Neuro-oncology

ATLANTA — Whole-brain radiation therapy can preserve neurocognitive function in patients with brain metastases, according to a 135-patient study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Jing Li reported that patients lived longer and had better neurocognitive function if their tumors shrank more than 45% during the 2 months after whole-brain radiation therapy (WBRT).

These “good responders” scored better on all eight neurocognitive tests used in the study, compared with “poor responders” with less than 45% tumor shrinkage at the 2-month mark. The effects were statistically significant over the course of the study on tests of executive function and fine motor coordination.

The effects were most dramatic in a small group of 7–9 long-term survivors who demonstrated cognitive improvement when tested 15 months after receiving WBRT.

Magnetic resonance imaging at 4 months showed that brain tumors had shrunk 80% on average from baseline by then in patients who would survive 15 months.

“Neurocognitive function is stable or improving over time in long-term survivors,” said Dr. Li of the University of Wisconsin at Madison. “It appears that the adverse impact of tumor growth on neurocognitive function is greater than that of whole brain radiation therapy. Therefore, improving response is a worthy aim in this patient population.”

Although WBRT is used to reduce neurologic symptoms caused by brain metastases, she said the treatment's effects on neurocognitive skills have up to now gone “largely unstudied.” The lack of data was attributable, she suggested, to inadequate assessment tools and the poor prognosis (4–6 months median survival) in the 10%–30% of cancer patients who develop brain metastases.

For this study, Dr. Li and her colleagues selected 135 of 208 patients in the control arm of a prospective, randomized, multicenter trial that compared WBRT alone with WBRT with motexafin gadolinium enhancement. Only those who survived until the first follow-up magnetic resonance image was taken 2 months later were eligible for the neurocognitive study. All neurocognitive participants had received 30 Gy of radiation in 10 fractions without motexafin gadolinium.

The investigators determined that median tumor shrinkage was 45% at two months for the entire population. They classified patients as good or poor responders based on their relationship to the median.

To determine changes in neurocognitive function, the researchers administered eight tests that had been validated in another pilot study and could be completed within 30 minutes.

The eight tests covered three neurocognitive domains: memory, executive function (decision-making capacity), and fine motor coordination.

Poor responders had a shorter time to neurocognitive deterioration on all eight tests, compared with the good responders, according to Dr. Li. She said this difference was statistically significant on two pegboard tests used to measure fine motor coordination (287 vs. 380 days and 291 vs. 401 days) and the Trail B test of executive function (331 vs. 462 days).

In a discussion of Dr. Li's presentation, Dr. Jeff A. Sloan suggested the differences might have been statistically significant on all eight tests had the investigators chosen a less stringent definition of neurocognitive deterioration. The criterion used was a decline of two standard deviations from baseline on two consecutive measurements or on the last follow-up visit before death.

“Two standard deviations is a huge change, a profound change,” Dr. Sloan of the Mayo Clinic in Rochester, Minn., said, praising the study for its rigor. “… [T]he bar was set so high, it is not surprising that only three of these eight [findings] were significant.”

ATLANTA — Whole-brain radiation therapy can preserve neurocognitive function in patients with brain metastases, according to a 135-patient study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Jing Li reported that patients lived longer and had better neurocognitive function if their tumors shrank more than 45% during the 2 months after whole-brain radiation therapy (WBRT).

These “good responders” scored better on all eight neurocognitive tests used in the study, compared with “poor responders” with less than 45% tumor shrinkage at the 2-month mark. The effects were statistically significant over the course of the study on tests of executive function and fine motor coordination.

The effects were most dramatic in a small group of 7–9 long-term survivors who demonstrated cognitive improvement when tested 15 months after receiving WBRT.

Magnetic resonance imaging at 4 months showed that brain tumors had shrunk 80% on average from baseline by then in patients who would survive 15 months.

“Neurocognitive function is stable or improving over time in long-term survivors,” said Dr. Li of the University of Wisconsin at Madison. “It appears that the adverse impact of tumor growth on neurocognitive function is greater than that of whole brain radiation therapy. Therefore, improving response is a worthy aim in this patient population.”

Although WBRT is used to reduce neurologic symptoms caused by brain metastases, she said the treatment's effects on neurocognitive skills have up to now gone “largely unstudied.” The lack of data was attributable, she suggested, to inadequate assessment tools and the poor prognosis (4–6 months median survival) in the 10%–30% of cancer patients who develop brain metastases.

For this study, Dr. Li and her colleagues selected 135 of 208 patients in the control arm of a prospective, randomized, multicenter trial that compared WBRT alone with WBRT with motexafin gadolinium enhancement. Only those who survived until the first follow-up magnetic resonance image was taken 2 months later were eligible for the neurocognitive study. All neurocognitive participants had received 30 Gy of radiation in 10 fractions without motexafin gadolinium.

The investigators determined that median tumor shrinkage was 45% at two months for the entire population. They classified patients as good or poor responders based on their relationship to the median.

To determine changes in neurocognitive function, the researchers administered eight tests that had been validated in another pilot study and could be completed within 30 minutes.

The eight tests covered three neurocognitive domains: memory, executive function (decision-making capacity), and fine motor coordination.

Poor responders had a shorter time to neurocognitive deterioration on all eight tests, compared with the good responders, according to Dr. Li. She said this difference was statistically significant on two pegboard tests used to measure fine motor coordination (287 vs. 380 days and 291 vs. 401 days) and the Trail B test of executive function (331 vs. 462 days).

In a discussion of Dr. Li's presentation, Dr. Jeff A. Sloan suggested the differences might have been statistically significant on all eight tests had the investigators chosen a less stringent definition of neurocognitive deterioration. The criterion used was a decline of two standard deviations from baseline on two consecutive measurements or on the last follow-up visit before death.

“Two standard deviations is a huge change, a profound change,” Dr. Sloan of the Mayo Clinic in Rochester, Minn., said, praising the study for its rigor. “… [T]he bar was set so high, it is not surprising that only three of these eight [findings] were significant.”

ATLANTA — Whole-brain radiation therapy can preserve neurocognitive function in patients with brain metastases, according to a 135-patient study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Jing Li reported that patients lived longer and had better neurocognitive function if their tumors shrank more than 45% during the 2 months after whole-brain radiation therapy (WBRT).

These “good responders” scored better on all eight neurocognitive tests used in the study, compared with “poor responders” with less than 45% tumor shrinkage at the 2-month mark. The effects were statistically significant over the course of the study on tests of executive function and fine motor coordination.

The effects were most dramatic in a small group of 7–9 long-term survivors who demonstrated cognitive improvement when tested 15 months after receiving WBRT.

Magnetic resonance imaging at 4 months showed that brain tumors had shrunk 80% on average from baseline by then in patients who would survive 15 months.

“Neurocognitive function is stable or improving over time in long-term survivors,” said Dr. Li of the University of Wisconsin at Madison. “It appears that the adverse impact of tumor growth on neurocognitive function is greater than that of whole brain radiation therapy. Therefore, improving response is a worthy aim in this patient population.”

Although WBRT is used to reduce neurologic symptoms caused by brain metastases, she said the treatment's effects on neurocognitive skills have up to now gone “largely unstudied.” The lack of data was attributable, she suggested, to inadequate assessment tools and the poor prognosis (4–6 months median survival) in the 10%–30% of cancer patients who develop brain metastases.

For this study, Dr. Li and her colleagues selected 135 of 208 patients in the control arm of a prospective, randomized, multicenter trial that compared WBRT alone with WBRT with motexafin gadolinium enhancement. Only those who survived until the first follow-up magnetic resonance image was taken 2 months later were eligible for the neurocognitive study. All neurocognitive participants had received 30 Gy of radiation in 10 fractions without motexafin gadolinium.

The investigators determined that median tumor shrinkage was 45% at two months for the entire population. They classified patients as good or poor responders based on their relationship to the median.

