Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma: Recursive Partitioning Analysis of the EORTC 26981/22981-NCIC CE3 Phase III Randomized Trial

Mirimanoff, R.O.; Gorlia, Thierry; Mason, Warren P.; Bent, Martin J. van den; Kortmann, Rolf Dieter; Fisher, Barbara; Reni, Michele; Brandes, Alba A.; Curschmann, J.; Villà, Salvador; Cairncross, Gregory; Allgeier, Anouk; Lacombe, Denis; Stupp, Roger

doi:10.1200/jco.2005.04.5963

Cited by 450 publications

(314 citation statements)

References 25 publications

(23 reference statements)

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“…Patients with lowgrade astrocytoma have a survival average of 7 -10 years in contrast to our population, which showed a survival median of 3.4 years. In the same manner, patients with high-grade astrocytomas, treated with chemotherapy and concomitant radiotherapy and posteriorly with adjuvant temozolamide, have a median survival of 12.1 -14.6 months (Mirimanoff et al, 2006), in contrast to the patients in our study who displayed a median survival of 7 months. These disparities could be accounted for by: (1) the nature of the studies (observational vs controlled studies), and (2) differences in the treatment schema.…”

Section: Discussionsupporting

confidence: 54%

Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis

et al. 2008

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Astrocytomas develop intense vascular proliferation, essential for tumour growth and invasiveness. Angiotensin II (ANGII) was initially described as a vasoconstrictor; recent studies have shown its participation in cellular proliferation, vascularisation, and apoptosis. We conducted a prospective study to evaluate the expression of ANGII receptors -AT1 and AT2 -and their relationship with prognosis. We studied 133 tumours from patients with diagnosis of astrocytoma who underwent surgery from 1997 to 2002. AT1 and AT2 were expressed in 52 and 44% of the tumours, respectively, when determined by both reverse transcriptase -polymerase chain reaction and immunohistochemistry. Ten per cent of low-grade astrocytomas were positive for AT1, whereas grade III and IV astrocytomas were positive in 67% (Po0.001). AT2 receptors were positive in 17% of low-grade astrocytomas and in 53% of highgrade astrocytomas (P ¼ 0.01). AT1-positive tumours showed higher cellular proliferation and vascular density. Patients with AT1-positive tumours had a lower survival rate than those with AT1-negative (Po0.001). No association to survival was found for AT2 in the multivariate analysis. Expression of AT1 and AT2 is associated with high grade of malignancy, increased cellular proliferation, and angiogenesis, and is thus related to poor prognosis. These findings suggest that ANGII receptors might be potential therapeutic targets for high-grade astrocytomas.

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Section: Discussionsupporting

confidence: 54%

Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis

et al. 2008

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“…Randomization was performed centrally with the use of an interactive voice-response system, with stratification according to study region (Western Europe, Eastern Europe, Asia, United States, or other) and recursive partitioning analysis class (III, IV, or V). 23 (There are six recursive partitioning analysis classes, of which classes III, IV, V, and VI are used to categorize glioblastoma, with higher numbers representing a worse prognosis. Class VI patients were considered too frail to participate in this study.…”

Section: Randomization and Treatmentmentioning

confidence: 99%

Bevacizumab plus Radiotherapy–Temozolomide for Newly Diagnosed Glioblastoma

Chinot¹,

Wick²,

Mason³

et al. 2014

N Engl J Med

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Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. Medicine, http://dx.doi.org/10.1056/NEJMoa1308345 New England Journal ofAccess to the published version may require subscription. N.B. When citing this work, cite the original published paper. Permanent link to this version:http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-89503T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med 370;8 nejm

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“…Recent trials in newly diagnosed GBM patients have shown that addition of temozolomide concomitant with radiotherapy increased median survival to 14.6 months [39], the first meaningful increase in survival in this patient population in about 25 years. Even with this advance, there is an obvious need for further advances in brain tumor treatment, particularly because most classes of patients do not receive a significant increase in survival with the addition of temozolomide [40]. Furthermore, if the effect of temozolomide in combination with a targeted radionuclide agent is the same as observed with external beam radiation, then investigation of 211 At-labeled chimeric 81C6 plus temozolomide should be considered.…”

Section: Potential Impact On Clinical Outcomementioning

confidence: 99%

Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodies

Zalutsky

Reardon

Pozzi

et al. 2007

Nuclear Medicine and Biology

111

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An attractive feature of targeted radionuclide therapy is the ability to select radionuclides and targeting vehicles with characteristics that are best suited for a particular clinical application. One combination that has been receiving increasing attention is the use of monoclonal antibodies specifically reactive to receptors and antigens that are expressed on tumor cells to selectively deliver the α-particle emitting radiohalogen 211 At to malignant cell populations. Promising results have been obtained in preclinical models with multiple 211 At-labeled mAbs; however, translation of concept to the clinic has been slow. Impediments to this process include limited radionuclide availability, the need for suitable radiochemistry methods operant at high activity levels, and the lack of data concerning toxicity of α-particle emitters in humans. Nonetheless, two clinical trials have been initiated to date with 211 At-labeled monoclonal antibodies and others are planned for the near future.

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Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma: Recursive Partitioning Analysis of the EORTC 26981/22981-NCIC CE3 Phase III Randomized Trial

Abstract: RPA retains its prognostic significance overall as well as in patients receiving RT with or without TMZ for newly diagnosed GBM, particularly in classes III and IV.

Cited by 450 publications

References 25 publications

Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis

Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis

Bevacizumab plus Radiotherapy–Temozolomide for Newly Diagnosed Glioblastoma

Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodies

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