Adaptive hypofractionated gamma knife radiosurgery in the acute management of large thymic carcinoma brain metastases
- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
- Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden
- Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
DOI:10.4103/sni.sni_391_16Copyright: © 2017 Surgical Neurology International This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Georges Sinclair, Heather Martin, Michael Fagerlund, Amir Samadi, Hamza Benmakhlouf, Ernest Doodo. Adaptive hypofractionated gamma knife radiosurgery in the acute management of large thymic carcinoma brain metastases. 26-May-2017;8:95
How to cite this URL: Georges Sinclair, Heather Martin, Michael Fagerlund, Amir Samadi, Hamza Benmakhlouf, Ernest Doodo. Adaptive hypofractionated gamma knife radiosurgery in the acute management of large thymic carcinoma brain metastases. 26-May-2017;8:95. Available from: http://surgicalneurologyint.com/surgicalint-articles/adaptive-hypofractionated-gamma-knife-radiosurgery-in-the-acute-management-of-large-thymic-carcinoma-brain-metastases/
Background:Brain metastases often lead to serious neurological impairment and life threatening states. Their acute management remains complex, particularly in the case of rare malignancies with aggressive evolution. In large single lesions, open surgery followed by radiation to the surgical cavity is widely regarded as the best approach; yet in many cases, microsurgery is not feasible due to the lesion's critical location and/or the number of brain metastases present. We report the effects of adaptive hypofractionated gamma knife radiosurgery in the acute management of critically located thymic carcinoma metastases.
Case Description:A 50-year-old male with metastatic thymic carcinoma was treated with radiosurgery for two large supratentorial brain metastases (M3 and M4) adjacent to eloquent areas and one smaller cerebellar metastasis (M2). M3 and M4 were treated with adaptive hypofractionated gamma knife radiosurgery, showing a dramatic volume reduction 4 weeks after treatment completion without radiation-induced side effects. Thirteen months later, two new small, threatening supratentorial lesions (M5-M6) were treated with the same technique. Interestingly, M2 (treated with standard single fraction) and M5-M6 developed local adverse radiation events. The patient's general and neurological status remained next to normal by the time of paper submission.
Conclusion:The application of adaptive hypofractionated radiosurgery in this acute setting proved effective in terms of rapid tumor ablation, with salvage of neurological functionality and limited toxicity. We have called the overall procedure rapid rescue radiosurgery (RRR). A systematic study of past and ongoing RRR-treatments is warranted and in progress.
Keywords: Adaptive hypofractionation, adverse radiation event, critical areas, gamma knife radiosurgery, recursive partitioning analysis, whole brain radiation induced cognitive impairment
Brain metastases often lead to serious neurological impairment and life threatening states. Their acute management remains complex, particularly in the case of rare malignancies such as thymic carcinoma. In large single lesions, open surgery followed by radiation to the surgical cavity is widely regarded as the best approach; yet in many cases, microsurgery is not feasible due to the lesion's critical location and/or the number of brain metastases present. Our case report describes the effects of adaptive hypofractionated gamma knife radiosurgery in the acute management of critically located brain metastases.
We present the case of a 50-year-old male patient reporting intermittent upper abdominal pain throughout 2012 and 2013. In February 2014, the patient experienced breathing difficulties and exacerbation of pain. Fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed high FDG uptake in a large, heterogeneous intrathoracic mass in the middle mediastinum abutting the right atrium and the right hemidiaphragm, without evidence of distant metastases. The patient underwent subtotal primary tumor resection in April 2014. The histopathology demonstrated a poorly differentiated thymic carcinoma though without primary malignant manifestation in the gland itself. The patient received three adjuvant chemotherapy sessions (Carboplatine/Vepesid) followed by fractionated radiotherapy (2 Gy/day, 30 sessions = 2 Gy × 30 = 60 Gy) to the right thoracic region (July to September 2014). The patient developed paroxysmal atrial fibrillation after thoracic surgery as well as a series of respiratory infections during and after his radiochemotherapy, though without serious sequelae. His general condition remained otherwise stable. By February 2015, the patient developed progressive expressive dysphasia. A brain magnetic resonance imaging (MRI) in May 2015 showed a 3.5 cm ring-enhancing lesion in the left temporal lobe with extensive edema (metastasis # 1 = M1). Speech impairment resolved shortly after gross total resection (GTR). The histopathology proved the lesion to be a thymic carcinoma metastasis with MIB 1 proliferation index of up to 50%. Postsurgical hypofractionated LINAC-radiotherapy (6 Gy/day, 5 sessions = 30 Gy) was delivered to the surgical cavity in June 2015. CT of the neck, thorax, and abdomen in September 2015 showed no signs of distant metastases. However, a follow-up brain MRI in October 2015 demonstrated three new intracranial lesions – the first a 1.9 cm lesion in the right cerebellar hemisphere (metastasis # 2 = M2), the second, a larger extra-axial left temporal mass measuring 3.9 cm with adjacent edema and mass effect threatening the hippocampus, uncus, and language areas (metastasis # 3 = M3), and the third, a 3.0 cm dural-based left parietal lesion exerting mass effect on the sensory cortex (metastasis # 4 = M4). There was no evidence of recurrence in the surgical cavity (M1). Although M2 was relatively small, M3 and M4 were quite large (≥3 cm) and both threatened eloquent areas of the brain. By this time, the patient once again developed expressive dysphasia and mental fatigue [Karnofsky Performance Score (KPS) 90–100], though without evidence of extracranial tumour proliferation (RPA 1) on prior screening CT scan September 2015; the patient remained free from systemic treatment at this stage and was referred to our unit for further management (October 2015).
