Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer

doi:10.1016/j.wneu.2016.01.062

World Neurosurgery

Volume 89, May 2016, Pages 455-463

https://doi.org/10.1016/j.wneu.2016.01.062 Get rights and content

Objective

The incidences of metastatic brain tumors from gynecologic cancer have increased. The results of Gamma Knife surgery (GKS) for the treatment of patients with brain metastases from gynecologic cancer (ovarian, endometrial, and uterine cervical cancers) were retrospectively analyzed to identify the efficacy and prognostic factors for local tumor control and survival.

Methods

The medical records were retrospectively reviewed of 70 patients with 306 tumors who underwent GKS for brain metastases from gynecologic cancer between January 1995 and December 2013 in our institution.

Results

The primary cancers were ovarian in 33 patients with 147 tumors and uterine in 37 patients with 159 tumors. Median tumor volume was 0.3 cm³. Median marginal prescription dose was 20 Gy. The local tumor control rates were 96.4% at 6 months and 89.9% at 1 year. There was no statistically significant difference between ovarian and uterine cancers. Higher prescription dose and smaller tumor volume were significantly correlated with local tumor control. Median overall survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and solitary brain metastasis were significantly correlated with satisfactory overall survival. Median activities of daily living (ADL) preservation survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and higher Karnofsky Performance Status score were significantly correlated with better ADL preservation.

Conclusions

GKS is effective for control of tumor progression in patients with brain metastases from gynecologic cancer, and may provide neurologic benefits and preservation of the quality of life.

Introduction

Brain metastases occur at incidences of 15%–40% with various types of primary cancer.1, 2, 3 The rates of metastases to the brain are about 40% from lung cancer and about 15% from breast cancer, whereas only 1%–2% of clinically diagnosed cases originate from the various gynecologic cancers (ovarian, endometrial, and uterine cervical cancers).1, 2, 3 However, the incidences of metastatic brain tumors from gynecologic cancer have increased, as with other primary cancers, as a result of the prolonged survival of patients with cancer resulting from earlier diagnosis and more effective systemic chemotherapy.

Brain metastases are generally treated with single or multimodality therapies, including surgical resection, whole-brain radiation therapy (WBRT), or stereotactic radiosurgery, depending on the systemic condition of the patient.1, 2, 3, 4 Radiosurgery is known to be effective against metastatic brain tumors from various primary cancers based on the palliation of neurologic symptoms,4, 5, 6 but the efficacy and safety are less discussed in the large population with brain metastases from gynecologic cancer, whose primary lesions might tend to be insensitive to radiation treatment.7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22

The present study retrospectively investigated the results of Gamma Knife (Elekta, Stockholm, Sweden) surgery (GKS) in patients with metastatic brain tumors from gynecologic cancer to assess the efficacy and the prognostic factors of local tumor growth control and survival.

Section snippets

Methods

A total of 70 women with metastatic brain tumors from primary gynecologic cancer, aged from 18 to 86 years (mean 59.4 ± 12.7 years), were treated with GKS at Yokohama Rosai Hospital between January 1995 and December 2013. All patients underwent periodic clinical and neuroradiologic follow-up magnetic resonance (MR) imaging after the initial radiosurgical procedure. The patients harbored 306 lesions with maximum diameter of less than 3 cm on the axial, coronal, and sagittal gadolinium-enhanced

Results

Retrospective review found that the 70 patients with 306 lesions (mean, 3.8 ± 1.9; range, 1–31 tumors per patient) underwent 107 separate GKS procedures (mean, 1.6 ± 0.8; range, 1–7 procedures per patient), including initial treatment of 153 lesions and additional treatment of 153 lesions. Patient characteristics at initial GKS are listed in Table 1 for the entire population and 2 groups are distinguished based on the primary cancer: 33 patients with ovarian cancer and 37 with uterine cancer

Discussion

Brain metastases from gynecologic cancers generally manifest in the relatively final stage of the progression of the primary cancer, similar to systemic metastases of the lung, liver, or bone, so are considered as a negative prognostic sign, and most patients with brain metastases from gynecologic cancer have poorer systemic condition compared with other primary cancers, such as lung or breast cancer.1, 2, 3 Therefore, radiosurgery is likely to be the optimum procedure for the treatment of

Conclusions

The present study showed that GKS was effective for control of local tumor growth of brain metastases from gynecologic cancer, and GKS can be performed as a salvage treatment to palliate neurologic symptoms and provide moderate quality of life for the remainder of the patient's life. Patients treated by GKS should be carefully followed up, and repeat GKS should be considered for local tumor growth control after early detection of recurrent tumor. Metastatic brain tumor from gynecologic cancer

