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Table of Contents
REVIEW ARTICLE
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 30-41

Role of postoperative imaging in neuro-oncology


Department of Neuroradiology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom

Date of Web Publication02-Nov-2021

Correspondence Address:
Dr. Vijay Sawlani
Department of Neuroradiology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Edgbaston, Birmingham, B15 2TH
United Kingdom
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJNO.IJNO_405_21

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  Abstract 


Postoperative imaging in primary and secondary brain tumors is becoming challenging due to advancements in molecular genetic classification of brain tumors influencing advancing treatment options. In this review, we summarize the standard-of-care practice, commonly encountered clinical and postoperative imaging issues. The timeline for follow-up imaging in low-grade, high-grade, and secondary tumors is discussed, particularly in reference to tumor and treatment-related effects. Standardized imaging protocols are essential for postoperative evaluation, which should always be read in the context of previous imaging. Where possible, advanced magnetic resonance imaging techniques, including multiparametric diffusion, perfusion, and spectroscopy imaging, should be used to differentiate between recurrent tumor and treatment-related changes. Surgical complications are often seen in the immediate and acute postoperative period and chemoradiotherapy-related complications following several weeks to months. The main aim of postoperative imaging is to evaluate expected and unexpected findings for appropriate management. Background information of tumor molecular genetics, histological grade, patient clinical status, and treatment given is essential for interpreting postoperative imaging.

Keywords: Glioma, metastasis, molecular genetic classification of brain tumor, radiology, postoperative imaging


How to cite this article:
Sawlani V, Patel M. Role of postoperative imaging in neuro-oncology. Int J Neurooncol 2021;4, Suppl S1:30-41

How to cite this URL:
Sawlani V, Patel M. Role of postoperative imaging in neuro-oncology. Int J Neurooncol [serial online] 2021 [cited 2021 Nov 27];4, Suppl S1:30-41. Available from: https://www.Internationaljneurooncology.com/text.asp?2021/4/3/30/329800




  Introduction Top


Postoperative imaging in primary and secondary brain tumors is gaining importance as much as preoperative imaging due to better understanding of molecular genetic classification, advances in chemoradiotherapy treatments, and gamma-knife and proton-beam therapies. An appropriate standardized imaging protocol is required to evaluate posttreatment changes at different time points of tumor treatment. The essential postoperative imaging protocol requires volumetric and postcontrast sequences. Multiparametric magnetic resonance imaging (MRI) including diffusion, perfusion and spectroscopy is useful in problem-solving cases and is encouraged where available, particularly in differentiating tumor and treatment-related changes in reference to surgery and chemoradiotherapy. In the immediate and acute (days to weeks) postoperative period imaging, it is important to assess for surgical complications, whereas early delayed (weeks to months) and late delayed (months to years) complications are related to chemoradiotherapy treatment.

Surgery-related complications

An understanding of the commonly encountered postoperative complications on imaging is essential for appropriate management. Postoperative restricted diffusion is seen surrounding the resection cavity in 64% of patients following tumor resection,[1] as a result of direct surgical trauma, vascular injury, and tumor devascularization and is reversible in most cases. However, in 1% of cases, postoperative cytotoxic edema in stroke can be seen, which shows contrast enhancement in the subacute phase and evolves on serial imaging as encephalomalacia develops. Therefore, it is important to correlate new enhancement with the immediate postoperative diffusion-weighted imaging (DWI) to not mistakenly diagnose tumor recurrence for postoperative infarct.[2] Other complications postresection include intracranial haemorrhage with an incidence of 1.6%.[2] Postresection infection is a less common complication typically seen in patients who are immunocompromised and can be seen as bone flap infection, subdural empyema, cerebritis, abscess, and meningitis [Figure 1].[2]
Figure 1: Postoperative complications following debulking of left frontal glioblastoma in a patient on steroids. (a) Preoperative T1WI. (b and c) Immediate postoperative magnetic resonance imaging pre- and post-contrast T1WI within 48 h showing small residual tumor and hematoma within the resection cavity and a shallow right frontal collection, (d) diffusion-weighted imaging shows resection-related reversible ischemic changes surrounding the cavity in the left frontal lobe. (e and f) Pre- and post-contrast T1WI 3 weeks later shows a progression of residual tumor. In addition, there is a new lesion in the right frontal lobe, (g and h) showing strongly restricted diffusion (arrow) and low apparent diffusion coefficient signal in keeping with right frontal lobe abscess formation

