- Email: [email protected]
Stereotactic Radiosurgery for Brain Metastasis from Melanoma
Perspectives Commentary on: Gamma Knife Surgery in Brain Melanomas: Absence of Extracranial Metastases and Tumor Volume Strongest Indicators of Prolonged Survival by Skeie et al. pp. 684-691.
Jason Sheehan, M.D., Ph.D. Professor of Neurological Surgery and Director of Stereotactic Radiosurgery Department of Neurological Surgery University of Virginia School of Medicine
Stereotactic Radiosurgery for Brain Metastasis from Melanoma Jason Sheehan and Zhiyuan Xu
T
he overall number of patients afflicted with melanoma appears to be on the rise (5). In the United States, the incidence of melanoma is 20.1 per 100 000 people per year and this is accompanied by an age-adjusted death rate of 2.7 per 100 000 people per year (1, 5). Brain metastases develop in 7% to 20% of patients with melanoma (2, 8, 11). Thus, melanoma patients with brain metastasis represent a frequent and, for that matter, challenging cohort for neurological surgeons. Stereotactic radiosurgery (SRS) has become a mainstay of treatment for patients with brain metastasis who have a small number of brain metastases, limited or absent extracranial disease, and a high performance status. Radiosurgery appears to increase the overall survival of selected patients with brain metastasis, and it has also helped to improve their quality of life (6). In particular, the use of radiosurgery alone (ie, without whole brain radiation therapy [WBRT]) has been shown to limit neurocognitive effects frequently associated with more conventional radiotherapy (3). Adverse neurocognitive and neuropsychological effects from WBRT are particularly worrisome as patients with brain metastasis live longer. The maximum appropriate number of intracranial metastases for radiosurgery appears to be a moving and, in fact, increasing target (12). After a detailed, contrast brain magnetic resonance imaging and treatment of all demonstrable metastases with radiosurgery, the median time to formation of a new metastasis in a recent study from our center was 8.8 months (14). This is longer than the median life expectancy of patients with brain metastasis. This finding coupled with the avoidance of adverse effects from WBRT and the apparent efficacy of SRS for patients with up to 10 metastases points to the likely expansion of SRS indications for patients with brain metastasis. Melanoma is traditionally considered a radioresistant histology, and, as such, many have called into question the utility of WBRT for patients with metastasis from melanoma (4). A computerized
Key words 䡲 Cerebral metastases 䡲 Malignant melanoma 䡲 Radiosurgery
Abbreviations and Acronyms SRS: Stereotactic radiosurgery WBRT: Whole brain radiation therapy
tomography analysis of response rates of 336 measurable metastatic lesions after WBRT (3000 cGy in 10 fractions) showed complete response rates of 0 for melanoma compared with 37% for small cell carcinoma, 35% for breast cancer, and 25% for squamous cell carcinoma (9). The radiobiology of radiosurgery is vastly different than that of WBRT, and radiosurgery has been able to overcome even those tumors considered radioresistant (10, 13). Single fraction doses of 18 to 24 Gy to the margin of a brain metastasis tend to overcome even the most resistant tumor histology. At present, a number of favorable prognostic factors have been identified for patients with brain metastasis from melanoma undergoing SRS. In the largest cohort of patients with brain metastasis analyzed, Sperduto et al. identified a higher Karnofsky performance status and a lower number of brain metastases as being the two significant prognostic factors related to survival in patients with brain metastasis from melanoma (15). Karnofsky performance status was stratified into three groups as follows: (1) ⬍70; (2) 70 to 80; and (3) 90 to 100. Number of brain metastases was also stratified into three groups: (1) ⬎3; (2) 2 to 3; and (3) 1. The investigators are to be commended for the scientific rigorousness of the study and the additional knowledge that it adds to the neurosurgical literature. In the current study, they retrospectively evaluated 77 patients with 143 brain metastases from melanoma. They observed an overall tumor control rate of 89.1%. Survival was improved in patients with absent extracranial disease and a total intracranial tumor volume less than 5 mL. WBRT was administered in 22% of patients. Median overall survival was 7 months. Thus, 78% of patients were spared WBRT and achieving a median survival more than that expected for even recursive partitioning analysis class I patients.
Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA To whom correspondence should be addressed: Jason Sheehan, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2011) 75, 5/6:602-603. DOI: 10.1016/j.wneu.2011.01.040
602
www.SCIENCEDIRECT.com
WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2011.01.040
PERSPECTIVES
Neurosurgeons remain willing and able to resect a surgically accessible metastasis exerting mass effect and causing focal deficits. However, this scenario is becoming less common as cancer patients undergo early surveillance magnetic resonance imaging of the brain as part of comprehensive staging. This leads to more frequent detection of metastases, particularly when they are small and asymptomatic. As such, for many recursive partitioning analysis class I and II patients, neurosurgeons at leading centers are performing upfront SRS. After SRS, patients can begin chemotherapy quickly to treat their systemic disease. Patients then undergo surveillance scans at 3-month intervals in what might be called a watch, wait, and see approach. This approach is particularly appealing for patients with radioresistant cancer histologies like melanoma. Patients, if they live long enough, will develop new or progressive intracranial disease. If the disease is limited and not exerting appreciable mass effect, repeat radiosurgery can be used. If the disease is widespread and diffuse (eg, many new metastases or meningeal carcinomatosis), WBRT can be used at that point. Such an approach uses WBRT when it likely provides maximum benefit to the patient and delays the onset of radiotherapyassociated toxicity. SRS also appears to be a cost-effective approach (7).
REFERENCES 1. Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK (eds): SEER Cancer Statistics Review, 1975–2007, Bethesda, MD: National Cancer Institute. Available at: http://seer.cancer.gov/csr/1975_2007/. Accessed January 16, 2010. 2. Balch CM, Soong SJ, Murad TM, Smith JW, Maddox WA, Durant JR: A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III). J Clin Oncol 1:126-134, 1983. 3. Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA: Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:10371044, 2009.
As neurosurgeons, we cannot cure a patient with stage IV cancer. Thus, our treatment approach must weigh the benefitto-risk profile at each point along the patient’s battle with cancer. Selection of the appropriate treatment option must factor in the patient’s intracranial disease, systemic disease, and the patient’s wishes. Patients are increasingly well informed about options and not hesitant to express specific preferences regarding intracranial treatments. The biases of patients, as well as that of clinicians, have likely contributed to the difficulty with patient accrual in several randomized trials designed to explore the role of SRS versus WBRT for patients with brain metastasis. Radiosurgery has proven to be a disruptive technology for patients with intracranial pathology. Patients with brain metastasis are no longer relegated to resection for a select few and the majority undergoing palliative steroids and WBRT. Such changes in dogma require scientific proof and time. Neurosurgeons performing SRS will almost certainly play an expanded role in the management of patients with brain metastasis. The current study sheds further light on the role of radiosurgery in patients with brain metastasis with radioresistant carcinoma histologies. Judicious use of radiosurgery affords prolonged survival and enhanced quality of life for many patients with brain metastasis.
6. Kondziolka D, Martin JJ, Flickinger JC, Friedland DM, Brufsky AM, Baar J, Agarwala S, Kirkwood JM, Lunsford LD: Long-term survivors after gamma knife radiosurgery for brain metastases. Cancer 104: 2784-2791, 2005.
ment for multiple brain metastases: 2-center retrospective review of 1508 cases meeting the inclusion criteria of the JLGK0901 multi-institutional prospective study. J Neurosurg 113 Suppl:4852, 2010.
7. Lee WY, Cho DY, Lee HC, Chuang HC, Chen CC, Liu JL, Yang SN, Liang JA, Ho LH: Outcomes and costeffectiveness of gamma knife radiosurgery and whole brain radiotherapy for multiple metastatic brain tumors. J Clin Neurosci 16:630-634, 2009.
