Keywords brain tumors - neuroimaging - radiology
Introduction
Following the discovery of X-rays, there were a few reports of imaging being utilized
for the diagnosis and localization of brain tumors, although of very limited utility.[1 ] A major leap in the field of neuroimaging came with the invention of computed tomography
(CT).[1 ] In the 1980s, when it was recognized that nuclear magnetic resonance (MR) could
be applied to medical imaging, magnetic resonance imaging (MRI) was introduced.[2 ] MRI has become a cornerstone in neuroimaging, based on its capability to demonstrate
soft tissues, with exquisite detail. Advanced MRI sequences, along with modalities
like positron emission tomography (PET), can now further help us by demonstrating
the pathophysiological underpinnings of brain tumors and be useful for preoperative
planning.
Epidemiology, Clinical Presentation in India and Global
Epidemiology, Clinical Presentation in India and Global
The most common brain tumors seen in adults are extra-axial lesions like meningiomas,
intra-axial lesions like gliomas, and pituitary gland tumors.[3 ] A published meta-analysis on primary brain tumors has estimated the worldwide incidence
rates to be 10.82 per 1,00,000 person-years.[4 ] Primary brain tumors are a very heterogeneous group with the incidence and prevalence
rates differing across tumor types. According to Porter et al, in the United States,
the highest incidence was for gliomas and meningiomas, measuring 6 per 1,00,000 person-years
for each.[5 ] The overall incidence of brain and spinal cord tumors is 5 to 10 per 1,00,000 in
India.[6 ] The majority (38.7%) of these lesions were astrocytomas.[6 ]
Clinically, presenting symptoms may be related to lesion localization. Examples include
focal seizures, sensory impairment, motor weakness, ataxia and cognitive disturbances
or personality changes.[7 ] Symptoms may also be generalized and nonspecific like headaches with vomiting, which
may point toward the underlying raised intracranial pressure.[7 ] Visual disturbances may occur either due to the former or the latter.
Clinical and Diagnostic Workup Excluding Imaging
Clinical and Diagnostic Workup Excluding Imaging
On clinical suspicion of a brain tumor, the primary investigative workup focuses on
imaging.[8 ] When the patient presents with a headache, a fundoscopy may be performed to look
for papilledema, which could be a sign of raised intracranial tension due to a brain
tumor. When a seizure is an initial presentation, electroencephalography is usually
performed.[8 ] Further, cerebrospinal fluid (CSF) markers based on the tumoral genetic material
and proteins like circulating tumor DNA and microRNA have been shown to aid in brain
tumor diagnosis.[9 ]
Obtaining a tissue sample after the identification of a brain tumor on imaging is
crucial for confirming the diagnosis and planning further treatment.[8 ] This importance is even more in the era of molecular diagnostics, where genotyping
is necessary for accurate prognostication.[8 ]
[10 ] The tissue sample is usually obtained by biopsy or upfront surgery.[8 ] Stereotactic biopsy has a low risk of morbidity and a good sampling rate with higher
chances of an accurate tissue diagnosis.[8 ]
[11 ] The genetic makeup of glioma may be identified by methods like DNA sequencing or
cheaper, more widely available alternatives like immunohistochemistry (IHC).[12 ] The diagnosis and classification of a brain tumor should be based on the World Health
Organization (WHO) 2021 classification system.[13 ]
Recommendations
The diagnostic modality of choice on clinical suspicion of a brain tumor is contrast-enhanced
MRI.[8 ]
The tissue sample from a diffuse infiltrative glioma is to be routinely subjected
to IHC for the detection of Isocitrate Dehydrogenase (IDH) 1 R132H mutant protein
and alpha-thalassemia mental retardation X-linked (ATRX) nuclear expression.[8 ]
When IDH1 mutation is not detected by IHC, DNA sequencing must be performed for the
detection of IDH1 or IDH2 mutations in all diffuse astrocytomas and oligodendrogliomas.