To determine changes in neurocognitive function, the researchers administered eight tests that had been validated in another pilot study and could be completed within 30 minutes.

The eight tests covered three neurocognitive domains: memory, executive function (decision-making capacity), and fine motor coordination.

Poor responders had a shorter time to neurocognitive deterioration on all eight tests, compared with the good responders, according to Dr. Li. She said this difference was statistically significant on two pegboard tests used to measure fine motor coordination (287 vs. 380 days and 291 vs. 401 days) and the Trail B test of executive function (331 vs. 462 days).

In a discussion of Dr. Li's presentation, Dr. Jeff A. Sloan suggested the differences might have been statistically significant on all eight tests had the investigators chosen a less stringent definition of neurocognitive deterioration. The criterion used was a decline of two standard deviations from baseline on two consecutive measurements or on the last follow-up visit before death.

“Two standard deviations is a huge change, a profound change,” Dr. Sloan of the Mayo Clinic in Rochester, Minn., said, praising the study for its rigor. “… [T]he bar was set so high, it is not surprising that only three of these eight [findings] were significant.”

The patient underwent initial precontrast computed tomography (CT) in the emergency department. This scan demonstrated a roughly 3-cm hyperdense mass that was centered on the right cavernous sinus. Associated vasogenic edema surrounded the mass. Additional foci of hypodensity were seen in the right centrum semiovale, said Dr. Gautam R. Mirchandani, director of neuroradiology at New York Methodist Hospital.

Pre- and postcontrast magnetic resonance imaging (MRI) on the next day demonstrated a heterogeneously—but avidly enhancing—extra-axial mass that corresponded with the CT finding. Regions of hypodensity seen on CT matched areas of restricted diffusion on diffusion-weighted imaging—representing acute infarction.

Magnetic resonance angiography (MRA) did not show the middle cerebral artery in that region because of the surrounding hypervascular lesion, which degrades the signal from that region. Flow-related enhancement was seen in more distal branches, suggesting that the middle cerebral artery was not occluded within the mass, but its branches were compromised. Of note, the regions of acute infarction correspond to the vascular territory of perforating vessels that arise from the proximal middle cerebral artery.

Further assessment of the mass was performed with CT angiography (CTA) to evaluate the relationship of the middle cerebral artery to the mass and to the regions of infarction. CTA demonstrated that the middle cerebral artery was not occluded within the lesion, although it was narrowed somewhat. Perforating vessels arising from the middle cerebral artery were also narrowed, likely causing her symptoms.

Based on the imaging characteristics, the clinical team was fairly confident that the avidly enhancing, extra-axial mass represented a meningioma, and surgical resection was planned.

Intraoperatively, frozen sections revealed histology consistent with adenocarcinoma, not with meningioma. Several specimens were sent to confirm this unexpected finding.

On postoperative review of the images, the two in-house neuroradiologists separately concurred that the imaging findings were still most consistent with a meningioma. “Even on re-review, I think it was reasonable to say that this looks like a meningioma,” said Dr. Mirchandani.

This conclusion was primarily based upon the extra-axial location and the avid enhancement. In addition, the tumor mass encased the near-by vessels, rather than occluding them. There was also no evidence of local osseous erosion, which is sometimes seen with other, more aggressive tumors. The absence of a known primary tumor made the possibility of a dural-based metastasis yet less likely.

Afterward, the patient was found to have a primary lung carcinoma, which had metastatically spread to the brain.

The patient arrested during the resection and underwent a prolonged resuscitation effort. She is currently intubated and on a ventilator. The patient is receiving supportive care, as she is still too ill for removal of the lung mass or undergo chemotherapy, said Dr. Susanna Horvath, director of the stroke program at New York Methodist Hospital.

“I think the teaching point in all this is that you have to look at the whole clinical scenario,” said Dr. Horvath.

By a large margin, enhancing, extra-axial masses represent meningiomas. Dural-based metastatic deposits, while possible, are seen much less often. Angiographic imaging can be very helpful in the evaluation of ischemic disease within the brain.

Precontrast CT shows a 3-cm mass near the right cavernous sinus.

Postcontrast T MRI shows the mass to be extra-axial and avidly enhancing. White matter hyperintensity corresponds to the hypodensity on CT.

DWI shows two foci of acute infarct on the right that are also visible on CT.

CTA demonstrates that the MCA within the mass is narrowed. Photos courtesy Dr. Gautam R. Mirchandani

The patient underwent initial precontrast computed tomography (CT) in the emergency department. This scan demonstrated a roughly 3-cm hyperdense mass that was centered on the right cavernous sinus. Associated vasogenic edema surrounded the mass. Additional foci of hypodensity were seen in the right centrum semiovale, said Dr. Gautam R. Mirchandani, director of neuroradiology at New York Methodist Hospital.

Pre- and postcontrast magnetic resonance imaging (MRI) on the next day demonstrated a heterogeneously—but avidly enhancing—extra-axial mass that corresponded with the CT finding. Regions of hypodensity seen on CT matched areas of restricted diffusion on diffusion-weighted imaging—representing acute infarction.

Magnetic resonance angiography (MRA) did not show the middle cerebral artery in that region because of the surrounding hypervascular lesion, which degrades the signal from that region. Flow-related enhancement was seen in more distal branches, suggesting that the middle cerebral artery was not occluded within the mass, but its branches were compromised. Of note, the regions of acute infarction correspond to the vascular territory of perforating vessels that arise from the proximal middle cerebral artery.

Further assessment of the mass was performed with CT angiography (CTA) to evaluate the relationship of the middle cerebral artery to the mass and to the regions of infarction. CTA demonstrated that the middle cerebral artery was not occluded within the lesion, although it was narrowed somewhat. Perforating vessels arising from the middle cerebral artery were also narrowed, likely causing her symptoms.

Based on the imaging characteristics, the clinical team was fairly confident that the avidly enhancing, extra-axial mass represented a meningioma, and surgical resection was planned.

Intraoperatively, frozen sections revealed histology consistent with adenocarcinoma, not with meningioma. Several specimens were sent to confirm this unexpected finding.

On postoperative review of the images, the two in-house neuroradiologists separately concurred that the imaging findings were still most consistent with a meningioma. “Even on re-review, I think it was reasonable to say that this looks like a meningioma,” said Dr. Mirchandani.

This conclusion was primarily based upon the extra-axial location and the avid enhancement. In addition, the tumor mass encased the near-by vessels, rather than occluding them. There was also no evidence of local osseous erosion, which is sometimes seen with other, more aggressive tumors. The absence of a known primary tumor made the possibility of a dural-based metastasis yet less likely.

Afterward, the patient was found to have a primary lung carcinoma, which had metastatically spread to the brain.

The patient arrested during the resection and underwent a prolonged resuscitation effort. She is currently intubated and on a ventilator. The patient is receiving supportive care, as she is still too ill for removal of the lung mass or undergo chemotherapy, said Dr. Susanna Horvath, director of the stroke program at New York Methodist Hospital.

“I think the teaching point in all this is that you have to look at the whole clinical scenario,” said Dr. Horvath.

By a large margin, enhancing, extra-axial masses represent meningiomas. Dural-based metastatic deposits, while possible, are seen much less often. Angiographic imaging can be very helpful in the evaluation of ischemic disease within the brain.

Precontrast CT shows a 3-cm mass near the right cavernous sinus.

Postcontrast T MRI shows the mass to be extra-axial and avidly enhancing. White matter hyperintensity corresponds to the hypodensity on CT.

DWI shows two foci of acute infarct on the right that are also visible on CT.

CTA demonstrates that the MCA within the mass is narrowed. Photos courtesy Dr. Gautam R. Mirchandani

The patient underwent initial precontrast computed tomography (CT) in the emergency department. This scan demonstrated a roughly 3-cm hyperdense mass that was centered on the right cavernous sinus. Associated vasogenic edema surrounded the mass. Additional foci of hypodensity were seen in the right centrum semiovale, said Dr. Gautam R. Mirchandani, director of neuroradiology at New York Methodist Hospital.