References (24)

M. Yamamoto et al.
Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study
Lancet Oncol
(2014)
K. Kawana et al.
Successful treatment of brain metastases from ovarian cancer using gamma-knife radiosurgery
Gynecol Oncol
(1997)
J.V. Brown et al.
Gamma-knife radiosurgery for the treatment of ovarian cancer metastatic to the brain
Gynecol Oncol
(2005)
Y.K. Lee et al.
Gamma-knife radiosurgery as an optimal treatment modality for brain metastases from epithelial ovarian cancer
Gynecol Oncol
(2008)
S. Yamada et al.
A case of multiple brain metastases of uterine leiomyosarcoma with a literature review
Surg Oncol
(2011)
X. Niu et al.
Brain metastases in women with epithelial ovarian cancer: multimodal treatment including surgery or gamma-knife radiation is associated with prolonged survival
J Obstet Gynaecol Can
(2013)
A.C. Walter et al.
Central nervous system metastasis in gynecologic cancer: symptom management, prognosis and palliative management strategies
Gynecol Oncol
(2015)
S. Matsunaga et al.
Semiquantitative analysis using thallium-201 SPECT for differential diagnosis between tumor recurrence and radiation necrosis after gamma knife surgery for malignant brain tumors
Int J Radiat Oncol Biol Phys
(2013)
E. Piura et al.
Brain metastases from ovarian carcinoma
ISRN Oncol
(2011)
E. Piura et al.
Brain metastases from endometrial carcinoma
ISRN Oncol
(2012)

E. Piura et al.

Brain metastases from cervical carcinoma: overview of pertinent literature

Eur J Gynaecol Oncol

(2012)

G. Bowden et al.

Gamma knife radiosurgery for the management of cerebral metastases from non-small cell lung cancer

J Neurosurg

(2015)

Cited by (19)

