Neurological imaging of brain damages after radiotherapy and/or chimiotherapy

doi:10.1016/j.neurad.2013.07.005

Journal of Neuroradiology

Volume 41, Issue 1, March 2014, Pages 52-70

https://doi.org/10.1016/j.neurad.2013.07.005 Get rights and content

Summary

Radiotherapy and chemotherapy may induce neurological toxicities with different appearances on CT and MRI scans. While optimized radiotherapy techniques have reduced some complications, new unwanted effects have occurred on account of therapeutic protocols involving the simultaneous use of radiotherapy and chemotherapy. Advances in radio-surgery, innovative anti-angiogenic therapies, as well as prolonged patient survival have led to the emergence of new deleterious side effects. In this report, we describe the early, semi-delayed, and late encephalic complications, while specifying how to identify the morphological lesions depending on the therapeutic protocol.

Introduction

Radiotherapy and chemotherapy both play an important role in cancer treatment. Advances made in radiation techniques and the use of optimized radiotherapy protocols have resulted in a significant decrease in the neurological toxicity that can arise during the course of malignant brain tumor therapy as well as in the treatment of benign head and neck (ENT) tumors.

However, a series of factors such as new protocols involving radio/chemotherapy, progress made in radiosurgery and increasing rates of long-term survivors have resulted in a rise in post-therapeutic brain damage, especially in patients who underwent radiation therapy during childhood. The survival of children suffering from brain tumors has clearly improved, but this has been associated with enhanced brain damage later on in adulthood. It should be noted that radiosurgery may also be used for lesions other than malignant tumors, most notably benign tumors such as meningiomas and neurinomas that come with high surgical risks as well as vascular malformations.

This report focuses on the neurological anomalies that are visible on brain imaging. Three types of complications are observed: acute; semi-delayed; and late. Acute complications are reversible on treatment discontinuation or modification, semi-delayed complications can mimic tumor recurrence, and late complications are well established and irreversible. The current challenge is to identify and characterize these complications as soon as possible to allow the initiation of rapid and appropriate treatment.

Section snippets

Acute complications

These arise during radio/chemotherapy or immediately after treatment cessation.

Semi-delayed complications

These are generally seen within 2 weeks and 6 months of stopping radio/chemotherapy, with a peak at 2 months.

Late complications

These may arise at any time from 6 months and several decades after the completion of radiotherapy.

Conclusion

For peri- and post-therapeutic monitoring of tumors involving the head and neck, it seems important to know precisely the therapeutic regimen used to best analyze and interpret any radiological investigations attempting to distinguish the phenomena of pseudoresponse, pseudoprogression and radionecrosis related to tumor evolution.

While optimization of dosimetry has been instrumental in reducing radiotherapy-related complications, the concomitant association of chemotherapy and the use of in-situ