Pre- and postcontrast magnetic resonance imaging (MRI) on the next day demonstrated a heterogeneously—but avidly enhancing—extra-axial mass that corresponded with the CT finding. Regions of hypodensity seen on CT matched areas of restricted diffusion on diffusion-weighted imaging—representing acute infarction.

Magnetic resonance angiography (MRA) did not show the middle cerebral artery in that region because of the surrounding hypervascular lesion, which degrades the signal from that region. Flow-related enhancement was seen in more distal branches, suggesting that the middle cerebral artery was not occluded within the mass, but its branches were compromised. Of note, the regions of acute infarction correspond to the vascular territory of perforating vessels that arise from the proximal middle cerebral artery.

Further assessment of the mass was performed with CT angiography (CTA) to evaluate the relationship of the middle cerebral artery to the mass and to the regions of infarction. CTA demonstrated that the middle cerebral artery was not occluded within the lesion, although it was narrowed somewhat. Perforating vessels arising from the middle cerebral artery were also narrowed, likely causing her symptoms.

Based on the imaging characteristics, the clinical team was fairly confident that the avidly enhancing, extra-axial mass represented a meningioma, and surgical resection was planned.

Intraoperatively, frozen sections revealed histology consistent with adenocarcinoma, not with meningioma. Several specimens were sent to confirm this unexpected finding.

On postoperative review of the images, the two in-house neuroradiologists separately concurred that the imaging findings were still most consistent with a meningioma. “Even on re-review, I think it was reasonable to say that this looks like a meningioma,” said Dr. Mirchandani.

This conclusion was primarily based upon the extra-axial location and the avid enhancement. In addition, the tumor mass encased the near-by vessels, rather than occluding them. There was also no evidence of local osseous erosion, which is sometimes seen with other, more aggressive tumors. The absence of a known primary tumor made the possibility of a dural-based metastasis yet less likely.

Afterward, the patient was found to have a primary lung carcinoma, which had metastatically spread to the brain.

The patient arrested during the resection and underwent a prolonged resuscitation effort. She is currently intubated and on a ventilator. The patient is receiving supportive care, as she is still too ill for removal of the lung mass or undergo chemotherapy, said Dr. Susanna Horvath, director of the stroke program at New York Methodist Hospital.

“I think the teaching point in all this is that you have to look at the whole clinical scenario,” said Dr. Horvath.

By a large margin, enhancing, extra-axial masses represent meningiomas. Dural-based metastatic deposits, while possible, are seen much less often. Angiographic imaging can be very helpful in the evaluation of ischemic disease within the brain.

Precontrast CT shows a 3-cm mass near the right cavernous sinus.

Postcontrast T MRI shows the mass to be extra-axial and avidly enhancing. White matter hyperintensity corresponds to the hypodensity on CT.

DWI shows two foci of acute infarct on the right that are also visible on CT.

CTA demonstrates that the MCA within the mass is narrowed. Photos courtesy Dr. Gautam R. Mirchandani

LOS ANGELES — Malignant and benign secondary brain tumors are a significant problem in childhood cancer survivors, especially those surviving leukemia and brain tumors, according to findings from the Childhood Cancer Survivor Study.

Exposure to cranial radiation increases the risk of these secondary tumors, which may arise years after treatment for the initial cancer, Joseph P. Neglia, M.D., reported at the annual meeting of the Child Neurology Society.

Of 14,327 survivors of childhood cancer—defined as those diagnosed with cancer before the age of 20—in the Childhood Cancer Survivor Study, 116 developed secondary brain tumors between 5 and 28 years after initial diagnosis. The tumors included 66 meningiomas, 40 gliomas, 6 primitive neuroectodermal tumors, 1 lymphoma, and 3 tumors for which the histology could not be determined. A total of 33 of the tumors—30 of the gliomas and 3 of the meningiomas—were malignant. The gliomas occurred sooner after the initial diagnosis (median 9 years) than the meningiomas (median 17 years) and were more common after primary leukemia, while meningiomas occurred more frequently after primary brain tumors, said Dr. Neglia of the University of Minnesota in Minneapolis.

“Radiation therapy exposure was associated with significant increased risks for the development of gliomas, meningiomas, or any central nervous system brain tumors,” he said.

Additionally, the study revealed a radiation dose-response relationship with glioma development.

“Patients who received radiotherapy doses between 3,000 and 4,490 cGy had the highest rate of glioma diagnoses,” Dr. Neglia said.

LOS ANGELES — Malignant and benign secondary brain tumors are a significant problem in childhood cancer survivors, especially those surviving leukemia and brain tumors, according to findings from the Childhood Cancer Survivor Study.

Exposure to cranial radiation increases the risk of these secondary tumors, which may arise years after treatment for the initial cancer, Joseph P. Neglia, M.D., reported at the annual meeting of the Child Neurology Society.

Of 14,327 survivors of childhood cancer—defined as those diagnosed with cancer before the age of 20—in the Childhood Cancer Survivor Study, 116 developed secondary brain tumors between 5 and 28 years after initial diagnosis. The tumors included 66 meningiomas, 40 gliomas, 6 primitive neuroectodermal tumors, 1 lymphoma, and 3 tumors for which the histology could not be determined. A total of 33 of the tumors—30 of the gliomas and 3 of the meningiomas—were malignant. The gliomas occurred sooner after the initial diagnosis (median 9 years) than the meningiomas (median 17 years) and were more common after primary leukemia, while meningiomas occurred more frequently after primary brain tumors, said Dr. Neglia of the University of Minnesota in Minneapolis.

“Radiation therapy exposure was associated with significant increased risks for the development of gliomas, meningiomas, or any central nervous system brain tumors,” he said.

Additionally, the study revealed a radiation dose-response relationship with glioma development.

“Patients who received radiotherapy doses between 3,000 and 4,490 cGy had the highest rate of glioma diagnoses,” Dr. Neglia said.

LOS ANGELES — Malignant and benign secondary brain tumors are a significant problem in childhood cancer survivors, especially those surviving leukemia and brain tumors, according to findings from the Childhood Cancer Survivor Study.

Exposure to cranial radiation increases the risk of these secondary tumors, which may arise years after treatment for the initial cancer, Joseph P. Neglia, M.D., reported at the annual meeting of the Child Neurology Society.

Of 14,327 survivors of childhood cancer—defined as those diagnosed with cancer before the age of 20—in the Childhood Cancer Survivor Study, 116 developed secondary brain tumors between 5 and 28 years after initial diagnosis. The tumors included 66 meningiomas, 40 gliomas, 6 primitive neuroectodermal tumors, 1 lymphoma, and 3 tumors for which the histology could not be determined. A total of 33 of the tumors—30 of the gliomas and 3 of the meningiomas—were malignant. The gliomas occurred sooner after the initial diagnosis (median 9 years) than the meningiomas (median 17 years) and were more common after primary leukemia, while meningiomas occurred more frequently after primary brain tumors, said Dr. Neglia of the University of Minnesota in Minneapolis.

“Radiation therapy exposure was associated with significant increased risks for the development of gliomas, meningiomas, or any central nervous system brain tumors,” he said.

Additionally, the study revealed a radiation dose-response relationship with glioma development.

“Patients who received radiotherapy doses between 3,000 and 4,490 cGy had the highest rate of glioma diagnoses,” Dr. Neglia said.

DENVER — Use of fractionated stereotactic radiotherapy provides excellent local control of acoustic neuroma with lower rates of facial sensory and motor nerve damage than neurosurgery, Stephanie E. Combs, M.D., said at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

Applying radiotherapy on a fractionated schedule allows delivery of higher doses to the tumor while avoiding the morbidity in normal tissues that occurs with single-dose radiosurgery, said Dr. Combs of the University of Heidelberg, Germany.

