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Rationale for Surgical Treatment of Brain Metastasis in Non-Small Cell Lung Cancer
EDITORIALS
Rationale for Surgical Treatment of Brain Metastasis in Non-Small Cell Lung Cancer Nael Martini, M.D. Brain metastases constitute nearly one-third of all observed recurrence in patients with resected non-small cell lung cancer, and twice that incidence is found at autopsy of all patients dying of lung cancer. The vast majority of the brain metastases occur in those patients with a histological diagnosis of adenocarcinoma as opposed to squamous or large cell carcinoma. In patients with controlled lung cancer in whom only brain metastases develop, the treatment of the brain is the factor that determines survival. Untreated patients with brain metastases have a median survival of 1 month. Steroid therapy increases the median survival by 2 months. Whole-brain irradiation increases survival by 3 to 6 months, and many authors have reported longer survival with combined surgical treatment and wholebrain irradiation. No benefit is derived from surgical treatment if the brain metastases are multiple or advanced systemic disease is also present. The treatment of choice for this group of patients is whole-brain irradiation alone. However, a third of the patients seen with brain metastases have solitary lesions. If no active disease is found in other organs, treatment by combined surgical intervention and irradiation can be effective. Factors affecting survival of the patients treated by operation include location of the brain metastases, extent of concurrent systemic disease, and neurological deficit at the time of presentation. The goal of the operation is complete excision of the tumor. However, the location of the metastasis affects resectability. Survival of patients with metastasis to the posterior fossa is poorer than for those with a supratentorial tumor. Fortunately, 85%of brain metastases occur in the supratentorial compartment and only 15% in the posterior fossa. No significant difference in survival is seen between patients with early versus late onset of brain metastases. However, those with severe neurological deficit have a shorter survival than patients with minimal neurological symptoms [l, 21. Therefore, those most likely to benefit from surgical resection are patients with a single surgically accessible brain metastasis, no other evident systemic disease or with disease confined to the primary lung site, and minimal neurological deficit. High-dose corticosteroid therapy reduces edema, thereby causing regression of neurological symptoms that is sometimes complete. It is the initial treatment prescribed to all patients. Surgical treatment or radiation
From the Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.
357 Ann Thorac Surg 42357-358, Oct 1986
therapy are usually started after three to four days of steroid therapy. The computed tomographic scan with contrast has become a very effective means of detecting and confirming brain metastases. "Double-dose" contrast scans are frequently done to identify patients with truly single metastases. More recently, magnetic resonance imaging is proving to be equally effective and may be particularly valuable for posterior fossa lesions. Although the surgically treated patients are reported to have longer survival than those treated with irradiation alone, most reviews either include uncontrolled studies or are based on historical controls treated with irradiation alone. In these reports, the patients who received surgical treatment were usually those with solitary metastases who had minimal systemic or neurological disease and consequently a longer expected survival; the patients treated with irradiation alone included patients with minimal as well as extensive disease including multiple brain metastases, and generally a poorer prognosis. The groups studied were therefore not comparable. Recently the Department of Neurology at Memorial Sloan-Kettering Cancer Center in collaboration with the Neurosurgical Service and the Department of Radiation Oncology attempted to compare treatment by operation with whole-brain irradiation versus whole-brain irradiation alone in a group of patients who were as similar as possible except for the method of treatment of their brain metastases [3]. From 1978 to 1982,43 patients with non-small cell lung cancer had resection of a solitary brain metastasis combined with whole-brain irradiation. They were matched with 43 patients treated by wholebrain radiation treatment alone. The median survival was significantly longer for patients treated with resection plus radiation therapy. For those with no evidence of metastases except in the brain, the median survival of surgically treated patients was 26 months compared with 14 months for those treated by whole-brain irradiation alone, a survival advantage of 12 months (p < .0001). In the review of Magilligan and co-workers, all patients treated surgically had neurological symptoms when first seen, all had solitary metastases, and in 14 of 41 or one-third of the patients, the neurological symptoms preceded the diagnosis of lung cancer, which is in keeping with our experience. Improvement in neurological symptoms was noted in most patients, operative mortality was low, and there was a clear survival advantage over patients treated by nonsurgical means, all of which are also in accord with most recent reports. Recurrence in the brain is observed in about one-third