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

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Mortality of early treatment for radiation-induced brain necrosis in head and neck cancer survivors: A multicentre, retrospective, registry-based cohort study
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Citation Excerpt :
As such, asymptomatic patients are usually monitored without any medical intervention until presenting with RN-related neurological symptoms.8,11 The mechanisms underlying RN involve blood-brain barrier dysfunction, leakage of intravascular inflammatory cytokines, microglia overreaction and subsequent cellular damage6,23–25; thus RN on brain MRI typically presents as a contrast-material enhanced white matter lesion with adjacent cerebral parenchymal edema, which if untreated would ultimately lead to cyst formation or even cerebral hernia.10,18 Although some RN could be asymptomatic with mild brain edema at the early stage, the majority of them would progress and eventually become irreversible without effective interventions.
The evidence of early treatment for radiation-induced brain necrosis (RN) in head and neck cancer survivors remains insufficient. This study aimed to determine whether early anti-RN treatment was associated with lower mortality.
In this cohort study, we utilized data from the Study in Radiotherapy-related Nervous System Complications (NCT03908502) and Hong Kong Cancer Registry. We included consecutive patients who had received radiotherapy (RT) for head and neck cancers and had subsequently developed RN between Jan 8, 2005 and Jan 19, 2020. Patients who had tumor progression before the diagnosis of RN, underwent surgical brain necrosis lesions resection before corticosteroids and/or bevacizumab treatment, had intracranial metastases before the diagnosis of RN, lacked follow-up data, or had a follow-up period of less than three months were excluded. Individual-level data were extracted from electronic medical records of the above-mentioned registries. The primary outcome was all-cause death. The vital status of each patient was confirmed through a standardized telephone interview. We compared patients who received early treatment (initiating bevacizumab or corticosteroids treatment within three months after RN diagnosis) with patients who did not (following a “watch-and-wait” policy).
Of 641 eligible patients, 451 patients (70·4%) received early treatment after RN diagnosis and 190 patients (29·6%) did not. Overall, 112 patients (17·5%) died, of whom 73 (16·2%) in the early treatment group and 39 (20·5%) in the watch-and-wait group, during a median follow-up of 3·87 years. The early treatment group showed a lower risk of all-cause death compared with the watch-and-wait group after adjusting for age, sex, absence or presence of neurological symptoms at baseline, RN lesion features on brain magnetic resonance imaging, history of stroke, prior tumor-related characteristics (TNM stage, RT dose and techniques, and chemotherapy), and the time interval from RT to RN (HR 0·48, 95%CI 0·30 to 0·77; p = 0·0027), and extensive sensitivity analyses yielded similar results. There was no significant difference in the effect of early treatment on post-RN survival among subgroups stratified by presence or absence of neurological symptoms at diagnosis (p for interaction=0·41).
Among head and neck cancer survivors with RN, initiating treatment early after RN diagnosis is associated with a lower risk of all-cause mortality as compared with following the watch-and-wait policy, irrespective of whether patients exhibit symptoms or not. Further prospective randomised studies would be needed to validate our findings since the observational study design might lead to some potential confounding. In the absence of data from randomised trials, our study will have an important implication for clinicians regarding the optimal timing of treatment for RN, and provides the foundation and supporting data for future trials on this topic.
National Natural Science Foundation of China (81925031, 81820108026, 81872549, 81801229, 82003389), the Science and Technology Program of Guangzhou (202007030001), Young Teacher Training Program of Sun Yat-sen University (20ykpy106), Key-Area Research and Development Program of Guangdong Province (2018B030340001), the National Medical Research Council Singapore Clinician Scientist Award (NMRC/CSA-INV/0027/2018, CSAINV20nov-0021), the Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme, NCCS Cancer Fund, the Kua Hong Pak Head and Neck Cancer Research Programme, and the National Research Foundation Clinical Research Programme Grant (NRF-CRP17-2017-05).
A novel nomogram to predict overall survival in head and neck cancer survivors with radiation-induced brain necrosis
2022, Radiotherapy and Oncology
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We screened consecutive patients being diagnosed with RN in the Radiotherapy-related Nervous System Complications Database (a single-center, observational study of radiation injuries in Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China, NCT03908502) from January 2005 through January 2020. Patients were included in this study if they met the following criteria: (1) had received and completed RT (+/− chemotherapy) for histologically confirmed head and neck cancers; (2) showed radiographic evidence of RN after RT without tumor recurrence or metastases [15]. The diagnosis of RN was made based on opinions from both neurologists and radiologists in accordance with the diagnostic criteria as reported in Supplementary Appendix S2.
The study aimed to develop and validate a novel nomogram to predict overall survival in head and neck cancer survivors following the diagnosis of radiation-induced brain necrosis (RN).
We included head and neck cancer survivors with RN from a radiation complications registry study. A total of 495 eligible patients were 7:3 randomly allocated to a training cohort and an internal validation cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select significant predictors of post-RN survival in the training cohort, and a multivariable Cox model was used to develop the nomogram. The performance of the nomogram was assessed using the internal validation cohort and externally validated using additional 88 RN patients.
We identified five predictors of post-RN survival using the training data: age, tumor progression before RN, lower cranial nerves injury, bilateral necrosis, and history of stroke. The nomogram showed favorable performance in the internal validation cohort (C-index 0.761, 95% CI 0.676 to 0.847) and in the external validation cohort (C-index 0.795, 95% CI 0.717 to 0.874). The decision curve analysis indicated that the nomogram was clinically useful when the probabilities of death ranging from 1% to 48% at 1 year, from 3% to 50% at 3 years, and exceeding 2% at 5 years after being diagnosed with RN.
In this LASSO-Cox model-based nomogram study, we developed and validated an easily applied model to predict overall survival in head and neck cancer survivors following an RN diagnosis.
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Accurate classification of gliomas is important as the treatment modalities are substantially different between WHO grade III and IV tumors. Patients with GBM have the worst prognosis with a median survival of approximately 12 months despite advances in surgery, radiation therapy, and chemotherapy [22–24]. The current histopathology-based classification system for gliomas is complicated by considerable interobserver variability [25].
The purpose of our study was to assess whether a model combining clinical factors, MR imaging features, and genomics would better predict overall survival of patients with glioblastoma (GBM) than either individual data type.
The study was conducted leveraging The Cancer Genome Atlas (TCGA) effort supported by the National Institutes of Health. Six neuroradiologists reviewed MRI images from The Cancer Imaging Archive (http://cancerimagingarchive.net) of 102 GBM patients using the VASARI scoring system. The patients’ clinical and genetic data were obtained from the TCGA website (http://www.cancergenome.nih.gov/). Patient outcome was measured in terms of overall survival time. The association between different categories of biomarkers and survival was evaluated using Cox analysis.
The features that were significantly associated with survival were: (1) clinical factors: chemotherapy; (2) imaging: proportion of tumor contrast enhancement on MRI; and (3) genomics: HRAS copy number variation. The combination of these three biomarkers resulted in an incremental increase in the strength of prediction of survival, with the model that included clinical, imaging, and genetic variables having the highest predictive accuracy (area under the curve 0.679 ± 0.068, Akaike's information criterion 566.7, P < 0.001).
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Original articleNeurological imaging of brain damages after radiotherapy and/or chimiotherapy

