Faculty Bibliography

Patients with acoustic neuromas have several options available to them. Large tumors with significant brain stem compression usually require surgical resection. For patients with small or medium-sized tumors, radiosurgery has become a common treatment, with excellent long-term results being reported. Patients must be comfortable with the concept of tumor control rather than tumor removal. Most seem to be satisfied with this concept if it allows them to avoid brain surgery. Surgeons should strive to educate their patients with information from the peer-reviewed literature. Confusion exists among patients, because the information from Internet sources, newsletters, support groups, and physicians has not always been validated and supported by outcomes data. Although we are asked to provide our opinions, our comments should not be based on myth, conjecture, training bias, or socioeconomic concerns.

BACKGROUND: Outcomes in patients with brain metastases from gastrointestinal tract cancers are not well defined. In this study we used precise, single-session, focal tumor irradiation (radiosurgery) in patients with brain metastases and evaluated the results. METHODS: Thirty-nine patients had brain metastases from gastrointestinal tract cancer and were treated with radiosurgery. Thirty-two also had whole brain radiotherapy. Primary lesions included colorectal cancer (n = 25), esophageal cancer (n = 11), cholangiocarcinoma (n = 1), duodenal cancer (n = 1), and jejunal cancer (n = 1). Seventy-two tumors were treated. RESULTS: The overall median survival was 9 months after diagnosis of metastatic brain disease and 5 months after radiosurgery. The 1-year survival rate after radiosurgery was 19%. The last imaging study of 49 tumors showed complete remission (CR) in 3 tumors (6.1%), partial remission (PR) in 27 tumors (55.1%), no change (NC) in 11 tumors (22.4%), and progression in 8 tumors (16.3%). The local tumor control rate (CR, PR, NC) was 84%. Two patients (5.1%) had a new or worsening neurologic deficit after radiosurgery. CONCLUSIONS: Stereotactic radiosurgery provides reasonable local control of brain metastases from gastrointestinal tract cancer with few side effects. However, it should be used judiciously in patients with active extracranial cancers since the expected survival may be limited.

BACKGROUND: Stereotactic radiosurgery is the principal therapeutic alternative to resecting benign intracranial tumors. The goals of radiosurgery are the long-term prevention of tumor growth, the maintenance of patient function, and the prevention of new neurological deficits or adverse radiation effects. Evaluation of long-term outcomes more than 10 years after radiosurgery is needed. METHODS: We evaluated 285 consecutive patients who underwent radiosurgery for benign intracranial tumors between 1987 and 1992. Serial imaging studies were obtained, and clinical evaluations were performed. Our series included 157 patients with vestibular schwannomas, 85 patients with meningiomas, 28 patients with pituitary adenomas, 10 patients with other cranial nerve schwannomas, and 5 patients with craniopharyngiomas. Prior surgical resection had been performed in 44% of these patients, and prior radiotherapy had been administered in 5%. The median follow-up period was 10 years. RESULTS: Overall, 95% of the 285 patients in this series had imaging-defined local tumor control (63% had tumor regression, and 32% had no further tumor growth). The actuarial tumor control rate at 15 years was 93.7%. In 5% of the patients, delayed tumor growth was identified. Resection was performed after radiosurgery in 13 patients (5%). No patient developed a radiation-induced tumor. Eighty-one percent of the patients were still alive at the time of this analysis. Normal facial nerve function was maintained in 95% of patients who had normal function before undergoing treatment for acoustic neuromas. CONCLUSION: Stereotactic radiosurgery provided high rates of tumor growth control, often with tumor regression, and low morbidity rates in patients with benign intracranial tumors when evaluated over the long term. This study supports radiosurgery as a reliable alternative to surgical resection for selected patients with benign intracranial tumors.

