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Noninvasive prediction of BRAF V600E mutation status of pleomorphic xanthoastrocytomas with MRI morphologic features and diffusion-weighted imaging

BMC Cancer volume 24, Article number: 1022 (2024) Cite this article

Abstract

Objectives

Seeking a noninvasive predictor for BRAF V600E mutation status of pleomorphic xanthoastrocytomas (PXAs) is essential for their prognoses and therapeutic use of BRAF inhibitors. We aimed to noninvasively diagnose BRAF V600E-mutated PXAs using MRI morphologic, DWI and clinical parameters.

Methods

The clinical findings, anatomical MRI characteristics, and diffusion parameters of 36 pathologically confirmed PXAs were retrospectively analyzed, and BRAF V600E-mutated (n = 16) and wild-type (n = 20) groups were compared. A binary logistic-regression analysis was performed, and a ROC curve was calculated to determine the independent predictors of BRAF V600E mutation status, diagnostic accuracy, and optimal cut-off value.

Results

A comparison of findings between groups showed that BRAF V600E-mutated PXAs were more frequent in children and young adults (≤ 35 years; P = 0.042) who often had histories of seizures (P = 0.004). Furthermore, BRAF V600E-mutated PXAs generally presented as solitary masses (P = 0.024), superficial locations with meningeal attachment (P < 0.001), predominantly cystic with mural nodules (P = 0.005), and had greater minimal ADC ratio (ADCratio) values of the tumor and peritumoral edema (P < 0.001). Binary logistic regression showed that age ≤ 35 years, solitary mass, superficial locations with meningeal attachment, and a greater minimal ADCratio of the tumor were independent predictors of BRAF V600E-mutated PXAs. The combination of all four independent predictors resulted in the highest sensitivity (100%) and specificity (90%), with AUC = 0.984.

Conclusion

The BRAF V600E mutation status of PXAs could be noninvasively predicted using clinical and MRI characteristics.

Critical relevance statement

The noninvasive diagnostic criteria for BRAF V600E-mutated PXAs could offer guidance for the administration of BRAF V600E mutation inhibitors in the future.

Key points

1. The relevant features of PXAs were analyzed according to BRAF V600E mutation status.

2. The BRAF V600E mutation status of PXAs can be accurately and noninvasively predicted.

3. The result can provide guidance for the administration of BRAF V600E mutation inhibitors.

Peer Review reports

Introduction

Pleomorphic xanthoastrocytoma (PXA) is a rare circumscribed astrocytic glioma, which was first reported by Kepes in 1979 [1]. The 2016 World Health Organization (WHO) recognized two distinct entities of PXAs based on histopathological characteristics: WHO grade II PXA and WHO grade III anaplastic PXA (APXA) with ≥ 5 mitoses/10 high-power fields (HPFs) [2]. Further, the fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS) (WHO CNS5) released in 2021 has designated PXAs as either WHO grade 2 or grade 3, instead of using the term “APXA” [3]. At the molecular level, the BRAF V600E mutation has emerged as a predominant feature of PXAs (60–78%) and has been added to the newest edition of the WHO guidelines [3, 4]. Notably, the clinical outcomes of PXAs are discouraging, with a recurrence rate of 30–92% after surgical resection with adjuvant treatment [5, 6].

Recently, considerable endeavours have been made to investigate the therapeutic use of BRAF inhibitors targeting BRAF V600E-mutated tumors, such as melanoma and Langerhans’ cell histiocytosis, which have exhibited satisfactory efficacy [7, 8]. Clinical trials have also shown that BRAF inhibitors used in BRAF V600E-mutated PXAs can offer clinical benefits and excellent radiological responses [9,10,11]. Therefore, BRAF V600E-targeted therapy could become a promising option for treating BRAF V600E-mutated PXA patients. Several studies have indeed considered this mutation as a favorable molecular prognosticator [12, 13]. This makes finding a more accurate and noninvasive predictor of BRAF V600E mutation status essential.