She presented a prospective uncontrolled study of 108 patients regularly followed for a median of 48.5 months after undergoing linear accelerator-based fractionated stereotactic radiotherapy (FSRT) for acoustic neuroma. The tumor was associated with neurofibromatosis in 13 patients. Of the 108 patients, 85 had not undergone any treatment prior to FSRT; the remainder underwent FSRT as a salvage procedure for tumor recurrence or progression after neurologic resection.

Actuarial local tumor control after FSRT was 94.3% at 3 years and 93% at 5 years, regardless of tumor size, the presence of neurofibromatosis, or patient age.

Of patients with serviceable hearing prior to FSRT, 94% demonstrated preservation of useful hearing at 5 years. Of the 18 patients who had facial nerve dysfunction prior to FSRT, all but 3 developed the problem secondary to neurosurgery. The rate of new-onset facial nerve dysfunction after FSRT was 2.3%; affected patients had neurofibromatosis and large volumes of irradiated tissue.

Moderate irreversible radiation-induced damage to the trigeminal nerve developed in 3.4% of patients. No new severe damage to the nerve developed as a result of FSRT, she said.

DENVER — Use of fractionated stereotactic radiotherapy provides excellent local control of acoustic neuroma with lower rates of facial sensory and motor nerve damage than neurosurgery, Stephanie E. Combs, M.D., said at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

Applying radiotherapy on a fractionated schedule allows delivery of higher doses to the tumor while avoiding the morbidity in normal tissues that occurs with single-dose radiosurgery, said Dr. Combs of the University of Heidelberg, Germany.

She presented a prospective uncontrolled study of 108 patients regularly followed for a median of 48.5 months after undergoing linear accelerator-based fractionated stereotactic radiotherapy (FSRT) for acoustic neuroma. The tumor was associated with neurofibromatosis in 13 patients. Of the 108 patients, 85 had not undergone any treatment prior to FSRT; the remainder underwent FSRT as a salvage procedure for tumor recurrence or progression after neurologic resection.

Actuarial local tumor control after FSRT was 94.3% at 3 years and 93% at 5 years, regardless of tumor size, the presence of neurofibromatosis, or patient age.

Of patients with serviceable hearing prior to FSRT, 94% demonstrated preservation of useful hearing at 5 years. Of the 18 patients who had facial nerve dysfunction prior to FSRT, all but 3 developed the problem secondary to neurosurgery. The rate of new-onset facial nerve dysfunction after FSRT was 2.3%; affected patients had neurofibromatosis and large volumes of irradiated tissue.

Moderate irreversible radiation-induced damage to the trigeminal nerve developed in 3.4% of patients. No new severe damage to the nerve developed as a result of FSRT, she said.

DENVER — Use of fractionated stereotactic radiotherapy provides excellent local control of acoustic neuroma with lower rates of facial sensory and motor nerve damage than neurosurgery, Stephanie E. Combs, M.D., said at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

Applying radiotherapy on a fractionated schedule allows delivery of higher doses to the tumor while avoiding the morbidity in normal tissues that occurs with single-dose radiosurgery, said Dr. Combs of the University of Heidelberg, Germany.

She presented a prospective uncontrolled study of 108 patients regularly followed for a median of 48.5 months after undergoing linear accelerator-based fractionated stereotactic radiotherapy (FSRT) for acoustic neuroma. The tumor was associated with neurofibromatosis in 13 patients. Of the 108 patients, 85 had not undergone any treatment prior to FSRT; the remainder underwent FSRT as a salvage procedure for tumor recurrence or progression after neurologic resection.

Actuarial local tumor control after FSRT was 94.3% at 3 years and 93% at 5 years, regardless of tumor size, the presence of neurofibromatosis, or patient age.

Of patients with serviceable hearing prior to FSRT, 94% demonstrated preservation of useful hearing at 5 years. Of the 18 patients who had facial nerve dysfunction prior to FSRT, all but 3 developed the problem secondary to neurosurgery. The rate of new-onset facial nerve dysfunction after FSRT was 2.3%; affected patients had neurofibromatosis and large volumes of irradiated tissue.

Moderate irreversible radiation-induced damage to the trigeminal nerve developed in 3.4% of patients. No new severe damage to the nerve developed as a result of FSRT, she said.

LOS ANGELES — Large meningiomas can be resected with good long-term outcomes and without damage to the facial nerve using a combined retrosigmoid-transpetrosal-transchochlear approach, Rita M. Schuman, M.D., reported.

Large meningiomas located in the space between the cerebellum and the pons can originate from any area of the dura on the posterior surface of the petrous bone. Tumor removal is surgically challenging due to tumor vascularity, neural attachment, and brainstem compression.

Surgeons at the Loyola Center for Cranial Base Surgery in Maywood, Ill., combined several traditional approaches in a single-stage procedure, employing both retrosigmoid and presigmoid dural openings in 29 patients with large meningiomas of the cerebellopontine angle. The combined approach allows for wider access.

The approach was selected because of the combination of poor hearing and large tumor size among the patients, Dr. Schuman, a resident, said at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

Tumors ranged in size from 3 cm to 4 cm (8 cases), 4.1 cm to 5 cm (14), 5.1 cm to 6 cm (4), and 6 cm or larger (3), according to a chart review from July 1995 to July 2004.

The most common presenting symptoms were hearing loss (25 patients) and unilateral tinnitus (22 patients). Only six patients had no cranial nerve involvement upon presentation.

Complete tumor removal was achieved in 19 of 29 (66%) patients, near-total removal in 7 (24%), and subtotal removal in 3 (10%).

Postoperative sequelae included three cases of facial paralysis (10.3%), one case of cranial nerve grade 5 deficit (3.4%), two cranial nerve grade 6 deficits (6.9%), one case of vocal cord paralysis (3.4%), and one of cerebrospinal fluid fistula (3.4%).

The facial nerve was preserved despite the surgery in 26 of 29 patients. At the 2-year follow-up, 20 of the patients with an intact facial nerve had good function in that nerve, and 6 had adequate function.

With an average of 4.6 years follow-up, there was no residual tumor in 19 patients; the tumors were stable in another six patients, and there were signs of tumor regrowth in four (13.8%) patients.

“[The] three different approaches together [provide] the neurosurgeon with a wider lateral access to the tumor, and long-term follow-up shows the recurrence rate is low, and the total tumor removal rate is high,” lead author John P. Leonetti, M.D., director of the Center and professor of otolaryngology at Loyola University, said in an interview.

CPA meningioma with internal auditory canal extension seen on axial MRI.

Complete resection of the meningioma is evident on postoperative CT scan. Photos courtesy Dr. John P. Leonetti

LOS ANGELES — Large meningiomas can be resected with good long-term outcomes and without damage to the facial nerve using a combined retrosigmoid-transpetrosal-transchochlear approach, Rita M. Schuman, M.D., reported.

Large meningiomas located in the space between the cerebellum and the pons can originate from any area of the dura on the posterior surface of the petrous bone. Tumor removal is surgically challenging due to tumor vascularity, neural attachment, and brainstem compression.

Surgeons at the Loyola Center for Cranial Base Surgery in Maywood, Ill., combined several traditional approaches in a single-stage procedure, employing both retrosigmoid and presigmoid dural openings in 29 patients with large meningiomas of the cerebellopontine angle. The combined approach allows for wider access.

The approach was selected because of the combination of poor hearing and large tumor size among the patients, Dr. Schuman, a resident, said at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

Tumors ranged in size from 3 cm to 4 cm (8 cases), 4.1 cm to 5 cm (14), 5.1 cm to 6 cm (4), and 6 cm or larger (3), according to a chart review from July 1995 to July 2004.

The most common presenting symptoms were hearing loss (25 patients) and unilateral tinnitus (22 patients). Only six patients had no cranial nerve involvement upon presentation.

