Gamma Knife Radiosurgery for Low-Grade Gliomas: Clinical Results at Long-Term Follow-Up of Tumor Control and Patients' Quality of Life

doi:10.1016/j.wneu.2017.02.041

World Neurosurgery

Volume 101, May 2017, Pages 540-553

https://doi.org/10.1016/j.wneu.2017.02.041 Get rights and content

Objective

First-line therapy for low-grade gliomas (LGGs) is surgery, in some cases followed by radiotherapy and chemotherapy. Gamma Knife radiosurgery (GKRS) has gained more relevance in the management of these tumors. The aim of this study was to assess efficacy and safety of GKRS for treatment of LGGs.

Methods

Between 2001 and 2014, 42 treatments were performed on 39 patients harboring LGGs; 48% of patients underwent previous surgery, and 20.5% underwent previous radiotherapy. Mean tumor volume was 2.7 cm³, and median margin dose was 15 Gy.

Results

Mean follow-up was 60.5 months (range, 6–164 months). Actuarial progression-free survival was 74.9%, 52.8%, and 39.1% at 1 year, 5 years, and 10 years; actuarial overall survival was 97.4%, 94.6%, and 91.8% at 9 months, 1 year, and 5 years. Solid tumor control was achieved in 69.2% of patients, whereas cystic enlargement was recorded in 12.9% of cases. At last follow-up, volume reduction was recorded in 57.7% of cases, and median volume decreased by 33.3%. Clinical improvement was observed in 52.4% of patients. Karnofsky performance scale score was improved in 15 patients (45.5%), unchanged in 17 patients (51.5%), and worsened in 1 patient (3%). Mean posttreatment scores of 36-item short form health survey domains did not significantly differ from scores in a healthy Italian population.

Conclusions

This study confirms safety and effectiveness of GKRS for LGGs in controlling tumor growth, relevantly improving patients' overall and progression-free survival. GKRS improved patients' functional performance and quality of life, optimizing social functioning and minimizing disease-related psychological impact.

Introduction

Low-grade gliomas (LGGs) represent a heterogeneous group of tumors, accounting for 20% of brain gliomas and 5.6% of all tumors within the central nervous system. Incidence is 0.10–0.46 per 100,000/year, varying significantly according to the histologic subtype and age at diagnosis.1, 2 As the highest incidence of LGGs is observed in young adults, it mainly affects the working active population. Social costs are high in terms of both welfare and reduction of the workforce.³ The goals of treatment include prolonging survival and reducing morbidity—hence preventing tumor progression and minimizing treatment-related complications.4, 5, 6, 7, 8, 9, 10 Treatment strategies vary based on tumor histology, anatomic location, age and general medical conditions of the patient.

At the present time, safe surgical resection is the first choice for treatment of resectable tumors. In cases of unresectable lesions, adjuvant radiotherapy (RT) and chemotherapy are the current standard of care.¹¹ However, as recent studies⁶ in both adult and pediatric populations have indicated that the extent of tumor resection affects overall survival, surgery continues to be the first choice when feasible. Longer progression-free survival (PFS) was also observed in patients receiving adjuvant RT after resection when compared with patients treated only in cases of evident tumor progression (PFS 5.3 years vs. 3.4 years).⁷ The role of chemotherapy is not widely established at the present time, although a recent report has demonstrated that combining chemotherapy with adjuvant RT in patients undergoing subtotal resection improves overall survival (OS) and PFS.¹² Moreover, chemotherapy is indicated in children with the aim to delay RT and prevent radiation-induced neurocognitive side effects.8, 10 Several reports in recent years have studied the role of radiosurgery in the treatment of LGGs, mostly reporting single-institution experiences limited to only a few cases.¹³

The present study reports a single-center experience of 39 patients with LGGs; 12 were treated by Gamma Knife radiosurgery (GKRS) as first line treatment, whereas GKRS was used as a rescue therapy after surgery, RT, or chemotherapy in the remaining 27 patients. Using subjective and objective scales, we evaluated oncologic and clinical results as well as patients' quality of life (QoL) and functional outcome. There are few studies focusing on health-related quality of life (HRQoL) in patients with LGGs, and most them refer to LGGs treated by surgery, RT, or chemotherapy.14, 15, 16, 17, 18 To the best of our knowledge, this represents the first study reporting objective HRQoL and functional assessment in patients with LGGs treated by GKRS.

Section snippets

Patient Population

Between March 2001 and July 2014, 39 patients with a radiologically or histologically diagnosed LGG underwent GKRS as primary treatment as well as salvage therapy after previous treatment failure at the Department of Neurosurgery of San Raffaele Hospital in Milan, Italy. Three patients (7.7%) underwent a second treatment at our institution because of tumor regrowth; thus, 42 cases were considered in the final statistical analysis. We retrospectively collected patients' demographic and clinical

Patient Characteristics

Age range of patients was 9–72 years (mean 34.5 years and median 31 years). Patient and tumor characteristics are summarized in Table 2. Three patients died during the follow-up period; tumor progression was the cause of death in all 3 cases. At the time of diagnosis, the median KPS score was 90 (range, 60–100). At the time of treatment, 33 cases (78.6%) had a KPS score >80, whereas 9 cases (21.4%) had a score <80. Between 2001 and 2014, 49 lesions were treated with GKRS, as 7 patients had

Discussion

Several reports in recent years have studied the role of radiosurgery in the treatment of LGGs, with most reporting single-institution experiences limited to only few cases.¹³ Review of the literature to date indicates there is still debate on prescription doses, with marginal doses for single-fraction treatment widely ranging from 10 to 20 Gy (median 14 Gy).¹³ It remains unclear whether WHO grade II astrocytomas require a higher dose for tumor control compared with lower grade lesions.