Researchers have assessed the values of anatomical MRI, diffusion-weighted imaging (DWI), and its derived apparent diffusion coefficient (ADC) in predicting the genetic features of certain brain tumors [14,15,16]. A recent study suggested that tumor properties, such as size, enhancement patterns, and ADC metrics, differ between BRAF subtypes of the 2016 WHO grade II PXA [17]. Additionally, patient age may help in diagnosis because it has been shown that BRAF V600E-mutated PXAs are more common in younger patients [13, 18]. Nonetheless, there are no studies investigating independent predictors of BRAF V600E-mutated PXAs.

In this study, according to the new 2021 WHO guidelines, we systematically analyzed clinical, pathological, and MRI features of PXAs based on BRAF V600E mutation status and tried to explore the noninvasive diagnostic criteria for BRAF V600E-mutated PXAs. The results could offer guidance for the administration of BRAF V600E mutation inhibitors in the future.

Materials and methods

Patient cohort

This study was approved by the Human Scientific Ethics Committee of the local hospital (No. 2019-KY-176). From January 2011 to August 2021, 60 patients with PXAs histopathologically according to 2016 WHO criteria received surgery at our hospital and the informed consents were obtained. Then, the histopathological evaluation was adapted to the new 2021 WHO guidelines. As shown in Fig. 1, the patient inclusion criteria were as follows: (1) known BRAF V600E status; (2) available preoperative MRI, including pre-contrast T1-weighted imaging (T1WI), contrast-enhanced T1WI (T1 + C), T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR) imaging, DWI, and corresponding ADC maps; and (3) no history of PXA treatment, including chemotherapy, radiotherapy, stereotactic biopsy, and surgery, before MRI examination. Exclusion criteria were as follows: (1) absence of any one of the preoperative MRI sequences, including T1WI, T1 + C, T2WI, FLAIR, DWI, and ADC; (2) insufficient image quality for analysis with significant artifacts; and (3) insufficient formalin-fixed and paraffin-embedded (FFPE) tumor tissues for analysis. The BRAF V600E mutation analysis was used the amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR), and the procedure is provided in the Supplementary A. Totally, 36 patients with PXAs were included.

Fig. 1
figure 1

Flowcharts of inclusion and exclusion criteria

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Image acquisition

We obtained all MR images on either 1.5 T or 3.0 T clinical MR scanners, including Siemens, Philips and GE Healthcare. The sequences included anatomical MRI (T1WI, T2WI, FLAIR, and T1 + C), and DWI. All DWI acquisitions used a spin echo single-shot echo-planar sequence with values of b = 0 and b = 1000 s/mm2. We generated the corresponding ADC maps using a monoexponential model on a voxel-by-voxel basis for all imaging planes on a dedicated workstation. Contrast-enhanced axial, sagittal, and coronal T1 + C images were acquired with the same parameters as pre-contrast T1WI after intravenous administration of a 0.1 mmol/kg dose of gadolinium-based contrast agent [Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), Bayer Healthcare, Leverkusen, Germany (n = 26), or Gadoteric Acid Meglumine Salt Injection, Hengrui Healthcare, Jiangsu, China (n = 10)]. Detailed information about the MR machines and imaging parameters are available in Supplementary B.

Evaluation criteria

Two experienced radiologists (J.Y. and C.P.G., each with more than 12 years of experience in neuroimaging) blinded to all clinical information and BRAF V600E mutation status analyzed the morphologic characteristics (number of tumors, location, size, superficial locations with meningeal attachment, ventricular involvement, degree of peritumoral edema, hemorrhage, necrosis, imaging pattern, and contrast enhancement) based on anatomical MRI, and diffusion parameters (diffusion characteristics, minimal ADC values, and ADCratio values of tumor and peritumoral edema) derived from DWI. Given that ADC values which were obtained from different magnetic field strengths and MR scanners might have introduced bias, it is essential to consider potential discrepancies. Additionally, the ADC value of the normal brain has been reported to change with age [19]. Therefore, the values were corrected by using standardized ADCratio values to facilitate data comparison and improve reliability. Specifically, we measured the minimal ADC values by placing at least six nonoverlapping regions of interest (ROIs) in the solid components of the tumors, avoiding cystic or necrotic parts, and we chose the lowest ADC value among several ROIs as the result. The minimal ADC value of ROIs was drawn in the peritumoral edema area. When no edema was observed, the ROI was set as the peritumoral region < 1 cm around the tumor. In three tumors with smaller solid components, only one ROI could be placed on the tumor. If there were multiple brain lesions, the largest that reflected diffusion-weighted findings for most PXAs lesions was selected as the target lesion to increase measurement accuracy. We placed six ROIs with the same dimensions on the normal contralateral thalamus to provide a reliable internal control, since the thalamus maintains its normal signal intensity on DWI even in cases of marked hydrocephalus [20, 21]. Finally, we calculated the ratios of tumor and peritumoral-edema minimal ADC values to the normal brain ADC value, which are called the minimal ADCratio values. The two radiologists (J.Y. and C.P.G.) collaborated on each patient’s MRI images via consensus reading. For controversial cases, another senior radiologist (J.L.C. with more than 33 years of experience in neuroimaging) reviewed the images and confirmed the conclusions. The details of morphologic assessment criteria are provided in Table 1.