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Radiation-related complications

Radiation-related injury is often categorized into acute (days to weeks), early delayed (weeks to months), and late delayed (months to years) complications. Acute and early delayed injury is a result of changes in vessel permeability and blood–brain barrier disruption, resulting in edema, and is usually reversible, resolving spontaneously. On imaging, acute radiation-related injury can be difficult to identify as the edema is often indistinguishable from tumoral vasogenic edema. In the early delayed period, there is transient demyelination that demonstrates enhancement usually in the radiation field; however, this also can be indistinguishable from a tumor on imaging. The issues surrounding this are discussed later in more detail.

Radiation necrosis or radionecrosis is a serious late delayed complication following radiation therapy resulting in an irreversible and progressive necrotic mass lesion and can be seen years following radiation therapy. The true rate is difficult to establish given that appearances can mimic tumor recurrence on MRI but is estimated to be between 5% and 25%.[3] The proposed pathophysiology of radiation necrosis is thought to be due to vascular injury and damage to glial cells resulting in demyelination and neo-angiogenesis with abnormal leaky vasculature. An increase in enhancing disease and perilesional edema alone is not specific to diagnose either tumor recurrence or radiation necrosis. Patterns of enhancement have previously been described in the literature to describe radiation necrosis such as “Swiss cheese,” “soap bubble” or “cut green pepper”; however these have shown to have a positive predictive value of only 25%.[4] The low predictive value of conventional MRI has led to the use of advanced techniques such as perfusion-weighted imaging (PWI), magnetic resonance spectroscopy (MRS) and PET to help distinguish between radiation necrosis and tumor recurrence [Figure 2]. Using dynamic susceptibility contrast (DSC) perfusion imaging with a relative cerebral blood volume (rCBV) cutoff of 2.1 has shown to give a high diagnostic accuracy to distinguish between the two entities.[5] Raised choline levels on MRS have shown to be a useful imaging parameter,[6] as have NOEMTR and AmideMTR on chemical exchange saturation transfer imaging.[7]
Figure 2: A case of radiation necrosis in a patient with previous craniospinal radiotherapy for medulloblastoma. (a-c) FLAIR and pre/postcontrast T1WI showing a ring-enhancing lesion in the right anterior temporal lobe (arrow). Multiparametric magnetic resonance imaging: (d-f) diffusion-weighted imaging, apparent diffusion coefficient and relative cerebral blood volume maps show no restricted diffusion or significantly raised perfusion. (g and h) Single-voxel spectroscopy shows mild elevation of Cho/Cr and raised lipid and lactate levels. Findings are consistent with radiation necrosis

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Vascular injury is another late delayed radiation-related complication, and is categorized into three main appearances: Radiation-induced vasculopathy, radiation-induced vascular proliferative lesions, and radiation-induced mineralizing microangiopathy.[2] Radiation-induced vasculopathy is the proliferation of vessel walls resulting in stenosis or occlusion, mainly affecting large basal cerebral arteries and as a result, patients are at increased risk for ischemia and infarcts. Radiation-induced vascular proliferative lesions include capillary telangiectasia and cavernous malformations [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d, [Figure 3]e, [Figure 3]f as a result of microvasculature injury and neoangiogenesis. Radiation-induced mineralizing microangiopathy is the formation of dystrophic microcalcifications within the brain parenchyma due to calcium deposition in damaged vessel walls and necrotic brain tissue, typically in the basal ganglia and subcortical white matter.[2]
Figure 3: Case of a left parieto-occipital diffuse glioma. The tumor was resected and treated with chemoradiotherapy 19 years ago with ongoing surveillance imaging since then. Most recent imaging (a) precontrast T1WI, (b and c) postcontrast axial and coronal T1WI, (e and f) axial and coronal FLAIR shows new thickened cortex with FLAIR signal hyperintensity (arrow), as well as cortical and leptomeningeal enhancement in the irradiated area (arrow), in keeping with SMART syndrome. (d) SWI shows foci of susceptibility changes indicating postradiotherapy cavernoma formation