Complete tumor removal was achieved in 19 of 29 (66%) patients, near-total removal in 7 (24%), and subtotal removal in 3 (10%).

Postoperative sequelae included three cases of facial paralysis (10.3%), one case of cranial nerve grade 5 deficit (3.4%), two cranial nerve grade 6 deficits (6.9%), one case of vocal cord paralysis (3.4%), and one of cerebrospinal fluid fistula (3.4%).

The facial nerve was preserved despite the surgery in 26 of 29 patients. At the 2-year follow-up, 20 of the patients with an intact facial nerve had good function in that nerve, and 6 had adequate function.

With an average of 4.6 years follow-up, there was no residual tumor in 19 patients; the tumors were stable in another six patients, and there were signs of tumor regrowth in four (13.8%) patients.

“[The] three different approaches together [provide] the neurosurgeon with a wider lateral access to the tumor, and long-term follow-up shows the recurrence rate is low, and the total tumor removal rate is high,” lead author John P. Leonetti, M.D., director of the Center and professor of otolaryngology at Loyola University, said in an interview.

CPA meningioma with internal auditory canal extension seen on axial MRI.

Complete resection of the meningioma is evident on postoperative CT scan. Photos courtesy Dr. John P. Leonetti

LOS ANGELES — Large meningiomas can be resected with good long-term outcomes and without damage to the facial nerve using a combined retrosigmoid-transpetrosal-transchochlear approach, Rita M. Schuman, M.D., reported.

Large meningiomas located in the space between the cerebellum and the pons can originate from any area of the dura on the posterior surface of the petrous bone. Tumor removal is surgically challenging due to tumor vascularity, neural attachment, and brainstem compression.

Surgeons at the Loyola Center for Cranial Base Surgery in Maywood, Ill., combined several traditional approaches in a single-stage procedure, employing both retrosigmoid and presigmoid dural openings in 29 patients with large meningiomas of the cerebellopontine angle. The combined approach allows for wider access.

The approach was selected because of the combination of poor hearing and large tumor size among the patients, Dr. Schuman, a resident, said at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

Tumors ranged in size from 3 cm to 4 cm (8 cases), 4.1 cm to 5 cm (14), 5.1 cm to 6 cm (4), and 6 cm or larger (3), according to a chart review from July 1995 to July 2004.

The most common presenting symptoms were hearing loss (25 patients) and unilateral tinnitus (22 patients). Only six patients had no cranial nerve involvement upon presentation.

Complete tumor removal was achieved in 19 of 29 (66%) patients, near-total removal in 7 (24%), and subtotal removal in 3 (10%).

Postoperative sequelae included three cases of facial paralysis (10.3%), one case of cranial nerve grade 5 deficit (3.4%), two cranial nerve grade 6 deficits (6.9%), one case of vocal cord paralysis (3.4%), and one of cerebrospinal fluid fistula (3.4%).

The facial nerve was preserved despite the surgery in 26 of 29 patients. At the 2-year follow-up, 20 of the patients with an intact facial nerve had good function in that nerve, and 6 had adequate function.

With an average of 4.6 years follow-up, there was no residual tumor in 19 patients; the tumors were stable in another six patients, and there were signs of tumor regrowth in four (13.8%) patients.

“[The] three different approaches together [provide] the neurosurgeon with a wider lateral access to the tumor, and long-term follow-up shows the recurrence rate is low, and the total tumor removal rate is high,” lead author John P. Leonetti, M.D., director of the Center and professor of otolaryngology at Loyola University, said in an interview.

CPA meningioma with internal auditory canal extension seen on axial MRI.

Complete resection of the meningioma is evident on postoperative CT scan. Photos courtesy Dr. John P. Leonetti

NEW ORLEANS — Fluorescence-guided surgery with 5-aminolevulinic acid appears to increase progression-free survival in malignant glioma, according to interim results of a multicenter study conducted in Germany, Walter Stummer, M.D., reported at the annual meeting of the American Association of Neurological Surgeons.

Participants in an ongoing study are being randomized to receive 20 mg/kg of 5-aminolevulinic acid (5-ALA) with fluorescence-guided surgery or conventional microsurgery, aided by white light. The German manufacturer Medac GmbH, which makes 5-ALA, designed the study with the researchersd. Eighteen centers are participating in the ALA-Glioma Study Group, said Dr. Stummer, of the University of Düsseldorf, a participating center.

5-ALA causes the accumulation of fluorescent porphyrins in malignant gliomas, which may help surgeons better identify and resect tumors intraoperatively. It is not approved for this use in the United States.

Dr. Stummer reported on the first 270 patients in an intent-to-treat population. (A total of 350 will be in the final analysis.) All patients were given an MRI preoperatively, during surgery, and on days 103, day 7, week 6, and every 3 months after surgery.

The cumulative 6-month progression-free survival rate was 41% for the 5-ALA group, compared with 21% for the control group. The 5-ALA patients had a median survival of 15.2 months, compared with 13.5 months for patients in the control group; however, the trial was not powered to show any difference in overall survival.

Sixty-five percent of postoperative MRIs done on the 5-ALA patients were devoid of residual contrast-enhancing tumor, compared with 36% in the control group (P < .001).

Patients who had less contrast in their MRIs had longer median survival—16 months, compared with 12 months in the control group (P < .001). “This study addresses the basic controversy in neurosurgery on whether maximal cytoreductive therapy of malignant gliomas is of benefit to patients,” said Dr. Stummer in a statement.

Results of the study “demonstrate that fluorescence guidance using 5-ALA enhances resections of malignant gliomas, and that enhanced resections are beneficial by translating into longer progression-free survival,” Dr. Stummer added.

In discussing the study at the meeting, Peter Black, M.D., chief of neurosurgical oncology at Dana-Farber Cancer Institute in Boston, said it provided class I evidence of improved survival.

The study also demonstrated a successful collaboration by the 18 centers, he said.

But, noted Dr. Black, since 5-ALA is not yet approved for this use in the United States, there is still a continuing need for other therapies.

NEW ORLEANS — Fluorescence-guided surgery with 5-aminolevulinic acid appears to increase progression-free survival in malignant glioma, according to interim results of a multicenter study conducted in Germany, Walter Stummer, M.D., reported at the annual meeting of the American Association of Neurological Surgeons.

Participants in an ongoing study are being randomized to receive 20 mg/kg of 5-aminolevulinic acid (5-ALA) with fluorescence-guided surgery or conventional microsurgery, aided by white light. The German manufacturer Medac GmbH, which makes 5-ALA, designed the study with the researchersd. Eighteen centers are participating in the ALA-Glioma Study Group, said Dr. Stummer, of the University of Düsseldorf, a participating center.

5-ALA causes the accumulation of fluorescent porphyrins in malignant gliomas, which may help surgeons better identify and resect tumors intraoperatively. It is not approved for this use in the United States.

Dr. Stummer reported on the first 270 patients in an intent-to-treat population. (A total of 350 will be in the final analysis.) All patients were given an MRI preoperatively, during surgery, and on days 103, day 7, week 6, and every 3 months after surgery.

The cumulative 6-month progression-free survival rate was 41% for the 5-ALA group, compared with 21% for the control group. The 5-ALA patients had a median survival of 15.2 months, compared with 13.5 months for patients in the control group; however, the trial was not powered to show any difference in overall survival.

Sixty-five percent of postoperative MRIs done on the 5-ALA patients were devoid of residual contrast-enhancing tumor, compared with 36% in the control group (P < .001).

Patients who had less contrast in their MRIs had longer median survival—16 months, compared with 12 months in the control group (P < .001). “This study addresses the basic controversy in neurosurgery on whether maximal cytoreductive therapy of malignant gliomas is of benefit to patients,” said Dr. Stummer in a statement.

Results of the study “demonstrate that fluorescence guidance using 5-ALA enhances resections of malignant gliomas, and that enhanced resections are beneficial by translating into longer progression-free survival,” Dr. Stummer added.