Stereotactic radiosurgery for brain metastases arising from gynecological malignancies: A retrospective treatment outcome analysis
2024, Journal of Clinical Neuroscience
This retrospective study aims to assess the efficacy of stereotactic radiosurgery (SRS) in the treatment of brain metastases (BM) originating from gynecological cancers. It focuses on local control (LC), distant tumor control (DTC), and overall survival (OS).
The analysis comprised 18 individuals with gynecological-origin BM treated with SRS at the Hadassah Medical Center from 2004 to 2021. Statistical analyses evaluate factors impacting LC, DTC, and OS.
A total of 36 BM of gynecological origin underwent SRS. The median age at the first SRS treatment was 60 years, with a median time of 24.5 months from the primary malignancy diagnosis to BM detection. The 12-month LC rate per patient was 84.6 %, and 5.6 % per BM. Only two instances of local recurrence were observed. The DTC at 12 months was 75 %, with a 29 % overall. Non-significant trends indicating a correlation with distant brain failure with increased cumulative volume and the occurrence of craniotomy before SRS. The median OS of the cohort was 16.5 months from SRS treatment. The 6, 12, 18, and 24-month survival rates were 77.8 %, 66.7 %, 50 %, and 22.2 % respectively. Higher number of BM was associated with lower OS (p = 0.046). On multivariate analysis, age was a significant factor for OS (p = 0.03), demonstrating that older age was associated with a more favorable prognosis.
This study supports SRS effectiveness for treating BM from gynecological cancers and suggests similar outcomes to more common malignancies.
Gamma Knife radiosurgery for gynecologic metastases to the brain: Analysis of pathology, survival, and tumor control
2023, Gynecologic Oncology
This study aims to evaluate the efficacy of stereotactic radiosurgery (SRS) in improving health outcomes of patients with gynecologic brain metastases.
Patients with gynecologic metastases treated with SRS from 2008 to 2020 were retrospectively reviewed. The median age at SRS was 63 years old (cervical 45.5, endometrial 65.5, ovarian 61). The median number of tumors was 3 (range 1–27), and cumulative tumor volume was 2.33 cc (range 0.03–45.63). Median margin dose prescribed was 16 Gy (range 14 Gy – 20 Gy). The median 12 Gy volume was 7.30 cc (range 0.21–74.14 cc). Outcome variables included overall survival (OS) after SRS, local tumor control (LTC), distant tumor control, and adverse radiation effect (ARE).
Fifty patients (4 cervical, 25 endometrial, and 21 ovarian cancer) were identified. The OS at 6 and 12 months after SRS was 48%, and 44%, respectively. Eight patients (16%) died from CNS disease progression. The number of brain metastases (p = 0.011) and the Karnofsky Performance Scale (KPS) ≥ 70 (p = 0.020) were significant predictors of OS. LTC rate at 6 and 12 months were 92%, and 87%, respectively. Margin dose ≥16Gy correlated with significantly better local tumor control (p = 0.0001) without increased risk of ARE (p = 0.055). The risk of developing new metastases at 6 and 12 months were 12% and 24% respectively. SRS-induced ARE events occurred in 7 patients.
Intracranial metastases from gynecologic malignancy can be effectively treated using SRS with low risk of neurotoxicity. Margin dose ≥16Gy can provide significantly better tumor control. Repeat SRS can be utilized to treat new metastases while avoiding the potential cognitive symptoms associated with WBRT.
Central nervous system metastasis from epithelial ovarian cancer- predictors of outcome
2023, Current Problems in Cancer
Citation Excerpt :
Survival time following CNS metastasis has varied widely across studies, presumably due to uneven distribution of several clinic-pathological and treatment related factors. Good performance score,19,29-32 presence of solitary brain metastasis9,23,27-29,33-35 and absence of extracranial disease27,28,30-37 have been identified as important predictors of outcome. Surgical resection of brain metastasis has also been associated favorable outcomes.9
Management of central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) is an unmet need. We analyzed data on 41 such patients to evaluate predictors of outcome. Between January, 2010 and December 2020, among 1028 patients with EOC treated at our institute 41 (3.98%) developed CNS metastasis. Median age of patients was 48 years, ranging from 22 to 75 years. Primary outcome measure was progression free survival (PFS). Overall survival (OS), and analysis of prognostic factors were secondary outcome measures. An intention to treat analysis was done. We also performed review the literature (n=2253) as regards to clinicopathological and radiological features, treatment received, survival outcomes and prognostic factors. Median time from diagnosis of EOC to CNS metastasis was 27 months (range: 0 to 101 months). 33(80.5%) patients had FIGO stage III-IV at baseline and serous carcinoma (75.6%) was common pathology subtype. Thirteen (31.7%) patients had isolated CNS metastasis and 28 (68.3%) had intra-abdominal disease in addition. Nineteen (46.3%) patients achieved complete response post treatment with surgery, radiation and chemotherapy. Median PFS and OS from the time of CNS metastasis is 12 (range:1 to 51) months and 33 (range: 1 to 71) months, respectively. Absence of extracranial disease and lower serum CA-125 at diagnosis of CNS metastasis were predictive of superior PFS and OS on multivariate analysis. CNS metastasis is a late event in EOC, post multiple lines of treatment. Patients with disease limited to brain and treated with surgical resection and chemoradiation have best outcome.
Age, pathology and CA-125 are prognostic factors for survival in patients with brain metastases from gynaecological tumours
2020, Clinical and Translational Radiation Oncology
Citation Excerpt :
It could be the case that differences in variables in the respective prognostic models causes the effect of performance status to differ between studies, as different clinical factors are corrected for. Also, the choice of performance status (KPS or ECOG) can be the cause of this discordance, as Matsunaga et al. and Johnston et al. also examined the effect of KPS, and found no significant effect [20,21]. A final possibility is that, due to the relatively high KPS in our dataset (median 80, with an IQR of 80–100), the effects of lower KPS are harder to determine.
