Renal Cell Carcinoma Brain Metastases Research Articles

Control Rate and Radionecrosis Risk after Radiosurgery for Brain Metastases from Renal Cell Carcinoma: The UCSF Experience from 1991-2007

Variable control rates have been reported for stereotactic radiosurgery (SRS) of renal cell carcinoma (RCC) brain metastases (BM); a possible explanation is the difficulty of distinguishing necrosis from tumor progression. Given our impression that necrosis is relatively common after SRS for RCC BM, we sought to define the incidence of and factors associated with necrosis.

Clinical Follow-Up Study for Brain Metastases of Renal Cell Carcinoma

Purpose: We reviewed the records of renal cell carcinoma (RCC) patients with brain metastases, analyzed about survival and prognosis after several palliative management. Materials and Methods: Between June 1998 and January 2008, 22 patients diagnosed to have brain metastases from RCC. We retrospectively reviewed their medical records, and analyzed clinical properties. Results: Of 278 patients with RCC, 22 patients (7.9%) diagnosed to have brain metastases. The pathological T stages and Fuhrman nuclear grade of RCC at the time of initial diagnosis were various (T1: 1 patient, T2: 5, T3: 8, T4: 3, Fuhrman grade 1: 0, 2: 4, 3: 10, 4: 6, unknown: 2). Most of RCC was clear cell carcinoma (17/22). Most symptoms suggesting brain metastases were neurologic. Median cancer specific survival (CSS) of WBRT, radiosurgery, or surgery group (13/22) was 4 months, conservative management group (9/22) was 1.5 months and CSS of the former group was significantly better. Median duration of development of brain metastasis after diagnosis of RCC was 28 month (1-120). There was no difference in CSS between patients with brain metastasis developed before and after 28 month (p=0.361). Conclusions: Brain metastases of RCC have poor prognostic course. Development interval of brain metastases did not affect survival. WBRT, radiosurgery or surgery group showed better survival. Active intervention may improve survival. (Korean J Urol 2009;50:224-228) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Brain metastasis from renal cell carcinoma

Patients with renal cell carcinoma brain metastases (RCCBM) are frequently excluded from trials and to the authors' knowledge no guidelines currently exist regarding central nervous system (CNS) surveillance or treatment. The objective of the current study was to assist in the creation of treatment guidelines. Patients undergoing evaluation for RCCBM from 1989 to 2006 were identified. Their characteristics, symptoms, pathologic variables, number and size of RCCBM, CNS treatment, CNS recurrence, overall survival, and use of systemic therapy were reviewed. A total of 138 patients were identified with RCCBM, of whom 92% had clear cell RCC and 95% had synchronous extracranial metastases. CNS symptoms were noted in 67% of patients. Symptomatic CNS tumors were larger (2.1 cm vs 1.3 cm; P < .001) and more frequently required a craniotomy (P < .001). The median overall survival after a diagnosis of RCCBM was 10.7 months; the 1-year, 2-year, and 5-year survival rates were 48%, 30%, and 12%, respectively. Median CNS recurrence was 9 months after RCCBM treatment. The initial number of tumors (>1 tumor) was found to be an independent predictor of CNS recurrence (hazards ratio of 3.72; P < .001). Those patients with 1 and >1 lesion had a median CNS recurrence-free survival of 13 months and 4 months, respectively (P < .001). Patients receiving interleukin-2 after CNS treatment had a response rate of 17%. Patients with metastatic RCC should undergo CNS screening to allow the identification of smaller lesions that are more amenable to treatment. Those patients with solitary RCCBM are less likely to develop CNS recurrence after local therapy. Selected patients with good performance status may exhibit prolonged survival and should be offered aggressive therapy.