In discussing the study at the meeting, Peter Black, M.D., chief of neurosurgical oncology at Dana-Farber Cancer Institute in Boston, said it provided class I evidence of improved survival.

The study also demonstrated a successful collaboration by the 18 centers, he said.

But, noted Dr. Black, since 5-ALA is not yet approved for this use in the United States, there is still a continuing need for other therapies.

NEW ORLEANS — Fluorescence-guided surgery with 5-aminolevulinic acid appears to increase progression-free survival in malignant glioma, according to interim results of a multicenter study conducted in Germany, Walter Stummer, M.D., reported at the annual meeting of the American Association of Neurological Surgeons.

Participants in an ongoing study are being randomized to receive 20 mg/kg of 5-aminolevulinic acid (5-ALA) with fluorescence-guided surgery or conventional microsurgery, aided by white light. The German manufacturer Medac GmbH, which makes 5-ALA, designed the study with the researchersd. Eighteen centers are participating in the ALA-Glioma Study Group, said Dr. Stummer, of the University of Düsseldorf, a participating center.

5-ALA causes the accumulation of fluorescent porphyrins in malignant gliomas, which may help surgeons better identify and resect tumors intraoperatively. It is not approved for this use in the United States.

Dr. Stummer reported on the first 270 patients in an intent-to-treat population. (A total of 350 will be in the final analysis.) All patients were given an MRI preoperatively, during surgery, and on days 103, day 7, week 6, and every 3 months after surgery.

The cumulative 6-month progression-free survival rate was 41% for the 5-ALA group, compared with 21% for the control group. The 5-ALA patients had a median survival of 15.2 months, compared with 13.5 months for patients in the control group; however, the trial was not powered to show any difference in overall survival.

Sixty-five percent of postoperative MRIs done on the 5-ALA patients were devoid of residual contrast-enhancing tumor, compared with 36% in the control group (P < .001).

Patients who had less contrast in their MRIs had longer median survival—16 months, compared with 12 months in the control group (P < .001). “This study addresses the basic controversy in neurosurgery on whether maximal cytoreductive therapy of malignant gliomas is of benefit to patients,” said Dr. Stummer in a statement.

Results of the study “demonstrate that fluorescence guidance using 5-ALA enhances resections of malignant gliomas, and that enhanced resections are beneficial by translating into longer progression-free survival,” Dr. Stummer added.

In discussing the study at the meeting, Peter Black, M.D., chief of neurosurgical oncology at Dana-Farber Cancer Institute in Boston, said it provided class I evidence of improved survival.

The study also demonstrated a successful collaboration by the 18 centers, he said.

But, noted Dr. Black, since 5-ALA is not yet approved for this use in the United States, there is still a continuing need for other therapies.

HOLLYWOOD, FLA. — Oral temozolomide should be added to radiotherapy for adults newly diagnosed with glioblastoma multiforme, according to updated guidelines for the management of central nervous system cancers.

Recent studies have shown that including the oral alkylating agent in the management of glioblastoma multiforme results in a clinically meaningful, statistically significant survival benefit with minimal additional toxicity, Steven Brem, M.D., said at the annual conference of the National Comprehensive Cancer Network (NCCN).

The new central nervous system cancer guidelines, issued in March, were developed by the NCCN, which comprises 19 member institutions that have been designated as comprehensive cancer centers by the National Cancer Institute. Last updated in 2004, the guidelines also recommend the use of chemotherapeutic polymer implants following glioblastoma resection, said Dr. Brem, chair of the central nervous system guidelines writing panel.

The inclusion of temozolomide in the updated guidelines comes on the heels of the Food and Drug Administration's (FDA's) March 16 approval of the drug for use in combination with radiotherapy for newly diagnosed glioblastoma, the most common type of primary brain tumor in adults, said Dr. Brem, leader of the neuro-oncology program at H. Lee Moffitt Cancer Center in Tampa, Fla.

Both the FDA approval and NCCN guideline update are based in large part on safety and efficacy data from a phase III study by the European Organisation for Research and Treatment of Cancer (EORTC) in which 573 patients newly diagnosed with glioblastoma were randomized to receive radiotherapy alone or in conjunction with temozolomide (N. Engl. J. Med. 2005;352:987–96). The temozolomide group saw a median survival improvement of 2.5 months—”a significant gain and one that can be built upon,” according to Dr. Brem.

With respect to polymer implants, the guidelines state that BCNU wafers (biodegradable 1,3-bis 2-chloroethyl-1-nitrosourea) should be implanted into the cavity created following glioblastoma resection. As the small white wafers erode, they release the chemotherapy agent carmustine directly to the tumor site over an extended period of time. The FDA approved the wafers for use in patients with newly diagnosed glioblastoma in February 2003 based on results of a series of randomized trials. The NCCN treatment update reflects these results as well as the findings of a 2003 phase III trial out of the University Hospital Eppendorf, Hamburg (Germany), in which 240 patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection, followed by postoperative external beam radiation. The BCNU group had a median survival improvement of 2.3 months and a 28% reduction in death risk. Additionally, time-to-decline and neuroperformance measures were significantly improved, and adverse events were comparable, with the exception of increased risk for cerebrospinal fluid leak and intracranial hypertension in the BCNU group (Neuro-oncol. 2003;5:79–88).

For patients in whom the wafers are not implanted, radiation therapy and treatment with temozolomide should be used, he said.

The updated guidelines also recommend aggressive treatment of metastases to the brain from other cancers. In general, surgery is indicated when there are fewer than four resectable metastatic lesions—depending on such factors as histologic type, location, and neurologic function. This recommendation is based on studies that have associated surgery via various modern techniques—image-guided navigation, functional mapping, awake craniotomy for eloquent area, and minimally invasive microneurosurgery—with a median drop in surgical mortality from 11% to 0%, said Dr. Brem. When there are more than three metastases or when surgery is not indicated, whole-brain radiation therapy—which has a 40%–60% response rate, depending on the tumor—should be used. “Where brain metastases were often viewed as fatal, we now consider them treatable. Where radiation [to the brain] was often perceived as too harmful, we now know that focused radiation can improve median survival time,” he said.

For patients with pain and disability resulting from metastatic spine tumors, the guidelines recommend reconstructive spinal surgery over medical management because the former is associated with better quality of life outcomes, said Dr. Brem.

The guidelines also outline the use of imaging as an accurate biomarker for monitoring central nervous system disease progression and recurrence, as well as treatment efficacy, he said.

The updated guidelines are posted atwww.nccn.org/professionals/physician_gls/default.asp

HOLLYWOOD, FLA. — Oral temozolomide should be added to radiotherapy for adults newly diagnosed with glioblastoma multiforme, according to updated guidelines for the management of central nervous system cancers.

Recent studies have shown that including the oral alkylating agent in the management of glioblastoma multiforme results in a clinically meaningful, statistically significant survival benefit with minimal additional toxicity, Steven Brem, M.D., said at the annual conference of the National Comprehensive Cancer Network (NCCN).

The new central nervous system cancer guidelines, issued in March, were developed by the NCCN, which comprises 19 member institutions that have been designated as comprehensive cancer centers by the National Cancer Institute. Last updated in 2004, the guidelines also recommend the use of chemotherapeutic polymer implants following glioblastoma resection, said Dr. Brem, chair of the central nervous system guidelines writing panel.

The inclusion of temozolomide in the updated guidelines comes on the heels of the Food and Drug Administration's (FDA's) March 16 approval of the drug for use in combination with radiotherapy for newly diagnosed glioblastoma, the most common type of primary brain tumor in adults, said Dr. Brem, leader of the neuro-oncology program at H. Lee Moffitt Cancer Center in Tampa, Fla.

