Object. Gamma knife radiosurgery (GKS) has become a well-established treatment modality in the management of selected patients with brain metastasis. The authors review the management patients with these tumors treated at a single center. Methods. Between 1994 and 2002, 458 consecutive patients with metastatic brain disease underwent GKS. There were 1305 lesions treated in 680 separate sessions. The histological diagnosis was melanoma in 231 (50%), lung cancer in 94 (20.5%), breast cancer in 38 (8.3%), renal cell carcinoma (RCC) in 29 (6.3%), colon carcinoma in 13 (2.8%), unknown primary site in 14 (3.1%), and other in 39 patients (8.5%). The median tumor volume was 0.9 cm3 and the median volume treated was 2.3 cm3. The median radiation dose was 18 Gy prescribed to a median isodose of 60%; the median dose was 20 Gy in melanoma, sarcoma, and RCC. Whole-brain radiotherapy (WBRT) either prior to or following GKS was performed in 114 patients (25%). Follow up ranged from 3 to 84 months with a median of 9 months. The median survival for all patients was 9 months and depended on tumor histology. Survival ranged from 6 months for patients with colon carcinoma, unknown primary tumors, and other tumors to 17 months for those with breast cancer. Median survival in patients with melanoma was 8 months. In multivariate analysis Karnofsky Performance Scale score (< 70 vs > 70), status of systemic disease (yes vs no), histological diagnosis, and total intracranial tumor volume were the only significant factors influencing survival. The number of brain metastases (one–five), WBRT (yes vs no), and age were not significant. Pattern of failure was different in patients with melanoma compared with those with other diagnoses. Cause of death in patients with melanoma was in 50% of the cases due to systemic disease and in 42% due to central nervous system causes, whereas it was 70% for the former and 23% for the latter in patients with other diagnoses. The treatment was well tolerated with significant late toxicity requiring craniotomy for removal of a necrotic focus in only 20 patients (4.7%). Conclusions. Gamma knife radiosurgery provided an excellent palliation with low incidence of toxicity. A Phase III prospective randomized trial is required to define the role of WBRT in combination with GKS.

During a 21-year period, 66 patients with uterine sarcomas were treated at California Medical Center. Histological diagnoses were mixed mesodermal sarcoma in 32 patients (48%), leiomyosarcoma in 24 (36%), and endometrial stromal sarcoma in 10 (15%) patients. The majority of patients (73%) had Stage I tumors. The treatment consisted of surgery alone in 27 (41%), surgery in combination with radiation therapy in 36 (55%), and radiation therapy alone in three (4%) patients. The overall 1-, 2-, and 5-year actuarial survival was 74%, 57%, and 38%, respectively. The 1-, 2-, and 5-year actuarial survival for the 27 surgery alone patients was 73%, 50%, and 25%, which compared with 75%, 61%, and 44% for the 36 surgery plus radiation therapy patients (P = 0.12). The disease-free survival was better for the surgery plus radiation therapy patients, as compared with the surgery alone group (38% vs. 18% at 5 years, P = 0.081). The 5-year survival by histology was 70% for the 10 endometrial stromal sarcoma patients, 40% for the 24 leiomyosarcoma patients, and 23% for the 32 mesodermal sarcoma patients (P = 0.064). As expected, survival depended on the stage of disease (P less than 0.0001). Treatment failure was observed in 35 (53%) patients, which included 9 (14%) with failure in the pelvis. There was no difference in the incidence of failure among patients in the three treatment groups and also in the three histologic groups. There was, however, a significant difference in the incidence of pelvic failure between surgery alone and surgery plus radiation therapy patients. In the 27 surgery alone patients, nine (33%) relapsed in the pelvis, whereas none of the 36 surgery plus radiation therapy patients had locoregional failure, P less than 0.0001. Adjuvant radiation therapy is an important treatment in the management of patients with sarcoma of the uterus.

GKRS is a safe and effective therapy in selected patients with pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus. A radiation dose higher than 15 Gy is probably needed to improve control of hormone-secreting adenomas. Longer follow-up is required for a more complete assessment of late toxicity and treatment efficacy.

Although metastatic melanoma to the brain continues to have a foreboding prognosis for long-term survival, gamma knife radiosurgery seems to be a relatively safe, noninvasive, palliative therapy, halting or reversing neurological progression in 77.8% of treated patients (35 of 45 patients). The survival rate matches or exceeds those previously reported for surgery and other forms of radiotherapy. Only 7.7% of the patients in our study population who died as a result of metastatic melanoma (2 of 26 patients) died as a result of neurological disease. The routine use of therapeutic level antiseizure medication is emphasized, considering the findings of our review.

A series of 474 patients with renal cell carcinoma (RCC), who had radical nephrectomy during a period of 15 years, was studied to assess the prognostic significance of various pathologic parameters (tumor stage [pT], lymph node status, metastasis, tumor grade, venous involvement) and value of preoperative embolization of renal artery. There were: 20 (4%) pT1, 204 (43%) pT2, 245 (52%) pT3, and 5 (1%) pT4 patients. All 474 patients underwent nephrectomy including a group of 118 (25%) patients (24 pT2, 90 pT3, and 4 pT4) who underwent preoperative embolization of the renal artery. To compare treatment outcomes in embolized patients with RCC, a group of 116 (24%) nonembolized patients with RCC was selected. This group was matched for sex, age, stage, tumor size, and tumor grade, with the embolized patients (p<0.01). All important prognostic factors were studied as to their influence on survival by the treatment group. The overall 5- and 10-year survival was 62% and 47%, respectively. The 5- and 10-year survival rates were significantly better (p<0.01) for patients with pT2 than for those with pT3 tumors (79% vs. 50% and 59% vs. 35%, respectively). Involvement of regional lymph nodes (N+) was an important prognostic factor for survival in patients with pT3 tumors. The 5-year survival for pT3 N+ was 39%, compared with 66% in those with pT3N0 (p<0.01). Preoperative embolization was also an important factor influencing survival. The overall 5- and 10-year survival for 118 patients embolized before nephrectomy was 62% and 47%, respectively, and it was 35% and 23%, respectively, for the matched group of 116 patients treated with surgery alone (p = 0.01). The most important finding of this study was an apparent importance of preoperative embolization in improving patients' survival. This finding needs to be interpreted with caution and confirmed in a prospective randomized trial.

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GKRS is a safe and effective treatment for selected patients with benign cavernous sinus tumors and is an important adjunct for treating postoperative tumor residual and/or recurrent tumor. Continued analysis of treated patients over an extended time is needed to evaluate long-term disease control and potential late GKRS complications.

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