Abstract
BACKGROUND
Cystic formation due to radiation necrosis in metastatic brain tumors is a rare condition. Surgical intervention is necessary if symptoms develop. Additionally, excising radiation necrosis lesions within the cyst is essential to prevent recurrence. Neuroendoscopic surgery is a minimally invasive method suitable for treating cystic diseases and accessing deep lesions in the brain. The authors herein present a method for removing radiation necrotic tissue from deep lesions of cystic radiation necrosis using neuroendoscopy.
OBSERVATIONS
Endoscopic surgery was performed in two patients with symptomatic cystic radiation necrosis. Both cases involved multilocular cysts, with radiation necrosis located deep within the cyst. The authors performed a small craniotomy of approximately 3 cm and opened the cyst. After removing its contents, an endoscope was used to closely observe the interior of the cyst. Removal of the septum within the cyst allowed the endoscope to be inserted deeply. The authors identified and excised the nodular lesion diagnosed as radiation necrosis in the deep tissue. Following the surgery, the cyst shrank rapidly, and symptoms disappeared. Both patients showed no recurrence of the lesions.
LESSONS
The authors performed minimally invasive surgery and achieved good outcomes. Endoscopic surgery was considered beneficial for treating cystic radiation necrosis.
Keywords: cystic radiation necrosis, endoscopic surgery, metastatic brain tumors, stereotactic radiosurgery
ABBREVIATIONS: AVM = arteriovenous malformation, CRN = cystic radiation necrosis, MRI = magnetic resonance imaging, PET = positron emission tomography, SRS = stereotactic radiosurgery.
Metastatic brain tumors are among the most common intracranial malignancies in patients with cancer, occurring in approximately 10% of them.1, 2 Treatments for metastatic brain tumors include surgery, radiation therapy (whole-brain radiation therapy and stereotactic radiosurgery [SRS]), and pharmacotherapy (chemotherapy, immunotherapy, and targeted agents).3, 4 Additionally, some studies have reported the use of laser interstitial thermal therapy for metastatic disease.5, 6 These treatments are combined based on the size and number of tumors, as well as the patient’s Karnofsky Performance Status. In recent years, radiation therapy for brain metastases has advanced significantly. Radiation necrosis, a characteristic complication of radiation therapy, occurs in approximately 7%–25% of cases.7, 8 Among these, cystic formation due to radiation necrosis is rare, occurring in only 0.9% of brain metastases treated with SRS.9 While some cases of radiation necrosis resolve with follow-up, patients experiencing symptoms require treatment.10 Medical treatments such as corticosteroids and bevacizumab are often utilized;11, 12 however, surgical treatment becomes necessary if these prove ineffective. On the other hand, symptoms of cystic radiation necrosis (CRN) often manifest as mass effect due to the cyst, and reported medical treatments are typically ineffective.13, 14 To investigate the surgical treatment of CRN in metastatic brain tumors, we conducted a literature search using keywords such as “radiation necrosis,” “brain metastasis,” and “cyst formation” in the PubMed database in January 2024. The study included cases in which SRS was performed for metastatic brain tumors and subsequent surgical treatment was conducted for CRN. We excluded cases in which radiotherapy was administered for brain tumors other than metastatic brain tumors or extracranial lesions, cases of radiation necrosis without cyst formation, and cases that did not involve surgical treatment. Reports on surgical treatments for CRN included five cases, which discussed resection, cyst fenestration, and drainage through the placement of an Ommaya reservoir.9, 13–16
Endoscopic surgery is particularly useful for treating cystic lesions and deep lesions in the brain, such as those in the intraventricular and basal ganglia regions. Advances in neuroendoscopic technology and devices have facilitated endoscopic resection for glioma.17, 18 Compared to microscopic surgery, endoscopic surgery is less invasive and offers the advantage of detailed observation of deep lesions. While there are no reports of CRN being treated with endoscopic surgery, we herein demonstrate for the first time the use of endoscopic surgery for CRN.
Illustrative Cases
Surgical Technique
We identified the location of the CRN using a neuronavigation system (StealthStation, Medtronic), and a 3-cm-small craniotomy was performed above the CRN. During the surgery, a 4-mm rigid endoscope, secured with an endoscope holder (Endoarm, Olympus), was utilized for visualization. After incising the dura, we confirmed the cyst and resected its wall. The interior of the cyst was filled with xanthochromic fluid, allowing for observation after its removal. While the cyst initially shrank upon opening, inserting the transparent sheath (Neuroport, Olympus) with a 10-mm diameter or the ViewSite Brain Access System (width 17 mm, height 11 mm, length 7 cm; Vycor Medical Inc.) prevented further shrinking, facilitating close observation of the inside of the cyst using the endoscope. These cysts were multilocular; therefore, the removal of septa allowed communication between cyst compartments. Subsequently, we could observe other components by inserting the endoscope into the next compartment. Observation of the interior compartments of the cyst revealed contrast-enhanced lesions on magnetic resonance imaging (MRI). This reddish nodular lesion was diagnosed as radiation necrosis, requiring removal to prevent cyst recurrence. The lesion was identified using an endoscope, carefully dissected from the surrounding tissue, and removed. No drainage tube or Ommaya reservoir was placed within the cyst after removing the necrotic tissue. The dura mater was tightly sutured, and the bone flap was secured with titanium plates. Patients resumed oral intake and ambulation the following day.
