Gamma Knife radiosurgery in the management of brainstem metastases

Background

Metastases to the brainstem portend a poor prognosis and present a challenge in clinical management. Surgical resection is rarely a viable option.

Methods

Post-treatment MRI scans of patients with brainstem metastases treated with radiosurgery were used to determine local control and disease progression. Median survival was calculated using Kaplan–Meier analysis. Univariate and multivariate analyses were performed using log-rank test and Cox proportional hazards model, respectively.

Results

Thirty-two consecutive patients with brainstem metastasis underwent Gamma Knife radiosurgery. Median age was 50 years. Median tumor volume was 0.71 cm³ and median tumor margin dose was 13 Gy. Seventeen of 32 patients received WBRT prior to stereotactic radiosurgery. Median survival was 5.2 months. There was a statistically significant difference in survival based on RTOG recursive partition analysis (RPA) class. Median survival of patients categorized as RPA class I was 19.2 months, RPA class II was 8.4 months, and RPA class III was 1.9 months. The overall local tumor control rate was 87.5%. There were no acute complications following stereotactic radiosurgery and no evidence of radiation necrosis noted on post-treatment MRI scans.

Conclusion

Stereotactic radiosurgery is an effective treatment for brainstem metastases and should be considered especially for patients with good performance status.     

The option of Linac-based radiosurgery in a Gamma Knife radiosurgery center

Objective

Due to the fundamental differences in treatment delivery, linear-accelerator-based radiosurgery can be complementary to Gamma Knife (GK) for intracranial lesions. We reviewed the effect of adding GK to an existing linear accelerator (Linac)-based radiosurgery practice and analyzed case selections for the two modalities.

Patients and methods

UC Davis Medical Center installed a Leksell Gamma Knife Model C in October 2003 to supplement an established Linac-based radiosurgery program. Radiosurgery indications for the 15 months before and after installation were compared.

Results

Radiosurgery cases expanded by twofold from 68 patients before GK installation to 139 after, with 106 treated by GK and 33 by Linac. Besides a major increase for trigeminal neuralgia and a general growth for acoustic neuroma, meningioma and brain metastases, case numbers for glioma and arteriovenous malformation (AVM) remained stable. Considering case selections for Linac, glioma decreased from 28 to 18%, while meningioma and metastases increased from 9 to 21% and 38–46%, respectively. The Linac patients receiving fractionated treatment also increased from 37 to 61%.

Conclusions

While the majority of patients were treated with GK, a significant proportion was judged to be suited for Linac treatment. This latter group included particularly patients who benefit from fractionated therapy.     

Clinical Results of Cyberknife? Radiosurgery for Spinal Metastases

Objective

Primary treatment of spinal metastasis has been external beam radiotherapy. Recent advance of technology enables radiosurgery to be extended to extracranial lesions. The purpose of this study was to determine the clinical effectiveness and safety of stereotactic radiosurgery using Cyberknife in spinal metastasis.

Methods

From June, 2002 to December, 2007, 129 patients with 167 spinal metastases were treated with Cyberknife. Most of the patients (94%) presented with pain and nine patients suffered from motor deficits. Twelve patients were asymptomatic. Fifty-three patients (32%) had previous radiation therapy. Using Cyberknife, 16-39 Gy in 1-5 fractions were delivered to spinal metastatic lesions. Radiation dose was not different regarding the tumor pathology or tumor volume.

Results

After six months follow-up, patient evaluation was possible in 108 lesions. Among them, significant pain relief was seen in 98 lesions (91%). Radiological data were obtained in 83 lesions. The mass size was decreased or stable in 75 lesions and increased in eight lesions. Radiological control failure cases were hepatocellular carcinoma (5 cases), lung cancer (1 case), breast cancer (1 case) and renal cell carcinoma (1 case). Treatment-related radiation injury was not detected.

Conclusion

Cyberknife radiosurgery is clinically effective and safe for spinal metastases. It is true even in previously irradiated patients. Compared to conventional radiation therapy, Cyberknife shows higher pain control rate and its treatment process is more convenient for patients. Thus, it can be regarded as a primary treatment modality for spinal metastases.     