13. Sheehan JP, Sun MH, Kondziolka D, Flickinger J, Lunsford LD: Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control. J Neurosurg 98:342349, 2003.
8. Mendez IM, Del Maestro RF: Cerebral metastases from malignant melanoma. Can J Neurol Sci 15:119123, 1988. 9. Nieder C, Astner ST, Grosu AL, Andratschke NH, Molls M: The role of postoperative radiotherapy after resection of a single brain metastasis. Combined analysis of 643 patients. Strahlenther Onkol 183: 576-580, 2007. 10. Niranjan A, Flickinger JC: Radiobiology, principle and technique of radiosurgery. Prog Neurol Surg 21:32-42, 2008.
4. Jenrette JM: Malignant melanoma: the role of radiation therapy revisited. Semin Oncol 23:759-762, 1996.
11. Schouten LJ, Rutten J, Huveneers HA, Twijnstra A: Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 94:2698-2705, 2002.
5. Klit A, Drejoe JB, Drzewiecki KT: Trends in the incidence of malignant melanoma in Denmark 1978 – 2007. Dan Med Bull 58:A4229, 2011.
12. Serizawa T, Yamamoto M, Sato Y, Higuchi Y, Nagano O, Kawabe T, Matsuda S, Ono J, Saeki N, Hatano M, Hirai T: Gamma Knife surgery as sole treat-
14. Sheehan JP, Yen CP, Nguyen J, Rainey JA, Dassoulas K, Schlesinger DJ: Timing and risk factors for new brain metastasis formation in patients initially treated only with Gamma Knife surgery. J Neurosurg 114:763-768, 2011.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Citation: World Neurosurg. (2011) 75, 5/6:602-603. DOI: 10.1016/j.wneu.2011.01.040 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com
WORLD NEUROSURGERY 75 [5/6]: 602-603, MAY/JUNE 2011
1878-8750/$ - see front matter © 2011 Elsevier Inc. All rights reserved.
www.WORLDNEUROSURGERY.org
603
Jason Sheehan, M.D., Ph.D. Professor of Neurological Surgery and Director of Stereotactic Radiosurgery Department of Neurological Surgery University of Virginia School of Medicine
Stereotactic Radiosurgery for Brain Metastasis from Melanoma Jason Sheehan and Zhiyuan Xu
T
he overall number of patients afflicted with melanoma appears to be on the rise (5). In the United States, the incidence of melanoma is 20.1 per 100 000 people per year and this is accompanied by an age-adjusted death rate of 2.7 per 100 000 people per year (1, 5). Brain metastases develop in 7% to 20% of patients with melanoma (2, 8, 11). Thus, melanoma patients with brain metastasis represent a frequent and, for that matter, challenging cohort for neurological surgeons. Stereotactic radiosurgery (SRS) has become a mainstay of treatment for patients with brain metastasis who have a small number of brain metastases, limited or absent extracranial disease, and a high performance status. Radiosurgery appears to increase the overall survival of selected patients with brain metastasis, and it has also helped to improve their quality of life (6). In particular, the use of radiosurgery alone (ie, without whole brain radiation therapy [WBRT]) has been shown to limit neurocognitive effects frequently associated with more conventional radiotherapy (3). Adverse neurocognitive and neuropsychological effects from WBRT are particularly worrisome as patients with brain metastasis live longer. The maximum appropriate number of intracranial metastases for radiosurgery appears to be a moving and, in fact, increasing target (12). After a detailed, contrast brain magnetic resonance imaging and treatment of all demonstrable metastases with radiosurgery, the median time to formation of a new metastasis in a recent study from our center was 8.8 months (14). This is longer than the median life expectancy of patients with brain metastasis. This finding coupled with the avoidance of adverse effects from WBRT and the apparent efficacy of SRS for patients with up to 10 metastases points to the likely expansion of SRS indications for patients with brain metastasis. Melanoma is traditionally considered a radioresistant histology, and, as such, many have called into question the utility of WBRT for patients with metastasis from melanoma (4). A computerized
Key words 䡲 Cerebral metastases 䡲 Malignant melanoma 䡲 Radiosurgery