Case 1
A 64-year-old woman presented with a left lung mass diagnosed as adenocarcinoma through biopsy. Concurrently, a metastatic tumor was identified in the right parietal lobe on MRI, and SRS (30 Gy in 5 fractions) was administered (Fig. 1A and B). Despite chemotherapy, multiple intracranial lesions were observed on MRI 18 months post-SRS, leading to SRS for the new lesions (20 Gy in 1 fraction). Surveillance MRI at 24 months post-SRS revealed increasing heterogeneous enhancement with multiple cysts in the right parietal lobe (Fig. 1C and D). Radiation necrosis was diagnosed on positron emission tomography (PET). The lesion had enlarged, resulting in the development of homonymous hemianopia and left-sided weakness; therefore, we started steroid treatment. Despite steroid treatment, the cyst progressively enlarged, and the patient’s symptoms worsened (Fig. 1E and F). Consequently, resection for the CRN was performed using neuroendoscopy. A 3-cm-diameter craniotomy was performed on the right parietal area. Cyst fenestration released xanthochromic fluid, and a Neuroport sheath was inserted into the cyst. The deep cyst wall was excised, revealing a mass consistent with an enhanced lesion deep within the cyst on preoperative MRI (Fig 2). The lesion was excised, and pathological analysis confirmed radiation necrosis without evidence of tumor recurrence or a cavernous malformation element. The surgery lasted 3 hours 32 minutes. Postoperatively, the patient experienced a resolution of symptoms and ceased steroid treatment. MRI after 50 months postsurgery showed no recurrence of the CRN (Fig. 1G).
FIG. 1.
Case 1. Axial T2-weighted and enhanced T1-weighted MRI. Initial MRI upon the diagnosis of lung cancer revealed a metastatic tumor in the right parietal lobe (A and B). Images obtained 24 months post-SRS showed radiation necrosis with multiple cysts still evident (C and D). Preoperative images showed an enlarged multilayer cyst with an edematous-appearing area and an enhanced lesion within the cyst (E and F). The cystic lesion notably disappeared, with only mild edema observed 50 months following endoscopic surgery (G).
FIG. 2.
Case 1. A 3-cm-diameter craniotomy was performed (A). Close observation of the interior of the cyst using an endoscope revealed septa deep within the cyst (B). Subsequently, the septa were removed. Reddish nodular lesions were visible deep within the cyst (C). We coagulated the lesion with bipolar forceps and removed it piecemeal. Pathological analysis confirmed radiation necrosis without evidence of tumor recurrence. As the removal proceeded, the deep cyst wall became visible (D and E). After the removal, we performed coagulation of the attachment area (F). The arrowhead indicates the septum, and arrows indicate the nodular lesion.
Case 2
A 73-year-old woman diagnosed with lung squamous cell carcinoma underwent chemotherapy. However, MRI revealed a metastatic tumor in the left frontal lobe (Fig. 3A and B). Consequently, SRS was administered (30 Gy in 5 fractions). Following tumor disappearance, a lesion was detected in the left frontal lobe, diagnosed as radiation necrosis using PET performed 12 months post-SRS. The lesion had enlarged; therefore, we initiated steroid treatment. However, MRI performed 42 months after SRS indicated the formation of a multilocular cyst with edema (Fig. 3C and D). Furthermore, despite increasing the steroid dose, the cyst progressively enlarged, and contrast-enhanced lesions were observed deep within the cyst (Fig. 3E and F). Disorientation and right hemiparesis developed, prompting neuroendoscopic surgery with a small craniotomy on the left frontal area (Fig. 4). Following cyst wall resection, a Viewsite system was inserted into the cyst. Upon observing the cyst interior, we identified and removed the deep cyst wall. Inspection of the interior of the deep part of the cyst revealed a reddish nodular lesion, which was excised and diagnosed as radiation necrosis with no recurrence or cavernous malformation elements on pathological examination. The operation duration was 2 hours 57 minutes. The patient’s symptoms markedly improved postsurgery, and surveillance MRI conducted 6 months later showed a reduction in the size of the CRN (Fig. 3G).