It should also be done in patients less than 55 years old with glioblastomas.[8 ]
[14 ]
All IDH-mutant gliomas should be tested for 1p/19q codeletion status when there is
ATRX retention.[8 ]
[15 ]
IDH-mutant astrocytomas must be interrogated for cyclin dependent kinase inhibitor
(CDKN) 2A/B homozygous deletions.[8 ]
[15 ]
To label an IDH-wild diffuse glioma as a glioblastoma, testing should be done for
a gain of chromosome 7 with a loss of chromosome 10, epidermal growth factor receptor
amplification and telomerase reverse transcriptase promoter mutation when there is
an absence of microvascular proliferation and necrosis.[8 ]
[15 ]
In diffuse midline gliomas, testing should be done for Lys27Met mutations in histone
3 genes (H3K27M) mutation.[8 ]
Imaging
Current recommendations for brain tumor MRI protocol include the following sequences:
2D T1-weighted imaging (T1WI), fluid-attenuated inversion recovery (FLAIR) 2D axials,
axial susceptibility-weighted imaging (SWI), DWI 2D axials, 3D T1 postcontrast. Advanced
imaging includes dynamic susceptibility (T2*) and dynamic contrast enhancement (T1)
perfusion-weighted imaging (PWI), magnetic resonance spectroscopy (MRS), diffusion
tensor imaging (DTI), and functional MRI (fMRI). Similarly, 3D T2WI and 3D postcontrast
T1W spoiled gradient recalled imaging are useful for neuronavigation/presurgical biopsy
planning.
Standard MRI brain tumor protocol is required to reduce the quantitative and qualitative
differences due to different protocols followed at various institutes.
[Table 1 ] gives an overview of the adult brain tumor protocol followed at our institute.
Table 1
Brain tumor protocol parameters
MR sequence
TE
TR
TI
FOV
Matrix
Slice thickness
Flip angle
2D axial T1 precontrast
20 milliseconds
2,200 milliseconds
NA
240 mm
320 × 256
3 mm
10–15 degrees
2D axial and sagittal T2WI
120 milliseconds
>2,600 milliseconds
NA
240 mm
480 × 480
3 mm
90 degrees
2D axial FLAIR
120 milliseconds
>6,500 milliseconds
2400 milliseconds
240 mm
320 × 256
3 mm
90 degrees
2D axial DWI (b = 0,1000 second mm2 )
70 milliseconds
>6,000 milliseconds
NA
240 mm
128 × 254
3 mm
90 degrees
3D axial T1 postcontrast
20 milliseconds
2,200 milliseconds
NA
256 mm
320 × 256
<1.5 mm
10–15 degrees
DSC (T2*) perfusion
25–23 milliseconds
2,400 milliseconds
NA
256 mm
320 × 256
<1.5 mm
30 degrees
Abbreviations: 2D, two-dimensional; FLAIR, fluid-attenuated axial inversion recovery;
FOV, field of view; DSC, dynamic susceptibility contrast; DWI, diffusion-weighted
imaging; MR, magnetic resonance; NA, not available; T2WI, T2-weighted imaging; TE,
echo time; TI, inversion time; TR, repetition time.
On imaging, larger lesions that show hemorrhage, necrosis, mass effect, profuse edema,
and a thick heterogeneous enhancement are usually aggressive and of higher grade.[16 ] Various tumors can be distinguished using structural imaging features such as calcifications.
For instance, calcifications, a feature of oligodendroglioma, may be seen in 90% of
cases while not so common in higher-grade gliomas (HGG).[17 ] Calcifications are also useful in differentiating between extra-axial dural-based
masses as meningiomas frequently have calcifications while solitary fibrous tumors
do not.[18 ]
Further, patterns of enhancement can also predict the type of tumor. Primary central
nervous system lymphoma (PCNSL) lesions, for example, enhance homogenously, along
the ventricles, or show linear enhancement along perivascular spaces; on the other
hand, immuno-deficient patients show ring-like enhancement.[19 ] “Notch sign” in lymphomas can be used to differentiate them from glioblastoma.[20 ] Glioblastoma is necrotic in the center and has thick enhancement near the periphery.[16 ]
Though structural imaging may narrow down the diagnostic possibility to a particular
tumor, the combination of DWI along with PWI ([Fig. 1 ]) can help predict the grade of the neoplasm and enhance diagnostic confidence. A
greater tumor grade may be determined by an increased cell density, which is shown
by hyperintensity on DWI and low apparent diffusion coefficient (ADC) values.[21 ]
[22 ]
[23 ] Higher ADC values are found in metastases and HGG compared with PCNSL.[21 ]
Fig.1 Characteristic imaging features in a case of glioblastoma. Fluid-attenuated axial
inversion recovery mixed signal intensity lesion (A) crossing across the midline via corpus callosum showing central blooming (compatible
with bleed) (B) along with diffusion heterogeneity (C) . On postcontrast images (D) irregular peripheral enhancement noted and on relative cerebral blood volume maps
(E) , increased perfusion noted in the corresponding region.
