MR Imaging Characteristics Associate with Tumor-Associated Macrophages in Glioblastoma and Provide an Improved Signature for Survival Prognostication

Zhou, Jean; Reddy, M. V. Ramana; Wilson, Bev; Blair, D.A.; Taha, Ahmad; Frampton, Chris; Eiholzer, Ramona A; Gan, P.Y.C.; Ziad, Fouzia; Thotathil, Ziad; Kirs, Stenar; Hung, Noelyn; Royds, Janice A.; Slatter, Tania L.

doi:10.3174/ajnr.a5441

Cited by 31 publications

(41 citation statements)

References 39 publications

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“…Caponegro et al also described a correlation between the presence of TAMs and a poorest prognosis in GB (Caponegro et al, 2018). Furthermore, a study based on magnetic resonance imaging in GB showed that highly aggressive tumors were also correlated with the presence of TAMs (Zhou et al, 2018). Taking into account these findings, the presence of TAMs in GB has been well proven.…”

Section: The Presence Of Tams In Gb: Reality or Not?mentioning

confidence: 90%

Targeting Tumor Associated Macrophages to Overcome Conventional Treatment Resistance in Glioblastoma

et al. 2020

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Section: The Presence Of Tams In Gb: Reality or Not?mentioning

confidence: 90%

Targeting Tumor Associated Macrophages to Overcome Conventional Treatment Resistance in Glioblastoma

et al. 2020

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“…In osteosarcomas, there is no difference in the clinical outcome [35]. However, ALT is associated with a better patient outcome in glioblastoma [36]. Differential prognosis of ALT may rely on the different genetic and epigenetic events responsible for TMMs.…”

Section: Telomere Maintenance By Telomerase or Altmentioning

confidence: 99%

Alternative Lengthening of Telomeres (ALT) in Tumors and Pluripotent Stem Cells

Zhao

Feng

Liu

2019

Genes

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A telomere consists of repeated DNA sequences (TTAGGG)n as part of a nucleoprotein structure at the end of the linear chromosome, and their progressive shortening induces DNA damage response (DDR) that triggers cellular senescence. The telomere can be maintained by telomerase activity (TA) in the majority of cancer cells (particularly cancer stem cells) and pluripotent stem cells (PSCs), which exhibit unlimited self-proliferation. However, some cells, such as telomerase-deficient cancer cells, can add telomeric repeats by an alternative lengthening of the telomeres (ALT) pathway, showing telomere length heterogeneity. In this review, we focus on the mechanisms of the ALT pathway and potential clinical implications. We also discuss the characteristics of telomeres in PSCs, thereby shedding light on the therapeutic significance of telomere length regulation in age-related diseases and regenerative medicine.

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“…The tumor-associated imaging abnormality on our patients' pre-surgical MR images were segmented by trained individuals. From these segmentations, we calculate the volume of the imaging abnormality (mm 3 ). Every patient in this cohort has a "T1Gd volume", quantifying the size of the imaging abnormality on the presurgical T1Gd image that was closest to the date of surgery.…”

Section: Biomedical Imagingmentioning

confidence: 99%

“…Cystic fluid is typically isointense with cerebrospinal fluid (CSF) on T2 and FLAIR MRI and has a notably smooth texture. While these cysts are more common in lower grade gliomas (e.g., juvenile pilocytic astrocytoma, ganglioglioma) and non-glioma tumors with good prognosis (e.g., hemangioblastoma), between 7-23% of GBM tumors can also present with a dominant central cyst (rather than central necrosis) ( Figure 1B) [2,3]. We will refer to these as cystic GBMs and those without a significant cystic component as noncystic GBMs.…”

Section: Introductionmentioning

confidence: 99%

“…A smaller study of 7 cystic and 14 noncystic GBMs treated between 2000 and 2009 found that patients with cystic GBM lived significantly longer after surgery [5]. Another recent study of patients with GBM treated between 2004 and 2014 found a survival benefit for those with cystic GBM (41 cystic, 139 noncystic) [6]. However, two of the largest studies to date found no survival benefit associated with presenting with a cyst.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of Prognostic Value of Cystic Features in Glioblastoma Relative to Sex and Treatment with Standard-of-Care

Curtin

Whitmire

Rickertsen

et al. 2019

Preprint

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Glioblastoma (GBM) is the most aggressive primary brain tumor and can have cystic components, identifiable through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7-23% of GBMs and report mixed results regarding their prognostic impact. Using our retrospective cohort of 493 patients with first-diagnosis GBM, we carried out an exploratory analysis on this potential link between cystic GBM and survival. Using pretreatment MRIs, we manually identified 88 patients with GBM that had a significant cystic component at presentation and 405 patients that did not. Patients with cystic GBM had significantly longer overall survival and were significantly younger at presentation. Within patients who received the current standard of care (SOC) (N=184, 40 cystic), we did not observe a survival benefit of cystic GBM. Unexpectedly, we did not observe a significant survival benefit between this SOC cystic cohort and patients with cystic GBM diagnosed before the standard was established (N=40 with SOC, N=19 without SOC); this significant SOC benefit was clearly observed in patients with noncystic GBM (N=144 with SOC, N=111 without SOC). When stratified by sex, this significant survival benefit was only preserved in male patients (N=303, 47 cystic). We report differences in the absolute and relative sizes of imaging abnormalities on MRI and the prognostic implication of cysts based on sex. We discuss hypotheses for these differences, including the possibility that the presence of a cyst could indicate a less aggressive tumor.Methods: Using pretreatment MRIs, we manually identified 88 patients with GBM that had a significant cystic component at presentation. Results: Compared to patients with noncystic GBM (N=405), patients with cystic GBM had significantly longer overall survival and were significantly younger at presentation. However, among patients who received the current standard-of-care treatment, cystic GBM (N=40) was not significant for outcome. We also did not observe a significant survival benefit when comparing this standard-of-care cystic cohort to patients with cystic GBM diagnosed before the standard was established (N=19), but the analogous result for patients with noncystic GBM gives a sizeable benefit, as expected (N=144, N=111, respectively). We also report differences in the absolute and relative sizes of imaging abnormalities on MRI and the prognostic implication of cysts based on sex. Conclusion: Together, these results may explain later studies that note no significant survival benefit for patients with cystic GBM receiving current standard-of-care. We discuss hypotheses for these observed differences, including the possibility that the presence of a cyst could indicate a less aggressive tumor.

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MR Imaging Characteristics Associate with Tumor-Associated Macrophages in Glioblastoma and Provide an Improved Signature for Survival Prognostication

Abstract: BACKGROUND AND PURPOSE:In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determined whether routine MR imaging features could predict molecular subtypes of glioblastoma that differ in the content of tumorassociated macrophages.

Cited by 31 publications

References 39 publications

Targeting Tumor Associated Macrophages to Overcome Conventional Treatment Resistance in Glioblastoma

Targeting Tumor Associated Macrophages to Overcome Conventional Treatment Resistance in Glioblastoma

Alternative Lengthening of Telomeres (ALT) in Tumors and Pluripotent Stem Cells

Assessment of Prognostic Value of Cystic Features in Glioblastoma Relative to Sex and Treatment with Standard-of-Care

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