FIG. 3.
Case 2. Axial T2-weighted and enhanced T1-weighted MRI. Pre-SRS MRI showed a metastatic brain tumor in the left frontal lobe (A and B). Images obtained 42 months after SRS revealed an enhanced lesion with a small cyst in the left frontal lobe (C and D). Preoperative images showed the enlarged cyst, with an enhanced lesion located deep within (E and F). MRI performed 6 months postoperatively showed shrinkage of the cystic lesion (G).
FIG. 4.
Case 2. A small craniotomy was performed (A). Drainage of the fluid within the cyst and removal of the septa deep within the cyst followed (B). Close observation of the interior of the cyst revealed a reddish nodular lesion located deep within the cyst (C). We identified the border between the reddish nodular lesion and the surrounding tissue (D). Subsequently, we resected the nodular lesion diagnosed as radiation necrosis (E). After removing the lesion, we confirmed that there was no residual lesion and could observe the cyst wall deep inside (F). The arrowhead indicates the septum, and arrows indicate the nodular lesion.
Patient Informed Consent
The necessary patient informed consent was obtained in this study.
Discussion
Observations
Radiation necrosis is a complication that typically arises approximately 1–2 years after radiation treatment.8 In some cases, radiation necrosis can be entirely asymptomatic, while in others, it can cause neurological symptoms necessitating treatment with medication or resection.8, 10 CRN has been reported in arteriovenous malformations (AVMs) with an incidence of 3%–5%;19, 20 however, it is rare in metastatic brain tumors. CRN typically occurs as a very late complication. In recent years, advancements in the treatment of systemic cancers and metastases have led to increasing survival rates for patients with brain metastases.3, 21 However, this long-term survival has resulted in a growing population of patients at risk for additional long-term side effects of therapies. Therefore, we must pay special attention to this complication.13, 14 The mechanism of delayed cyst formation after radiation for metastatic brain tumors remains unclear; however, previous reports have suggested that radiation injures blood vessel walls within the degenerated or scar tissue, leading to increased vascular permeability and subsequent cyst formation.15, 22 In the delayed cyst formation of AVM after SRS, it has been reported that radiation-induced inflammation leads to angiomatous changes, such as the development of newly formed capillary vessels. Subsequently, repeated minor hemorrhages from the angiomatous lesion in the enhanced nodule result in cyst formation, which enlarges due to increased protein content and osmotic pressure. The content of the cyst has been reported to be xanthochromic with a high protein concentration.23
There are a limited number of reports detailing surgical treatment for CRN in cases of metastatic brain tumors, including procedures such as removal, cyst fenestration, drainage, and Ommaya reservoir placement (Table 1).9, 13–16 In most of these cases, medical treatments such as steroids or antivascular endothelial growth factor monoclonal antibodies were administered before surgery. As in our cases, histological examination of specimens obtained via excision and biopsy of CRN showed no evidence of metastatic brain tumor recurrence but did reveal necrosis. For patients with symptomatic CRN, although steroid therapy can temporarily lead to symptomatic relief in the early stages, surgical treatment becomes necessary.24 Following treatment, symptoms typically improve rapidly once the cyst shrinks, although recurrence within 6 months has been reported after fenestration or resection.12, 13 The placement of an Ommaya reservoir is less invasive than open surgical fenestration, although it can necessitate continuous or repeat drainage.14, 15 The causes of CRN recurrence in patients with metastatic brain tumors have not been reported. In cases of AVM, cyst formation is associated with an enhanced angiomatosis nodule. Therefore, wide opening of the cyst and removal of the lesion are necessary for effective cyst treatment.23
TABLE 1.
