Retrospective Study of Metastatic Melanoma and Renal Cell Carcinoma to the Brain with Multivariate Analysis of Prognostic Pre-Treatment Clinical Factors.

Patients with brain metastasis from renal cell carcinoma (RCC) or melanoma have historically had very poor prognoses of less than one year. Stereotactic radiosurgery (SRS) can be an effective treatment for patients with these tumors. This study analyzes the effect of pretreatment prognostic factors on overall survival (OS) for RCC and melanoma patients with metastasis to the brain treated with SRS. A total of 122 patients with brain metastases from either RCC or melanoma were grouped by age at brain metastasis diagnosis, whether they received whole brain radiation therapy (WBRT) in addition to SRS, or they underwent surgical resection, Karnofsky Performance Score (KPS), number of brain metastases, and primary tumor. Median survival times for melanoma patients and RCC patients were 8.20 ± 3.06 and 12.70 ± 2.63 months, respectively. Patients with >5 metastases had a significantly shorter median survival time (6.60 ± 2.45 months) than the reference group (1 metastasis, 10.70 ± 13.40 months, p = 0.024). Patients with KPS ≤ 60 experienced significantly shorter survival than the reference group (KPS = 90-100), with median survival times of 5.80 ± 2.46 months (p < 0.001) and 45.20 ± 43.52 months, respectively. We found a median overall survival time of 12.7 and 8.2 months for RCC and melanoma, respectively. Our study determined that a higher number of brain metastases (>5) and lower KPS were statistically significant predictors of a lower OS prognosis.

Gamma knife treatment of brainstem metastases.

The management of brainstem metastases is challenging. Surgical treatment is usually not an option, and chemotherapy is of limited utility. Stereotactic radiosurgery has emerged as a promising palliative treatment modality in these cases. The goal of this study is to assess our single institution experience treating brainstem metastases with Gamma Knife radiosurgery (GKRS). This retrospective chart review studied 41 patients with brainstem metastases treated with GKRS. The most common primary tumors were lung, breast, renal cell carcinoma, and melanoma. Median age at initial treatment was 59 years. Nineteen (46%) of the patients received whole brain radiation therapy (WBRT) prior to or concurrent with GKRS treatment. Thirty (73%) of the patients had a single brainstem metastasis. The average GKRS dose was 17 Gy. Post-GKRS overall survival at six months was 42%, at 12 months was 22%, and at 24 months was 13%. Local tumor control was achieved in 91% of patients, and there was one patient who had a fatal brain hemorrhage after treatment. Karnofsky performance score (KPS) >80 and the absence of prior WBRT were predictors for improved survival on multivariate analysis (HR 0.60 (p = 0.02), and HR 0.28 (p = 0.02), respectively). GKRS was an effective treatment for brainstem metastases, with excellent local tumor control.

Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis.

Benign neurofibromas and malignant peripheral nerve sheath tumors are serious complications of neurofibromatosis type 1. The epidermal growth factor receptor is not expressed by normal Schwann cells, yet is overexpressed in subpopulations of Nf1 mutant Schwann cells. We evaluated the role of EGFR in Schwann cell tumorigenesis. Expression of EGFR in transgenic mouse Schwann cells elicited features of neurofibromas: Schwann cell hyperplasia, excess collagen, mast cell accumulation, and progressive dissociation of non-myelin-forming Schwann cells from axons. Mating EGFR transgenic mice to Nf1 hemizygotes did not enhance this phenotype. Genetic reduction of EGFR in Nf1(+/-);p53(+/-) mice that develop sarcomas significantly improved survival. Thus, gain- and loss-of-function experiments support the relevance of EGFR to peripheral nerve tumor formation.

Rubinstein-Taybi syndrome in children with tethered spinal cord.