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Radiation-induced leukoencephalopathy refers to white matter injury usually without necrosis, thought to be related to direct axonal injury or secondary injury from vascular compromise, appearing as progressive, symmetrical, confluent T2/FLAIR hyperintensity involving predominantly the periventricular white matter [Figure 4]. The incidence is unclear but has been reported in 34% of patients receiving whole-brain radiation treatment after 6 months of follow-up.[8] Patients may be asymptomatic or present with neurocognitive decline and there is a poor correlation between imaging and symptoms. It is important to be aware that some patients may be on immunosuppressive treatments, and therefore, can develop progressive multifocal leukoencephalopathy, which is generally more asymmetrical and affects the subcortical U fibres, and it is important to be able to distinguish between the two entities.[2]
Figure 4: Leukoencephalopathy following whole-brain radiotherapy for brain metastases. (a and b) Axial T2WI and coronal FLAIR showing extensive, confluent and symmetrical white matter T2/FLAIR signal hyperintensity. (c and d) Diffusion-weighted imaging and postcontrast T1WI show no restricted diffusion or contrast enhancement

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Another late delayed phenomenon is stroke-like migraine attacks after radiation therapy syndrome, consisting of migraine-like symptoms in patients who have had previous radiotherapy treatment. It is proposed to be related to reversible vascular dysregulation resulting in disruption, typically affecting the posterior cerebral hemispheres or cerebellum with gyriform T2/FLAIR hyperintensity and enhancement, with some cases also showing diffusion restriction [Figure 3],[9] and usually, this improves or resolves on follow-up imaging. Finally, radiation-induced tumors are an uncommon but serious complication and can occur decades following radiation therapy [Figure 5]. These can be low grade or high grade, with meningioma being the most common radiation-induced tumor.[10]
Figure 5: Multiple radiation-induced meningiomas. (a and b) Axial and (c) coronal postcontrast T1WI demonstrating multiple radiation-induced intracranial meningiomas (parasagittal, left tentorial, and left frontal) in a patient who had cranial radiotherapy decades previously for leukaemia as a child

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Chemotherapy-related complications

Chemotherapy agents can result in toxicity to various structures in the central nervous system, with the structure, type, and extent of involvement varying according to the agent and dose administered. White matter is particularly vulnerable to chemotherapy-related injury, most commonly resulting in a toxic leukoencephalopathy, and many chemotherapy agents can potentiate the effects of radiation-related brain injury. On imaging, the appearances are typically of T2/FLAIR hyperintensity in the frontoparietal white matter and on DWI, there may be focal or diffuse areas of reversible restricted diffusion, which improve over time after stopping the causative chemotherapy agent.[11]


  Postoperative Imaging Assessment of Diffuse Low-Grade Glioma Top


The current 2016 World Health Organization (WHO) classification categorizes gliomas into low-grade (WHO I–II) and high-grade (WHO III–IV) gliomas based on an integrated diagnosis from the combination of histological features and molecular biomarkers such as presence or absence of isocitrate dehydrogenase mutations and loss or maintenance of the whole-arm of chromosomes 1p and 19q.[12] Low-grade gliomas are considered to be slower growing and radiographically distinct from high-grade gliomas, appearing as T2/FLAIR hyperintense lesions with often indistinct margins with minimal, if any, contrast enhancement.[13]