Literature review of cases of surgical treatment for CRN
| Authors & Year | Type of Radiation (Gy/fractions) | Origin | Time to Cyst Formation From Radiation (mos) | Symptomatic/Symptoms | Surgical Tx | Clinical Outcome |
|---|---|---|---|---|---|---|
| Alattar et al., 20189 | SRS (22/1) | Breast | 35 | Yes/aphasia | Cyst fenestration | Recurrence |
| SRS (NA/NA) | NA | 5 | Yes/NA | Cyst fenestration | Improvement | |
| SRS (NA/NA) | NA | 37 | Yes/NA | Cyst fenestration | Improvement | |
| SRS (NA/NA) | NA | 10 | Yes/NA | Cyst fenestration | Improvement | |
| Giantini-Larsen et al., 202313 | SRS (22/1) | Melanoma | 84 | Yes/Sz, Gerstmann syndrome | Cyst fenestration | Improvement |
| SRS (30/5) | Breast | 60 | Yes/headache, gait instability, visual field cut | Cyst fenestration | Recurrence | |
| WBRT (30/10) + SRS (NA/NA) | Breast | 48 | Yes/visual field cut | Cyst fenestration | Improvement | |
| Aizawa et al., 201814 | WBRT (40/16) + SRS (22/1) | Mucoepidermoid carcinoma | 123 | Yes/partial paralysis | Ommaya reservoir | Needed continuous drainage |
| Ishikawa et al., 200915 | SRS (20/1) | Breast | 48 | Yes/NA | Ommaya reservoir | Improvement |
| SRS (25/1) | Lung | 48 | Yes/NA | Ommaya reservoir | Improvement | |
| SRS (20/1) | Ovarian | 58 | Yes/hemiparesis, consciousness disorder | Ommaya reservoir | Improvement | |
| SRS (20/1) | Kidney | 71 | Yes/NA | Ommaya reservoir | Needed drainage | |
| SRS (24/1) | Lung | 37 | Yes/NA | Ommaya reservoir | Needed drainage | |
| Matsuda et al., 202116 | SRS (NA/NA) | NA | 85 | NA/NA | Cyst fenestration | NA |
| SRS (NA/NA) | NA | 96 | NA/NA | Cyst fenestration | NA | |
| Present cases | SRS (30/5) | Lung | 24 | Yes/hemiparesis, visual field cut | Endoscopic op | Improvement |
| SRS (30/5) | Lung | 42 | Yes/hemiparesis, consciousness disorder | Endoscopic op | Improvement |
NA = not available; Sz = siezure; Tx = treatment; WBRT = whole-brain radiation therapy.
Among the surgical treatments for CRN, only fenestration can be performed with a small incision and craniotomy; however, observation of the interior of CRN remains challenging. Utilizing a microscope for observing the cyst’s interior and removing the cyst wall and necrotic lesions requires a large craniotomy. Furthermore, based on our cases and previous reports, CRN often presents as multilocular cysts. Thus, when approaching deep cysts, it is essential to consider the presence of blind spots.
Endoscopic surgery has emerged as an effective method for treating deep-seated and intraventricular tumors. Recently, several reports have demonstrated the successful resection of intraparenchymal tumors using endoscopy.17, 18 Endoscopy offers several advantages over microsurgery, including enhanced illumination and depth of view, as well as a minimized wound and craniotomy.18 Utilizing an endoscope at various angles allows for detailed visualization of tumors and cysts. Surgeons can prevent cyst shrinkage and ensure sufficient working space for manipulation by inserting a sheath. Moreover, the interior of a multilocular cyst can be accessed by removing the septa within the cyst and passing the endoscope through it.
In the present cases, preoperative MRI revealed that the CRN lesions were multilocular and contained enhanced nodular lesions deep within them. Therefore, in addition to fenestration to establish communication between each cyst, we needed to remove these enhanced lesions. During the surgery, a small craniotomy was performed, and by removing the septum of the cyst and using an endoscope, we were able to fully observe the interior of the cyst, thereby confirming the presence of contrast-enhanced lesions and removing them. The wound was small, making the procedure less invasive. Postoperative neurological symptoms improved in both reported cases, and there were no recurrences during the follow-up period.
A limitation of this approach is that the endoscope would be unnecessary if nodular lesions are superficial on the cyst. While we diagnosed radiation necrosis through PET and the clinical course, it is also essential to consider the possibility of tumor recurrence. Although endoscopic surgery has been shown to be effective for CRN, there are no reports on the long-term outcomes of CRN treated with endoscopy, warranting further examination.
Lessons
In this study, we reported two cases of CRN treated with endoscopic surgery. CRN following SRS in cases of metastatic brain tumors is rare and can require surgical intervention. We demonstrated that endoscopic surgery is effective for CRN. Further investigation is needed for long-term evaluation.
Acknowledgments
We would like to thank Editage for the English-language editing and all other contributors who did not meet the authorship requirements.
Disclosures
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Author Contributions
Conception and design: Shoda, Yamada, Ohe. Acquisition of data: Shoda, Nakayama, Ohe. Analysis and interpretation of data: Shoda. Drafting the article: Shoda. Critically revising the article: Shoda, Nakayama. Reviewed submitted version of manuscript: Shoda, Nishiwaki. Approved the final version of the manuscript on behalf of all authors: Shoda. Statistical analysis: Shoda. Administrative/technical/material support: Shoda. Study supervision: Shoda, Nakayama.
Supplemental Information
Previous Presentations
Portions of this work were presented at the 30th Annual Meeting of the Japanese Society for Neuroendoscopy, Nagoya, Japan, November 17, 2023.
Correspondence
Kenji Shoda: Gifu University Graduate School of Medicine, Gifu, Japan. shoda.kenji.t7@f.gifu-u.ac.jp.
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