Recommendations for T1W Pre- and Postcontrast Images
Recommendations for T1W Pre- and Postcontrast Images
Before contrast administration, T1 shortening may be seen due to broken-down blood
products, mineralization, fat, and melanin.
The integrity of the blood–brain barrier can be demonstrated by T1 postcontrast imaging.
The degree/pattern of contrast enhancement may not be useful to predict the grade
of neoplasm.
Recommendations for T2W image/FLAIR images:
T2/FLAIR hyperintensity may be seen in vasogenic and cytotoxic edema/nonenhancing
regions of the tumor/white matter pathology.
T2/FLAIR mismatch is highly specific for IDH mutant 1p/19 q non-co deleted diffuse
astrocytoma.[24 ] This, however, needs to be differentiated from the “bright rim” sign of dysembryoplastic
neuroepithelial tumor.
Recommendations for SWI/GRE (Gradient Echo)
Recommendations for SWI/GRE (Gradient Echo)
For identifying regions of increased MR susceptibility. Blooming can be seen in areas
of broken-down blood products, increased tumoral vascularity (higher percent of deoxyhemoglobin),
and mineralization.
Recommendations for DWI/ADC map:
The image is weighted by the degree of water molecule diffusion and can be represented
as an ADC map.
A bright signal on DWI with a low ADC may be seen in densely packed cellular tumors/cytotoxic
edema.
Kitis et al showed that lower-grade gliomas (LGG) have considerably high minimum ADC
values than HGGs.[25 ]
Apart from gliomas, it was found by Bozdağ et al that high-grade meningiomas had a
lower mean, minimum, and maximum ADC values than low-grade meningiomas (900, 850,
950 × 10−6 mm2 /s). This was in addition to a notable relation with tumor grading and proliferation
(Ki -67, mitotic indices).[26 ]
Differentiating lymphoma from glioblastoma can at times be challenging. ADC values
are lower in lymphoma than those in HGG. In a study by Makino et al, with an ADC cutoff
of 1.0 × 10 − 3 mm2/s, it was possible to differentiate PCNSL from glioblastoma.[27 ]
Recommendations for MRS
Lower N-Acetylaspartate (NAA) and creatine levels, higher lactate along with lipid
levels, and higher NAA/choline, as well as choline/creatine ratios, were found in
HGGs, implying that metabolite measurement can be used to predict tumor grade, although
metabolically active non-neoplastic etiologies like demyelination may have a similar
pattern.[28 ]
Recommendations for MR Perfusion—DSC (Dynamic Susceptibility Contrast)/T2*Perfusion
Recommendations for MR Perfusion—DSC (Dynamic Susceptibility Contrast)/T2*Perfusion
An important perfusion parameter in T2 * perfusion is relative cerebral blood volume
(rCBV). It is common to find high-grade tumors to have enhanced perfusion, as shown
by elevated rCBV.[28 ]
[29 ]
In a meta-analysis that compared nine studies, HGGs were shown to have considerably
higher absolute and relative tumor blood volumes compared with LGGs.[30 ]
In comparison to traditional MRI findings, Law et al observed increased rCBV (1.75)
in HGGs compared with LGGs; however, oligodendroglioma is an exception among gliomas,
where increased rCBV may be linked to fine intratumoral capillaries rather than malignant
potential and neo-angiogenesis.[28 ]
A steady increase in rCBV within a tumor over time may forecast the interval change
of a previously low-grade neoplasm to a higher grade.[31 ]
PWI is less useful for grading in meningiomas as all grades show elevated perfusion
due to the common expression of vascular endothelial growth factor (VEGF), an angiogenesis
marker.[32 ]
PCNSL lesions can also be distinguished from metastases and glioblastomas using DSC-MRI.