358 The Annals of Thoracic Surgery
Vol 42 No 4 October 1986
of the long-term survivors following craniotomy; and most recurrences are at the original intracranial site, which suggests a focus of residual tumor. This high rate of relapse in the brain points to the need for more effective adjuvants postoperatively. More importantly, repeat resection results in a 1 year survival of 30% and is therefore recommended when feasible. Our current view on management of solitary brain metastases is as follows: when the brain lesion is detected first and the search for the primary tumor is negative, resection of the cranial metastasis is the treatment of choice. When the brain metastasis presents subsequent to the resection of the lung carcinoma and no other site of recurrence is present, resection of the intracranial lesion is again the treatment of choice. When both brain and lung lesions are detected simultaneously, if both lesions are resectable, craniotomy is done first and thoracotomy shortly thereafter. This approach applies to patients seen with neurological signs and symptoms as well as to those with asymptomatic brain metastases detected on a routine computed tomographic search. If either the lung or brain lesion is suspected to be unresectable, surgical treatment is directed first to the site where resectability is questioned most; otherwise treatment by nonsurgical means is recommended. Although my colleagues and I favor postoperative whole-brain irradiation for all patients who have had resected brain metastases, there are no firm data to sup-
port or negate this recommendation. Also no data are available to indicate whether whole-brain irradiation or focal radiation therapy to the area of metastasis is less likely to cause late neurological sequelae in long-term survivors. The one-year survival of 55% and the mean survival of 2.3 years reported by Magilligan and colleagues are essentially similar to ours. Surgical treatment should be offered to patients with single surgically accessible brain metastases, no evident systemic disease elsewhere, and a primary cancer confined to the lung and surgically manageable. Although Magilligan and associates reported no statistical difference in outcome attributable to whole-brain irradiation, we favor this treatment for its potential ability to sterilize the tumor bed, even in patients who have had an apparent complete surgical excision.
References 1. Sundaresan N, Galicich JH: Surgical treatment of brain metastases: clinical and computerized tomography evaluation of the results of treatment. Cancer 55:1382, 1985 2. Sundaresan N, Galicich JH: Surgical treatment of single brain metastases from non-small cell lung cancer. Cancer Invest 3:207, 1985 3. Patchell RA, Cirrincione C, Thaler HT, et al: Single brain metastases: surgery plus radiation or radiation alone. Neurology 36:447, 1986
Rationale for Surgical Treatment of Brain Metastasis in Non-Small Cell Lung Cancer Nael Martini, M.D. Brain metastases constitute nearly one-third of all observed recurrence in patients with resected non-small cell lung cancer, and twice that incidence is found at autopsy of all patients dying of lung cancer. The vast majority of the brain metastases occur in those patients with a histological diagnosis of adenocarcinoma as opposed to squamous or large cell carcinoma. In patients with controlled lung cancer in whom only brain metastases develop, the treatment of the brain is the factor that determines survival. Untreated patients with brain metastases have a median survival of 1 month. Steroid therapy increases the median survival by 2 months. Whole-brain irradiation increases survival by 3 to 6 months, and many authors have reported longer survival with combined surgical treatment and wholebrain irradiation. No benefit is derived from surgical treatment if the brain metastases are multiple or advanced systemic disease is also present. The treatment of choice for this group of patients is whole-brain irradiation alone. However, a third of the patients seen with brain metastases have solitary lesions. If no active disease is found in other organs, treatment by combined surgical intervention and irradiation can be effective. Factors affecting survival of the patients treated by operation include location of the brain metastases, extent of concurrent systemic disease, and neurological deficit at the time of presentation. The goal of the operation is complete excision of the tumor. However, the location of the metastasis affects resectability. Survival of patients with metastasis to the posterior fossa is poorer than for those with a supratentorial tumor. Fortunately, 85%of brain metastases occur in the supratentorial compartment and only 15% in the posterior fossa. No significant difference in survival is seen between patients with early versus late onset of brain metastases. However, those with severe neurological deficit have a shorter survival than patients with minimal neurological symptoms [l, 21. Therefore, those most likely to benefit from surgical resection are patients with a single surgically accessible brain metastasis, no other evident systemic disease or with disease confined to the primary lung site, and minimal neurological deficit. High-dose corticosteroid therapy reduces edema, thereby causing regression of neurological symptoms that is sometimes complete. It is the initial treatment prescribed to all patients. Surgical treatment or radiation
From the Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.