Both the FDA approval and NCCN guideline update are based in large part on safety and efficacy data from a phase III study by the European Organisation for Research and Treatment of Cancer (EORTC) in which 573 patients newly diagnosed with glioblastoma were randomized to receive radiotherapy alone or in conjunction with temozolomide (N. Engl. J. Med. 2005;352:987–96). The temozolomide group saw a median survival improvement of 2.5 months—”a significant gain and one that can be built upon,” according to Dr. Brem.

With respect to polymer implants, the guidelines state that BCNU wafers (biodegradable 1,3-bis 2-chloroethyl-1-nitrosourea) should be implanted into the cavity created following glioblastoma resection. As the small white wafers erode, they release the chemotherapy agent carmustine directly to the tumor site over an extended period of time. The FDA approved the wafers for use in patients with newly diagnosed glioblastoma in February 2003 based on results of a series of randomized trials. The NCCN treatment update reflects these results as well as the findings of a 2003 phase III trial out of the University Hospital Eppendorf, Hamburg (Germany), in which 240 patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection, followed by postoperative external beam radiation. The BCNU group had a median survival improvement of 2.3 months and a 28% reduction in death risk. Additionally, time-to-decline and neuroperformance measures were significantly improved, and adverse events were comparable, with the exception of increased risk for cerebrospinal fluid leak and intracranial hypertension in the BCNU group (Neuro-oncol. 2003;5:79–88).

For patients in whom the wafers are not implanted, radiation therapy and treatment with temozolomide should be used, he said.

The updated guidelines also recommend aggressive treatment of metastases to the brain from other cancers. In general, surgery is indicated when there are fewer than four resectable metastatic lesions—depending on such factors as histologic type, location, and neurologic function. This recommendation is based on studies that have associated surgery via various modern techniques—image-guided navigation, functional mapping, awake craniotomy for eloquent area, and minimally invasive microneurosurgery—with a median drop in surgical mortality from 11% to 0%, said Dr. Brem. When there are more than three metastases or when surgery is not indicated, whole-brain radiation therapy—which has a 40%–60% response rate, depending on the tumor—should be used. “Where brain metastases were often viewed as fatal, we now consider them treatable. Where radiation [to the brain] was often perceived as too harmful, we now know that focused radiation can improve median survival time,” he said.

For patients with pain and disability resulting from metastatic spine tumors, the guidelines recommend reconstructive spinal surgery over medical management because the former is associated with better quality of life outcomes, said Dr. Brem.

The guidelines also outline the use of imaging as an accurate biomarker for monitoring central nervous system disease progression and recurrence, as well as treatment efficacy, he said.

The updated guidelines are posted atwww.nccn.org/professionals/physician_gls/default.asp

HOLLYWOOD, FLA. — Oral temozolomide should be added to radiotherapy for adults newly diagnosed with glioblastoma multiforme, according to updated guidelines for the management of central nervous system cancers.

Recent studies have shown that including the oral alkylating agent in the management of glioblastoma multiforme results in a clinically meaningful, statistically significant survival benefit with minimal additional toxicity, Steven Brem, M.D., said at the annual conference of the National Comprehensive Cancer Network (NCCN).

The new central nervous system cancer guidelines, issued in March, were developed by the NCCN, which comprises 19 member institutions that have been designated as comprehensive cancer centers by the National Cancer Institute. Last updated in 2004, the guidelines also recommend the use of chemotherapeutic polymer implants following glioblastoma resection, said Dr. Brem, chair of the central nervous system guidelines writing panel.

The inclusion of temozolomide in the updated guidelines comes on the heels of the Food and Drug Administration's (FDA's) March 16 approval of the drug for use in combination with radiotherapy for newly diagnosed glioblastoma, the most common type of primary brain tumor in adults, said Dr. Brem, leader of the neuro-oncology program at H. Lee Moffitt Cancer Center in Tampa, Fla.

Both the FDA approval and NCCN guideline update are based in large part on safety and efficacy data from a phase III study by the European Organisation for Research and Treatment of Cancer (EORTC) in which 573 patients newly diagnosed with glioblastoma were randomized to receive radiotherapy alone or in conjunction with temozolomide (N. Engl. J. Med. 2005;352:987–96). The temozolomide group saw a median survival improvement of 2.5 months—”a significant gain and one that can be built upon,” according to Dr. Brem.

With respect to polymer implants, the guidelines state that BCNU wafers (biodegradable 1,3-bis 2-chloroethyl-1-nitrosourea) should be implanted into the cavity created following glioblastoma resection. As the small white wafers erode, they release the chemotherapy agent carmustine directly to the tumor site over an extended period of time. The FDA approved the wafers for use in patients with newly diagnosed glioblastoma in February 2003 based on results of a series of randomized trials. The NCCN treatment update reflects these results as well as the findings of a 2003 phase III trial out of the University Hospital Eppendorf, Hamburg (Germany), in which 240 patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection, followed by postoperative external beam radiation. The BCNU group had a median survival improvement of 2.3 months and a 28% reduction in death risk. Additionally, time-to-decline and neuroperformance measures were significantly improved, and adverse events were comparable, with the exception of increased risk for cerebrospinal fluid leak and intracranial hypertension in the BCNU group (Neuro-oncol. 2003;5:79–88).

For patients in whom the wafers are not implanted, radiation therapy and treatment with temozolomide should be used, he said.

The updated guidelines also recommend aggressive treatment of metastases to the brain from other cancers. In general, surgery is indicated when there are fewer than four resectable metastatic lesions—depending on such factors as histologic type, location, and neurologic function. This recommendation is based on studies that have associated surgery via various modern techniques—image-guided navigation, functional mapping, awake craniotomy for eloquent area, and minimally invasive microneurosurgery—with a median drop in surgical mortality from 11% to 0%, said Dr. Brem. When there are more than three metastases or when surgery is not indicated, whole-brain radiation therapy—which has a 40%–60% response rate, depending on the tumor—should be used. “Where brain metastases were often viewed as fatal, we now consider them treatable. Where radiation [to the brain] was often perceived as too harmful, we now know that focused radiation can improve median survival time,” he said.

For patients with pain and disability resulting from metastatic spine tumors, the guidelines recommend reconstructive spinal surgery over medical management because the former is associated with better quality of life outcomes, said Dr. Brem.

The guidelines also outline the use of imaging as an accurate biomarker for monitoring central nervous system disease progression and recurrence, as well as treatment efficacy, he said.

The updated guidelines are posted atwww.nccn.org/professionals/physician_gls/default.asp

LOS ANGELES — The first human case of West Nile virus infection this year was diagnosed in Los Angeles in early February, perhaps setting the stage for an early and virulent season for the far western United States.

“Since West Nile virus was [first] detected in 1999, we've seen a lengthening period of transmission,” said Ned Hayes, M.D., of the Centers for Disease Control and Prevention's Division of Vector-Borne Infectious Diseases in Fort Collins, Colo.

As the virus has spread south and west across the United States, new “ecological dynamics” have influenced transmission patterns, he explained.

A wetter than normal winter in California and the Southwest may suit mosquitoes well, meaning physicians will need to be especially alert to possible cases of the now reportable disease.

The Los Angeles County Department of Health Services announced an infection in an older man in east Los Angeles County on Feb. 8. As of mid-February, state and federal health officials had not completed confirmatory tests on the case.

Symptoms of West Nile infection include fever, headache, fatigue, body aches, skin rash, and swollen lymph nodes.

More serious manifestations of West Nile encephalitis or meningitis include neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and a paralysis that can resemble polio.

“It doesn't matter whether we've had one case or five; if you see encephalitis or meningitis, you look for West Nile virus,” said Laurene Mascola, M.D., chief of the acute communicable disease control unit of Los Angeles County.

The first bird carrying the virus was found in mid-January, whereas no bird evidence was confirmed in California until the end of March in 2004. Twelve birds in eight counties had been found to have the virus by mid-February. “It's pretty much all up and down the state,” said Robert Miller, a spokesman for the California Department of Health Services in Sacramento.