PCNSL has reduced rCBV compared with metastases and glioblastomas. This is because
PCNSL lesions are angiocentric rather than angiogenic, meaning that they surround
pre-existing blood vessels rather than create new ones.[33 ]
[34 ]
[35 ] Metastases might have variable rCBV values depending on the primary lesion.
The dynamic passage of contrast through a region can be plotted as a signal intensity
to time or a mean curve (MC). Another useful perfusion metric in MC analysis is percentage
signal recovery (PSR), which measures the tendency of the MC to return to the baseline.
The PSR may be used to evaluate the integrity of the blood–brain barrier.[34 ]
[35 ]
[36 ] Studies in which preloading has not been utilized for minimizing the T1 impact of
gadolinium-based contrast agents in DSC-perfusion images found that lymphoma has the
greatest PSR, followed by metastases and glioblastoma.[34 ]
[35 ]
[36 ]
[37 ] The elevated PSR in PCNSL ([Fig. 2 ]) is due to T1 effects associated with the accumulation of contrast in the tumor
interstitium dominating T2* effects.[35 ]
PSR normally returns close to baseline in gliomas, while in brain metastases and extra-axial
tumors, PSR may not return to baseline due to increased contrast extravasation.
Fig. 2 Case of diffuse large B cell lymphoma. T2-weighted imaging reveals a small area of
hyperintensity in the genu of the corpus callosum. (A) . Percentage signal recovery is high (red curve) on dynamic susceptibility contrast
perfusion imaging in lymphoma with mild elevation in relative cerebral blood volume
(B) .
Recommendations for MR Perfusion—Dynamic Contrast Enhancement (DCE) / T1 Perfusion
Recommendations for MR Perfusion—Dynamic Contrast Enhancement (DCE) / T1 Perfusion
Another PWI technique that can be used for tumor grading is DCE, a T1-based approach
to estimate tumor capillary permeability ([Fig. 3 ]). Higher K-trans values suggest a high grade/recurrent/progressive tumor and are
extremely useful to discriminate tumor recurrence from radiation necrosis. However,
the complexity of postprocessing, poor technique standardization, and lack of clinical
validation are the drawbacks to widespread use.[38 ]
Fig. 3 Case of IDH wild glioblastoma in the right temporal lobe. The lesion represents heterogeneous
hyperintensity on T2-weighted imaging (A) as well as elevated K trans value of 0.322 on dynamic contrast enhancement perfusion
imaging (B).
Recommendations for MR Perfusion—Arterial Spin Labeling (ASL)
Recommendations for MR Perfusion—Arterial Spin Labeling (ASL)
The parameter that is obtained is cerebral blood flow (CBF) without contrast administration.
Increased CBF indicates a higher grade/recurrent lesion.
eASL has an additional advantage over ASL in terms of more accurate quantification
of various metrics of tissue perfusion.
Recommendations for Diffusion Tensor Imaging (DTI)
Recommendations for Diffusion Tensor Imaging (DTI)
Imaging of white matter fiber arrangement using the property of anisotropic diffusion
of water molecules.
Fractional anisotropy (FA), an important DTI metric is a measure of the integrity
of white matter tracts. Other metrics include mean diffusivity, and planar anisotropy.
Tractograms are used to visualize the white matter tract directionality and predict
displacement/ infiltration by the tumor. This can be used for preoperative planning.
In addition, within brain neoplasms, disrupted tissue architecture results in altered
FA that correlates with tumor cellularity.[39 ] Glioblastoma patients who show higher DTI abnormality in preoperative images have
a long tumor progression-free survival and increased overall survival.[40 ]
[41 ]
The limitations of tractography are the ability to resolve only a single fiber direction
for a given voxel, while most voxels in the image contain multiple fiber directions[42 ]
[43 ] and the crossing fiber problem that can be overcome with higher-order models like
high angular resolution diffusion imaging that are more time-consuming.
Recommendations for Functional Magnetic Resonance Imaging (fMRI)
Recommendations for Functional Magnetic Resonance Imaging (fMRI)
Areas of functional activation can be detected from the local fluctuations in the
blood-oxygen levels in the brain.
This property is exploited by task-based fMRI for preoperative identification of functional
areas, useful in surgical planning.