The role of stereotactic radiosurgery in metastasis to the spine

Objective

The incidence and prevalence of spinal metastases are increasing, and although the role of radiation therapy in the treatment of metastatic tumors of the spine has been well established, the same cannot be said about the role of stereotactic radiosurgery. Herein, the authors present a systematic review regarding the value of spinal stereotactic radiosurgery in the management of spinal metastasis.

Methods

A systematic literature search for stereotactic radiosurgery of spinal metastases was undertaken. Grades of Recommendation, Assessment, Development, and Education (GRADE) working group criteria was used to evaluate the qualities of study datasets.

Results

Thirty-one studies met the study inclusion criteria. Twenty-three studies were of low quality, and 8 were of very low quality according to the GRADE criteria. Stereotactic radiosurgery was reported to be highly effective in reducing pain, regardless of prior treatment. The overall local control rate was approximately 90%. Additional asymptomatic lesions may be treated by stereotactic radiosurgery to avoid further irradiation of neural elements and further bone-marrow suppression. Stereotactic radiosurgery may be preferred in previously irradiated patients when considering the radiation tolerance of the spinal cord. Furthermore, residual tumors after surgery can be safely treated by stereotactic radiosurgery, which decreases the likelihood of repeat surgery and accompanying surgical morbidities. Encompassing one vertebral body above and below the involved vertebrae is unnecessary. Complications associated with stereotactic radiosurgery are generally self-limited and mild.

Conclusion

In the management of spinal metastasis, stereotactic radiosurgery appears to provide high rates of tumor control, regardless of histologic diagnosis, and can be used in previously irradiated patients. However, the quality of literature available on the subject is not sufficient.     

Retrospective study of 19 patients with intramedullary spinal cord metastasis

Object

Intramedullary spinal cord metastasis (ISCM) is a rare but devastating complication of cancer. Due to both widespread MRI availability and longer survival of cancer patients, the probability of discovering an ISCM during the course of the disease has increased and raised issues regarding the management of these patients, and particularly the place of surgery. In this study, we assess predictive factors for surgical outcome and survival.

Patients and methods

We retrospectively reviewed a series of 19 patients consecutively admitted in our institution from 1993 to 2006 for ISCM, representing the second largest series published in the literature. MRI was performed on all patients. Thirteen underwent microsurgical excision of ISCM. Functional outcome was evaluated and factors influencing survival were statistically analyzed.

Results

Median survival was statistically longer when surgery was performed (7.4 vs. 2.6 months). Preoperative neurological status, nature of primary cancer, presence of systemic and/or CNS metastases influenced survival, but differences were without statistical significance. Neurological status improved in 58% (11/19) of operated patients.

Conclusions

Optimal management of patients with ISCM is difficult due to the wide variety of clinical situations and the lack of controlled studies on the results of different therapeutic options. Diagnosis should be made as early as possible and surgical resection should be considered as the primary treatment whenever feasible, particularly in the case of rapidly progressive neurological deficits and when a clear cleavage plane exists. Our study shows that surgery could result in both increased survival rate and significant improvement of neurological function.     

Gamma knife radiosurgery for orbital tumors

Objective

This study was performed to investigate the radiological and functional outcomes of patients with orbital tumors treated by gamma knife radiosurgery (GKS).

Patients and methods

Fifteen patients with orbital tumors (7 meningiomas, 3 cavernous hemangiomas, 2 schwannomas, 2 metastatic tumors and 1 adenoid cystic carcinoma of the lacrimal gland) were treated. Seven patients with preserved vision and tumors located near the optic nerve were treated with multisession (3 or 4 fractions) radiosurgery. The mean tumor volume was 3695 mm³ (737–13,300). The median marginal dose was 14 Gy (13–20) in single-session radiosurgery, and the median cumulative marginal dose was 20 Gy (15–20) in multisession radiosurgery.

Results

After a mean follow-up of 20.9 months (6–50), tumor control was confirmed in 12 of 15 patients. Three patients with malignant lesions had to undergo another operation due to tumor progression. Of the 13 patients whose preoperative vision was preserved, 6 patients showed improvement in visual acuity and/or visual field, 4 patients showed no change in vision, and 3 patients showed deterioration (2 related to tumor progression).