Table 1 Imaging feature characterization and quantification using anatomical MRI and DWI
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Statistical analysis

We performed a Kolmogorov–Smirnov test to analyze whether continuous variables were normally distributed. All quantitative variables are presented as mean ± standard deviation (SD). We compared results between the BRAF V600E-mutated and wild-type (WT) groups using Fisher’s exact test for categorical variables and Student’s t-test for continuous variables. We performed a comparative analysis between the WHO grade 2 and 3 groups using Student’s t-test for continuous variables. We compared the strength of an association between two variables using Pearson’s correlation analysis. We compared the potential collinearity effects among the correlated predictor variables using collinearity analysis. A binary logistic-regression analysis was performed to determine independent predictors of BRAF V600E mutation status after adjusting for pathological grade. We assessed the optimal cut-off value of the minimal ADCratio using a receiver operating characteristic (ROC) curve. We used a four-fold table and the ROC curve to calculate diagnostic performances values, including sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CIs). Positive predictive value (PPV), negative predictive value (NPV), and Youden index (YI) were calculated per the corresponding formula. Statistical analyses were conducted using SPSS software version 21.0 (IBM Corp., Armonk, NY, USA). P < 0.05 (two-tailed) was considered statistically significant.

Results

Clinical and pathological findings

All clinical and pathological findings are summarized in Table 2. A total of 36 cases, aged 8 to 67 years, were included in the study, with 7 being children. In 16 of the 36 cases, tumor tissue exhibited BRAF V600E mutation; the other 20 were BRAF V600E-WT. BRAF V600E-mutated PXA patients tended to be children and young adults of ≤ 35 years (26 ± 13 vs. 43 ± 18 years; P < 0.05). There was no significant difference in sex between the two groups (P = 0.722). There was a significant inter-group difference in symptoms (P = 0.004): patients with BRAF V600E-mutated PXAs more often had histories of seizures. There was a statistically significant difference in the pathological grade between the two groups (P = 0.001). In the BRAF V600E-mutated group, 75% (12/16) of cases were pathologically classified as WHO grade 2, while in the BRAF V600E-WT group, 85% (17/20) of cases were classified as WHO grade 3.

Table 2 Clinical and pathological findings of PXAs stratified by BRAF V600E mutation status
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MRI characteristics