Resting-state fMRI at present is used as a research tool.
Recommendations for the Screening of the Entire Neuraxis
Recommendations for the Screening of the Entire Neuraxis
The primary intracerebral malignancies that may need entire neuraxial screening for
drop metastases or multicentricity include medulloblastoma, ependymoma, pineal gland
malignancies, germinoma, choroid plexus carcinoma.[44 ]
[Flowcharts 1 ] and [2 ] show an algorithm for the interpretation of MR images in patients with a suspected
brain tumor.[45 ] Postchemoradiotherapy effects may be classified as early and late effects. Early
effects may occur in the first 3 to 4 months after treatment, while delayed effects
can occur from 6 months to years after treatment.[46 ] Chemotherapy further exacerbates these effects by increasing the disruption of the
blood-brain barrier.
Flowchart 1 Image interpretation algorithm 1. FLAIR, fluid-attenuated axial inversion recovery;
MRI, magnetic resonance imaging.
Flowchart 2 Image interpretation algorithm 2. ADC, apparent diffusion coefficient; MR, magnetic
resonance; NAA,—; rCBV, relative cerebral blood volume.
Pseudoprogression is a type of early post-treatment effect that can occur in the first
3 to 6 months. Pseudoresponse is again an early type of reaction seen when HGGs are
treated with anti-VEGF agents.[47 ]
Radiation necrosis ([Fig. 4 ]) is due to severe local tissue response to radiation. Although it usually occurs
3 to 12 months after radiotherapy, it can even occur several years or decades later.[47 ] It has been described as having a Swiss cheese enhancement pattern.[46 ] However, the identification of radiation necrosis based on the pattern of enhancement
alone can prove to be difficult.[46 ] DWI and advanced MRI sequences like PWI and MRS can help with the diagnosis in these
cases. Studies on post-treatment DWI and PWI have shown that recurrent tumors have
reduced ADC and increased rCBV values compared with post-treatment effects ([Fig. 5 ]).[46 ] Chemical exchange saturation transfer MRI and PET using amino acid radiotracers
(rather than fluorodeoxyglucose) have demonstrated the capability to differentiate
tumor recurrence/residue and post-therapy changes.[48 ]
[49 ]
Fig. 4 Post-treatment change in the form of radiation necrosis in a patient after resection
of a higher-grade glioma followed by postoperative radiotherapy. (A) There is fluid-attenuated axial inversion recovery (FLAIR) hyperintensity surrounding
the operative cavity. (B) There is heterogeneous “swiss-cheese” enhancement within. (C) On susceptibility-weighted imaging, there are multiple foci of blooming in the hyperintensity
that most likely represent postradiotherapy cavernomas. (D) No restriction on diffusion-weighted imaging and (E, F) no elevated relative cerebral blood volume on perfusion imaging within the FLAIR
hyperintensity and the enhancing area as compared with the contralateral side on perfusion
color map and dynamic susceptibility contrast -curves.
Fig. 5 Recurrence in the postoperative higher grade glioma patient. (A) Fluid-attenuated axial inversion recovery image is noted to show a heterogeneous
hyperintensity in the left parietal lobe. (B) Heterogeneous enhancement on postcontrast scan has been seen. (C) Susceptibility-weighted imaging shows blood products that are most likely postoperative.
(D, E) There is heterogeneous diffusion on diffusion-weighted imaging and apparent diffusion
coefficient with a few areas of restriction. (F) Dynamic susceptibility contrast-perfusion image shows elevated relative cerebral
blood volume within the enhancing region. (G) Spectroscopy with intermediate echo time shows significantly elevated choline with
a lactate peak.
Recommendations in the Imaging of Treated Brain Tumors
Recommendations in the Imaging of Treated Brain Tumors
Identification of post-treatment effects is of importance as these can be followed
up with or without medical management while the recurrence warrants treatment.
Advanced MRI sequences like DWI, PWI, MRS, and PET-CT may be used to differentiate
post-treatment changes from recurrence or residual lesions.[46 ]
Radiographic response assessment: Given the wide range of interpretations, it is not
unexpected that tumor response reporting in radiology varies as well. An evaluation
of post-therapeutic response in gliomas is done using modified Response Assessment
in Neuro-Oncology (mRANO) criteria.[50 ]
[51 ]
Recommendations for mRANO Criteria
Recommendations for mRANO Criteria
Response of the tumor is determined in comparison to baseline images (pretreatment
image for recurrent glioblastoma and postradiation scan for newly detected glioblastoma).
