Role of Surgical Resection in Patients with Single Large Brain Metastases: Feasibility, Morbidity, and Local Control Evaluation

doi:10.1016/j.wneu.2016.06.098

World Neurosurgery

Volume 94, October 2016, Pages 6-12

https://doi.org/10.1016/j.wneu.2016.06.098 Get rights and content

Objective

The aim of this study was to evaluate the safety and the feasibility of surgery for single large brain metastases.

Methods

This retrospective study included 69 patients. All received a “supramarginal resection” according to functional boundaries, defined as a microsurgical excision with an extension larger at least 5 mm greater than the enhancing T1-weighted magnetic resonance imaging (MRI) sequence borders with dural attachment radicalization. Hypofractionated stereotactic radiosurgery on the tumor bed, using 30 Gy in 3 fractions, was performed within 1 month after surgery. Clinical outcome was evaluated at 30 days postoperative and by MRI performed every 3 months. The appearance of postoperative neurologic deficits, local control (LC), brain distant progression (BDP), and overall survival were evaluated.

Results

Clinical remission of symptomatology was obtained in 90.5% of patients. None of them had new neurologic deficits or worsening of preoperative functional status. No major complications or cerebrospinal fluid leakage occurred. No residual tumor was detected on postoperative MRI. The median follow-up was 24 months (range 4−33 months). The 1- to 2-year LC was 100%. Twenty-four (29% of) patients had new BDP, and 75% had extracranial progression. The median 1- to 2-year overall survival was 24 months, 91.3% and 73%. At the last observation time, 15 patients (21.7%) were dead and 54 patients (78.3%) were alive.

Conclusion

Supramarginal resection along with dural attachment radicalization have proved to be safe and effective for selected patients with single large brain metastases.

Introduction

Brain metastases (BMs) occur in 20% to 40% of adult cancer patients, and their incidence has increased from 2 to 5 times over the past 40 years.1, 2 Treatment options include surgery, whole-brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). As a single modality, none of these are able to obtain an adequate local control (LC) of large BMs (≥2.1 cm) and therefore a combined approach, if doable, is recommended.3, 4, 5, 6, 7 Several factors influence LC, and among these the role of surgical resection is not yet clearly defined. Various surgical strategies have been adopted: “piecemeal resection,” “en bloc resection,” and “supramarginal resection” with the aim to achieve a resection as wide as possible keeping functional neurologic integrity. Recent literature data comparing the different surgical modalities showed how the extent of resection affects tumor LC and patients' survival.8, 9, 10, 11 Specifically, moving from the hypothesis that it is the irregular tumor–brain interface that influences the incomplete surgical resection and the high rate of local recurrences, Kamp proposed the aggressive “supramarginal resection” as a suitable surgical strategy able to overcome this limitation compared with “piece-meal” or “en bloc resection.”¹² The choice of one over other surgical strategies must consider the following factors: 1) BM location; on this issue the tumor functional grade (TFG) that considers the relationship between the lesion and surrounding functional structures is the mainly adopted system, categorizing the lesions in Grade I, if located in a noneloquent area, Grade II if located near eloquent areas, and Grade III, if located in pure eloquent areas⁹; 2) surgeon experience; and 3) availability of intraoperative neurophysiologic monitoring and mapping techniques. In addition, a maximal safe resection is advisable to allow an ideal condition for adjuvant radiation therapy (RT) treatment. In our department, we choose to treat patients with single large BMs located in noneloquent or near-eloquent areas (TFG I−II) using a “supramarginal resection” along with a “dural attachment” radicalization if present. The chance that the BM could infiltrate and grow within the dura may affect the rate of local control, and therefore a meningeal removal should be considered in the surgical plan aimed at reaching a complete excision. To evaluate the impact of this surgical strategy, we reviewed a set of our patients with single large brain metastases treated with surgery followed by hypofractionated stereotactic radiosurgery (HSRS) on the tumor bed. The primary objective of this analysis was to evaluate the safety and feasibility of supramarginal resection in terms of appearance of new postoperative neurologic deficits and its impact on brain local control. In addition, brain distant progression (BDP) and overall survival (OS) were evaluated as well.