MRI is suggested within 48 h from surgery to assess the extent of resection of low-grade glioma and is one of the most relevant prognostic factors.[14] During postoperative treatment monitoring, serial contrast-enhanced MRI may identify new areas of contrast enhancement or significant changes in tumor size, suggesting malignant transformation. However, given that disease is predominantly nonenhancing, the Response Assessment in Neuro-oncology Working Group (RANO) criteria for low-grade gliomas use percent change in T2/FLAIR disease rather than contrast enhancement for determination of response and progression. Postoperative imaging is always read in conjunction with previous imaging, particularly the first postoperative scan to accurately assess slowly growing tumors [Figure 6]. Measurements performed on 3D FLAIR imaging have shown to be superior to those on 2D FLAIR imaging.[15] However, one of the challenges in determining treatment response remains the difficulty in accurately measuring the tumor in two dimensions due to the more accurate assessment of extension of irregularly shaped lesions. Work is ongoing work to determine if a volumetric assessment of T2/FLAIR disease is a more reliable and sensitive measure of response.[16]
Figure 6: Slow growth of a low-grade tumor. T2WI demonstrating (a) preoperative right mesial frontal lesion, (b) postoperative image following partial resection, confirming World Health Organization grade 2 oligodendroglioma. (c-h) T2WI showing an increase in signal abnormality over a 9-year period indicating slow growth of the tumor, leading to further resection and chemoradiotherapy treatment. Comparison with all previous imaging is essential for assessment of growth in slow-growing low-grade tumors (arrows)

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Advanced MRI techniques such as DWI, PWI, and MRS add physiological and metabolic information to conventional structural MRI.[15],[17] The apparent diffusion coefficient from DWI is considered an indirect measure of tumor cellularity, as a proliferating tumor restricts diffusion of extracellular water, and therefore, apparent diffusion coefficient (ADC) values are lower in low-grade gliomas that are transforming to high-grade gliomas.[15] PWI quantifies changes associated with neo-angiogenesis, correlating with glioma malignancy, primarily through the DSC technique-derived rCBV.[15] MRS-derived ratios of Cho/Cr and Cho/NAA have shown to distinguish between low- and high-grade gliomas[18] and can be useful in the postoperative treatment monitoring period to identify foci of malignant transformation or to differentiate between radiation-related changes or tumor progression. Low ADC (<1000), high rCBV (>2.0), and high Cho/Cr ratio (>1.8) are suggestive of high-grade transformation even in nonenhancing lesions.[17] Positron-emission tomography (PET) imaging with radiolabeled amino acids such as 11C-MET, 18F-FET, and 18F-FDOPA has shown a moderately high accuracy to discriminate between low- and high-grade gliomas.[15] Amino acid PET can also be helpful in cases where MRI is inconclusive for detecting malignant transformation and treatment-related changes from true progression, with high sensitivity and specificity; however, the limited availability of amino acid PET and use of ionizing radiation limits its widespread use.[19]


  Postoperative Imaging Assessment of Glioblastoma Top


The current standard treatment for patients with glioblastoma is a maximum safe surgical resection followed by radiotherapy with concurrent daily temozolomide (TMZ), followed by at least six cycles of adjuvant TMZ as per the Stupp protocol.[20] Neuroimaging with MRI is the primary method to evaluate disease status and for treatment response assessment. These include the immediate postoperative MRI (IP-MRI), a preradiotherapy MRI (PR-MRI), a postradiotherapy treatment baseline MRI (TB-MRI), followed by regular interval imaging during adjuvant TMZ and posttreatment monitoring imaging.[21]