Lesions can be measurable and/or nonmeasurable. Measurable lesions demonstrate contrast
enhancement with clearly defined margins, on 2 or more axial sections (preferably
5 mm axial slices with no interslice gap). The lesion should be at least 10 mm in
size (maximum diameter) if the slice thickness is less than 5 mm and twice the slice
thickness if the slice thickness is more than 5 mm. Nonmeasurable lesions show poorly
defined margins that cannot be measured, lack contrast enhancement, and/or are too
small to measure (<10 mm in maximum diameter).
It divides the radiographic/clinical response into four types: (1) Complete response
(CR), (2) partial response (PR), (3) progressive disease (PD), (4) stable disease
(SD).
CR: Disappearance of all measurable enhancement and nonmeasurable disease, with scans
done at least 4 weeks apart. CR seen on the first scan is preliminary and on the second
scan is durable. If the second scan shows enhancing lesion compared with the preliminary
CR, then it is a pseudoresponse and preliminary PD. Clinically with CR, the patient
should improve/be stable with no corticosteroid usage (except for physiological dose).
PR: Measurable enhancement showing more than or equal to50% reduction in the sum of
perpendicular diameter and/or more than or equal to 65% reduction in total lesion
volume with scans done at least 4 weeks apart. The first scan showing PR compared
with baseline is preliminary PR. If the second scan shows progression compared with
preliminary PR, then it is pseudoresponse and preliminary PD and for a confirmed PD,
at least two sequential scans must show an increase in tumor size. If the second scan
shows a PR, then it is a durable PR. Clinically, with PR the patient should improve/be
stable with no corticosteroid usage (except for physiological dose).
PD: Measurable enhancement showing more than or equal to 25% increase in the sum of
perpendicular diameter or more than or equal to 40% increase in lesion volume in 2
sequential scans done more than or equal to 4 weeks apart. The first scan showing
PD is preliminary PD and if the second scan also shows PD, then it is confirmed PD.
If a second scan done 4 weeks later shows SD or PR/CR, then it is pseudoprogression
and is labeled as preliminary PD. Clinically with PD, the patient should have significant
worsening not attributable to any other illness/steroid dose.
SD: The patient not qualifying for CR/PR/PD is clinically stable with reduced/stable
steroid dose intake compared with baseline.
mRANO criteria are yet to be widely adopted in clinical radiology practice, owing
in part to the strict guidelines that must be followed, and limitations such as high
interobserver variability in interpretation, dependence on clinical status and treatment
history, and consistency in taking multiple measurements over time. Relying on gadolinium
enhancement for assessing therapeutic response was a fundamental shortcoming of the
RANO criteria as both tumor progression and post-treatment change can show enhancement.
After the advent of immunotherapy for glial neoplasms, immunotherapy response assessment
for neuro-oncology has been introduced to overcome the challenges in radiology reporting
which is a slight modification of the mRANO criteria. The main differences are 1.
Patients on immunotherapy with new contrast-enhancing lesions outside the radiation
field will not fall under the PD category, 2. Unlike RANO, a follow-up scan after
3 months is required to confirm disease progression as the therapeutic effect of immunotherapy
may be delayed.