Summary

Introduction

Section snippets

Acute complications

Semi-delayed complications

Late complications

Conclusion

Disclosure of interest

J Neurol Sci

J Neuroradiol

Rev Neurol (Paris)

Int J Radiat Oncol Biol Phys

Rev Neurol (Paris)

Int J Radiat Oncol Biol Phys

Lancet

Lancet Oncol

Int J Radiat Oncol Biol Phys

Rev Neurol (Paris)

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

J Neuroradiol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Neurologia

Clin Neurol Neurosurg

Oral Oncol

J Vasc Surg

J Neuroradiol

Rev Neurol (Paris)

Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema

AJNR Am J Neuroradiol

Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma

J Clin Oncol

Mechanisms of radiation injury to the central nervous system: implications for neuroprotection

Mol Interv

Drug-induced thrombotic microangiopathy

Semin Thromb Hemost

Changes in anti-thrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study

Haematologica

Clinical and radiological features of brain neurotoxicity caused by antitumor and immunosuppressant treatments

Neurol Sci

Two cases of cerebral sinus venous thrombosis following chemotherapy for non-seminomatous germ cell tumor

Case Rep Oncol

Cerebral ischemic events and anti-cancer therapy

Rev Neurol (Paris)

Acute methotrexate neurotoxicity: findings on diffusion-weighted imaging and correlation with clinical outcome

AJNR Am J Neuroradiol

Cerebral vasculopathy and multiple infarctions in a woman with carcinomatous meningitis while on treatment with intrathecal methotrexate

J Neurooncol

Ischemic stroke and intracranial hemorrhage in glioma patients on antiangiogenic therapy

J Neurooncol

Neurologic complications of brain radiotherapy: contribution of experimental studies

Bull Cancer

Oligodendrocytes in the adult rat spinal cord undergo radiation-induced apoptosis

Cancer Res

Biphasic patterns of memory deficits following moderate-dose partial-brain irradiation: neuropsychologic outcome and proposed mechanisms

J Clin Oncol

Supratentorial gliomas: neuropsychological study of long-term survivors

Rev Neurol (Paris)

Pseudoprogression and pseudoresponse: imaging challenges in the assessment of post treatment glioma

AJNR Am J Neuroradiol

Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemo irradiation with temozolomide

Cancer

Comparison of 3 Tesla proton MR spectroscopy, MR perfusion and MR diffusion for distinguishing glioma recurrence from post treatment effects

J Magn Reson Imaging

MR spectroscopy in radiation injury

AJNR Am J Neuroradiol

Original article
Neurological imaging of brain damages after radiotherapy and/or chimiotherapy