Section snippets

Patients and Procedures

The present retrospective study includes 69 patients with single large BMs (≥2.1 cm). All patients were treated with supramarginal resection plus HSRS on the resection cavity. All patients were treated in agreement with the Helsinki declaration. This study was based on a retrospective analysis of treatment charts and received approval by the local ethical committee. All patients signed at admission a consent to the use of their data for scientific scope. To define the appropriate therapy, each

Patients and Treatments

From January 2011 to March 2015, among consecutive patients referred to our institution for BMs, 69 patients with a single large lesion were included in this analysis. Of these patients, 42 (61%) were female and 27 (39%) were male, with a median age of 51 years (range 33−77 years). The most common primary cancers were breast, lung, and melanoma. BMs were present at diagnosis in 24 patients (35%), whereas they developed after primary tumor treatment in 45 patients (65%), at a median time of 21

Discussion

The role of surgical resection in patients with single large BMs is not clearly defined yet and is a topic of debate. Few data are available about the better surgical strategies.9, 10, 11, 12, 19 Nevertheless, the surgical methodology used could be a critical point because an incomplete surgical resection might be a reason for the high rate of local brain relapse. Several methods are described in the literature: “piecemeal resection” defined as an intralesional surgical excision, “en bloc

Conclusion

Supramarginal resection along with dural attachment radicalization was a safe and effective approach for surgical treatment of single large brain metastases from different solid tumors in selected patients.