Brain tumor reporting and data system (BT-RADS) was created to make MRI reporting
of post-treatment brain tumors easier and more consistent by assigning scores from
0 to 4 to the patients' images.[51 ]
[52 ] Score 0—new baseline study, score 1—improvement in imaging findings, score 2—stable
imaging findings, score 3—worsening imaging findings and is divided into three subgroups
depending on the underlying cause (post-therapy effect= 3a, the combined effect of
treatment changes and tumor progression= 3b, tumor progression favored= 3c). Score
4—worsening of imaging findings likely indicating tumor progression. T2* perfusion
and DWI can help categorize patients better, into individual subgroups in BT-RADS
score 3. Each category in BT-RADS is linked to a specific management decision leading
to better communication between the referring physician and the radiologist.[53 ]
[54 ]
Principles of Management
General management should precede definitive treatment. When the presentation is in
the emergency setting with a depressed sensorium or status epilepticus, the initial
measures should focus on the maintenance of the airway, respiratory efforts, blood
pressure, heart rate, and seizure control.[53 ]
[54 ]
[55 ] Dexamethasone may be used to treat peritumoral edema.[56 ]
Recommendations
In a diffuse infiltrating glioma seen on imaging, the treatment of choice is the maximum
possible safe resection followed by radiotherapy and chemotherapy. If resection is
not feasible due to the eloquence of adjacent areas or the poor general condition
of the patient, a stereotactic biopsy may be considered for deciding on further management.[8 ]
[11 ]
[57 ] Management decisions without histological diagnosis should be stringently avoided
and may only be taken in unusual situations like difficulty in biopsy as in elderly
patients with comorbidities or where imaging very apparently shows a large HGG.[8 ]
For IDH-mutant astrocytoma, WHO grade 2 the treatment is the maximum possible resection.
This is followed by radiotherapy and chemotherapy with the PCV (lomustine, procarbazine,
and vincristine) regimen in patients with subtotal resection and/or when the patient
is over 40 years old.[8 ]
[57 ]
[58 ]
For IDH-mutant astrocytoma, WHO grade 3 and grade 4, maximum possible resection, followed
by radiotherapy and chemotherapy with temozolomide.[8 ]
[57 ]
[58 ]
For IDH-mutant, 1p/19q-co deleted oligodendroglioma, WHO grade 2 and 3, treatment
is the maximum possible resection. If further treatment is needed, it is radiotherapy,
followed by chemotherapy with the PCV regimen.[8 ]
[57 ]
[58 ]
For IDH-wild glioblastoma, aged less than 70 years, the standard of care is maximum
possible resection, followed by concomitant radiotherapy and daily chemotherapy with
temozolomide plus 6 cycles of maintenance temozolomide. Elderly patients who are not
suitable candidates for combined radio and chemotherapy are to be managed based on
O6 -methylguanine-DNA methyl-transferase (MGMT) methylation status.[8 ]
[57 ]
[58 ]
[59 ]
For incidentally detected, asymptomatic meningiomas, conservative management with
follow-up is recommended. Surgery, with Simpson grade 1 resection, is indicated for
meningiomas that grow or become symptomatic. Radiosurgery may be offered in patients
who cannot undergo surgery when the tumor is relatively small with no significant
mass effect. Patients with subtotally resected WHO grade 1 meningiomas or WHO grade
2 meningiomas with Simpsons grade 1 to 3 resection may be followed up or given adjuvant
radiotherapy. WHO grade 2 meningiomas with Simpsons grade 4 or 5 resections should
be given adjuvant radiotherapy. Maximal possible resection, followed by radiotherapy,
is recommended in WHO grade 3 meningiomas.[59 ]
[60 ]
Transsphenoidal resection is recommended for enlarging, symptomatic, nonfunctioning
pituitary adenomas with mass effect and for functional adenomas. Radiotherapy may
be used as adjuvant therapy for residual lesions. Follow-up is recommended for pituitary
incidentalomas that are asymptomatic and surgery, if there is significant tumor growth
on follow-up. Prolactinomas are generally treated with dopamine agonists. Surgery
is reserved for cases with inadequate response. Radiotherapy may be used for residue
after dopamine agonists or surgery.[61 ]
For primary CNS lymphoma, systemic chemotherapy is the first line of management.[62 ]
[63 ] Surgery may be considered in a superficially located large lesion that is causing
a significant mass effect. For induction chemotherapy, high-dose intravenous methotrexate
is the agent of choice and it may be combined with other chemotherapeutic agents.
For consolidation, high-dose chemotherapy with autologous stem cell transplantation
is as efficacious as whole-brain radiotherapy (WBRT).[63 ]
Brain metastases are to be treated with the best combination of multimodality treatment.