The radiosurgical plan was designed based on a series of factors – past/present radiological evolution, tumor localization, identification of organs at risk (OAR), tumor volume, histopathological traits of prior resected metastasis (M1), general and neurological health status (KPS/RPA), absence of extracranial tumor activity at the time of radiosurgery, positive outcome after microsurgery, and good response to prior anti-tumoral treatments (including chemotherapy and extra/intracranial radiation). Our strategy aimed to rapidly relieve/salvage the language areas, the hippocampus, and the post-central gyrus from the larger left-sided lesions (M3 and M4) within a time frame of 7 days (treatment time between RS1 and RS3) to 4 weeks (MRI at 1 month). Because of the patient's previous positive response to extra and intracranial radiotherapy, we considered the tumor to be radiosensitive and proceeded to plot a peripheral prescription dose biologically isoeffective to the cranial hypofractionated treatment delivered to the surgical cavity earlier (6 Gy × 5). To achieve maximal probability of local tumor control while minimizing the risk of focal radiation-induced adverse reaction, treatment settings included an adaptive and MRI-guided hypofractionated radiosurgical approach; the procedure would allow tumor bed dose distribution readjustments in relation to local tumor volume variations during the course of treatment. The treatment was structured on three radiosurgeries (RS) delivered every third day i.e., day 1 (RS 1), day 4 (RS 2), and day 7 (RS 3). Cranial fixation was achieved by applying a Leksell Coordinate Frame G (Elekta AB, Stockholm) prior to each RS. A stereotactic MRI was performed before each RS session (s-MRI 1, 2, 3) for proper gross tumor volume (GTV) delineation; we set no margins to the GTV (GTV = CTV = PTV). As described in Tables
LGP-based tumor volume estimates covering time of treatment (Day 1 to Day 7) and follow up period (1 to 7 months). *M3 showed signs of hemorrhage at RS 2 (Day 4) and RS 3 (Day 7); bleeding zones were included in the field of treatment (GTV); see
The radiological evolution during the course of treatment proved interesting for all concerned lesions. M2 developed increased central necrosis between s-MRI 1 (day 1) and s-MRI 2 (day 4). M3 developed local hemorrhage at s-MRI 2 (day 4) while its solid component suffered a slight volume reduction at s-MRI 3 (day 7) [Tables
M4: Axial, coronal and sagittal contrast enhanced T1 weighted MR images show significant tumor reduction at 1 month (center column) and 7 months (right column) respectively after RRR. Left column shows tumor size at day 1 (RS 1). Significant tumor reduction at 1 month (center column) and 7 months (right column)
(a) M2's evolution on amino acid PET. 11C-Methionine PET (MET PET, left), MET PET fused with MRI CE T1 (middle) and MRI CE T1 weighted (right) axial images at 7 months demonstrating intermediate focal MET uptake in the medial aspect of the ring enhancing right cerebellar lesion (T/N ratio = 1.5 compared to contralateral mirrored tissue) and local edema. (b) MET PET (left) at 10 months now demonstrating T/N ratio = 1.3, diminished compared to MET PET 3 months prior, MET PET fused with MRI CE T1 (middle) and MRI CE T1 weighted (right): suspected ARE
MET PET and MR imaging at 13 months: (a) Axial MET PET (b) axial MET PET + MRI CET1 (c) axial MRI CET1 (d) axial T2 (e) axial DWI (f) axial ADC (g) MR perfusion rCBV (h) reoriented CET1 demonstrating M5 and M6's proximity to the surgical area as well as new nodular rim enhancement of the surgical cavity
Extracranial tumor screening in November 2016 showed no recurrence. By the time of paper submission, the patient's clinical condition was assessed as good (KPS 90–100/RPA 1) without ongoing antitumoral therapy. The patient remains on low dose cortisone due to M5-M6's ARE. Further clinical and radiological follow up (including MRI and PET scans) are planned to carefully monitor M5-M6's evolution and identify further brain metastatic development.
The management of brain metastases remains complex and requires tailored treatment, often including microsurgery, different radiotherapeutic modalities, chemotherapy, as well as targeted therapy.[
Based on our institutional experience and previous reports,[
We have achieved similar results on a number of cases with large metastatic brain lesions with more common histopathological traits; a retrospective analysis covering the short and long-term outcome of RRR on these cases will be the subject of our next two papers.
In this particular case, Rapid Rescue Radiosurgery (RRR) proved highly effective in achieving next to comparable surgical decompression results on two large aggressive metastatic brain lesions. However, particular factors such as the tumor's histopathology/intrinsic radiosensitivity as well as RPA-surrogate factors could have played a substantial role in the outcome of the treatment. We believe this procedure has the potential to become an important surgical tool in the future management of large unresectable metastases. Retrospective analysis of all cases treated with RRR as well as further prospective studies are warranted and indeed ongoing.
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Conflicts of interest
There are no conflicts of interest.
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