Abbreviations and Acronyms SRS: Stereotactic radiosurgery WBRT: Whole brain radiation therapy
tomography analysis of response rates of 336 measurable metastatic lesions after WBRT (3000 cGy in 10 fractions) showed complete response rates of 0 for melanoma compared with 37% for small cell carcinoma, 35% for breast cancer, and 25% for squamous cell carcinoma (9). The radiobiology of radiosurgery is vastly different than that of WBRT, and radiosurgery has been able to overcome even those tumors considered radioresistant (10, 13). Single fraction doses of 18 to 24 Gy to the margin of a brain metastasis tend to overcome even the most resistant tumor histology. At present, a number of favorable prognostic factors have been identified for patients with brain metastasis from melanoma undergoing SRS. In the largest cohort of patients with brain metastasis analyzed, Sperduto et al. identified a higher Karnofsky performance status and a lower number of brain metastases as being the two significant prognostic factors related to survival in patients with brain metastasis from melanoma (15). Karnofsky performance status was stratified into three groups as follows: (1) ⬍70; (2) 70 to 80; and (3) 90 to 100. Number of brain metastases was also stratified into three groups: (1) ⬎3; (2) 2 to 3; and (3) 1. The investigators are to be commended for the scientific rigorousness of the study and the additional knowledge that it adds to the neurosurgical literature. In the current study, they retrospectively evaluated 77 patients with 143 brain metastases from melanoma. They observed an overall tumor control rate of 89.1%. Survival was improved in patients with absent extracranial disease and a total intracranial tumor volume less than 5 mL. WBRT was administered in 22% of patients. Median overall survival was 7 months. Thus, 78% of patients were spared WBRT and achieving a median survival more than that expected for even recursive partitioning analysis class I patients.
Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA To whom correspondence should be addressed: Jason Sheehan, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2011) 75, 5/6:602-603. DOI: 10.1016/j.wneu.2011.01.040
602
www.SCIENCEDIRECT.com
WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2011.01.040
PERSPECTIVES
Neurosurgeons remain willing and able to resect a surgically accessible metastasis exerting mass effect and causing focal deficits. However, this scenario is becoming less common as cancer patients undergo early surveillance magnetic resonance imaging of the brain as part of comprehensive staging. This leads to more frequent detection of metastases, particularly when they are small and asymptomatic. As such, for many recursive partitioning analysis class I and II patients, neurosurgeons at leading centers are performing upfront SRS. After SRS, patients can begin chemotherapy quickly to treat their systemic disease. Patients then undergo surveillance scans at 3-month intervals in what might be called a watch, wait, and see approach. This approach is particularly appealing for patients with radioresistant cancer histologies like melanoma. Patients, if they live long enough, will develop new or progressive intracranial disease. If the disease is limited and not exerting appreciable mass effect, repeat radiosurgery can be used. If the disease is widespread and diffuse (eg, many new metastases or meningeal carcinomatosis), WBRT can be used at that point. Such an approach uses WBRT when it likely provides maximum benefit to the patient and delays the onset of radiotherapyassociated toxicity. SRS also appears to be a cost-effective approach (7).
REFERENCES 1. Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK (eds): SEER Cancer Statistics Review, 1975–2007, Bethesda, MD: National Cancer Institute. Available at: http://seer.cancer.gov/csr/1975_2007/. Accessed January 16, 2010. 2. Balch CM, Soong SJ, Murad TM, Smith JW, Maddox WA, Durant JR: A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III). J Clin Oncol 1:126-134, 1983. 3. Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA: Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:10371044, 2009.