Brain metastases originating from gynaecological tumours are a rare phenomenon, but have an increasing incidence due to better targeted therapies. This study aimed to identify factors that predict survival in these patients, which can be used in creating a robust prognostic tool for shared decision making.
We identified a consecutive cohort of 73 patients treated for gynaecological brain metastases in two tertiary institutions. Baseline demographics, pathology and serum CA-125 were included in a multivariable Cox proportional hazards model.
Median overall survival in our cohort was 14.4 months, with a one-year survival of 56.4% and a two-year survival of 39.1%. Thirty-eight patients (52.1%) had ovarian carcinoma as the primary malignancy. The following factors were significantly associated with survival: age (HR 1.05 per year), CA-125 (HR 1.02 par 50 U/ml), and uterine and vulvar primary tumours (when compared to ovarian carcinoma, with HRs 3.07 and 8.70). A post-hoc analysis with primary tumour site reclassified into ovary versus non-ovary showed a HR of 0.50 for ovarian primary tumour type.
We have found that age, pathology and CA-125 are prognostic factors for survival in patients with brain metastases from gynaecological tumours. Our findings may provide a foundation for future development of prediction models, for the benefit of both patients and physicians.
Gamma Knife Surgery for Brain Metastases from Uterine Malignant Tumor
2020, World Neurosurgery
Uterine malignant tumors (uterine cervical carcinoma [UCC], uterine endometrial carcinoma, and uterine sarcoma) are common in women. Brain metastases from uterine malignant tumors are rare, but its incidence has been increasing. The present study aimed to investigate the characteristics of brain metastases from uterine malignant tumors, evaluate predictive factors, and assess the efficacy of Gamma Knife surgery (GKS) for metastases from uterine malignant tumors.
We retrospectively reviewed the records of patients with brain metastases from uterine malignant tumors treated at Tokyo Gamma Unit Center from 2005 to 2017.
We identified 37 patients: 16 had UCC, 12 had uterine endometrial carcinoma, and 9 had uterine sarcoma. Their median age at diagnosis of brain metastases was 54.0 years. The median interval from diagnosis of uterine malignant tumor to brain metastases was 21.0 months, the median number of brain metastases was 3.0, and the median Karnofsky Performance Status at first GKS was 80%. The median survival after first GKS was 6.0 months. All patients had other metastases. Six-month and 1-year survival after first GKS were 48.9% and 32.6%, respectively, and the tumor control rate at 6 months after GKS was 90.8%. Brain metastases from UCC were significantly correlated with good tumor control (P = 0.024). Multivariate analysis determined that Karnofsky Performance Status was significantly associated with patient survival (P = 0.001).
The results of our study suggest that GKS is an acceptable choice for controlling brain metastases from uterine malignant tumors. In particular, GKS provides excellent local control for metastases from UCC.
Linear accelerator-based radiosurgery and hypofractionated stereotactic radiotherapy for brain metastasis secondary to gynecologic malignancies: A single institution series examining outcomes of a rare entity
2018, Gynecologic Oncology Reports
Citation Excerpt :
Despite the reduction in brain recurrence and neurologic deaths, surgical intervention followed by WBRT (or WBRT alone) does not result in an increased actuarial survival or length of time patients were able to function independently (Kasper et al., 2017). However, because of the rarity of gynecologic BM, there are relatively few studies that evaluate the influence of stereotactic radiosurgery and radiotherapy on overall survival time, disease-free progression, and local control of gynecologic brain metastasis (Anupol et al., 2002; Aoyama et al., 2006; Kim et al., 2017; Matsunaga et al., 2016; McMeekin et al., 2001; Mehta et al., 2005). This study aims to evaluate the pre-existing literature and conduct an institutional analysis of patients treated with SRS and hypofractionated stereotactic radiotherapy (SRT) to determine survival, tumor control, and disease-free progression in patients diagnosed with gynecologic brain metastasis.
The use of SRS and fSRT to determine overall survival, tumor control, and local-disease free progression in patient diagnosed with gynecologic brain metastasis.
In this retrospective review, 11 patients aged 50 to 85 (median age of 71) were treated with linear accelerator-based SRS and hypofractionated SRT for brain metastasis secondary to gynecologic malignancies. In total, 16 tumors were treated from 2007 to 2017. Patients were treated to a median dose of 24 Gy (range 15 to 30 Gy) in 3 Fx (range 1 to 5). Median follow-up from SRS or SRT was 4 months (range 3–38 months).
The actuarial 1-year overall survival rate was 26% with a median overall survival of 8 months. In addition, 1-year actuarial local control rate was 83.3% and the 1-year distant brain control rate was 31%. One patient experienced toxicity that presented as seizures after 7 months (due to minimal edema) that required anticonvulsants. There was no other acute or late treatment-related toxicity.
Conclusion: Linear-accelerator based SRS or fSRT is safe and effective for control of local tumor growth in brain metastases secondary to gynecologic malignancies. The course of disease remains aggressive as seen by poor overall survival and distant failure rate.

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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 Surgery for Metastatic Brain Tumors from Gynecologic Cancer

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conclusions

Lancet Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Surg Oncol

J Obstet Gynaecol Can

Gynecol Oncol

Int J Radiat Oncol Biol Phys

Brain metastases from ovarian carcinoma

ISRN Oncol

Brain metastases from endometrial carcinoma

ISRN Oncol

Brain metastases from cervical carcinoma: overview of pertinent literature

Eur J Gynaecol Oncol

Gamma knife radiosurgery for the management of cerebral metastases from non-small cell lung cancer

J Neurosurg

Original Article
Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer