Radiosurgery for the treatment of spinal melanoma metastases

BACKGROUND: The role of stereotactic radiosurgery in treating metastatic melanoma involving the spine has previously been limited. Conventional external beam radiotherapy lacks the precision to allow delivery of large single-fraction doses of radiation and simultaneously to limit the dose delivered to radiosensitive structures such as the spinal cord. This study evaluated the clinical efficacy of radiosurgery for the treatment of melanoma spinal metastases in 28 patients. METHODS: Thirty-six melanoma spine metastases were treated with a single-session radiosurgery technique (1 cervical, 11 thoracic, 13 lumbar, and 11 sacral) with a follow-up period of 3-43 months (median 13 months). Tumor volume ranged from 4.1 to 153 cm3 (mean 47.6 cm3). Twenty-three of the 36 lesions had received prior external beam irradiation. RESULTS: Maximum tumor dose was maintained at 17.5-25 Gy (mean 21.7 Gy). Spinal cord volume receiving > 8 Gy ranged from 0.0 to 0.7 cm3 (mean 0.26 cm3); spinal canal volume at the cauda equina level receiving > 8 Gy ranged from 0.0 to 3.5 cm3 (mean 0.98 cm3). No radiation-induced toxicity occurred during the follow-up period. Axial and radicular pain improved in 27 of 28 patients (96%) who were treated primarily for pain. Long-term tumor control was seen in 3 of 4 cases treated primarily for radiographic tumor progression. Two patients went on to require open surgical intervention for tumor progression resulting in neurological deficit. CONCLUSIONS: Spinal radiosurgery offers a therapeutic modality for the safe delivery of large dose fractions of radiation therapy in a single fraction for the management of spinal metastases in patients with advanced melanoma that are often poorly controlled with alternative conventional external beam radiation therapy, and is successful even in patients with previously irradiated lesions.     

Stereotactic interstitial radiosurgery for cerebral metastases

OBJECT: The Photon Radiosurgery System (PRS) is a miniature x-ray generator that can stereotactically irradiate intracranial tumors by using low-energy photons. Treatment with the PRS typically occurs in conjunction with stereotactic biopsy, thereby providing diagnosis and treatment in one procedure. The authors review the treatment of patients with brain metastases with the aid of the PRS and discuss the indications, advantages, and limitations of this technique. METHODS: Clinical characteristics, treatment parameters, neuroimaging-confirmed outcome, and survival were reviewed in all patients with histologically verified brain metastases who were treated with the PRS at the Massachusetts General Hospital between December 1992 and November 2000. Local control of lesions was defined as either stabilization or diminution in the size of the treated tumor as confirmed by Gd-enhanced magnetic resonance imaging. Between December 1992 and November 2000, 72 intracranial metastatic lesions in 60 patients were treated with the PRS. Primary tumors included lung (33 patients), melanoma (15 patients), renal cell (five patients), breast (two patients), esophageal (two patients), colon (one patient), and Merkle cell (one patient) cancers, and malignant fibrous histiocytoma (one patient). Supratentorial metastases were distributed throughout the cerebrum, with only one cerebellar metastasis. The lesions ranged in diameter from 6 to 40 mm and were treated with a minimal peripheral dose of 16 Gy (range 10-20 Gy). At the last follow-up examination (median 6 months), local disease control had been achieved in 48 (81%) of 59 tumors. An actuarial analysis demonstrated that the survival rates at 6 and 12 months were 63 and 34%, respectively. Patients with a single brain metastasis survived a mean of 11 months. Complications included four patients with postoperative seizures, three with symptomatic cerebral edema, two with hemorrhagic events, and three with symptomatic radiation necrosis requiring surgery. CONCLUSIONS: Stereotactic interstitial radiosurgery performed using the PRS can obtain local control of cerebral metastases at rates that are comparable to those achieved through open resection and external stereotactic radiosurgery. The major advantage of using the PRS is that effective treatment can be accomplished at the time of stereotactic biopsy.     

Radiosurgery for brain metastases

This article presents the state of art in radiosurgery as a new therapeutic strategy of brain metastases. Radiosurgery of brain metastases is ten years old and we propose to make an update of the literature. X-rays and gamma-rays are commonly used for radiosurgery and does not make a difference for dosimetry and precision. Selected patients for this treatment have usually good Karnofsky status and the mean size of their metastases is about 20 mm. Mean number of metastases treated in the same procedure is 2. Most frequent primary sites are lung and breast, but also kidney and skin (malignant melanoma) which are supposed to be radioresistant and so often untreatable by other techniques. Usual dose administrated ranges between 15 and 25 Grays in center of target with a 80% isodose in peripheral. Results are quite good for local control (80% to 100%) but survival does not seem to be improved (11 months). Radiation complication rate is 4% and sometimes hemorrhagic complications occur (1 to 2%). For local control, quality of life and cost/benefit ratio, there are strong arguments in favor of radiosurgery, especially for radioresistant metastases in spite of the lack of improvement of survival duration. Moreover published studies do not allow any comparison with efficacy of surgery and radiosurgery, whole brain radiosurgery and radiosurgery of the present metastases. Evaluations are still going on in several centers. Their results will allow more precise indications of this technique.     

Surgical management of cerebral metastases from melanoma: outcome in 147 patients treated at a single institution over two decades

OBJECT: The aim of this study was to review the outcome of patients who underwent surgery for treatment of cerebral metastatic melanoma. METHODS: A retrospective analysis was performed in 147 patients with cerebral metastases from melanoma who were treated surgically at a single institution between 1979 and 1999. Almost all patients underwent postoperative wholebrain radiation therapy. The mean patient age was 53 years (range 17-76 years); 69% of patients were male. A single cerebral metastasis was identified in 84% of patients, although 56% had synchronous extracranial metastases. The 30-day postoperative mortality rate was 2% and neurological symptoms resolved or improved in 78% of patients. Recurrence of intracerebral disease was seen in 55% of patients and 26% died of intracerebral metastases. Twenty-four patients underwent reoperation for recurrent cerebral disease. The median survival duration from the time of surgery for all patients was 8.5 months; the 3- and 5-year survival rates were 9% and 5%, respectively. Factors that significantly influenced survival on univariate analysis were the number of cerebral metastases (p = 0.015), a macroscopically complete excision (p < 0.05), and reoperation for recurrence (p = 0.02). The presence of extracranial metastases did not significantly influence survival. On multivariate analysis only the number of cerebral metastases significantly affected survival (p = 0.04). CONCLUSIONS: For the majority of patients with cerebral metastases from melanoma, surgery with adjuvant radiation therapy is a treatment option that improves neurological symptoms and produces minimal morbidity. Long-term survival (> 3 years) most likely occurs in patients with a single cerebral metastasis and no demonstrable extracranial disease. Reoperation for recurrent cerebral disease may be appropriate in selected cases.     

Repeated gamma knife surgery for multiple brain metastases from renal cell carcinoma

OBJECT: The aim of this study was to evaluate the therapeutic profile of repeated gamma knife surgery (GKS) for renal cell carcinoma that has metastasized to the brain on multiple occasions. METHODS: Data from this study were culled from a single institution and cover a 6-year period of outpatient radiosurgery. A standard protocol for indication, dose planning, and follow up was established. In cases of distant or local recurrences, radiosurgery was undertaken repeatedly (up to six times in one individual). Seventy-five patients harboring 350 cerebral metastases were treated. Relief from pretreatment neurological symptoms occurred in 72% of patients within a few days or a few weeks after the procedure. The actuarial local tumor control rate after the initial GKS was 95%. In patients free from relapse of intracranial metastases after repeated radiosurgery, long-term survival was 91% after 4 years; median survival was 11.1+/-3.2 months after radiosurgery and 4.5+/-1.1 years after diagnosis of the primary kidney cancer. Survival following radiosurgery was independent of patient age and sex, side of the renal cell carcinoma, pretreatment of the cerebrum by using radiotherapy or surgery, number of brain metastases and their synchronization with the primary renal cell carcinoma, and the frequency of radiosurgical procedures. In contrast, survival was dependent on the patient's clinical performance score and the extracranial tumor status. Tumor bleeding was observed in seven patients (9%) and late radiation toxicity (LRT) in 15 patients (20%). Treatment-related morbidity was moderate and mostly transient. Late radiation toxicity was encountered predominantly in long-term survivors. CONCLUSIONS: Outpatient repeated radiosurgery is an effective and only minimally invasive treatment for multiple brain metastases from renal cell cancer and is recommended as being the method of choice to control intracranial disease, especially in selected patients with limited extracranial disease. Physicians dealing with such patients should be aware of the characteristic aspects of LRT.     

The expanding role of neurosurgeons in the management of brain metastases

BACKGROUND: Brain metastases are the most common type of intracranial tumor. Until recently, whole brain fractionated radiation therapy (WBRT) was the mainstay of treatment, thereby confining the role of neurosurgeons to resection of an occasional solitary, accessible, and symptomatic brain metastasis. Median survival after surgery and radiation typically ranged from 5 to 11 months. METHODS: We analyzed various demographic incidence reports and our series of brain metastasis patients treated with radiosurgery. During a 15-year interval (1987-2002), radiosurgery was performed on 5,032 patients of whom 1,088 (21.6%) had metastatic brain tumors. RESULTS: In the United States, 266,820 to 533,640 new cases of brain metastases will be diagnosed in the year 2003. Evidence to date demonstrates that radiosurgery provides effective local tumor control for brain metastases. Important prognostic factors affecting patient survival include the absence of active systemic disease, the patient's preoperative performance status, age, and the number of metastases. Survival and local tumor control rates attained with radiosurgery are superior to those of either conventional surgery or WBRT. The morbidity associated with radiosurgery of brain metastasis is very low, and the mortality rate approaches zero. CONCLUSIONS: Compelling evidence indicates that radiosurgery is an effective neurosurgical management strategy for intracranial brain metastases. Quite often, favorable tumor control and survival can be achieved without WBRT. With radiosurgery as a therapeutic option, neurosurgeons now have a vastly expanded armamentarium for treatment of patients with brain metastases. The large number of patients with brain metastases who require care by a neurosurgeon for optimal treatment has significant implications for both the patterns of neurosurgical training and practice in the United States.     

Stereotactic interstitial radiosurgery with a miniature X-ray device in the minimally invasive treatment of selected tumors in the thalamus and the basal Ganglia

The aim of this study was to evaluate the role of interstitial radiosurgery (IR) using the photon radiosurgery system (PRS) in the treatment of selected tumors within the thalamus and the basal ganglia. The PRS is a miniature X-ray generator that was developed for interstitial irradiation. This series included 14 patients (5 with glioblastomas, 4 with low-grade astrocytomas and 5 with metastases) harboring spheroidal lesions with dimensions ranging from 13 to 42 mm (mean 30 mm). After stereotactic biopsy, a radiation dose ranging from 6 to 15.4 Gy (mean 11.3 Gy) was delivered at the target volume margins. Follow-up varied from 3 to 26 months (mean 10.2 months). In the group of glioblastomas, 3 patients died (3-12 months after the procedure) because of tumor progression, while the remaining had tumor control. Two patients with metastases died from systemic disease (4-9 months after the treatment), and 3 were alive and well at the end of the study. Local control was achieved in all metastases. Patients with low-grade astrocytomas were well and imaging studies showed tumor control PRS IR is a minimally invasive procedure for the treatment of selected glial or secondary brain tumors. Compared to conventional radiosurgery (brachytherapy and external radiosurgery), PRS IR presents dose delivery characteristics useful for the treatment of tumors in the thalamus and basal ganglia, without inconveniences such as handling radioisotopes, the need of expensive facilities and radiation protection measures. Although the clinical value needs further investigations, PRS IR seems to be effective in metastases while it provides less benefit in malignant gliomas. PRS IR could have a major role in the treatment of low-grade astrocytomas.     

Factors affecting the outcome after treatment for metastatic melanoma to the brain

Background

Because of the difficulties inherent to the treatment of metastatic melanoma to the brain including high rates of disease progression and local treatment failure, we attempted to determine the prognostic factors that impacted the outcome of these patients, and reviewed patient outcome based on primary treatment with either surgical resection or SRS.

Methods

A retrospective review identified 37 patients treated for metastatic melanoma between July 2002 and April 2007. Information was obtained documenting systemic disease, preoperative symptoms, tumor size and location, disease recurrence, primary and secondary treatments, and survival time.

Results

Two patients were alive as of March 2008. The median survival time for patients primarily treated with surgical resection was 9.7 months compared to 7.9 months for patients initially treated with SRS. Solitary brain metastases and the absence of both preoperative hemorrhage and lung metastases served as prognostic factors increasing survival in both groups. Four patients undergoing primary treatment with SRS required subsequent surgical intervention secondary to radiation necrosis (3 patients) or local recurrence (1 patient). All 4 had lesions greater than 1.5 cm. For surgical patients, planned postoperative treatment with either radiosurgery or radiation therapy increased survival time to 12.3 months vs 7.3 months.

Conclusions

Patients with positive prognostic factors including solitary brain lesions, absence of hemorrhage preoperatively, and absence of lung disease are viable candidates for aggressive, surgical intervention followed by adjuvant therapy with radiosurgery or conventional radiation therapy. Other patients should be considered for more conservative treatment with radiosurgery or other palliative treatments.     

Malignant transformation of spinal meningeal melanocytoma. Case report and review of the literature

Meningeal melanocytomas are rare tumors and malignant transformation of these lesions is even rarer. The authors report on a case of a 57-year-old man who presented with a melanocytoma located at the L5-S1 level. After gross-total resection of the tumor, it recurred 1 year later as a malignant melanoma. In addition, multiple subcutaneous metastases were found at that time. The patient was treated with radiation therapy (5000 cGy). Five months later metastases in the liver and the left ninth rib were discovered. The pertinent literature is reviewed and disease criteria are presented to distinguish meningeal melanocytoma from malignant melanoma and from meningiomas or schwannomas containing melanotic pigment. Patients and investigators should be cautioned that a meningeal melanocytoma may recur and transform into a malignant melanoma.     

Single brain metastasis

Opinion statement  The management of single brain metastases has evolved substantially over the last decade. The advent of triple-dose contrast-enhanced MRI scans has improved the radiologists’ capacity to resolve small tumors, and, thereby, has resulted in a declining percentage of brain metastases classified as single. Only 25% to 30% of brain metastases are single; single brain metastases in the absence of systemic metastases are termed solitary. Randomized trials suggest that patients not in imminent danger of herniation are best managed initially with dexamethasone 2 to 4 mg administered orally twice daily. The routine use of prophylactic anticonvulsants is discouraged. Patients with refractory progressive systemic tumor likely to prove fatal within 3 to 6 months should receive fractionated whole brain radiotherapy. Patients with highly radiosensitive primary tumors such as small cell lung cancer, lymphoma, and germinoma should also receive whole brain radiotherapy. Patients with inactive or controllable systemic cancer and good performance status benefit from the addition of local strategies like surgery or radiosurgery to whole brain radiotherapy. Although surgery and radiosurgery have not been compared in a randomized controlled trial, data suggest that results are similar. Consequently, for most metastases that fall within the size constraints of radiosurgery (3.5 cm or smaller in diameter), radiosurgery is preferred for its relatively noninvasive nature. Patients with larger or cystic tumors, with obstructive hydrocephalus, or neurologic instability despite corticosteroids are best treated with craniotomy. Fractionated whole brain radiation following surgical or radiosurgical management of single brain metastasis appears to decrease the risk of recurrent brain metastasis, although it has not been shown to improve survival. We recommend its use in most patients, although patients with tumors likely to be highly resistant to fractionated radiotherapy or at high risk of radiation neurotoxicity may reasonably defer its use.     

Metastatic malignant melanoma of unknown primary site to the brain: A case report

Introduction and importanceThe natural history of metastatic melanoma in the absence of a known primary site has been poorly defined. The disease usually presents a significant cause of morbidity and mortality. Around 90% of melanomas have cutaneous origin, but still there are melanomas that could be found in visceral organs or lymph nodes with unknown primary site. Spontaneous regression of the primary site could be an explanation. The disease is frequently diagnosed after treatment for known extracranial metastases and has a poor outcome despite various local and systemic therapeutic approaches.Case presentationHerein, we present a case of a 43-year old female presented with history of headaches and enlarged a left inguinal lymph node. Notably, no cutaneous lesions could be identified by history or on physical examination. CT-scan of the brain revealed a space occupying lesion and the inguinal lymph node biopsy confirmed the diagnosis of metastatic malignant melanoma. The patient succumbed shortly after establishment of diagnosis.Clinical discussionMost patients with brain metastases from malignant melanoma are diagnosed after treatment for known extracranial metastases and have a poor outcome despite various local and systemic therapeutic approaches.ConclusionMetastatic melanomas of brain with unknown primary present a significant morbidity and mortality and confer a poor prognosis. Delay in diagnosis and treatment is of serious concern when it comes to improve the prognosis of patients with this disease. The optimal treatment depends on the objective situation, often surgery, radiosurgery, whole brain radiotherapy and chemotherapy can be used in combination to obtain longer remissions and optimal symptom relieve.     

Stereotactic Radiosurgery for Brain Metastases From Breast Cancer

Background: Stereotactic radiosurgery is an alternative to resection or to radiotherapy alone for patients with brain metastases. Outcomes after radiosurgery for patients with brain metastases specifically from breast cancer have not been defined.Methods: We retrospectively studied survival and tumor control for all patients with brain metastases from breast cancer who underwent gamma knife stereotactic radiosurgery at the University of Pittsburgh. Univariate and multivariate analyses were used to determine which prognostic factors significantly affected survival.Results: Thirty patients underwent radiosurgery between 1990 and 1997. A total of 58 metastases were treated. The median length of survival for all patients was 13 months from radiosurgery and 18 months from diagnosis of brain metastases. The tumor control rate on follow-up imaging was 93%. On multivariate analysis, the only factor that correlated with longer survival was the absence of multiple brain metastases. Age, presence of systemic disease, previous whole brain radiation, location, and total tumor volume did not significantly affect survival. Four patients had tumors with evidence of radiation-induced edema after radiosurgery but did not require resection. Two patients underwent delayed resection for tumor growth after radiosurgery.Conclusions: Stereotactic radiosurgery is an effective treatment for brain metastases from breast cancer and is associated with a low complication rate.     

Stereotactic radiosurgical treatment of brain metastases.

In a series of 33 patients with reasonably controlled primary cancers, stereotactic radiosurgery was used to treat 52 brain metastases. After a mean radiological follow-up time of 5.5 months, six lesions (12%) had stabilized in size, 26 (50%) were significantly reduced, and 15 (29%) had disappeared. One large melanoma metastasis progressed relentlessly despite treatment. Five lesions (9%) had decreased in size slightly before enlarging. In two of these lesions, biopsy revealed only necrosis. In almost all cases, treatment was associated with decreased peritumoral edema. However, a group of patients with large metastases and extensive prior brain irradiation has been identified in whom prolonged symptomatic cerebral edema poses a problem. It is concluded that radiosurgery is a viable alternative to surgical resection for some cases of brain metastasis.     

Multiple brain metastases from malignant melanoma with long-term survival

We present a case of multiple malignant melanoma metastases in the brain who is leading a normal life 16 years after the brain secondaries were managed by surgical resection, stereotactic radiation and chemotherapy. The primary lesion in the left upper arm was excised 4 years prior to the brain metastases. His most recent MRI shows him to be disease free. To the best of our knowledge, this is longest survival reported of any patient with multiple brain metastases from malignant melanoma.     

Gamma knife radiosurgery for cavernous sinus metastases and invasion

BACKGROUND: We evaluated the efficacy of gamma knife radiosurgery for cavernous sinus metastases and invasion. METHOD: We treated and followed up 21 patients with cavernous sinus metastases and invasion using gamma knife radiosurgery. Nine of these patients had nasopharyngeal cancer, and 12 had distant metastases from other cancers. The volume of tumors ranged from 2.9 to 50.0 (median 9.9) mL. and the radiation dose to the tumor margin was 10 to 21 (median 14) Gy. RESULTS: The median follow-up period was 9 months. Clinical symptoms were improved in 48% of the patients after treatment, and tumor growth control was obtained in 67% of the patients at their final follow-up. The actual 1- and 2-year tumor growth control rates were 68% and 43%, respectively. The mean survival time was 13 months. No patient had radiation injury. CONCLUSION: Gamma knife radiosurgery is a very useful therapeutic option for the treatment of cavernous sinus metastases and invasion, either as initial treatment or as an adjunct treatment for recurrences even in preirradiated patients.     