The MRI morphologic characteristics and diffusion parameters are summarized in Tables 3 and 4. BRAF V600E-mutated tumors were solitary lesions; all multiple lesions were found in the BRAF V600E-WT group (P = 0.024). Notably, 5 out of 6 multiple lesions in this group were classified as WHO grade 3. Solitary lesions were located in the cerebral hemisphere [BRAF V600E-mutated: n = 16 (Fig. 2); BRAF V600E-WT: n = 11 (Fig. 3)], thalamus (BRAF V600E-WT: n = 1), pineal gland (BRAF V600E-WT: n = 1), or cerebellum (BRAF V600E-WT: n = 1). Multiple lesions were located in the cerebral hemisphere (n = 4), cerebral hemisphere + ventricle (n = 1; Fig. 4), or cerebral hemisphere + thalamus (n = 1). Nine of the 16 BRAF V600E-mutated patients and 10 of the 20 BRAF V600E-WT patients had temporal-lobe involvement. Furthermore, 10 BRAF V600E-mutated cases (Fig. 2) and one BRAF V600E-WT case had superficial lesions with obvious meningeal contact, indicating that BRAF V600E-mutated PXAs tended to be superficial locations with meningeal attachment (P < 0.001). Neither ventricular involvement (P = 0.722) nor tumor size (P = 0.320) differed significantly between the two groups; nor did degree of peritumoral edema (P = 0.493), hemorrhage (P = 0.303), or necrosis of lesions (P = 0.637). There was, however, a significant inter-group difference in imaging patterns (P = 0.005): BRAF V600E-mutated PXAs tended to be predominantly cystic with mural nodules (Fig. 2). There was no significant difference in contrast enhancement of lesions’ solid components between the two groups (P = 0.109).

Table 3 MRI morphologic features of BRAF V600E-mutated and BRAF-WT PXAs
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Table 4 Differences of diffusion parameters between BRAF V600E-mutated and BRAF-WT PXAs
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Fig. 2
figure 2

T1WI (a), T2WI (b), FLAIR (c), T1 + C (d), DWI (e), ADC map (f), and histopathological photomicrograph (g) of BRAF V600E-mutated PXA. The solitary mass presented as predominantly cystic with a mural nodule attached to the meninges (d, e; red arrow), superficial on the right temporal-occipital lobe, with intense homogeneous enhancement (d; red arrow) and restricted diffusion of the mural nodule (e; red arrow). ROIs of the tumor parenchyma (red ring) and peritumoral edema (green ring) are placed in the lowest signal intensity on the ADC map (f). The case was pathologically confirmed WHO grade 2 PXA (g; H&E staining; ×400)

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Fig. 3
figure 3

T1WI (a), T2WI (b), FLAIR (c), T1 + C (d), DWI (e), ADC map (f), and histopathological photomicrograph (g) of BRAF V600E-WT PXA. The solitary mass presented as predominantly solid on the right temporal lobe, with intense homogeneous enhancement (d; red arrow) and restricted diffusion of the mural nodule (e; red arrow). ROIs of the tumor parenchyma (red ring) and the peritumoral region < 1 cm around the tumor (green ring) are placed in the lowest signal intensity on the ADC map (f). The case was pathologically confirmed WHO grade 3 PXA (g; H&E staining; ×400)

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Fig. 4
figure 4

T1WI (a), T2WI (b), FLAIR (c), T1 + C (d–f), DWI (g), ADC map (h) of BRAF V600E-WT PXA. The mass presented as multicentric, involving the right parietal lobe, parieto-occipital lobe, and trigone of right lateral ventricle (d-f; red arrow) and with restricted diffusion of the parietal lesion (g; red arrow). ROIs of the tumor parenchyma (red ring) and peritumoral edema (green ring) are placed in the lowest signal intensity on the ADC map (h)

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Notably, there was no significant difference in the occurrence of edema between the two groups (P = 0.637). Specifically, three cases of BRAF V600E-mutated PXAs and two WT cases did not exhibit edema. The minimal ADC value of ROIs was set within the peritumoral region, while the remaining cases were placed in the peritumoral edema area. Lesions did not significantly differ in diffusion characteristics between the two groups (P > 0.999). There was a significant inter-group difference in minimal ADC and ADCratio values of tumor and peritumoral edema (P < 0.001). As shown in in Supplemental Table S1, there was a significant inter-group difference in minimal ADC and ADCratio values of tumor and peritumoral edema between WHO grade 2 and grade 3 PXAs (P < 0.05).

Predictive factors

We found a correlation between the history of seizures and the superficial locations with meningeal attachment of tumors (R = 0.476, P = 0.003). There was no obvious collinearity among the related prediction variables [variance inflation factor (VIF) < 10]. The results are summarized in Supplemental Table S2.