Conclusions

To date, there is no consensus in the literature regarding standardized management of LGGs. Surgery represents the first-line therapy for most of these lesions, in some cases followed by RT and chemotherapy. In the last 2 decades. GKRS has gained progressively more relevance in management of these lesions in selected cases. The results of the present study confirmed the safety and effectiveness of GKRS in controlling tumor growth, relevantly improving patients' OS and PFS. Additionally, this is

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Low grade gliomas
2022, Progress in Brain Research
Low grade gliomas concern grade I and grade II tumors. The only grade one tumor is the pilocytic astrocytoma. This is a well-defined tumor with characteristic histology, often accompanied by a cyst. GKNS has been used in surgically inaccessible tumors since 1994. More recently it has been demonstrated that the tumors are more treatment resistant in adults than in children.
Grade II tumors include oligodendrogliomas and grade II diffuse astrocytomas. The standard treatment for oligodendrogliomas us total removal followed by fractionated radiotherapy. GKNS has been shown to be of benefit in smaller tumors which have not responded to other treatment. It may also have a role as an ancillary treatment in smaller Grade II astrocytomas.
Gamma Knife radiosurgery as primary treatment of low-grade brainstem gliomas: A systematic review and metanalysis of current evidence and predictive factors
2021, Critical Reviews in Oncology/Hematology
Citation Excerpt :
Actuarial analysis confirms a significantly higher SD rate in RT group (Edwards et al., 1994; Fisher et al., 1998; Milstein et al., 1989; Pollack et al., 1994, 1996; Ryu et al., 2015; Upadhyaya et al., 2017; Vandertop et al., 1992; Wechsler-Jentzsch et al., 1988) in the short to medium term (<60 months) (57.8 vs 4.5 %; p < 0.001), losing significance at long term analysis (p = 0.12). The only significant difference in the long-term is the higher rate of PR achievement after SRS-GK (Barcia et al., 1994; Boethius et al., 2002; El-Shehaby et al., 2015; Gagliardi et al., 2017; Hadjipanayis et al., 2002; Kano et al., 2009; Kihlstrom et al., 1994; Liao et al., 2012; Weintraub et al., 2012; Yen et al., 2007) compared to RT (Edwards et al., 1994; Fisher et al., 1998; Milstein et al., 1989; Pollack et al., 1994, 1996; Ryu et al., 2015; Upadhyaya et al., 2017; Vandertop et al., 1992; Wechsler-Jentzsch et al., 1988) (65.2 vs 14.2 %; p = 0.03). Considering the pediatric population, overall data, without any time stratification, confirm a significant advantage of RT (Edwards et al., 1994; Fisher et al., 1998; Milstein et al., 1989; Pollack et al., 1994, 1996; Ryu et al., 2015; Upadhyaya et al., 2017; Vandertop et al., 1992; Wechsler-Jentzsch et al., 1988) and SRS-GK (Barcia et al., 1994; Boethius et al., 2002; El-Shehaby et al., 2015; Gagliardi et al., 2017; Hadjipanayis et al., 2002; Kano et al., 2009; Kihlstrom et al., 1994; Liao et al., 2012; Weintraub et al., 2012; Yen et al., 2007) on SD and PR, respectively.
The current standard of care for surgically inaccessible low-grade brainstem gliomas (BS-LLGs) is external-beam radiotherapy (RT). Developments toward more innovative conformal techniques have focused on decreasing morbidity, by limiting radiation to surrounding tissues. Among these Gamma Knife radiosurgery (SRS-GK) has recently gained an increasingly important role in the treatment of these tumors.
Although SRS-GK has not yet been compared with conventional RT in patients harboring focal BS-LGGs, clinical practice has been deeply influenced by trials performed on other tumors.
This is the first meta-analysis on the topic, systematically reviewing the most relevant available evidence, comparing RT and SRS-GK as primary treatments of BS-LGGs, focusing on survival, clinical outcome, oncological control, and complications. Predictive factors have been systematically evaluated and analyzed according to statistical significance and clinical relevance.
Gamma Knife radiosurgery as salvage therapy for gangliogliomas after initial microsurgical resection
2021, Journal of Clinical Neuroscience
Gangliogliomas (GG) are considered WHO grade I rare tumors. While they commonly manifest as temporal lobe epilepsy, they can be located anywhere in the brain. Primary treatment is complete microsurgical resection. Remnant or recurrent GG can benefit from radiation therapy. Here, we present a series of GG who received Gamma Knife radiosurgery (GKR) after initial microsurgery.
Between October 2009 and February 2020, four patients benefitted from such approach. The median age at surgery was 16 years (mean 17, 11–25) and at the time of GKR was 22.5 years (mean 23, 19–28). Initial clinical symptom was epilepsy in 3 cases and incidental in one. Biopsy was firstly performed in one case. One patient had stereotactic electroencephalography. The respective anatomical locations were right parieto-occipital, sylvian, left paraventricular and left inferior parietal.
Gamma Knife radiosurgery was performed after a median time of 3.5 years after initial gross total microsurgical resection (GTR). The median follow-up after GKR was 54 months (mean 58.5, 6–120). The median marginal dose was 18 Gy (mean 17.5, 16–18). The median target volume was 0.5 mL (mean 0.904, 0.228–2.3). The median prescription isodose volume was 0.6 mL (mean 0.9, 0.3–2.4). At last follow-up, GG majorly decreased in 3 patients, remained stable in one.
Gamma Knife radiosurgery is safe and effective for remnant GG after GTR. Primary treatment remains microsurgical resection, especially in cases with symptomatic mass effect or with epilepsy. Single fraction GKR can be a valuable option for remnant or recurrent tumors after initial resection.
Radiotherapy in the Management of Paediatric Low-Grade Gliomas
2019, Clinical Oncology
Paediatric low-grade (World Health Organization grade I–II) gliomas (LGGs) represent a spectrum of primary central nervous system tumours. Local tumour control is the cornerstone in the general management of childhood gliomas. Surgery is the primary treatment of choice in the majority. Non-surgical treatments are recommended for progressive or symptomatic inoperable disease. Although chemotherapy is increasingly used as first non-surgical treatment, radiotherapy remains standard as salvage treatment or as primary treatment in selected cases in which surrounding normal tissue can be optimally preserved. The role of targeted therapies is currently under investigation in clinical trials. Modern high-precision radiotherapy techniques, including proton therapy, have the potential to improve long-term toxicities. There is therefore an urgent need for prospective studies to compare the efficacy and safety of modern radiotherapy with systemic treatment in children with LGGs. New information on molecular genetic patterns in LGGs may also have an impact on the selection and sequencing of radiotherapy.
Stereotactic radiosurgery in the management of oligodendroglioma
2019, Oligodendroglioma: Clinical Presentation, Pathology, Molecular Biology, Imaging, and Treatment
Stereotactic radiosurgery (SRS) has revolutionized local treatment of brain tumors, especially metastases. For oligodendrogliomas, the use of additional treatment modalities such as SRS is considered primary, adjunctive, and salvage therapy. The available limited experience with SRS for oligodendrogliomas indicates that it is safe and effective. For a very select group of patients unfit for surgical resection or with small residual or recurrent lesions, SRS may represent a safe, reasonable treatment option. Reirradiation with SRS at recurrence seems to be safe, but evidence is limited. Given the very limited number of papers on SRS for oligodendrogliomas, this chapter will include all low-grade gliomas (LGGs).
Role of Stereotactic Radiosurgery in Glial Tumors
2023, Neurology India