Conclusions

As with intracranial tumors with similar pathologies, GKS may be an effective treatment option for orbital tumors. Multisession radiosurgery may be a good strategy for increasing the possibility of visual function preservation in selected cases in which the lesion is adjacent to the optic apparatus.     

Treatment of recurrent high grade gliomas with hypofractionated stereotactic image-guided helical tomotherapy

Objective

Salvage treatment of high grade gliomas that progress after standard therapy of resection and adjuvant chemoradiation therapy includes repeat surgical resection, second line chemotherapy, re-irradiation, or often a combination of the above. We present a series on patients treated with hypofractionated stereotactic image-guided helical tomotherapy and discuss the efficacy of this new technology in the treatment of high grade gliomas.

Materials and methods

Between June 2005 and August of 2008, eight patients with recurrent high grade gliomas were treated with salvage radiation therapy using hypofractionated stereotactic image-guided helical tomotherapy after image documentation of disease progression. Median age was 48.5 years with 4 females and 4 males. Median KPS at time of treatment was 65. All patients had either Grade III or IV gliomas at time of treatment with previous history of involved field fractionated radiotherapy. Median total dose given was 2500 cGy in 500 cGy fractions.

Results

The median planning target volume was 69.5 cm³. Five of the eight patients were alive at the time of last follow-up with a median survival of 7.6 months. Radiographic documented control was seen in six of the eight patients with median local control of 4.6 months. Acute Radiation Therapy Oncology Group (RTOG) toxicity scores measured zero in all patients with only one patient requiring a reoperation following treatment.

Conclusions

Hypofractionated stereotactic image-guided helical tomotherapy provides an alternative to other stereotactic radiation therapy and radiosurgery options for treatment of recurrent high grade gliomas.     

Gamma knife radiosurgery for intracranial cavernous malformations

Objectives

To analyze and evaluate the role of Gamma knife radiosurgery (GKRS) and clinical outcome in patients with intracranial cavernous malformations.

Patients and methods

The medical records of 96 patients who underwent radiosurgery at our institute were reviewed retrospectively.

Results

After a mean follow-up period of 4.3 years, 33 cases out of 44 (75.0%) with complaint of seizure had cleared or got improved, 9 (20.5%) were not improved and 2 (4.5%) got worse. Of the 100 lesions in the 96 patients, 24 (24.0%) had the lesions shrinkage on the follow-up imagings. One patient (1.6%) with symptom of headache and dizziness got worse and three patients (3.1%) presented with new cranial nerve palsy. We have compared the treatment results between different marginal dose groups and find that low marginal dose can get better therapeutic efficacy but with less complications.

Conclusion

GKRS is an effective and microinvasive treatment option for intracranial cavernous malformations.     

Intraindividual comparison of histopathological diagnosis obtained by stereotactic serial biopsy to open surgical resection specimen in patients with intracranial tumours

Background

There are concerns in the literature about the accuracy of histopathological diagnosis obtained by stereotactic biopsy in patients with brain tumours. The aim of this study was to analyse intraindividually the histopathological accuracy of stereotactic biopsies of intracerebral lesions in comparison to open surgical resection.

Materials and methods

Between 2007 and 2011 a total of 635 patients underwent stereotactic serial biopsy in our department. Among these patients we identified 51 patients, who underwent magnetic resonance (MR) based stereotactic biopsy and subsequent open resection within 30 days. Mortality and morbidity data as well as final histopathological diagnoses of both procedures were compared with regard to tumour grade and tumour cell type. Patients with discrepancies between the histological diagnosis obtained by biopsy and open resection were classified into three subgroups (same cell type but different grading; same grading but different cell type and different grading as well as different cell type).

Results

The mean number of tissue samples taken by stereotactic serial biopsy from each patient was 12 (range 7–21). Minor morbidity was 6% and major morbidity was 14% after open surgery compared to no morbidity after stereotactic biopsy. Mortality was 2% after stereotactic biopsy (one patient died after stereotactic biopsy as a result of a fatal bleeding) compared to 0% in the resection group. Silent bleeding rate without any clinical symptoms was 8% in the biopsy group. A complete correlation of histopathological findings between the biopsy group and the resection group was achieved in 76% and was increased to 90% by analyzing clinical and neuroradiological information. In patients with recurrence the correlation was higher (94%) than for patients with primary brain lesions (67%). The discrepancies between the open resection group and biopsy group were analysed.