To noninvasively predict the BRAF V600E mutation status of PXAs based on inter-group comparisons (Tables 2, 3 and 4), we incorporated differences of clinical parameters, morphologic characteristics, minimal ADCratio values of tumor and peritumoral edema, and pathological grade into the binary logistic regression. Results showed that younger age of onset (≤ 35 years), solitary mass, superficial locations with meningeal attachment, and a greater minimal ADCratio of the tumor were independent predictors of BRAF V600E mutation after adjusting for pathological grade. Based on the ROC analysis, the optimal cut-off point for minimal ADCratio of the tumor for predicting BRAF V600E mutation was 0.863, which provided the greatest sensitivity (100%) and specificity (65%).

Diagnostic performance of each independent predictor of BRAF V600E mutation status and of various combinations thereof is listed in Supplemental Table S3 Combining all four independent predictors resulted in the highest AUC at 0.984 (Fig. 5). Sensitivity, specificity, PPV, NPV, and YI were 100%, 90%, 88.9%, 100%, and 90%, respectively.

Fig. 5
figure 5

ROC curves for each of the independent predictors of BRAF V600E-mutated PXAs and each combination thereof. (a) Age ≤ 35 years (AUC = 0.694), (b) solitary mass (AUC = 0.650), (c) superficial locations with meningeal attachment (AUC = 0.788), (d) greater ADCratio of tumor (AUC = 0.850), and (e) combination of all four independent predictors (AUC = 0.984)

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Discussion

In the current study, we systematically investigated the clinical, morphologic, and diffusion features of BRAF V600E-mutated and WT PXAs according to the 2021 WHO standard. The results indicated significant differences between the two groups in seven signs: age, symptoms, number of lesions, superficial locations with meningeal attachment, imaging pattern, minimal ADCratio of tumor, and minimal ADCratio of edema. We also found a significant inter-group difference in pathological grade. More importantly, we found that age ≤ 35 years, solitary mass, superficial locations with meningeal attachment, and a greater minimal ADCratio of the tumor were independent predictors of BRAF V600E-mutated PXAs after adjusting for pathological grade. Of these, a minimal ADCratio of the tumor was most predictive with a threshold of 0.863, conferring the greatest sensitivity (100%) and specificity (65%). Notably, the combination of all independent predictors resulted in the largest AUC, 0.984, which could be considered reliable for noninvasive prediction of BRAF V600E mutation status.

Although PXAs can be encountered in all age groups (from infancy to the ninth decade of life) [20], our data showed that patients with BRAF V600E mutations were generally younger, which is in line with prior studies [13, 18]. In addition, age ≤ 35 years was associated with a greater likelihood of BRAF V600E mutation. Notably, previous studies have shown that age is an independent risk factor for the survival of PXAs, and a younger age is more strongly correlated with better prognosis [13, 22]. The most common manifestation of PXAs is a long history of seizures [5, 22], which was more prevalent (81.1%) in the BRAF V600E-mutated group in the present study. This suggests that seizures may be intimately associated with BRAF V600E-mutated PXAs. However, it should be noted that PXAs carrying the BRAF V600E mutation tend to be located in superficial locations. Previous reports have established that tumors with superficial locations preferentially involve cortical areas and are therefore likely to cause seizures [23, 24]. Thus, a possible explanation is that the higher frequency of seizures in our BRAF V600E-mutated group may have been caused indirectly by the tumor’s predilection for superficial locations. This speculation also resonated with our finding of a significant correlation between seizures and superficial locations in PXAs. The underlying mechanism remains unclear and warrants further investigation.

We analyzed morphologic descriptors measured on anatomical MRI and noted significant differences in characteristics between BRAF V600E-mutated and WT PXAs. First, the tumors had a predilection for the supratentorial cortex and superficial growth, with meningeal involvement [20, 25]; however, BRAF V600E-mutated PXAs were more likely to exhibit these characteristics. Although the findings were inconsistent with those reported by Huang et al., this may be because almost all PXAs showed a superficial location in their limited samples [17]. A relevant histopathological study indicated that cortical dysplasia may play a possible preneoplastic role in the subsequent development of PXAs [26]. This could also partly explain PXA’s preference for the supratentorial cortex. Additionally, there are two types of imaging patterns [25]: (1) a cystic mass containing a mural nodule and (2) a solid mass with or without cystic changes. In our study, BRAF V600E-mutated PXAs were more likely to be predominantly cystic with mural nodules, whereas BRAF V600E-WT PXAs tended to be solid masses. Moreover, our study demonstrated that BRAF V600E-mutated tumors tended to present as solitary lesions, whereas the BRAF V600E-WT group encompassed all occurrences of multiple lesions observed in the study. Additionally, multiple lesions were more often presented as WHO grade 3. A previous study also demonstrated that multicentricity should be considered an anaplastic phenotype in PXAs, suggesting that multicenter lesions are more aggressive than single lesion [27]. Overall, these results emphasize the strong association between certain MRI morphologic findings and BRAF mutation status.