Brain metastasis from renal cell carcinoma: Presentation, recurrence, survival and implications for systemic therapy

5097 Background: Patients with renal cell carcinoma brain metastasis (RCCBM) are frequently excluded from clinical trials. NCCN guidelines do not give clear recommendations regarding central nervous system (CNS) surveillance or therapy. We set out to define who should be screened and who should be considered for clinical trials after treatment of CNS lesions. Methods: A database of information was reviewed to determine presentation, clinical symptoms, number and size of lesions, use of and response to systemic therapy, treatment of BM, CNS disease free survival after treatment of original BM (CNS recurrence), and overall survival from time of diagnosis of BM. Results: A total of 138 patients with RCCBM were identified of whom 95% underwent treatment for their BM. Clear cell histology accounted for 92% of patients and 93% of patients had concomitant metastasis. Patients had CNS symptoms in 67% of cases. Symptomatic CNS tumors were larger (2.1 vs 1.3 cm, p <0.001) and more likely to receive a craniotomy (p<...

Gamma knife radiosurgery for melanoma/renal cell carcinoma brain metastases 1 -10 lesions with optimized margin dose: Improved tumor control and survival

8581 Background: Radioresistant brain metastases melanoma/renal cell carcinoma cause significant morbidity and mortality: response to whole brain external beam radiotherapy (WBXRT) is minimal, chemotherapy role is investigative, and surgery has its indications and limitations. Reports of survival with Gamma Knife Radiosurgery (GK) is mixed. Reports indicate that 80 to 90% of tumor failure following GK is in the margin: recent multivariate analyses indicate tumor control dependence on margin dose. This study evaluates the impact of better control of brain lesions and consequent reduction of CNS death on overall survival. Methods: Between 10/2002 and 12/2005, 24 consecutive patients with melanoma and renal cell carcinoma male/female radio 14/10, 20 melanoma and 4 renal cell were treated by WBXRT followed by GK radiosurgery utilizing optimized margin dose. Dose was (16 - 20 Gy) to the 50% line with adequate margin to reduce systematic and other associated errors. This was achieved by combining the separate errors associated with the procedure; extent of tumor infiltration beyond gross tumor margin; GK/procedure mechanical precision limitations; MRI image transfer spatial limitations and beam profile margin dose sensitivity. Karnofsky Performance status was 70 - 90%. Follow-up period was 52 months. Results: The mean survival period for the 24 patients with 1 - 10 lesions was 14.11 months: median survival by Kaplan-Meier was 12.0 months. This result is a significant improvement on the 5.5 months reported earlier from this institution for 1 - 5 lesions treated with non-optimized GK dosage; and data by Lavin, et al, at 8 months for predominantly solitary lesions. Conclusions: Melanoma and renal cell carcinoma brain metastases respond very well to GK radiosurgery with optimized margin dose: mean survival for these patients with 1 -3 and 4 - 10 lesions is 14.11 months and comparable to the survival of patients with brain metastases from lung and breast patients: More studies along this line are called for. Patients with multiple metastatic brain lesions from melanoma and renal cell cancers stand to benefit. No significant financial relationships to disclose.

Pathologic Complete Response in Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery

Renal cell carcinoma (RCC) is often regarded as a radiation-resistant tumor. However, radiation therapy (RT) in the form of stereotactic radiosurgery (SRS) or whole-brain irradiation has been used to treat brain metastases from RCC. To date, there have been no clinical pathologic correlative findings before and after RT. Herein, we present a case of a patient with brain metastases from RCC treated with SRS. The diagnosis of clear-cell RCC was made in 2001 after right radical nephrectomy. He was also found to have lung metastases at diagnosis. He presented with neurologic symptoms in 2004, and magnetic resonance imaging showed 3 brain lesions with a significant amount of edema consistent with brain metastases. The largest lesion caused a midline shift and was surgically resected. Pathology revealed metastatic RCC. The other 2 smaller brain lesions were treated at 20 Gy respectively with shaped-beam SRS using the BrainLab Novalis® system. No whole-brain irradiation was delivered. However, the patient had difficulty weaning off his steroids, and a magnetic resonance imaging performed 6 months after SRS was read as “progression of the lesions.” He then underwent resection of both the irradiated brain lesions. Pathologic examination revealed necrotic tissues without any viable tumor identified. The patient has since been doing very well, now 18 months after SRS and 5 years from the Initials diagnosis. This is the first reported case that demonstrates that precise high-dose radiation in the form of SRS can cause significant tumor cell death (pathologic complete response) in radiation-resistant brain metastases from RCC. This finding also provides a rationale to deliver stereotactic body RT for primary and metastatic RCC extracranially. A prospective clinical trial using stereotactic body RT for primary and metastatic RCC is under way.