Birds are an important player in the transmission cycle of West Nile virus and are carefully tracked, although mosquitoes are the direct vectors infecting humans.

California and the Southwest, where the disease struck hardest in 2004, have warmer climates than the northeastern states, where the virus first took hold in the United States. Mosquito vectors also differ, with Culex pipiens most common in the Northeast and C. tarsalis and C. quinquefasciatus often the culprits in the West.

C. tarsalis was a common vector in Colorado, where West Nile virus infected almost 3,000 people in 2003, killing 63. “It's a very efficient vector. It avidly bites humans and also bites birds, and it seems to transmit the virus very well.”

Dr. Hayes urged physicians to test for West Nile virus and report cases to their state health departments, which notify the CDC. “We have no way of knowing what's happening [in terms of transmission patterns] unless practicing physicians report their cases,” he said in an interview.

A special online registry for physicians reporting pregnant patients infected with the virus has been established by the CDC at its Web site, http://www.cdc.gov

West Nile virus infected 2,470 people in 40 states in 2004, resulting in 88 deaths. The highest number of cases was in 2003, when 9,862 infections and 264 deaths were reported. States have been variably affected over time. For example, Nebraska had 1,942 cases in 2003 but just 49 in 2004.

Though some have speculated that disease patterns may reflect herd immunity, Dr. Hayes discounted that theory. He said that even in the most concentrated “hot zones,” antibodies have been detected in just 3%-5% of the population.

On the other hand, changes in weather, bird migration and infection patterns, mosquito abatement, and basic prevention strategies such as wearing mosquito repellant, may change human infection rates over time.

LOS ANGELES — The first human case of West Nile virus infection this year was diagnosed in Los Angeles in early February, perhaps setting the stage for an early and virulent season for the far western United States.

“Since West Nile virus was [first] detected in 1999, we've seen a lengthening period of transmission,” said Ned Hayes, M.D., of the Centers for Disease Control and Prevention's Division of Vector-Borne Infectious Diseases in Fort Collins, Colo.

As the virus has spread south and west across the United States, new “ecological dynamics” have influenced transmission patterns, he explained.

A wetter than normal winter in California and the Southwest may suit mosquitoes well, meaning physicians will need to be especially alert to possible cases of the now reportable disease.

The Los Angeles County Department of Health Services announced an infection in an older man in east Los Angeles County on Feb. 8. As of mid-February, state and federal health officials had not completed confirmatory tests on the case.

Symptoms of West Nile infection include fever, headache, fatigue, body aches, skin rash, and swollen lymph nodes.

More serious manifestations of West Nile encephalitis or meningitis include neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and a paralysis that can resemble polio.

“It doesn't matter whether we've had one case or five; if you see encephalitis or meningitis, you look for West Nile virus,” said Laurene Mascola, M.D., chief of the acute communicable disease control unit of Los Angeles County.

The first bird carrying the virus was found in mid-January, whereas no bird evidence was confirmed in California until the end of March in 2004. Twelve birds in eight counties had been found to have the virus by mid-February. “It's pretty much all up and down the state,” said Robert Miller, a spokesman for the California Department of Health Services in Sacramento.

Birds are an important player in the transmission cycle of West Nile virus and are carefully tracked, although mosquitoes are the direct vectors infecting humans.

California and the Southwest, where the disease struck hardest in 2004, have warmer climates than the northeastern states, where the virus first took hold in the United States. Mosquito vectors also differ, with Culex pipiens most common in the Northeast and C. tarsalis and C. quinquefasciatus often the culprits in the West.

C. tarsalis was a common vector in Colorado, where West Nile virus infected almost 3,000 people in 2003, killing 63. “It's a very efficient vector. It avidly bites humans and also bites birds, and it seems to transmit the virus very well.”

Dr. Hayes urged physicians to test for West Nile virus and report cases to their state health departments, which notify the CDC. “We have no way of knowing what's happening [in terms of transmission patterns] unless practicing physicians report their cases,” he said in an interview.

A special online registry for physicians reporting pregnant patients infected with the virus has been established by the CDC at its Web site, http://www.cdc.gov

West Nile virus infected 2,470 people in 40 states in 2004, resulting in 88 deaths. The highest number of cases was in 2003, when 9,862 infections and 264 deaths were reported. States have been variably affected over time. For example, Nebraska had 1,942 cases in 2003 but just 49 in 2004.

Though some have speculated that disease patterns may reflect herd immunity, Dr. Hayes discounted that theory. He said that even in the most concentrated “hot zones,” antibodies have been detected in just 3%-5% of the population.

On the other hand, changes in weather, bird migration and infection patterns, mosquito abatement, and basic prevention strategies such as wearing mosquito repellant, may change human infection rates over time.

LOS ANGELES — The first human case of West Nile virus infection this year was diagnosed in Los Angeles in early February, perhaps setting the stage for an early and virulent season for the far western United States.

“Since West Nile virus was [first] detected in 1999, we've seen a lengthening period of transmission,” said Ned Hayes, M.D., of the Centers for Disease Control and Prevention's Division of Vector-Borne Infectious Diseases in Fort Collins, Colo.

As the virus has spread south and west across the United States, new “ecological dynamics” have influenced transmission patterns, he explained.

A wetter than normal winter in California and the Southwest may suit mosquitoes well, meaning physicians will need to be especially alert to possible cases of the now reportable disease.

The Los Angeles County Department of Health Services announced an infection in an older man in east Los Angeles County on Feb. 8. As of mid-February, state and federal health officials had not completed confirmatory tests on the case.

Symptoms of West Nile infection include fever, headache, fatigue, body aches, skin rash, and swollen lymph nodes.

More serious manifestations of West Nile encephalitis or meningitis include neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and a paralysis that can resemble polio.

“It doesn't matter whether we've had one case or five; if you see encephalitis or meningitis, you look for West Nile virus,” said Laurene Mascola, M.D., chief of the acute communicable disease control unit of Los Angeles County.

The first bird carrying the virus was found in mid-January, whereas no bird evidence was confirmed in California until the end of March in 2004. Twelve birds in eight counties had been found to have the virus by mid-February. “It's pretty much all up and down the state,” said Robert Miller, a spokesman for the California Department of Health Services in Sacramento.

Birds are an important player in the transmission cycle of West Nile virus and are carefully tracked, although mosquitoes are the direct vectors infecting humans.

California and the Southwest, where the disease struck hardest in 2004, have warmer climates than the northeastern states, where the virus first took hold in the United States. Mosquito vectors also differ, with Culex pipiens most common in the Northeast and C. tarsalis and C. quinquefasciatus often the culprits in the West.

C. tarsalis was a common vector in Colorado, where West Nile virus infected almost 3,000 people in 2003, killing 63. “It's a very efficient vector. It avidly bites humans and also bites birds, and it seems to transmit the virus very well.”

Dr. Hayes urged physicians to test for West Nile virus and report cases to their state health departments, which notify the CDC. “We have no way of knowing what's happening [in terms of transmission patterns] unless practicing physicians report their cases,” he said in an interview.

A special online registry for physicians reporting pregnant patients infected with the virus has been established by the CDC at its Web site, http://www.cdc.gov

West Nile virus infected 2,470 people in 40 states in 2004, resulting in 88 deaths. The highest number of cases was in 2003, when 9,862 infections and 264 deaths were reported. States have been variably affected over time. For example, Nebraska had 1,942 cases in 2003 but just 49 in 2004.

Though some have speculated that disease patterns may reflect herd immunity, Dr. Hayes discounted that theory. He said that even in the most concentrated “hot zones,” antibodies have been detected in just 3%-5% of the population.

On the other hand, changes in weather, bird migration and infection patterns, mosquito abatement, and basic prevention strategies such as wearing mosquito repellant, may change human infection rates over time.