Neuro-oncology

WASHINGTON — A new preoperative grading system for adult hemispheric low-grade gliomas produced accurate prognoses for disease stage, Dr. Edward F. Chang said at the annual meeting of the American Association of Neurological Surgeons.

“There are few standards for guiding both the medical and surgical management of low-grade gliomas,” said Dr. Chang, a third-year resident in the department of neurologic surgery at the University of California, San Francisco. To construct a system, Dr. Chang reviewed 280 patients who had undergone operations for histologically confirmed grade 2 gliomas (from biopsy to maximal surgical resection) during 1989–2005 at UCSF.

Median patient age was 38 years at presentation. Most (88%) had seizures. A majority had a Karnofsky Performance Scale score of 100 or 90. Most tumors were in the frontal (72%) or temporal lobe (34%); median diameter was 4.5 cm.

In the follow-up period, patients survived for a median of 12 years; 65 died. A total of 134 events of progression or recurrence occurred. The median time of progression-free survival was 6 years.

The investigators used four variables highly predictive of lower survival in their grading. (See box.) The strongest was the presence of tumor in “eloquent” brain regions, particularly the sensorimotor cortex (specifically the pre- and postsensory gyri), perisylvian dominant language areas, insular areas, basal ganglia-internal capsule, thalamus, and hypothalamus. Tumor presence in an area of eloquence was the only significant, independent predictor of progression or recurrence.

The interobserver reliability of the grading system had a kappa value of 0.86 between a neurosurgery resident and an attending neurosurgeon blinded to the outcome of a subset of 200 random cases from the study.

When the study sample was graded, the median survival fell from 16 years for patients with low risk to nearly 11 years for those with intermediate risk and 8 years high risk. The median period of progression-free survival dropped as risk grew.

The researchers also analyzed predictors of the extent of resection. Tumors in an area of eloquence had a diameter greater than 4 cm with diffuse borders on MRI; tumors in the temporal lobe were significantly more likely to be treated with subtotal resection; parietal tumors were significantly more likely to undergo gross total resection.

The grading system currently is undergoing external validation.

Low-Grade Glioma Grading System

▸ Age 50 years or older

▸ Karnofsky Performance Scale score less than 90

▸ Maximum tumor diameter more than 4 cm

▸ Tumor located in “eloquent” area

A “yes” answer is given a score of 1 and a “no,” a score of 0. The categories for risk of death or progression were defined as:

Low = 0–1

Intermediate = 2

High = 3–4

Source: Dr. Chang

WASHINGTON — A new preoperative grading system for adult hemispheric low-grade gliomas produced accurate prognoses for disease stage, Dr. Edward F. Chang said at the annual meeting of the American Association of Neurological Surgeons.

“There are few standards for guiding both the medical and surgical management of low-grade gliomas,” said Dr. Chang, a third-year resident in the department of neurologic surgery at the University of California, San Francisco. To construct a system, Dr. Chang reviewed 280 patients who had undergone operations for histologically confirmed grade 2 gliomas (from biopsy to maximal surgical resection) during 1989–2005 at UCSF.

Median patient age was 38 years at presentation. Most (88%) had seizures. A majority had a Karnofsky Performance Scale score of 100 or 90. Most tumors were in the frontal (72%) or temporal lobe (34%); median diameter was 4.5 cm.

In the follow-up period, patients survived for a median of 12 years; 65 died. A total of 134 events of progression or recurrence occurred. The median time of progression-free survival was 6 years.

The investigators used four variables highly predictive of lower survival in their grading. (See box.) The strongest was the presence of tumor in “eloquent” brain regions, particularly the sensorimotor cortex (specifically the pre- and postsensory gyri), perisylvian dominant language areas, insular areas, basal ganglia-internal capsule, thalamus, and hypothalamus. Tumor presence in an area of eloquence was the only significant, independent predictor of progression or recurrence.

The interobserver reliability of the grading system had a kappa value of 0.86 between a neurosurgery resident and an attending neurosurgeon blinded to the outcome of a subset of 200 random cases from the study.

When the study sample was graded, the median survival fell from 16 years for patients with low risk to nearly 11 years for those with intermediate risk and 8 years high risk. The median period of progression-free survival dropped as risk grew.

The researchers also analyzed predictors of the extent of resection. Tumors in an area of eloquence had a diameter greater than 4 cm with diffuse borders on MRI; tumors in the temporal lobe were significantly more likely to be treated with subtotal resection; parietal tumors were significantly more likely to undergo gross total resection.

The grading system currently is undergoing external validation.