Clinical Study of Brain Metastasis of Renal Cell Carcinoma

Objectives: To evaluate the natural history and the efficacy of treatments for renal cell carcinoma (RCC) with brain metastasis, we reviewed 18 patients with this disease. Methods: Out of 325 cases with RCC treated at Osaka University Hospital from 1957 to 1993, 18 (5.5%, male:female ratio 16:2) cases developed brain metastases. Median follow-up was 44 months after the initial treatment of the primary lesion. Twelve patients had surgical resection of brain metastases (surgical group), and 7 of them received adjuvant radiotherapy. Six patients with poor performance status were treated with supportive therapy alone (nonsurgical group). Results: Of 18 RCC patients with brain metastasis, 16 were male and 2 female. All brain metastases except for 1 case were symptomatic. Median interval between the initial treatment of the primary lesion and the diagnosis of brain metastasis was 19 months. The most frequent metastatic site prior to brain was the lung, which was detected in 7 cases (38.9%). Median survival of the entire group, measured from the onset of brain metastasis, was 9.5 months. One-year survival rate after the diagnosis of brain metastasis was 43.2% (64.8% in surgical group, 0% in nonsurgical group), 3-year 18.5% and 5-year 0%. Among 109 metastatic RCC, 14 patients were treated by lymphokine-activated killer (LAK) therapy. Out of 14 metastatic RCC patients treated by LAK therapy, 3 (21.4%) developed brain metastases. On the other hand, out of 95 metastatic RCC patients without LAK therapy, 15 (15.8%) had brain metastases. There was no significant difference in the rate of brain metastases between these two groups. Conclusion: There was a trend for prognosis of the surgical group to be better compared to that of the nonsurgical group, although it is not statistically significant. The optimum treatment for brain metastasis of RCC remains undefined, but our data suggested surgical resection in selected patients might contribute to prolonged survival of patients with brain metastasis. LAK therapy was not necessarily the risk factor of the brain metastasis.

Statements from the university

Low-grade neuroepithelial tumors are frequent neuropathological findings in patients with pharmacoresistant epilepsies. Little is known regarding epileptogenic mechanisms in this group of neoplasms with gangliogliomas (GG) as the most common entity. Presence of hemosiderin deposits in GG points to impairment of the blood-brain barrier (BBB). Therefore, we hypothesized a potential role of BBB dysfunction and astrocytic albumin uptake as potential epileptogenic factor in GG.Prussian blue staining and fluorescent double-immunohistochemistry with antibodies against albumin, GFAP, CD34 and GLUT-1 were used to analyze hemosiderin deposits and astroglial albumin accumulation in tumor and adjacent pre-existing brain tissue of GG (n = 10) and several control groups, i.e. dysembryoplastic neuroepithelial tumors (DNT; n = 5), focal cortical dysplasia with balloon cells (FCD IIb; n = 10), astrocytomas WHO grade II (n = 5) and clear renal cell carcinoma brain metastases (RCCM, n = 6).Our results revealed strong hemosiderin deposits in GG. Intriguingly, we noted substantial albumin uptake exclusively in neoplastic glial cell components of GG and DNT, whereas no significant albumin was present in perilesional reactive astrocytes. Strikingly, we did not observe substantial albumin uptake in further controls.Glial albumin uptake was restricted to long-term epilepsy associated, vasculature-containing tumors. Intratumoural BBB dysfunction in concert with subsequent accumulation of albumin by neoplastic glial cell elements represent a new putatively epileptogenic mechanism for long-term epilepsy-associated tumors.