Immediate postoperative magnetic resonance imaging

IP-MRI is performed with intravenous contrast to determine the extent of resection and assess for residual disease. The challenge arises as postoperatively reactive enhancement is present and can mimic a residual tumor. There are varied opinions as to the optimal timing of the IP-MRI study; however, current practice of imaging within 72 h of surgery to distinguish between reactive enhancement and residual tumor is based on a very early study.[22] Studies since then have demonstrated that postoperative reactive parenchymal, dural, and leptomeningeal enhancement is seen in about a third of patients who have IP-MRI within 72 h,[23] and can be seen as early as 17 h following surgery and increasing with time.[24],[25] Thin linear enhancement is more likely but not always associated with reactive change, and thick linear or nodular enhancement has a fairly high specificity for residual tumor.[26],[27] More recent studies have proposed that postoperative MRI should be performed as early as possible[28] and at least within 45 h following surgery,[27] and a close analysis of enhancement patterns along with a comparison to the presurgical MRI study is essential to help discriminate between residual tumor and reactive enhancements.[23] Intraoperative MRI (iMRI) has been shown to be superior to an early postoperative MRI, demonstrating a lower incidence of reactive change, and therefore, better ability to distinguish residual tumor; however, the recommendation is that an additional DWI study is performed in the early postoperative period as ischemic lesions can be overlooked on the iMRI.[29]

Preradiotherapy magnetic resonance imaging

Chemoradiotherapy treatment involves radiotherapy 60 Gy in 30 daily fractions over 6 weeks and typically begins 3–6 weeks following surgery to allow for postoperative recovery. Radiotherapy planning of the gross tumor volume is defined on the planning CT study using the co-registered preoperative and postoperative CE-T1WI and T2-FLAIR MRI sequences.[30] Due to the time interval between the postoperative MRI and planning CT, a shift of normal brain tissue occurs with filling of parts of the resection cavity, leading to inaccurate registration between the postoperative MRI and planning CT study,[31] and interval tumor growth or reactive enhancement may therefore, change findings. Many centers also obtain a repeat MRI at the time of radiotherapy to ensure accurate co-registration of the target volumes. It has been shown that patients with evidence of tumor growth between the IP-MRI and PR-MRI have a shorter survival[32] and the information from the PR-MRI can be useful for the clinical management of patients by reducing the ratio of patients diagnosed with pseudoprogression.[33] The issue still remains that glioblastoma infiltration is present diffusely beyond the extent of the visible enhancing lesion on MRI.[34] There is evidence that advancing imaging techniques at the postoperative or PR-MRI time point can be useful to identify tumor infiltration and predict recurrence; these include low ADC on DWI,[35],[36] high choline[17] and lactate-to-NAA ratio on MRS,[37] and 18F-FET-PET.[38]

Postradiotherapy treatment baseline magnetic resonance imaging and early posttreatment imaging

After completion of radiotherapy and concomitant TMZ chemotherapy, a TB-MRI is usually performed at 4 to 6 weeks following completion of radiotherapy, which gives an early assessment of the response to treatment.[39] In many cases, radiological features of disease progression are observed within the first 3–6 months following radiotherapy treatment, by an increase in enhancing disease. In a proportion of these, increases in edema, mass effect, and contrast enhancement within the high-dose radiotherapy volume are transient and resolve over time without intervention.[40] This phenomenon is known as “pseudoprogression,” and in cases of early enhancing disease, the reported incidence of pseudoprogression varies according to the criteria used, but is seen in approximately one-third of cases, and is seen more often in patients who show MGMT promoter methylation.[41],[42],[43],[44],[45] Although the pathological process is not clearly understood, histological features associated with pseudoprogression are bland necrosis, fibrosis, gliosis, edema, demyelination, and vascular hyalinization.[46] Patients with pseudoprogression usually remain clinically asymptomatic and have a longer overall survival compared with those with true tumor progression.