Conclusion

Stereotactic MR guided serial biopsy is a minimal invasive procedure with low morbidity and high diagnostic accuracy for diagnosis and grading of brain tumours. Diagnostic accuracy of stereotactic biopsy can be enhanced further by careful interpretation of neuroradiological and clinical information.     

Efficacy and Safety of Fractionated Stereotactic Radiosurgery for Large Brain Metastases

Objective

To investigate the efficacy and safety of fractionated stereotactic radiosurgery for large brain metastases (BMs).

Methods

Between June 2011 and December 2013, a total of 38 large BMs >3.0 cm in 37 patients were treated with fractionated Cyberknife radiosurgery. These patients comprised 16 men (43.2%) and 21 women, with a median age of 60 years (range, 38-75 years). BMs originated from the lung (n=19, 51.4%), the gastrointestinal tract (n=10, 27.0%), the breast (n=5, 13.5%), and other tissues (n=3, 8.1%). The median tumor volume was 17.6 cc (range, 9.4-49.6 cc). For Cyberknife treatment, a median peripheral dose of 35 Gy (range, 30-41 Gy) was delivered in 3 to 5 fractions.

Results

With a median follow-up of 10 months (range, 1-37 months), the crude local tumor control (LTC) rate was 86.8% and the estimated LTC rates at 12 and 24 months were 87.0% and 65.2%, respectively. The median overall survival (OS) and progression-free survival (PFS) rates were 16 and 11 months, respectively. The estimated OS and PFS rates at 6, 12, and 18 months were 81.1% and 65.5%, 56.8% and 44.9%, and 40.7% and 25.7%, respectively. Patient performance status and preoperative focal neurologic deficits improved in 20 of 35 (57.1%) and 12 of 17 patients (70.6%), respectively. Radiation necrosis with a toxicity grade of 2 or 3 occurred in 6 lesions (15.8%).

Conclusion

These results suggest a promising role of fractionated stereotactic radiosurgery in treating large BMs in terms of both efficacy and safety.     

Preliminary Report of Multisession Gamma Knife Radiosurgery for Benign Perioptic Lesions: Visual Outcome in 22 Patients

Objective

Radiosurgery may be contraindicated for lesions adjacent to the optic pathways because of the substantial risk of visual complication. Multisession radiosurgery has been tried as a compromise between single session radiosurgery and fractionated radiotherapy. The purpose of this study is to evaluate the outcomes of multisession gamma knife radiosurgery (GKRS) in 22 patients with perioptic lesions of benign pathology.

Methods

In all 22 cases, the lesions were within 1 mm of the optic apparatus and were therefore not considered suitable for single session radiosurgery. Radiation was delivered in 3 to 4 fractions with a median cumulated marginal dose of 20 Gy (range, 15-20 Gy).

Results

During a mean follow-up of 29 months (range, 14-44 months), tumor control was achieved in 21 patients. Visual function improved in 7 patients, remained unchanged in 14 patients, and deteriorated in 1 patient with tumor progression. No other complication was observed.

Conclusion

This preliminary result supports the idea that multisession GKRS may be an effective and safe alternative for treatment in perioptic lesions that are unsuitable for single session radiosurgery.     

Tumor neuroendocrino bien diferenciado intradural-extramedular primario del filum terminale. Presentación de un caso y revisión de la literatura

Objective

To present a case of a well-differentiated primary intradural-extramedullary neuroendocrine tumor of the filum terminale and to conduct a literature review.

Surgical management of carcinoid tumors metastatic to the spine: Report of three cases

Background

Carcinoid tumors are rare, slow-growing neuroendocrine tumors that most frequently arise from the gastrointestinal tract or the lungs. Common sites of carcinoid metastases include lymph nodes, liver, lungs, and bone, with rare metastasis to the spine. We report three patients who presented with spinal cord compression secondary to carcinoid metastases to the spine.

Methods

Three patients presented with symptoms characteristic of spinal cord compression, including neck pain, radiculopathy, thoracic pain, weakness and numbness. All three patients underwent radiographic work-up and surgical treatment.

