurs either from the bulk of the mass or within 20 mm from the border of its enhanced part identifiable on T 1 -weighted magnetic resonance (MR) imaging, and the presence of such local recurrence may be associated with impaired prognosis. 2,3,12,13,23,25,32,34,35,43,44,54) Therefore, various methods for improvement of tumor control at the time of both initial and salvage treatment have been proposed, such as inclusion of the marginal brain tissue in the high dose area during FRT, 4,17,20,26,31-33, 35,49,50) additional dose boost with stereotactic radiosurgery, 14,18,41) brachytherapy, 10,36,43) implantation of Gliadel wafers (Guilford Pharmaceuticals Inc., Baltimore, Maryland, USA), 53) or various types of intralesional immunotherapy. 7,42) The majority of studies on progression of intracranial gliomas after initial treatment have included many cases with incomplete surgical tumor removal.…”

Section: Introductionmentioning

confidence: 99%

“…management was encountered in 67% to 97% of cases (Table 3), 2,3,12,23,25,31,32,34,35,43,54) but comparison of different studies is difficult due to differences in treatment strategy, proportion of patients with total surgical tumor removal, postoperative surveillance, length of follow-up, as well as definition and categorization of the tumor progression. Nevertheless, aggressive resection of the neoplasm may…”

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confidence: 99%

“…Several previous studies found that local recurrence of glioblastoma was associated with impaired prognosis. 2,12,25,44) In particular, the median survival was 17.3, 14.8, and 26.1 months in patients with recurrence inside, at the margin, and outside the irradiation field. 2) In contrast, our 22 patients with regional or marginal progression of the tumor had significantly longer (p ＝ 0.04) OS compared to patients with distant or multiple recurrences.…”

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Patterns of Intracranial Glioblastoma Recurrence After Aggressive Surgical Resection and Adjuvant Management: Retrospective Analysis of 43 Cases

Konishi

Muragakı

Iseki

et al. 2012

Neurol. Med. Chir.(Tokyo)

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The present retrospective study evaluated the recurrence patterns after aggressive surgical removal of intracranial glioblastomas in 43 consecutive adult patients. The resection rate of the enhanced lesion on magnetic resonance imaging was 100% and 95-99% in 22 and 21 cases, respectively. All patients received postoperative fractionated radiotherapy (60 Gy in 30 fractions) with additional chemotherapy (25 cases) or vaccine therapy (18 cases). During follow-up (median 17 months), tumor recurrence was identified in 33 patients, most frequently regional within the wall of the resection cavity (20 cases). No clinical factor differed significantly between the groups of patients with regional or marginal tumor progression (N ＝ 22) and patients with distant or multiple recurrences (N ＝ 8). Progression-free survival did not differ significantly between these two groups (p ＝ 0.27). However, overall survival was significantly longer (p ＝ 0.04) in patients with regional or marginal tumor progression, and constituted 90% and 54% at 1 and 2 years after surgery, respectively, compared to 75% and 0% in patients with distant or multiple recurrences. Aggressive surgical resection and adjuvant management of intracranial glioblastoma may change its recurrence pattern. Tumor progression appears in the wall of the resection cavity or within 2 cm from its margin in approximately half of patients.

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Recurrence Pattern After Temozolomide Concomitant With and Adjuvant to Radiotherapy in Newly Diagnosed Patients With Glioblastoma: Correlation With MGMT Promoter Methylation Status

Abstract: After the administration of TMZ concomitant with and adjuvant to RT in patients with GBM, the pattern of, and time to, recurrence are strictly correlated with MGMT methylation status.

Cited by 347 publications

References 19 publications

Extended field stereotactic radiosurgery for recurrent glioblastoma

Extended field stereotactic radiosurgery for recurrent glioblastoma

MGMT promoter methylation in malignant gliomas: ready for personalized medicine?

Patterns of Intracranial Glioblastoma Recurrence After Aggressive Surgical Resection and Adjuvant Management: Retrospective Analysis of 43 Cases

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