BACKGROUND: Aggressive (atypical or malignant) meningiomas are difficult tumors to manage. We review the local control and survival rates of patients with aggressive meningiomas after multi-modality therapy that included stereotactic radiosurgery (SRS). METHODS: Thirty patients had SRS for treatment of malignant (n = 12) or atypical (n = 18) meningiomas. There were 17 (57%) males and 13 (43%) females with an average age of 58 years. The mean number of prior surgical resections was two. The median imaging follow-up was 2.3 (0.1-11.4) years; median clinical follow-up was 3.8 (0.25-11.5) years. RESULTS: After SRS, the overall median time until progression of neurologic signs was 48.0 (+/-6.51) months. Median time to neurologic progression was significantly worse for patients treated late after recurrence versus early after craniotomy. Atypical meningiomas had 5- and 10-year overall actuarial survival rates of 59% (+/-13), while malignant meningiomas had 5- and 10-year overall actuarial survival rates of 59% (+/-16) and 0%. These curves were not significantly different from one another. Atypical meningiomas had a 5-year progression-free survival (PFS) of 83% (+/-7%), while malignant meningiomas had a 5-year PFS of 72% (+/-10) (p = 0.018). On multivariate analysis, early SRS and smaller tumor volumes were associated with better PFS, while younger age was associated with better survival. One patient had an adverse radiation effect after SRS. CONCLUSIONS: Stereotactic radiosurgery is an important adjuvant management strategy for residual tumors identified early after craniotomy and partial resection. Aggressive use of early boost radiosurgery following craniotomy and radiation therapy is recommended for patients with malignant meningiomas.

PURPOSE: To better evaluate tumor control and toxicity from radiosurgery for brain metastases, we analyzed these outcomes in patients who had survived at least 1 year after radiosurgery. METHODS AND MATERIALS: We evaluated the results of gamma knife stereotactic radiosurgery (SRS) for 208 brain metastases in 137 patients who were followed for a median of 18 months (range 12-122) after radiosurgery. The median patient age was 53 years (range 3-83). Ninety-nine patients had solitary metastases. Thirty-eight had multiple tumors. Sixty-nine patients underwent initial SRS with whole brain radiotherapy (WBRT), 39 had initial SRS alone, and 27 patients had failed prior WBRT. The median treatment volume was 1.9 cm(3) (range 0.05-21.2). The median marginal tumor dose was 16 Gy (range 12-25). The most common histologic types included non-small-cell lung cancer, breast cancer, melanoma, and renal cell carcinoma, which comprised 37.0%, 22.6%, 13.0%, and 9.13% of the lesions, respectively. Forty-five tumors were associated with extensive edema. RESULTS: At 1 and 5 years, the local tumor control rate was 89.6% +/- 2.1% and 62.8% +/- 6.9%, distal intracranial relapse occurred in 23% +/- 3.6% and 67.1% +/- 8.7%, and postradiosurgical sequelae developed in 2.8% +/- 1.2% and 11.4% +/- 3.5% of patients, respectively. Multivariate analysis found that local control decreased with tumor volume (p = 0.0002), SRS without WBRT (p = 0.008), and extensive edema (p = 0.024); distal intracranial recurrence correlated with younger patient age (p = 0.0018); and postradiosurgical sequelae increased with increasing tumor volume (p = 0.0085). CONCLUSION: Long-term control of brain metastases and complication rates in this selective series of patients surviving >or=1 year after radiosurgery were similar to previously reported actuarial estimates. Large metastases and metastases associated with extensive edema can be difficult to control by radiosurgery, particularly without WBRT.

PURPOSE: To evaluate tumor control and outcome from radiosurgery of meningiomas diagnosed by imaging without pathologic verification. METHODS AND MATERIALS: A total of 219 meningiomas diagnosed by imaging criteria underwent gamma knife radiosurgery to a median marginal tumor dose of 14 Gy (range 8.9-20), a median treatment volume of 5.0 cm(3) (range 0.47-56.5), and a median maximal dose of 28 Gy (range 22-50). The median follow-up was 29 months (range 2-164). RESULTS: Tumor progression developed in 7 cases, 2 of which turned out to be different tumors (metastatic nasopharyngeal adenoid cystic carcinoma and chondrosarcoma). One tumor was controlled, but the development of other brain metastases suggested a different diagnosis. The actuarial tumor control rate was 93.2% +/- 2.7% at 5 and 10 years. The actuarial rate of identifying a diagnosis other than meningioma was 2.3% +/- 1.4% at 5 and 10 years. The actuarial rate of developing any postradiosurgical injury reaction was 8.8% +/- 3.0% at 5 and 10 years. No pretreatment variables correlated with tumor control in univariate or multivariate analysis. The risk of postradiosurgery sequelae was lower (5.3% +/- 2.3%) in patients treated after 1991 (with stereotactic MRI and lower doses; p = 0.0104) and tended to increase with treatment volume (p = 0.0537). CONCLUSION: Radiosurgery of meningioma diagnosed by imaging without tissue confirmation is associated with a high rate of tumor control and acceptable morbidity but carries a small risk (2.3%) of an incorrect diagnosis.