Surgery may be considered in solitary brain metastases or when there is a significant
mass effect with raised intracranial pressure. Surgery may also be considered in patients
with multiple brain metastases, especially when the prognosis is favorable. Stereotactic
radiosurgery, WBRT, or systemic chemotherapy with agents based on the primary tumor
may also be considered.[64 ]
Follow-Up Imaging and Management of Recurrent Disease Including Specific Interventional
and Palliative Measures
Follow-Up Imaging and Management of Recurrent Disease Including Specific Interventional
and Palliative Measures
The imaging appearance after tumor resection, chemotherapy, and radiotherapy is very
complex and is influenced by multiple factors. These include blood products after
the surgery, inflammatory response, and edema caused by the surgery or chemoradiation.[46 ] Apart from post-treatment changes like radiation necrosis, pseudoprogression, and
pseudoresponse, there may be residual or a recurrent tumor ([Fig. 5 ]) at the margins of the resection cavity that is of particular concern.
Recommendations
In diffuse infiltrating gliomas, a postoperative scan within 24 to 48 hours is recommended,
preferably with contrast-enhanced MRI to assess the extent of resection.[8 ]
[65 ] A baseline MRI is done after 3 to 4 weeks after the completion of radiotherapy.[8 ] After the completion of therapy, imaging may be performed in 2- to 6-month intervals.
But, the duration of intervals may be prolonged or shortened, depending on the extent
of residual disease, and histological and genetic characteristics of the tumors. For
example, IDH mutant gliomas may be followed up at 3- to 6-month intervals while IDH-wild
gliomas at 2- to 3-month intervals. However, in the event of suspected disease progression,
a shorter interval of 4 to 8 weeks may be adopted to confirm the same. In the rare
event of a possible glioma being followed up without proper histological diagnosis,
a shorter interval of approximately 2 to 3 months between imaging sessions is recommended.[8 ] When there is a recurrence, the prior treatment and the patient's functional status
usually are considered for decision-making. A second surgery may be considered.[8 ]
Patients with incidentally detected, suspected meningiomas that are asymptomatic and
patients with treated WHO grade 1 meningiomas are to be followed up with annual MR
examinations for 5 years. Thereafter, follow-ups may be farther apart depending on
the age, and the clinical condition of the patient. For treated WHO grade 2, biannual
follow-up is recommended for 5 years as they have an increased risk of recurrence.
Following this, yearly follow-up is recommended.[60 ] Fractionated radiotherapy may be used in patients with recurrent meningiomas.[60 ]
For pituitary incidentalomas that are microadenomas, an annual scan for 2 to 3 years
is recommended. After this, the follow-up intervals may be prolonged if there is no
increase in size. For incidentally detected pituitary macroadenomas, annual imaging
follow-up with visual field charting every 6 to 12 months is recommended.[61 ] Aggressive pituitary lesions, after the completion of treatment, are to be followed
up every 3 to 12 months by imaging depending on the rate of tumor growth and proximity
to important anatomical structures. This may be coupled with endocrine evaluation
depending on the clinical scenario.[66 ]
Brain metastases are to be followed up at intervals of 3 months. If there is any recurrence
or progression during follow-up, the treatment decision depends on the patient's general
condition, degree of progression, and the initial treatment. Treatment options include
surgery, radiotherapy, and systemic chemotherapy.[64 ]
Synoptic Reporting Formats
Synoptic Reporting Formats
Structured reporting better conveys the anatomical and pathophysiological information
from the radiologist to the referring physician. A CT or an MR scan report for a brain
tumor should have a detailed description of the number of tumors, their specific location,
and their distance from eloquent structures as this plays a very important role in
preoperative decision-making. The dimensions of the tumor along three different axes
are to be mentioned; more specifically the sizes of the T2, FLAIR abnormality, and
the enhancing area on the postcontrast T1W image are to be mentioned separately when
the tumor is partially enhancing.[67 ]
Information about the extent of T2, FLAIR white matter hyperintensity adjacent to
the tumor which may represent edema, the mass effect due to the tumor visible as effacement
of ventricles, CSF spaces and midline shift are also to be conveyed in the report.
Tumoral characteristics on DWI, SWI, PWI, and the effect of the tumor on adjacent
vascular structures are also very important.
The presence of additional pathology in the neuroparenchyma like white matter disease
or diffuse neuroparenchymal volume loss and calvarial pathology are all significant
clinically and need to be mentioned. Finally, the radiological impression should include
a possible list of differentials based on the imaging findings following the recent
WHO 2021 nomenclature of brain tumors.