OBJECT: The authors identified eight patients with Rubinstein-Taybi syndrome (RTS) and examined how the underlying conditions of this syndrome can impede the detection of symptoms associated with a tethered spinal cord. They also reviewed the literature and did not find any published series describing such an association with this syndrome. METHODS: In this retrospective review, the authors report the diagnosis, treatment, and outcome of tethered spinal cord in eight children (age range 2-14 years) with RTS. The patients presented between 1995 and 2003 with neurogenic bladder, decreased activity, gait disturbance, and low-back pain. The children were examined using whole-spine magnetic resonance (MR) imaging and, in recent years, their spinal cord movement was assessed using cine MR imaging. After undergoing lumbar laminectomy and spinal cord untethering procedures, six patients experienced improvement in symptoms associated with tethered spinal cord such as pain, urinary tract infection, incontinence, spasticity, and neurogenic bladder. CONCLUSIONS: Although some underlying conditions of RTS may mask the symptoms of a tethered spinal cord in children, careful attention to the patient's medical history as provided by his or her parents may aid in early diagnosis, evaluation, and treatment, thus preventing further neurological deterioration and leading to improved outcomes.

Vertebral column subtraction osteotomy for recurrent tethered cord syndrome in adults: a cadaveric study.

OBJECT: The standard treatment for lumbosacral tethered cord syndrome (TCS) in adults is surgical detethering. In patients with recurrent TCS, additional detethering operations are associated with increased risk of complications and subsequent scar formation. The authors studied the effect of undertaking a vertebral column subtraction osteotomy (VCSO) at the thoracolumbar junction to shorten the vertebral column and reduce neural element tension. METHODS: A model of TCS, developed in fresh-frozen human cadavers, was evaluated in three experiments. In Experiment 1, VCSO of 20 to 25 mm was performed at the T11-12 level. The vertebral column was sequentially shortened and the reduction in tension was measured separately in the terminal filum and the L-1 to S-3 or S-4 nerve roots. In Experiments 2 and 3 the reduction in tension was measured in the spinal cord after a VCSO and after simulating a traditional detethering operation. Vertebral column shortening produced tension reduction in all experiments. Tension decreased to less than 0.6 g in the terminal filum, L1-S3/4 nerve roots, and spinal cord after closure of a 20- to 25-mm VCSO. The mean +/- standard deviation of the deltatension/deltadistance was -0.242 +/- 0.019 g/mm for the terminal filum, -0.246 +/- 0.019 g/mm for the lumbar nerve roots, and -0.216 +/- 0.040 g/mm for the sacral nerve roots. A simulated traditional detethering operation required significant neural element release (detethering) to achieve spinal cord tension reduction equivalent to VCSO. CONCLUSIONS: A VCSO significantly reduced neural tension at the thoracolumbar junction. This novel procedure may provide an alternative to traditional surgical detethering when scarring is excessive and the risk of complications and retethering are high.

Pretreatment clinical prognostic factors for brain metastases from breast cancer treated with Gamma Knife radiosurgery.

BACKGROUND: Brain metastases significantly affect morbidity and mortality rates for patients with metastatic breast cancer. Treatment for brain metastases lengthens survival, and options such as stereotactic radiosurgery (SRS) can increase survival to 12 months or longer. This study retrospectively analyzes the prognostic factors for overall survival (OS) for patients with one or multiple brain metastases from breast cancer treated with SRS. METHODS: Between December 2001 and May 2015, 111 patients with brain metastases from breast cancer were grouped by potential prognostic factors including age at diagnosis, Karnofsky Performance Status (KPS) score, number of brain metastases, and whether or not they received adjuvant treatments such as whole brain radiotherapy (WBRT) or surgical resection. Survival rates were determined for all groups, and hazard ratios were calculated using univariate and multivariate analyses to compare differences in OS. RESULTS: Median OS was 16.8 ± 4.22 months. Univariate analysis of patients with a KPS ≤60 and multivariate analysis of KPS 70-80 showed significantly shorter survival than those with KPS 90-100 (5.9 ± 1.22 months, 21.3 ± 11.69 months, and 22.00 ± 12.56 months, P = 0.024 and < 0.001). Other results such as age ≥65 years and higher number of brain metastases trended toward shorter survival but were not statistically significant. No difference in survival was found for patients who had received WBRT in addition to SRS (P = 0.779). CONCLUSION: SRS has been shown to be safe and effective in treating brain metastases from breast cancer. We found our median survival to be 16.8 ± 4.22 months, an increase from other clinical reports. In addition, 38.4% of our population was alive at 2 years and 15.6% survived 5 years. Significant prognostic factors can help inform clinical treatment decisions. This study found that KPS was a significant prognostic indicator of OS in these patients.