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The use of steroids was not associated with response to 2-SSRS (P = 1.000). Surgery has traditionally been the mainstay treatment for LBMs.6 However, resection is invasive, is possibly unsuitable for tumors in eloquent areas, and may delay systemic treatment.35
Multisession staged stereotactic radiosurgery (SRS) represents an alternative approach for management of large brain metastases (LBMs), with potential advantages over fractionated SRS. This study investigated clinical efficacy and safety of 2-stage stereotactic radiosurgery (2-SSRS) in patients with LBMs.
Patients with LBMs treated with 2-SSRS between 2014 and 2020 were evaluated. Demographic, clinical, and radiologic data were obtained. Volumetric measurements at first SRS session, second SRS session, and follow-up imaging studies were obtained. Characteristics that might predict response to 2-SSRS were evaluated through Fisher exact or Mann-Whitney U test.
The study included 24 patients with 26 LBMs. Median (range) marginal doses for first and second SRS sessions were 15 Gy (14–18 Gy) and 15 Gy (12–16 Gy), respectively. Median (range) tumor volumes at first SRS session, second SRS session, and 3-month follow-up were 8.1 cm³ (1.5–28.5 cm³), 3.3 cm³ (0.8–26.1 cm³), and 2.2 cm³ (0.2–10.1 cm³), respectively. Of 26 lesions, 24 (92%) demonstrated early local control following the first SRS session, with 17 lesions (71%) demonstrating a decrease of ≥30% in T1 postcontrast MRI volume before the second SRS session and 3 lesions (12%) remaining stable. Eventually, 4 lesions showed disease progression after 2-SSRS. The median time to local progression was not reached; the median time to intracranial progression was 9.1 months.
Our study supports the effectiveness and safety of 2-SSRS as a treatment modality for patients with LBMs, especially in poor surgical candidates. The local failure rate and low occurrence of adverse effects are comparable to other staged radiosurgery studies.
Neurosurgical approaches to the treatment of intracranial metastases
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Brain metastases are the most common intracranial tumor and are a leading cause of morbidity and mortality for patients with systemic cancer. Surgical resection is an important diagnostic and therapeutic option for patients presenting with new or recurrent brain metastasis. As surgical technology and techniques have progressed, more lesions can be safely resected, and minimally invasive options, such as MRI-guided laser interstitial therapy and minimally invasive craniotomies, reduce surgical morbidity for patients. Adjuvant therapies such as stereotactic radiosurgery and chemotherapy continue to play an important role in comprehensive management of the patient with brain metastases.
Techniques for Open Surgical Resection of Brain Metastases
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Purely Meningeal Intracranial Relapse of Melanoma Brain Metastases After Surgical Resection and Immunotherapy as a Unique Disease Progression Pattern: Our Experience and Review of the Literature
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We present a case of 72-year-old man with a history of metastatic melanoma diagnosed in 2015 presenting a stable disease in treatment with dabrafenib.
The patient had been surgically treated for a presumed intracranial parietooccipital metastasis. He presented 1 month later with a meningeal lesion associated with a subdural hematoma. A second surgical treatment confirmed the diagnosis of meningeal recurrence of metastatic melanoma.
The most recent literature lacks studies defining the clinical phenomena of an early recurrence of intracranial melanoma with de novo involvement of dural compartment in patients in treatment with a target immunotherapy. The aim of this present study is to report a case of early recurrence of intracranial melanoma metastases with evidence of fast immunohistochemical and macroscopical mutation of pathologic elements, with an analysis of literature that shows the lack of well-described occurrences.
Single versus Multifraction Stereotactic Radiosurgery for Large Brain Metastases: An International Meta-analysis of 24 Trials
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Meta-regression did not demonstrate a statistically significant relationship for 1-year LC as a function of increasing tumor volume for SF-SRSD lesions (P = .28) or MF-SRSD lesions (P = .81), as shown in Figures 4A and 4B, respectively. There were 588 large brain metastasis postoperative cavities across 9 studies25,35,36,38,42,44,47-49 in the SRSP group whose rates of LC at 1-year were evaluated; rates ranged from 34%25 to 100%.42 Figure E5 (available online at https://dx.doi.org/10.1016/j.ijrobp.2018.10.038) depicts the forest plot for these studies stratified by fractionation scheme.
Multifraction (MF) stereotactic radiosurgery (SRS) purportedly reduces radionecrosis risk over single-fraction (SF) SRS in the treatment of large brain metastases. The purpose of the current work is to compare local control (LC) and radionecrosis rates of SF-SRS and MF-SRS in the definitive (SF-SRS_D and MF-SRS_D) and postoperative (SF-SRS_P and MF-SRS_P) settings.
Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were used to select articles in which patients had “large” brain metastases (Group A: 4-14 cm³, or about 2-3 cm in diameter; Group B: >14 cm³, or about >3 cm in diameter); 1-year LC and/or rates of radionecrosis were reported; radiosurgery was administered definitively or postoperatively. Random effects meta-analyses using fractionation scheme and size as covariates were conducted. Meta-regression and Wald-type tests were used to determine the effect of increasing tumor size and fractionation on the summary estimate, where the null hypothesis was rejected for P < .05.
Twenty-four studies were included, published between 2008 and 2017, with 1887 brain metastases. LC random effects estimate at 1 year was 77.6% for Group A/SF-SRS_D and 92.9% for Group A/MF-SRS_D (P = .18). LC random effects estimate at 1 year was 77.1% for Group B/SF-SRS_D and 79.2% for Group B/MF-SRS_D (P = .76). LC random effects estimate at 1 year was 62.4% for Group B/SF-SRS_P and 85.7% for Group B/MF-SRS_P (P = .13). Radionecrosis incidence random effects estimate was 23.1% for Group A/SF-SRS_D and 7.3% for Group A/MF-SRS_D (P = .003). Radionecrosis incidence random effects estimate was 11.7% for Group B/SF-SRS_D and 6.5% for Group B/MF-SRS_D (P = .29). Radionecrosis incidence random effects estimate was 7.3% for Group B/SF-SRS_P and 7.5% for Group B/MF-SRS_P (P = .85). Metaregression assessing 1-year LC and radionecrosis as a continuous function of increasing tumor volume was not statistically significant.
Treatment for large brain metastases with MF-SRS regimens may offer a relative reduction of radionecrosis while maintaining or improving relative rates of 1-year LC compared with SF-SRS. These findings are hypothesis-generating and require validation by ongoing and planned prospective clinical trials.
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The current chapter covers the topics of brain metastases and neoplastic meningitis. We anticipate that with advances in systemic treatments, radiation therapy, and surgical technique, treatment will change in the following years. Our aims in this chapter are provide a review of existing evidence-based literature that is the basis for current treatment guidelines and to discuss potential future developments based on small cohorts and studies.

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: Conflict of interest statement: L. Cozzi acts as scientific advisor to Varian Medical Systems and is a clinical research scientist at Humanitas Cancer Center. All other coauthors have no conflicts of interest.

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Original ArticleRole of Surgical Resection in Patients with Single Large Brain Metastases: Feasibility, Morbidity, and Local Control Evaluation

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Patients and Procedures

Patients and Treatments

Discussion

Conclusion

Cancer Treat Rev

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Treatment of brain metastases

J Clin Oncol

Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin

J Neurosurg

Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial

JAMA

Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study

J Clin Oncol

Original Article
Role of Surgical Resection in Patients with Single Large Brain Metastases: Feasibility, Morbidity, and Local Control Evaluation