Low-Grade Glioma Grading System

▸ Age 50 years or older

▸ Karnofsky Performance Scale score less than 90

▸ Maximum tumor diameter more than 4 cm

▸ Tumor located in “eloquent” area

A “yes” answer is given a score of 1 and a “no,” a score of 0. The categories for risk of death or progression were defined as:

Low = 0–1

Intermediate = 2

High = 3–4

Source: Dr. Chang

WASHINGTON — A new preoperative grading system for adult hemispheric low-grade gliomas produced accurate prognoses for disease stage, Dr. Edward F. Chang said at the annual meeting of the American Association of Neurological Surgeons.

“There are few standards for guiding both the medical and surgical management of low-grade gliomas,” said Dr. Chang, a third-year resident in the department of neurologic surgery at the University of California, San Francisco. To construct a system, Dr. Chang reviewed 280 patients who had undergone operations for histologically confirmed grade 2 gliomas (from biopsy to maximal surgical resection) during 1989–2005 at UCSF.

Median patient age was 38 years at presentation. Most (88%) had seizures. A majority had a Karnofsky Performance Scale score of 100 or 90. Most tumors were in the frontal (72%) or temporal lobe (34%); median diameter was 4.5 cm.

In the follow-up period, patients survived for a median of 12 years; 65 died. A total of 134 events of progression or recurrence occurred. The median time of progression-free survival was 6 years.

The investigators used four variables highly predictive of lower survival in their grading. (See box.) The strongest was the presence of tumor in “eloquent” brain regions, particularly the sensorimotor cortex (specifically the pre- and postsensory gyri), perisylvian dominant language areas, insular areas, basal ganglia-internal capsule, thalamus, and hypothalamus. Tumor presence in an area of eloquence was the only significant, independent predictor of progression or recurrence.

The interobserver reliability of the grading system had a kappa value of 0.86 between a neurosurgery resident and an attending neurosurgeon blinded to the outcome of a subset of 200 random cases from the study.

When the study sample was graded, the median survival fell from 16 years for patients with low risk to nearly 11 years for those with intermediate risk and 8 years high risk. The median period of progression-free survival dropped as risk grew.

The researchers also analyzed predictors of the extent of resection. Tumors in an area of eloquence had a diameter greater than 4 cm with diffuse borders on MRI; tumors in the temporal lobe were significantly more likely to be treated with subtotal resection; parietal tumors were significantly more likely to undergo gross total resection.

The grading system currently is undergoing external validation.

Low-Grade Glioma Grading System

▸ Age 50 years or older

▸ Karnofsky Performance Scale score less than 90

▸ Maximum tumor diameter more than 4 cm

▸ Tumor located in “eloquent” area

A “yes” answer is given a score of 1 and a “no,” a score of 0. The categories for risk of death or progression were defined as:

Low = 0–1

Intermediate = 2

High = 3–4

Source: Dr. Chang

CHICAGO — Temozolomide may not be incompatible with immunologic approaches for the treatment of glioblastoma, based on data from a small analysis presented at the annual meeting of the American Society of Clinical Oncology.

Vaccinating patients who have glioblastoma multiforme (GBM) with dendritic cells and either acid-eluted peptides or an antigen-specific peptide has shown promising results in extending patient survival. Likewise, temozolomide (Temodar) has been shown to prolong survival in these patients and has become part of a standard treatment regimen.

However, temozolomide also often induces a profound and long-lasting lymphopenia that could limit immunotherapeutic approaches, such as vaccination.

“This preliminary experience suggests that sequential administration of chemotherapy and immunotherapy may not be deleterious,” wrote Dr. John H. Sampson, who is an associate professor of surgery at Duke University in Durham, N.C., and his colleagues.

This analysis involved patients from two ongoing trials, who are newly diagnosed with GBM, are epidermal growth factor receptor variant III (EGFRvIII)-positive, and have had complete resection.

In the ACTIVATE trial, patients received radiation (approximately 60 Gy) and concurrent temozolomide (50–75 mg/m

Peripheral blood counts were monitored in patients. Grade 2 lymphopenia (less than 800 lymphocytes per mcL of blood) was induced in all patients receiving temozolomide after the first cycle. Grade 3 lymphopenia (less than 500 lymphocytes per mcL of blood) was induced in 70% of patients after the first cycle of temozolomide. However, lymphocyte counts returned to normal after treatment with the drug was stopped.

Regulatory T cells increased from 5% to 12% after the combination of temozolomide and radiation. Cycles of temozolomide do not appear to have diminished EGFRvIII-specific CD3-positive/CD8-positive T cells producing interferon-gamma. EGFRvIII-specific IgG responses were induced and maintained during temozolomide.

Dr. Sampson did not report having any relevant conflicts of interest.

CHICAGO — Temozolomide may not be incompatible with immunologic approaches for the treatment of glioblastoma, based on data from a small analysis presented at the annual meeting of the American Society of Clinical Oncology.