In clinical practice, it is difficult to differentiate between true progression and pseudoprogression; conventional MRI scans utilizing CE-T1WI and T2/FLAIR sequences have a low diagnostic accuracy for distinguishing between these two entities at early timepoints, from 3 weeks to 3 months postradiotherapy, due to similar imaging appearances.[47] Treatment is, therefore, continued with short interval imaging (4–6 weeks) and when progression is identified on consecutive imaging, true progression is confirmed. Some patients inevitably continue ineffective treatment, are delayed from receiving alternative treatments, or face potential exclusion from entering clinical trials as a result of deterioration in clinical status. Early and accurate diagnosis between true progression and pseudoprogression is essential to optimize treatment strategies and improve outcome.

A recent review article has shown that advanced MRI techniques that can assess physiological and metabolic properties of tissue have shown to be useful; these include ADC from DWI, fractional anisotropy from DTI, DSC perfusion, DCE perfusion, arterial spin labeling, MRS, ferumoxytol rCBV, amide proton transfer-weighted imaging, parametric response mapping, and perfusion MRI-fractional tumor burden (pMRI-FTB).[48] Combining advanced MRI techniques in a multiparametric protocol has shown to provide a higher degree of confidence in assessing glioblastoma treatment response [Figure 7] and [Figure 8].[49],[50],[51],[52] PET is another imaging modality that can be used to distinguish between true progression and pseudoprogression. The most widely used tracer, fluorodeoxyglucose (FDG), has a limited role; however, it has a higher accuracy in combination with advanced MRI techniques.[53] Other tracers with low background brain activity have shown to be more useful than FDG-PET, such as MET-PET, FET-PET, or FDOPA-PET,[48] but are less available. Many studies have shown that radiomics in combination with machine learning is promising but requires further validation.[54],[55],[56],[57],[58],[59],[60]
Figure 7: True progression in posttreatment glioblastoma with low MGMT promoter methylation (<10%). (a) Preoperative postcontrast T1WI. (b) Immediate postoperative contrast-enhanced T1WI showing resection of the right frontal glioblastoma. (c) Early postchemoradiotherapy postcontrast T1WI at 6 weeks shows a significant increase in contrast enhancement. Multiparametric magnetic resonance imaging at this timepoint demonstrates: (d) areas of restricted diffusion on diffusion-weighted imaging and apparent diffusion coefficient (<1000), (e) a high relative cerebral blood volume ratio on perfusion-weighted imaging (>2.0), (f) a very high Cho/Cr ratio (3.8), high Cho/NAA ratio on magnetic resonance spectroscopy. All parameters suggest a poor response and disease progression

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Figure 8: Pseudoprogression in posttreatment glioblastoma. (a) Preoperative T1WI. (b) Postoperative T1WI showing resection of the left frontal glioblastoma. (c) Early postchemoradiotherapy postcontrast T1WI at 4 weeks shows an increase in contrast enhancement (arrow). Multiparametric magnetic resonance imaging at this timepoint demonstrates (d and e) areas of free diffusion on diffusion-weighted imaging and apparent diffusion coefficient, (f) a low relative cerebral blood volume ratio on perfusion-weighted imaging, (g) a low Cho/Cr ratio, a low Cho/NAA ratio and presence of lipid and lactate on magnetic resonance spectroscopy. All these parameters suggest features of pseudoprogression. (h) Follow-up postcontrast T1WI at 12 months showing a further decrease in enhancement (arrow) confirming pseudoprogression

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Imaging during adjuvant temozolomide and posttreatment monitoring

MRI should be performed every 3 months following radiotherapy, or earlier if there is evidence of clinical progression, and ideally on similar MRI equipment and scanner field strength to limit variability.[61] In cases of confirmed progression, management involves second-line treatments or supportive care depending on the patient's prior treatment, performance status, and risk.