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: Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Original ArticleGamma Knife Radiosurgery for Low-Grade Gliomas: Clinical Results at Long-Term Follow-Up of Tumor Control and Patients' Quality of Life

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Patient Population

Patient Characteristics

Discussion

Conclusions

Lancet

Int J Radiat Oncol Biol Phys

Eur J Cancer

World Neurosurg

J Clin Epidemiol

Health Policy

Int J Radiat Oncol Biol Phys

CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011

Neuro Oncol

Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas

J Neuropathol Exp Neurol

Health-related quality of life aspects in patients with low-grade glioma

Adv Tech Stand Neurosurg

The dilemma of low grade glioma

J Neurol Neurosurg Psychiatry

Surgery of low-grade gliomas: towards a “functional neurooncology.”

Curr Opin Oncol

Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas

J Clin Oncol

Guidelines on management of low-grade gliomas: report of an EFNS-EANO Task Force

Eur J Neurol

Practice changing mature results of RTOG study 9802: another positive PCV trial makes adjuvant chemotherapy part of standard of care in low-grade glioma

Neuro Oncol

Feasibility and efficacy of repeated chemotherapy for progressive pediatric low-grade gliomas

Pediatr Blood Cancer

Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma

N Engl J Med

Stereotactic radiosurgery of deeply seated low grade gliomas

Acta Neurochir Suppl

Compromised health-related quality of life in patients with low-grade glioma

J Clin Oncol

Low grade gliomas in eloquent locations—implications for surgical strategy, survival and long term quality of life

PLoS One

Quality of life in low-grade glioma patients receiving temozolomide

Neuro Oncol

Health-related quality of life in stable, long-term survivors of low-grade glioma

J Clin Oncol

Gamma Knife radiosurgery for low-grade tectal gliomas

Acta Neurochir

Radiosurgical dose selection for brain metastasis

Prog Neurol Surg

The clinical evaluation of chemotherapeutic agents in cancer

Original Article
Gamma Knife Radiosurgery for Low-Grade Gliomas: Clinical Results at Long-Term Follow-Up of Tumor Control and Patients' Quality of Life