OBJECTIVE: Whole brain radiotherapy (WBRT) provides benefit for patients with brain metastases but may result in neurological toxicity for patients with extended survival times. Stereotactic radiosurgery in combination with WBRT has become an important approach, but the value of WBRT has been questioned. As an alternative to WBRT, we managed patients with stereotactic radiosurgery alone, evaluated patients' outcomes, and assessed prognostic factors for survival and tumor control. METHODS: One hundred seventy-two patients with brain metastases were managed with radiosurgery alone. One hundred twenty-one patients were evaluable with follow-up imaging after radiosurgery. The median patient age was 60.5 years (age range, 16-86 yr). The mean marginal tumor dose and volume were 18.5 Gy (range, 11-22 Gy) and 4.4 ml (range, 0.1-24.9 ml). Eighty percent of patients had solitary tumors. RESULTS: The overall median survival time was 8 months. The median survival time in patients with no evidence of primary tumor disease or stable disease was 13 and 11 months. The local tumor control rate was 87%. At 2 years, the rate of local control, remote brain control, and total intracranial control were 75, 41, and 27%, respectively. In multivariate analysis, advanced primary tumor status (P = 0.0003), older age (P = 0.008), lower Karnofsky Performance Scale score (P = 0.01), and malignant melanoma (P = 0.005) were significant for poorer survival. The median survival time was 28 months for patients younger than 60 years of age, with Karnofsky Performance Scale score of at least 90, and whose primary tumor status showed either no evidence of disease or stable disease. Tumor volume (P = 0.02) alone was significant for local tumor control, whereas no factor affected remote or intracranial tumor control. Eleven patients developed complications, six of which were persistent. Nineteen (16.5%) of 116 patients in whom the cause of death was obtained died as a result of causes related to brain metastasis. CONCLUSION: Brain metastases were controlled well with radiosurgery alone as initial therapy. We advocate that WBRT should not be part of the initial treatment protocol for selected patients with one or two tumors with good control of their primary cancer, better Karnofsky Performance Scale score, and younger age, all of which are predictors of longer survival.

In this study, we evaluated the results in four patients with nongerminomatous germ cell tumors (NGGCT) of the pineal region. All underwent radiosurgery in conjunction with surgical resection, fractionated radiotherapy or chemotherapy. Four male patients with pineal region NGGCT were treated with radiosurgery. The mean age was 16.5 years. Three patients had histological confirmation by stereotactic biopsy or craniotomy prior to radiosurgery. One patient was diagnosed by serum and CSF tumor markers. The mean tumor volume was 10.5 cm(3). Radiosurgery was performed with mean maximum and marginal doses of 28 and 14 Gy, respectively. At last follow-up, three patients were alive and one was dead. The mean follow-up after diagnosis and after radiosurgery was 34 and 25 months, respectively. At last follow-up, two tumors had regressed, one was unchanged and one had progressed. No patient had complications after radiosurgery. Radiosurgery can play an important adjuvant role for NGGCT patients who also undergo multimodal management. In the case of prepubertal patients, radiosurgery may play an important role by reducing the radiation dose to the surrounding normal brain.

Stereotactic radiosurgery provided clinicians the ability to administer high single-doses of radiation to intracranial targets with relative safety. Analysis of clinical outcome from radiosurgery calls into question some of the radiobiological principles that have guided conventional fractionated radiotherapy in the past. The response of the tumor or target tissue being irradiated, as well as the response of the surrounding normal tissue, seems predominantly determined by the tumor or target vasculature. Injury to the tumor or target vasculature appears to contribute to the probability of developing normal tissue complications. Estimations of alpha/beta values from radiosurgical dose-response data consistently yield values that conflict with values from fractionated radiotherapy and with linear-quadratic theory. This indicates that projections from high-dose single-fractions to fractionated dose-equivalents made using the linear-quadratic formula are unreliable. Radiobiological analysis of clinical data from radiosurgery provides models for guiding treatment to achieve desired effects and provide reliable estimates of complications.