In contrast to pseudoprogression which is generally observed within the first 3–6 months following radiotherapy, radiation necrosis is a later process, seen mostly between 6 and 24 months after radiotherapy but can occur up to several years later.[62] This is a severe tissue reaction to radiotherapy, more progressive, and the proposed mechanism is thought to be related to vascular endothelial injury, glial and white matter damage, and changes to the fibrinolytic enzyme system, leading to perivascular coagulative necrosis.[63] Advanced MRI techniques have shown to be useful to distinguish between radiation necrosis and recurrent tumor; however, studies have shown that multimodal combination or multiparametric MRI has the best diagnostic accuracies.[64],[65]

Imaging assessment criteria

Imaging of glioblastoma as well as other high-grade glial tumors during the adjuvant chemotherapy and posttreatment monitoring period should be assessed by the RANO criteria. This takes account of the contrast-enhancing tumor, noncontrast-enhancing surrounding T2/FLAIR signal change, clinical status, and use of corticosteroids. The updated RANO criteria in 2010 addressed the issue of pseudoprogression, specifying that within the first 12 weeks following completion of radiotherapy, true tumor progression can only be attributed if there is new contrast enhancement outside the radiation field or if there is histological confirmation of tumor progression.[66] The inclusion of T2/FLAIR disease criteria is important as up to 40% of patients treated with bevacizumab showed an increase in nonenhancing disease despite the contrast-enhancing disease remaining stable.[13] The criteria discussed issues surrounding pseudoresponse after treatment with anti-angiogenic therapies, where an apparent response is due to the normalization of abnormally permeable tumor vessels rather than a true treatment response, and therefore, imaging responses should persist for at least 4 weeks before they are considered as true responses. In 2016, the immunotherapy RANO (iRANO) guidelines were developed to further address this issue, with the key addition of guidelines to continue immunotherapy treatment for 3 months if immunotherapy treatment was initiated within 6 months, as long as there is no significant clinical decline. On repeat imaging, if patients have a subsequent progressive disease, they can be classified as having true progression, which is backdated to the date of the initial radiographic progressive disease.[67] If imaging findings at the 3-month follow-up study meet the criteria for stable disease, partial response or complete response according to RANO criteria, compared to the previous MRI study meeting the criteria for progressive disease, and there is no clinical decline, patients should be considered as responding to immunotherapy treatment. The iRANO criteria also applied to low-grade gliomas and brain metastases (BM) being treated with immunotherapy agents.


  Metastases Top


Postoperative imaging of BM is recommended with the following European consensus guidelines: (i) parameter matched pre- and postcontrast inversion recovery (IR) – prepared, isotropic 3D T1-weighted gradient echo (IR-GRE); (ii) axial 2D T2W turbo spin-echo acquired after injection of gadolinium-based contrast agent and before postcontrast 3D T1W images; (iii) axial 2D or 3D T2W FLAIR; (iv) axial 2D or 3D DWI; and (v) postcontrast 2D T1W spin-echo images,[68] similar to the primary brain tumor protocol.

For patients receiving systemic therapy for intracranial metastases, imaging within 1 month of initiating therapy with subsequent imaging every 6 weeks until 12 weeks, then every 9 weeks until 48 weeks, then every 3 months, or as clinically indicated, is suggested.[69] For patients receiving whole-brain radiotherapy, imaging should occur every 3 months for the 1st year, and thereafter, every 4–6 months.[69] For patients receiving stereotactic radiosurgery (SRS), imaging should generally occur every 2–3 months for the 1st year and thereafter increasing the interval to 4–6 months.[70]