Vaccinating patients who have glioblastoma multiforme (GBM) with dendritic cells and either acid-eluted peptides or an antigen-specific peptide has shown promising results in extending patient survival. Likewise, temozolomide (Temodar) has been shown to prolong survival in these patients and has become part of a standard treatment regimen.

However, temozolomide also often induces a profound and long-lasting lymphopenia that could limit immunotherapeutic approaches, such as vaccination.

“This preliminary experience suggests that sequential administration of chemotherapy and immunotherapy may not be deleterious,” wrote Dr. John H. Sampson, who is an associate professor of surgery at Duke University in Durham, N.C., and his colleagues.

This analysis involved patients from two ongoing trials, who are newly diagnosed with GBM, are epidermal growth factor receptor variant III (EGFRvIII)-positive, and have had complete resection.

In the ACTIVATE trial, patients received radiation (approximately 60 Gy) and concurrent temozolomide (50–75 mg/m

Peripheral blood counts were monitored in patients. Grade 2 lymphopenia (less than 800 lymphocytes per mcL of blood) was induced in all patients receiving temozolomide after the first cycle. Grade 3 lymphopenia (less than 500 lymphocytes per mcL of blood) was induced in 70% of patients after the first cycle of temozolomide. However, lymphocyte counts returned to normal after treatment with the drug was stopped.

Regulatory T cells increased from 5% to 12% after the combination of temozolomide and radiation. Cycles of temozolomide do not appear to have diminished EGFRvIII-specific CD3-positive/CD8-positive T cells producing interferon-gamma. EGFRvIII-specific IgG responses were induced and maintained during temozolomide.

Dr. Sampson did not report having any relevant conflicts of interest.

CHICAGO — Temozolomide may not be incompatible with immunologic approaches for the treatment of glioblastoma, based on data from a small analysis presented at the annual meeting of the American Society of Clinical Oncology.

Vaccinating patients who have glioblastoma multiforme (GBM) with dendritic cells and either acid-eluted peptides or an antigen-specific peptide has shown promising results in extending patient survival. Likewise, temozolomide (Temodar) has been shown to prolong survival in these patients and has become part of a standard treatment regimen.

However, temozolomide also often induces a profound and long-lasting lymphopenia that could limit immunotherapeutic approaches, such as vaccination.

“This preliminary experience suggests that sequential administration of chemotherapy and immunotherapy may not be deleterious,” wrote Dr. John H. Sampson, who is an associate professor of surgery at Duke University in Durham, N.C., and his colleagues.

This analysis involved patients from two ongoing trials, who are newly diagnosed with GBM, are epidermal growth factor receptor variant III (EGFRvIII)-positive, and have had complete resection.

In the ACTIVATE trial, patients received radiation (approximately 60 Gy) and concurrent temozolomide (50–75 mg/m

Peripheral blood counts were monitored in patients. Grade 2 lymphopenia (less than 800 lymphocytes per mcL of blood) was induced in all patients receiving temozolomide after the first cycle. Grade 3 lymphopenia (less than 500 lymphocytes per mcL of blood) was induced in 70% of patients after the first cycle of temozolomide. However, lymphocyte counts returned to normal after treatment with the drug was stopped.

Regulatory T cells increased from 5% to 12% after the combination of temozolomide and radiation. Cycles of temozolomide do not appear to have diminished EGFRvIII-specific CD3-positive/CD8-positive T cells producing interferon-gamma. EGFRvIII-specific IgG responses were induced and maintained during temozolomide.

Dr. Sampson did not report having any relevant conflicts of interest.

CHICAGO — Combining dendritic cell vaccination with imiquimod for the treatment of glioblastoma more than doubled survival in an intervention group compared to a conventionally treated control group in a small phase I trial presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Two-year survival—the primary clinical end point—for 19 patients treated with the dendritic cell vaccines was 68%, and 3-year survival was 43%. In comparison, only 26% of control patients at the University of California, Los Angeles, survived to 2 years, and only 20% survived to 3 years.

To date, the median progression-free survival and median overall survival in the vaccinated group are 18 months and 34 months, respectively. This compared with 7 months and 15 months, respectively, for control patients from the published literature.

Dr. Linda Liau, a neurosurgeon at UCLA, and her colleagues presented immunologic response data for 13 patients with newly diagnosed glioblastoma multiforme (GBM). Patients underwent resection, followed by a 6-week course of radiation and chemotherapy with temozolomide. Two weeks prior to the first immunization, patients underwent MRI. One week before the first immunization, patients underwent leukapheresis and immunologic assays.