We also discovered that the minimal ADCratio values of the tumor and peritumoral edema in the BRAF V600E-mutated group were greater than those in the BRAF V600E-WT group. The retrospective design of this study led to variations in magnetic field strengths and MRI scanners, potentially introducing bias into the ADC values. Thus, we utilized standardized ADCratios to enhance the reliability of our findings. Similar findings regarding ADC values of the tumor have been reported in the 2016 WHO grade II PXAs [17]. This might be due to markedly high cellularity and a high nuclear/cytoplasmic ratio in the BRAF V600E-WT PXAs. The ADC values of brain tumors are inversely related to cellularity and have shown capability of genotyping gliomas [15, 16, 28, 29]. Previous studies have consistently demonstrated that lower ADC values in tumors are associated with isocitrate dehydrogenase (IDH) WT gliomas and poor clinical outcomes [15, 16]. As observed in this study, minimal ADCratio values in the peritumoral area of BRAF V600E-mutated PXAs were greater, which mirrors a previous study on H3 K27M-mutated gliomas [29], indicating a lower cell density adjacent to the tumor area. This hypothesis was supported by Pavlisa et al., who demonstrated that ADC values of peritumoral tissue are inversely related to cellularity [30]. Furthermore, the minimal ADCratio values of the tumor and peritumoral edema in WHO grade 3 were found to be lower compared to those observed in WHO grade 2 PXAs. It was noted that WHO grade 3 PXAs were predominantly found in the WT group. This observation aligns with findings reported by Huang et al. [17]. Therefore, we hypothesize that the low ADC values in the WT group reflect WHO grade 3. Taken together, these findings suggest that minimal ADCratio values of the tumor and peritumoral edema could adequately reflect the biological and histological characteristics of PXAs.

More importantly, the binary logistic regression showed that age ≤ 35 years, solitary mass, superficial locations with meningeal attachment, and minimal ADCratio of the tumor were significant independent predictors of BRAF V600E-mutated status in PXAs. Of these, a minimal ADCratio threshold for tumors of 0.863 provided the greatest sensitivity and specificity in defining BRAF V600E-mutated PXAs and could be considered reliable for predicting BRAF V600E mutation status. This finding was in accordance with previously published results, also showing that the minimal ADCratio of tumors provided the largest AUC and thus was an accurate predictor of gene mutation status in gliomas [16, 29]. Combining all independent predictors resulted in the largest AUC of 0.984. Therefore, our study indicated that DWI might be a powerful tool for predicting BRAF V600E mutation in PXAs. Furthermore, when combined with anatomical-MRI findings and clinical characteristics, DWI had greater potential to noninvasively predict such mutations.

Limitations

We acknowledge several limitations to our study. First, it employed a retrospective design and single-center sampling. Further prospective studies of multicenter patient populations are needed. Second, it was limited by the small number of samples. Future prospective studies with expanded sample sizes are needed to confirm this diagnostic potential. Additionally, we obtained ADC values from different MR scanners, which might have introduced bias, although we have corrected for it by using a standardized ADCratio to improve reliability. It is advisable to implement an artificial intelligence algorithm for the analysis of differences in MRI scans in a larger-scale future study. Finally, due to the small sample size and insufficient follow-up time, this study offers no further survival analysis. The relationship between BRAF V600E status and outcomes should be considered in a larger future study.