Prolonged Survival following Repetitive Stereotactic Radiosurgery in a Patient with Intracranial Metastatic Renal Cell Carcinoma.

Patients with metastatic renal cell carcinoma (RCC) to the brain have a very poor prognosis of three months if left untreated. SRS is an effective treatment modality in numerous patients. This case exemplifies the utility of stereotactic radiosurgery (SRS) in prolonging survival and maintaining quality of life in a patient with RCC. This 64-year-old female patient initially presented to her primary care physician 22 months after a left nephrectomy for RCC with complaints of mild, intermittent headaches and difficulty with balance. An MRI revealed five cerebellar lesions suspicious for intracranial metastasis. The patient's first GKRS treatment targeted four lesions with 22 Gy at the 50% isodose line. She underwent a total of seven GKRS treatments over the next 60 months for recurrent metastases to the brain. 72 months and 12 months have now passed since her brain metastases were first discovered and since her last GKRS treatment, respectively, and this woman is alive with considerable quality of life and no evidence of metastatic reoccurrence. This case shows that repeated GKRS treatments, with minimal surgical intervention, can effectively treat multiple intracranial lesions in select patients, prolonging survival and avoiding iatrogenic neurocognitive decline while maintaining a high quality of life.

Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM (rGBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery (GKRS) salvage therapy. Following a PubMed search for studies using GKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rGBM treatment. In this review, we compare Overall survival following diagnosis, Overall survival following salvage treatment, Progression-free survival, Time to recurrence, Local tumor control, and adverse radiation effects. This report discusses results for rGBM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates (from diagnosis, range: 16.7-33.2 mo; from salvage, range: 9-17.9 mo). Three studies identified median progression-free survival (range: 4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects (range: 0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rGBM patient. However, there needs to be a randomized clinical trial to test GKRS for rGBM before the possibility of selection bias can be dismissed.

Video-assisted thoracoscopic dissection of the brachial plexus: cadaveric study and illustrative case.

OBJECTIVE: Standard surgical approaches to the brachial plexus require an open operative technique with extensive soft tissue dissection. A transthoracic endoscopic approach using video-assisted thoracoscopic surgery (VATS) was studied as an alternative direct operative corridor to the proximal inferior brachial plexus. METHODS: VATS was used in cadaveric dissections to study the anatomic details of the brachial plexus at the thoracic apex. After placement of standard thoracoscopic ports, the thoracic apex was systematically dissected. The limitations of the VATS approach were defined before and after removal of the first rib. The technique was applied in a 22-year-old man with neurofibromatosis who presented with a large neurofibroma of the left T1 nerve root. RESULTS: The cadaveric study demonstrated that VATS allowed for a direct cephalad approach to the inferior brachial plexus. The C8 and T1 nerve roots as well as the lower trunk of the brachial plexus were safely identified and dissected. Removal of the first rib provided exposure of the entire lower trunk and proximal divisions. After the fundamental steps to the dissection were identified, the patient underwent a successful gross total resection of a left T1 neurofibroma with VATS. CONCLUSION: VATS provided an alternative surgical corridor to the proximal inferior brachial plexus and obviated the need for the extensive soft tissue dissection associated with the anterior supraclavicular and posterior subscapular approaches.