As neurosurgeons, we cannot cure a patient with stage IV cancer. Thus, our treatment approach must weigh the benefitto-risk profile at each point along the patient’s battle with cancer. Selection of the appropriate treatment option must factor in the patient’s intracranial disease, systemic disease, and the patient’s wishes. Patients are increasingly well informed about options and not hesitant to express specific preferences regarding intracranial treatments. The biases of patients, as well as that of clinicians, have likely contributed to the difficulty with patient accrual in several randomized trials designed to explore the role of SRS versus WBRT for patients with brain metastasis. Radiosurgery has proven to be a disruptive technology for patients with intracranial pathology. Patients with brain metastasis are no longer relegated to resection for a select few and the majority undergoing palliative steroids and WBRT. Such changes in dogma require scientific proof and time. Neurosurgeons performing SRS will almost certainly play an expanded role in the management of patients with brain metastasis. The current study sheds further light on the role of radiosurgery in patients with brain metastasis with radioresistant carcinoma histologies. Judicious use of radiosurgery affords prolonged survival and enhanced quality of life for many patients with brain metastasis.
6. Kondziolka D, Martin JJ, Flickinger JC, Friedland DM, Brufsky AM, Baar J, Agarwala S, Kirkwood JM, Lunsford LD: Long-term survivors after gamma knife radiosurgery for brain metastases. Cancer 104: 2784-2791, 2005.
ment for multiple brain metastases: 2-center retrospective review of 1508 cases meeting the inclusion criteria of the JLGK0901 multi-institutional prospective study. J Neurosurg 113 Suppl:4852, 2010.
7. Lee WY, Cho DY, Lee HC, Chuang HC, Chen CC, Liu JL, Yang SN, Liang JA, Ho LH: Outcomes and costeffectiveness of gamma knife radiosurgery and whole brain radiotherapy for multiple metastatic brain tumors. J Clin Neurosci 16:630-634, 2009.
13. Sheehan JP, Sun MH, Kondziolka D, Flickinger J, Lunsford LD: Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control. J Neurosurg 98:342349, 2003.
8. Mendez IM, Del Maestro RF: Cerebral metastases from malignant melanoma. Can J Neurol Sci 15:119123, 1988. 9. Nieder C, Astner ST, Grosu AL, Andratschke NH, Molls M: The role of postoperative radiotherapy after resection of a single brain metastasis. Combined analysis of 643 patients. Strahlenther Onkol 183: 576-580, 2007. 10. Niranjan A, Flickinger JC: Radiobiology, principle and technique of radiosurgery. Prog Neurol Surg 21:32-42, 2008.
4. Jenrette JM: Malignant melanoma: the role of radiation therapy revisited. Semin Oncol 23:759-762, 1996.
11. Schouten LJ, Rutten J, Huveneers HA, Twijnstra A: Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 94:2698-2705, 2002.
5. Klit A, Drejoe JB, Drzewiecki KT: Trends in the incidence of malignant melanoma in Denmark 1978 – 2007. Dan Med Bull 58:A4229, 2011.
12. Serizawa T, Yamamoto M, Sato Y, Higuchi Y, Nagano O, Kawabe T, Matsuda S, Ono J, Saeki N, Hatano M, Hirai T: Gamma Knife surgery as sole treat-
14. Sheehan JP, Yen CP, Nguyen J, Rainey JA, Dassoulas K, Schlesinger DJ: Timing and risk factors for new brain metastasis formation in patients initially treated only with Gamma Knife surgery. J Neurosurg 114:763-768, 2011.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Citation: World Neurosurg. (2011) 75, 5/6:602-603. DOI: 10.1016/j.wneu.2011.01.040 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com
WORLD NEUROSURGERY 75 [5/6]: 602-603, MAY/JUNE 2011
1878-8750/$ - see front matter © 2011 Elsevier Inc. All rights reserved.
www.WORLDNEUROSURGERY.org
603