Primary malignant melanoma of the right colon

The small and large intestines are the most common sites for metastases from cutaneous malignant melanoma. However, primary melanomas in these sites are exceedingly rare. There are several case reports of patients with primary melanoma of the small bowel, but finding of a solitary primary melanoma in the colon is exceedingly rare. We describe a patient that was operated on for bowel obstruction due to colonic intussusception resulting from a right colonic tumor. Histopathological examination confirmed a diagnosis of malignant melanoma. A thorough postoperative investigation did not reveal a primary lesion in any other site. Two years after surgery, there was no evidence for recurrent disease. The treatment and prognosis of metastatic and primary melanoma of the gastrointestinal tract is discussed as well as the embryonic base for development of primary malignant melanoma of the intestine. Primary malignant melanoma of the intestine is an extremely rare lesion that may arise in the large bowel as well. It must be differentiated from other intestinal tumors and mandates a thorough investigation to rule out the possibility of being a metastasis from another more common primary site.     

Node-positive transcranial recurrent melanoma: is an aggressive resection warranted?

Locally advanced, node-positive recurrence of malignant melanoma is a harbinger of distant metastases and signifies poor prognosis. However, the clinical course may vary due to the unpredictable biology of malignant melanoma. The presented patient developed a recurrent melanoma of the scalp that eroded through the skull and involved regional lymph nodes with extracapsular extension. He was treated with wide local excision of the recurrence, bilateral posterolateral neck dissection, and immediate microvascular reconstruction followed by adjuvant radiation therapy. The patient remains free of disease at 12 years. This case illustrates that an aggressive resection should be considered for the operable patients with locally advanced recurrent melanoma to render them disease free surgically.     

Stereotactic radiosurgery using the 201 cobalt-60 source gamma knife

Although Lars Leksell introduced the concept of stereotactic radiosurgery 40 years ago, the role of radiosurgery in the treatment of vascular malformations and benign or malignant intracranial tumors is only now being defined. Radiosurgery can be definitive therapy for small or medium-sized arteriovenous malformations and histologically benign tumors. For patients with more complex or recurrent tumors and for patients with vascular malformations that have not been eliminated by open surgery or endovascular embolization, radiosurgery has an adjunctive and often decisive therapeutic role. Selected malignant tumors, especially solitary metastases, have responded dramatically to radiosurgery, obviating the need for craniotomy and prolonged hospitalization in this group of patients.     

Treatment of brain metastases in renal cell carcinoma: radiotherapy, radiosurgery, or surgery?

Metastases from renal cell carcinoma raise specific therapeutic problems because they are relatively unresponsive to whole brain radiation therapy and tend to bleed. Recently, stereotactically guided high-precision irradiation as a single dose application (radiosurgery) showed promising treatment results for selected patients with brain metastases from renal cell carcinoma. Radiosurgery appears attractive due to its low risk and minimal invasiveness. Multiple lesions can be treated at the same time and retreatments can be performed for local or distant recurrences.     

Actual doubling time values of pulmonary metastases from malignant melanoma.

The growth rate of pulmonary metastases was determined in 18 patients with pulmonary metastases from histologically proven malignant melanoma. From chest radiograms 81 metastases were measured 51 consecutive times, and 120 values for doubling time were obtained. metastases with diameters of 15.0 mm or less grew significantly faster (arithmetic mean=24.9 days) than metastases with diameters over 15.0 mm (arithmetic mean=51.0 days). The difference is statistically significant (P less than 0.050). In about one-tenth (9.2%) of all measurements the values for doubling time are considerably lengthened (arithmetic mean=182.2 days). The determination of doubling time values may be considered as a useful parameter in the selection of patients for treatment of pulmonary metastases from malignant melanoma.