Results

One patient continued to have decreased strength in her right upper extremity, but was able to participate in physical therapy; another patient's numbness eventually resolved after completion of physical therapy; and the third patient's pain dramatically improved after surgery. One patient died more than two years post-surgery due to widespread metastasis; the other two remain alive more than two years post-surgery.

Conclusions

Carcinoid tumor metastases rarely cause spinal cord compression, but should be considered when patients present with neurological symptoms consistent with cord compression. Work-up should include magnetic resonance imaging (MRI), computed tomography (CT) of the spine, and perhaps CT-guided biopsy. Surgery is indicated for symptomatic spinal cord compression in patients with carcinoid tumors.     

Salt-and-pepper eye pain and brainstem stroke

Background and purpose

The salt-and-pepper pain is a characteristic sensory disturbance confined to the eyes and regional facial structures. Although a poor prognosis has been mentioned in previously reported patients, the precise pathomechanism and clinical significance are still unknown.

Patients and methods

We report four patients with ocular salt-and-pepper pain, and review the clinical course, neuroimaging and prognosis in another eight patients reported in the literature.

Results

In our series, they were three men and one woman, and their underlying cause was pontine hemorrhage; hypertensive hemorrhage in three and cavernous hemangioma in one patient, respectively. In these 12 salt-and-pepper patients, the identifiable etiology was exclusively brainstem stroke. Life-threatening or disable neurological deterioration ensued within 24 h after pain onset in all patients. Their ocular pain subsided rapidly after neurological deterioration occurred. A dual excitation of nociceptive quinothalamic pain fiber and disinhibition of trigeminosensory system from pontine reticular formation and cerulotrigeminospinal circuit may be responsible for this pain.

Conclusion

In clinical practice, ocular salt-and-pepper pain in quiet eyes should be alerted for intracranial pathology and neurological deterioration until underlying cause is identified.     

Effects of non-pharmacological pain treatments on brain states

Objective

To (1) evaluate the effects of a single session of four non-pharmacological pain interventions, relative to a sham tDCS procedure, on pain and electroencephalogram- (EEG-) assessed brain oscillations, and (2) determine the extent to which procedure-related changes in pain intensity are associated with changes in brain oscillations.

Methods

30 individuals with spinal cord injury and chronic pain were given an EEG and administered measures of pain before and after five procedures (hypnosis, meditation, transcranial direct current stimulation [tDCS], neurofeedback, and a control sham tDCS procedure).

Results

Each procedure was associated with a different pattern of changes in brain activity, and all active procedures were significantly different from the control procedure in at least three bandwidths. Very weak and mostly non-significant associations were found between changes in EEG-assessed brain activity and pain.

Conclusions

Different non-pharmacological pain treatments have distinctive effects on brain oscillation patterns. However, changes in EEG-assessed brain oscillations are not significantly associated with changes in pain, and therefore such changes do not appear useful for explaining the benefits of these treatments.

Significance

The results provide new findings regarding the unique effects of four non-pharmacological treatments on pain and brain activity.     

Survival of brain metastatic patients treated with gamma knife radiosurgery alone

Purpose

To evaluate the impact of gamma knife radiosurgery (GKRS) alone on the survival of brain metastasis patients.

Methods

Fifty patients, 17 men and 33 women, with 169 metastatic tumors were retrospectively reviewed. Before therapy, their mean Karnofsky Performance Score was 78. The majority of their primary cancers stemmed from the lung (56%). Thirty-five patients harbored multiple tumors. The mean tumor volume was 3.7 ml. The mean margin dose was 16 Gy. The mean/median clinical follow-up period was 37/25 weeks.

Results

The overall image-proven tumor control rate was 76%, and the median tumor progression-free period was 26 weeks after radiosurgery. The survival rate of the patients was 58% and 30% at 6 and 12 months, respectively, and the overall median post-radiosurgery survival time was 38 weeks. Both uni- and multi-variate Cox analyses demonstrated that patients with KPS ≧ 80 or who were in Recursive Partitioning Analysis Class I survived significantly longer (p < 0.05).

Conclusions

Patients treated with GKRS alone can prolong their median lifespan by a range of 6–10 months if they are in a good pre-GKRS functional state.