Improvement in treatment results of glioblastoma over the last three decades and beneficial factors

Kawano, Hiroto; Hirano, Hirofumi; Yonezawa, Hajime; Yunoue, Shunji; Yatsushiro, Kazutaka; Ogita, Mikio; Hiraki, Yoshiyuki; Uchida, Hiroyuki; Habu, Mika; Shimizu, Fujio; Oyoshi, Tatsuki; Bakhtiar, Yuriz; Sugata, Sei; Yamahata, Hitoshi; Hanaya, Ryousuke; Tokimura, Hiroshi; Arita, Kazunori

doi:10.3109/02688697.2014.967750

Cited by 20 publications

(19 citation statements)

References 28 publications

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“…In our patient, the dose was reduced to maintain regular treatment, with a total of 108 TMZ cycles administered. The IDH1 mutation is a good prognostic factor in gliomas (10) and, in recent chemoradiotherapy treatments, its presence was associated with prolonged survival time of patients with malignant glioma, even those with glioblastoma (11). …”

Section: Discussionmentioning

confidence: 99%

Anaplastic astrocytoma cells not detectable on autopsy following long-term temozolomide treatment: A case report

Hirano

Kawahara

Niiro

et al. 2017

Molecular and Clinical Oncology

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We herein present an autopsy case of a glioma patient who received long-term treatment with temozolomide (TMZ). The patient, a 35-year-old man with a hypointense tumor of the left frontal lobe, without contrast enhancement following gadolinium (Gd) administration on T1-weighted images, underwent tumor removal surgery, after which the tumor was diagnosed as anaplastic astrocytoma. By the third round of surgery, the tumor had progressed to anaplastic astrocytoma with contrast enhancement following Gd administration, and the patient received 60 Gy of external beam radiotherapy and nimustine hydrochloride (ACNU)-based chemotherapy. After the fifth tumor removal surgery, TMZ was substituted with ACNU chemotherapy, which suppressed tumor progression. Following the 41st TMZ treatment, hemorrhage was observed in the residual tumor, and the hematoma had been replaced by a hemangioma. The hemangioma and surrounding brain tissue was removed during the sixth surgery. The patient survived for 14 years and 9 months after the initial surgery, but succumbed to hydrocephalus due to bleeding from hemangiomas. The histopathological specimens of the first to the sixth surgeries revealed mutant isocitrate dehydrogenase 1 (IDH1; R132H point mutation) and p53-positive tumor cells, but cells positive for the R132H mutation or p53 could not be detected by immunohistochemistry in the autopsy specimens of the brain after 108 courses of TMZ treatment. Mutant IDH1 (R132H) cells were also not detected in the autopsy specimens of the brain by polymerase chain reaction analysis.

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Section: Discussionmentioning

confidence: 99%

Anaplastic astrocytoma cells not detectable on autopsy following long-term temozolomide treatment: A case report

Hirano

Kawahara

Niiro

et al. 2017

Molecular and Clinical Oncology

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“…Between 2000 and 2015, which is the period during which our patients underwent surgery, the 5-aminolevulinic acid-induced fluorescence technique and intraoperative magnetic resonance imaging to identify residual tumor were introduced in our hospital. Thus, the resection rate improved over time (5). This made it difficult to compare the OS of all the patients with malignant glioma in the BEV era (June, 2013-present) with that of those in the pre-BEV era, as the resection rates differed significantly.…”

Section: Discussionmentioning

confidence: 99%

“…Limited resection was performed in 10-20% of the cases in a large series of malignant gliomas. The prognosis in these patients was reported to be rather poor (5,6). However, patients who had undergone biopsy or limited resection, referred to as a surgically nearly-naive population, may be an adequate cohort for elucidating the independent effect of BEV on OS, unaffected by the extent of surgical removal.…”

Section: Introductionmentioning

confidence: 99%

“…These phase III studies included patients undergoing surgical removal of varying extent. The extent of surgical removal of the tumor is well-known to strongly affect OS in glioblastoma (4)(5)(6). However, maximal surgical resection may be hindered by various factors, including patient age, physical condition, tumor location and extent, and multiplicity of the lesions.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of bevacizumab therapy for unresectable malignant glioma: A retrospective analysis

Yonezawa

Hirano

Uchida

et al. 2016

Molecular and Clinical Oncology

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Abstract. Bevacizumab (BEV), an inhibitor of vascular endothelial growth factor A, has been used for primary and recurrent malignant gliomas in Japan since June, 2013. Previous randomized controlled studies demonstrated that BEV prolonged the progression-free survival, but not the overall survival (OS) of patients with newly diagnosed glioblastoma. The aim of the present study was to elucidate the effect of BEV on the OS of patients with unresectable malignant gliomas. Of the 440 cases of malignant glioma initially treated in our institute between 2000 and 2015, 88 were not suitable for maximal resection due to patient age, physical condition, tumor location and extent, or the patient's wishes. Based on the biopsy results, the pathological diagnosis was glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglioma in 60, 19 and 9 patients, respectively. Kaplan-Meier and log-rank analyses were performed to investigate the effect of BEV on OS. OS was longer in the BEV group (n=24) compared with that in the non-BEV group [n=64; median survival time (MST), 566 vs. 243 days, respectively; hazard ratio (HR)=0.413; 95% confidence interval (CI): 0.216-0.787; P=0.003]. In the 41 patients who received temozolomide (TMZ) and radiotherapy and the 31 patients with glioblastoma who received TMZ and radiotherapy, OS was longer in the BEV group compared with that in the non-BEV group (MST, 568 vs. 334 days, HR=0.404, 95% CI: 0.175-0.933, P=0.016; and MST, 566 vs. 160 days, HR=0.253, 95% CI: 0.099-0.646, P=0.001, respectively). In the Cox hazard model analysis of 41 patients who underwent TMZ-based chemoradiotherapy after biopsy, the use of BEV was the strongest independent beneficial factor associated with prolonged OS (HR=0.101; P=0.0002). Our retrospective survey suggested that BEV prolongs the OS of patients with unresectable malignant gliomas. However, these results must be verified by a well-designed prospective randomized controlled trial.

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“…High average age of patients at primary glioblastoma onset, tumor location, its infiltrative nature and still insufficient understanding of the glioblastoma pathophysiology makes complete surgical removal of the GBM often impossible (11). However, due to novel therapeutic modalities the median survival rate has extended from 8-9 months to 15-16 months in the period from 2006 to 2010 (12). GBM are presumably originating from glial i.e., astrocyte cells.…”

Section: Aptamers In Gliomamentioning

confidence: 99%

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

Delač

Motaln

Ulrich³

et al. 2015

Cytometry Pt A

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Aptamers are short single-stranded nucleic acids (RNA or ssDNA), identified by an in vitro selection process, denominated SELEX, from a partially random oligonucleotide library. They bind to a molecular target, a protein or other complex macromolecular structures of interest with high affinity and specificity, comparable to those of antibodies. Recently, aptamer selection protocols were developed for targeting living cells, including tumors. Chemical modifications of the aptamers and modalities of their detection and delivery systems are already available with high selectivity and targeting ability for the desired cancer cell type, making them promising for diagnosis and therapy. Glioblastoma multiformae represents the most malignant and fatal stage of glioma, and is also the most frequent brain tumor. Glioblastoma-specific aptamers were developed by either targeting the whole cell surface or known glioma biomarkers. These aptamers may gain importance for imaging, tumor cell isolation from biopsies and drug delivery. In biomedical imaging techniques, aptamers coupled with radionuclide or fluorescent labels, bioconjugates and nanoparticles offer an advanced, noninvasive manner for defining the glioblastoma tissue border. Though single modality aptamer imaging probes have some limitations, these are overcome by the use of multimodal probes. Due to selectivity and chemical characteristics, aptamers can be coupled to functionalized nanoparticles and loaded with a drug, appeared promising for in vivo targeting of glioblastoma. Finally, aptamers are effective mediators for gene silencing when coupled to small interfering RNA and a viral vector, thus providing a novel tool with enhanced targeting capability in drug delivery, designed for tailored treatment of glioblastoma patients. V C 2015 International Society for Advancement of Cytometry Key terms aptamer; SELEX; cancer biomarkers; cell and target protein; imaging; drug delivery; glioblastoma; nanoparticles APTAMERS AND THE SELEX TECHNOLOGY IN CANCER APTAMERS, first introduced by Tuerk and Gold (1) and Ellington and Szostak (2), are short chains of DNA or RNA oligonucleotides that bind to small molecules, peptides, and macromolecules, such as proteins of various sizes and conformations. These are identified by an in vitro selection method in a stepwise evolutionary process from a combinatorial library of partial randomized oligonucleotides, consisting of up to 10 15 different sequences and secondary and tertiary structures by a method called SELEX (Systematic Evolution of Ligands by EXponential enrichment). It begins with a pool of variable oligonucleotide sequences with multiple rounds of target exposure of the combinatorial RNA or DNA library, followed by elution of target binders and enrichment of those by RT-PCR or PCR procedures are performed. These results in exponential increase of oligonucleotides with improved ligand to target binding in the previously combinatorial library, which finally is narrowed down to a homogeneous population of high-affinity...

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Improvement in treatment results of glioblastoma over the last three decades and beneficial factors

Abstract: We observed a gradual improvement in glioblastoma outcome, presumably because of improvements in therapeutic modalities for surgery, anticancer agents, and radiation, but the efficacy of CK-SRT remains unclear.

Cited by 20 publications

References 28 publications

Anaplastic astrocytoma cells not detectable on autopsy following long-term temozolomide treatment: A case report

Anaplastic astrocytoma cells not detectable on autopsy following long-term temozolomide treatment: A case report

Efficacy of bevacizumab therapy for unresectable malignant glioma: A retrospective analysis

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

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