Conclusion

Herein, by analyzing differences in clinical and MRI characteristics between BRAF V600E-mutated and BRAF V600E-WT patients with PXAs, we found that age ≤ 35 years, superficial locations with meningeal attachment, solitary mass, and a greater minimal ADCratio of the tumor were independent predictors of BRAF V600E-mutated PXAs. Moreover, combining all independent predictors could accurately predict the mutational status. These findings suggested that the BRAF V600E mutation status of PXAs could be noninvasively predicted using clinical and MRI characteristics with high specificity and sensitivity, therefore potentially offering guidance for therapeutic interventions.

Data availability

The major data and materials in this study are shown in the article or Supplementary Materials. Others are available from the corresponding author on reasonable request.

Abbreviations

PXA:

Polymorphic xanthoastrocytoma

WHO:

World Health Organization

APXA:

Anaplastic PXA

HPF:

High-power field

CNS:

Central Nervous System

DWI:

Diffusion-weighted imaging

ADC:

Apparent diffusion coefficient

T1WI:

T1-weighted imaging

T1 + C:

Contrast-enhanced T1WI

T2WI:

T2-weighted imaging

FLAIR:

Fluid-attenuated inversion recovery imaging

FFPE:

Formalin-fixed and paraffin-embedded

ARMS:

Amplification refractory mutation system

PCR:

Polymerase chain reaction

Gd-DTPA:

Gadolinium-diethylenetriamine pentaacetic acid

SD:

Standard deviation

ROC:

Receiver operating characteristic area

WT:

Wild-type

AUC:

Receiver operating characteristic area under the curve

CI:

Confidence interval

PPV:

Positive predictive value

NPV:

Negative predictive value

YI:

Youden index

VIF:

Variance inflation factor

IDH:

Isocitrate dehydrogenase

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Acknowledgements

We thank all authors, reviewers, and editor for their critical discussion of this manuscript and apologize to those not mentioned due to space limitations.

Funding

This work was supported by the National Natural Science Foundation of China (grant number 82102149), the Excellent Youth Talent Cultivation Program of Innovation in Health Science and Technology of Henan Province (grant number YXKC2022061), the Key Program of Medical Science and Technique Foundation of Henan Province (grant number SBGJ202002062), the Guangdong Basic and Applied Basic Research Foundation (grant number 2019A1515011143).

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Author notes

  1. Jing Yan and Cuiping Guo contributed equally to this work.

Authors and Affiliations

  1. Department of MRI, The First Affiliated Hospital of Zhengzhou University, Jianshe Dong Road 1, Zhengzhou, Henan Province, 450052, China

    Jing Yan, Hongwei Zheng, Yinhua Li, Mengjiao Duan, Chaoli Zhang & Jingliang Cheng

  2. Department of Radiology, Children’s Hospital of Hangzhou, 195 Wenhui Road, Hangzhou, Zhejiang Province, 310014, China

    Cuiping Guo

  3. Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Jianshe Dong Road 1, Zhengzhou, Henan Province, 450052, China

    Li Cui

  4. Department of Medical Imaging, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong Province, 510060, China

    Xiaofei Lv & Gui Fu

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  1. Jing Yan
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Contributions

Writing original draft: J Yan, CP Guo. Conceptualization: J Yan, XF Lv, G Fu, JL Cheng. Formal analysis: J Yan, CP Guo. Data processing: J Yan, CP Guo, HW Zheng, YH Li, MJ Duan, CL Zhang. Resources: J Yan, L Cui, HW Zheng, YH Li, MJ Duan, CL Zhang. Review and editing: G Fu, JL Cheng. All authors approved the final version of the manuscript. All authors are accountable for accuracy and integrity of the article.

Corresponding authors

Correspondence to Gui Fu or Jingliang Cheng.

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This research is approval by the Human Scientific Ethics Committee of the First Affiliated Hospital of Zhengzhou University (approval number: 2019-KY-176).

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Yan, J., Guo, C., Zheng, H. et al. Noninvasive prediction of BRAF V600E mutation status of pleomorphic xanthoastrocytomas with MRI morphologic features and diffusion-weighted imaging. BMC Cancer 24, 1022 (2024). https://doi.org/10.1186/s12885-024-12713-9

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BMC Cancer

ISSN: 1471-2407

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