The RANO BM working group has produced criteria to determine treatment response and progression in BM,[71] given the various challenges and complexity in BM. RANO-BM criteria define measurable disease as lesions measuring 10 mm or larger; however, there is also guidance for smaller lesions, and there is also incorporation of corticosteroid use and issues relating to pseudoprogression from SRS and immunotherapy. Discussion at a multidisciplinary team meeting, short interval imaging, and the use of advanced imaging techniques, such as PWI, MRS, or PET imaging, are suggested to help distinguish true progression from pseudoprogression or radiation-related changes. Although the mechanisms of treatment effects after SRS are not yet fully understood, it is thought that microvascular damage is induced, which leads to indirect tumor cell death with release of cell death toxins leading to a spread of vasogenic fluid into the brain parenchyma with associated inflammation, edema, and abnormal vessel permeability. Radiation-related changes which are often confusingly and synonymously used with “radiation necrosis” in the literature are therefore associated with regions of hypoperfusion due to radiation-induced vascular endothelial damage and coagulative necrosis. In contrast, tumor recurrence is associated with increased angiogenesis, hyperperfusion with higher blood volume, and increased choline on MRS reflecting cell membrane turnover. Combining these advanced imaging techniques in a multiparametric MRI approach has shown to be more useful than any technique in isolation to distinguish tumor recurrence from SRS-related treatment changes [Figure 9] and [Figure 10].[72] Delayed contrast MRI performed at 70 min has also shown to be useful in detecting radiation-induced changes from tumor recurrence and can be visually represented through subtraction maps, also known as treatment response assessment maps, between the early 5 min and delayed 70 min time points.[73] In a tumor, the high vascularity shows a rapid rise in contrast as well as rapid clearance, whereas areas of treatment-related changes or low vascularity show accumulation of contrast and pooling on the delayed phase [Figure 10].
Figure 9: Progression of brain metastasis from primary breast carcinoma. (a) Postcontrast T1WI showing brain metastasis in the left perirolandic region. (b) Postcontrast T1WI 5 months after stereotactic radiosurgery treatment showing a slight reduction in size of the lesion. (c-e) Postcontrast T1WI and FLAIR at 12 and 14 months after stereotactic radiosurgery treatment showing an increase in the size of the lesion and surrounding edema. Multiparametric magnetic resonance imaging demonstrates: (f) a low apparent diffusion coefficient on diffusion-weighted imaging, (g) a raised relative cerebral blood volume ratio on perfusion-weighted imaging, and (h and i) a high Cho/Cr ratio and presence of lipid and lactate on magnetic resonance spectroscopy. Significant low apparent diffusion coefficient (<1000), high relative cerebral blood volume (>2.0) and high choline/creatine levels (>1.8) suggest predominant disease progression despite the high lipid levels, which are expected after stereotactic radiosurgery treatment

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Figure 10: Treatment-related changes in a brain metastasis from primary renal cell carcinoma. (a) Postcontrast T1WI showing brain metastasis in the right occipital region. (b) Postcontrast T1WI 5 months after stereotactic radiosurgery treatment showing an increase in the size of the right occipital lesion. (c) Delayed contrast magnetic resonance imaging at 70-min shows pooling of contrast within and around the lesion (arrow). (d) Treatment response assessment map showing predominant pooling of contrast (arrow). Multiparametric magnetic resonance imaging demonstrates: (e) free diffusion on apparent diffusion coefficient, (f) a low relative cerebral blood volume ratio on perfusion-weighted imaging, and (g) a normal Cho/Cr ratio and predominant lipid peak on magnetic resonance spectroscopy. All these parameters suggest a good response and stereotactic radiosurgery-induced changes. (h) Follow-up imaging at 10 months shows the stability of lesion size confirming treatment-related changes

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  Conclusion Top


The purpose of postoperative imaging is to evaluate expected and unexpected tumor and treatment-related changes. The recent WHO brain tumor classification based on an integrated diagnosis including molecular characteristics and advancement in various treatment options has made a direct impact on posttreatment imaging appearances. It has made the interpretation of postoperative/posttreatment imaging more challenging. Accurate assessment of imaging at appropriate time points requires background information of molecular genetics of the tumor, clinical status of the patient, and treatment timescales, particularly TMZ and gamma-knife treatments. The response assessment criteria for primary and secondary tumors which were initially produced for clinical trials are making their way into clinical practice. Standardized imaging protocol and multiparametric MRI at appropriate time points and standardized measurements are key factors for posttreatment response assessment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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