357 Ann Thorac Surg 42357-358, Oct 1986
therapy are usually started after three to four days of steroid therapy. The computed tomographic scan with contrast has become a very effective means of detecting and confirming brain metastases. "Double-dose" contrast scans are frequently done to identify patients with truly single metastases. More recently, magnetic resonance imaging is proving to be equally effective and may be particularly valuable for posterior fossa lesions. Although the surgically treated patients are reported to have longer survival than those treated with irradiation alone, most reviews either include uncontrolled studies or are based on historical controls treated with irradiation alone. In these reports, the patients who received surgical treatment were usually those with solitary metastases who had minimal systemic or neurological disease and consequently a longer expected survival; the patients treated with irradiation alone included patients with minimal as well as extensive disease including multiple brain metastases, and generally a poorer prognosis. The groups studied were therefore not comparable. Recently the Department of Neurology at Memorial Sloan-Kettering Cancer Center in collaboration with the Neurosurgical Service and the Department of Radiation Oncology attempted to compare treatment by operation with whole-brain irradiation versus whole-brain irradiation alone in a group of patients who were as similar as possible except for the method of treatment of their brain metastases [3]. From 1978 to 1982,43 patients with non-small cell lung cancer had resection of a solitary brain metastasis combined with whole-brain irradiation. They were matched with 43 patients treated by wholebrain radiation treatment alone. The median survival was significantly longer for patients treated with resection plus radiation therapy. For those with no evidence of metastases except in the brain, the median survival of surgically treated patients was 26 months compared with 14 months for those treated by whole-brain irradiation alone, a survival advantage of 12 months (p < .0001). In the review of Magilligan and co-workers, all patients treated surgically had neurological symptoms when first seen, all had solitary metastases, and in 14 of 41 or one-third of the patients, the neurological symptoms preceded the diagnosis of lung cancer, which is in keeping with our experience. Improvement in neurological symptoms was noted in most patients, operative mortality was low, and there was a clear survival advantage over patients treated by nonsurgical means, all of which are also in accord with most recent reports. Recurrence in the brain is observed in about one-third
358 The Annals of Thoracic Surgery
Vol 42 No 4 October 1986
of the long-term survivors following craniotomy; and most recurrences are at the original intracranial site, which suggests a focus of residual tumor. This high rate of relapse in the brain points to the need for more effective adjuvants postoperatively. More importantly, repeat resection results in a 1 year survival of 30% and is therefore recommended when feasible. Our current view on management of solitary brain metastases is as follows: when the brain lesion is detected first and the search for the primary tumor is negative, resection of the cranial metastasis is the treatment of choice. When the brain metastasis presents subsequent to the resection of the lung carcinoma and no other site of recurrence is present, resection of the intracranial lesion is again the treatment of choice. When both brain and lung lesions are detected simultaneously, if both lesions are resectable, craniotomy is done first and thoracotomy shortly thereafter. This approach applies to patients seen with neurological signs and symptoms as well as to those with asymptomatic brain metastases detected on a routine computed tomographic search. If either the lung or brain lesion is suspected to be unresectable, surgical treatment is directed first to the site where resectability is questioned most; otherwise treatment by nonsurgical means is recommended. Although my colleagues and I favor postoperative whole-brain irradiation for all patients who have had resected brain metastases, there are no firm data to sup-
port or negate this recommendation. Also no data are available to indicate whether whole-brain irradiation or focal radiation therapy to the area of metastasis is less likely to cause late neurological sequelae in long-term survivors. The one-year survival of 55% and the mean survival of 2.3 years reported by Magilligan and colleagues are essentially similar to ours. Surgical treatment should be offered to patients with single surgically accessible brain metastases, no evident systemic disease elsewhere, and a primary cancer confined to the lung and surgically manageable. Although Magilligan and associates reported no statistical difference in outcome attributable to whole-brain irradiation, we favor this treatment for its potential ability to sterilize the tumor bed, even in patients who have had an apparent complete surgical excision.
References 1. Sundaresan N, Galicich JH: Surgical treatment of brain metastases: clinical and computerized tomography evaluation of the results of treatment. Cancer 55:1382, 1985 2. Sundaresan N, Galicich JH: Surgical treatment of single brain metastases from non-small cell lung cancer. Cancer Invest 3:207, 1985 3. Patchell RA, Cirrincione C, Thaler HT, et al: Single brain metastases: surgery plus radiation or radiation alone. Neurology 36:447, 1986