The vaccines were composed of autologous dendritic cells that have been pulsed with lysates from GBM tumor cells. Preclinical studies have demonstrated that dendritic cells are preferentially responsible for the sensitization of naive T cells in their first exposure to antigen.

Each patient initially received three vaccinations at 2-week intervals. Four patients received 1 million dendritic cells per immunization; four others received 5 million dendritic cells per immunization, and the remaining five received 10 million dendritic cells per immunization.

Patients without tumor progression subsequently received booster injections every 3 months combined with topical administration of imiquimod, which is a toll-like receptor-7 agonist that enhances both the innate and acquired immune response. Imiquimod (Aldara) is indicated for the treatment of actinic keratosis, superficial basal cell carcinoma, and external genital and perianal warts.

Immunologic responses to tumor antigens were monitored using several methods. Clinical tumor growth was monitored by MRI every 2 months.

The control group consisted of a total of 191 patients with GBM at UCLA, who received standard treatment. The average age of the patients in the vaccinated and control groups was 51 and 49 years, respectively.

“It appears that vaccination approaches in general are very successful,” said Dr. Albert Wong of Stanford University Palo Alto, Calif., who reviewed the poster during a discussion session.

Almost all of the patients had de novo infiltration of T lymphocytes into CNS tumors. In addition, CNS tumors were found to be expressing known tumor-associated antigens. Five patients also had an increase in tumor antigen-specific CD8-positive T cells with vaccination.

The relationship between response to tumor antigens and patient survival was somewhat disappointing. “In my opinion, there was not a strong correlation between the response to these defined tumor antigens and patient response,” Dr. Wong said.

In general there is a need for better surrogate markers to assess immune response. Perhaps the best may be the infiltration of T cells into the tumor, he added.

In terms of safety, no grade 3 or 4 adverse events were reported. The most frequent adverse events were low-grade fever, injection-site itching and pain, and arthralgia and myalgia. Seizures also occurred that were possibly related to the vaccines; however, seizures are also typical in GBM patients.

An important next step is to identify what the true tumor antigens are, in order to better refine the vaccine. Dr. Wong likened the current generation of dendritic cell vaccines to using foxglove to treat “x,” when it would really be better to extract and use the active component, digitalis.

Dr. Liau did not disclose any conflicts of interest. The study was sponsored in part by Northwest Biotherapeutics Inc., which is developing the technology behind the vaccines. A phase II clinical trial, sponsored by Northwest Biotherapeutics Inc., is underway.

CHICAGO — Combining dendritic cell vaccination with imiquimod for the treatment of glioblastoma more than doubled survival in an intervention group compared to a conventionally treated control group in a small phase I trial presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Two-year survival—the primary clinical end point—for 19 patients treated with the dendritic cell vaccines was 68%, and 3-year survival was 43%. In comparison, only 26% of control patients at the University of California, Los Angeles, survived to 2 years, and only 20% survived to 3 years.

To date, the median progression-free survival and median overall survival in the vaccinated group are 18 months and 34 months, respectively. This compared with 7 months and 15 months, respectively, for control patients from the published literature.

Dr. Linda Liau, a neurosurgeon at UCLA, and her colleagues presented immunologic response data for 13 patients with newly diagnosed glioblastoma multiforme (GBM). Patients underwent resection, followed by a 6-week course of radiation and chemotherapy with temozolomide. Two weeks prior to the first immunization, patients underwent MRI. One week before the first immunization, patients underwent leukapheresis and immunologic assays.

The vaccines were composed of autologous dendritic cells that have been pulsed with lysates from GBM tumor cells. Preclinical studies have demonstrated that dendritic cells are preferentially responsible for the sensitization of naive T cells in their first exposure to antigen.

Each patient initially received three vaccinations at 2-week intervals. Four patients received 1 million dendritic cells per immunization; four others received 5 million dendritic cells per immunization, and the remaining five received 10 million dendritic cells per immunization.

Patients without tumor progression subsequently received booster injections every 3 months combined with topical administration of imiquimod, which is a toll-like receptor-7 agonist that enhances both the innate and acquired immune response. Imiquimod (Aldara) is indicated for the treatment of actinic keratosis, superficial basal cell carcinoma, and external genital and perianal warts.

Immunologic responses to tumor antigens were monitored using several methods. Clinical tumor growth was monitored by MRI every 2 months.

The control group consisted of a total of 191 patients with GBM at UCLA, who received standard treatment. The average age of the patients in the vaccinated and control groups was 51 and 49 years, respectively.

“It appears that vaccination approaches in general are very successful,” said Dr. Albert Wong of Stanford University Palo Alto, Calif., who reviewed the poster during a discussion session.

Almost all of the patients had de novo infiltration of T lymphocytes into CNS tumors. In addition, CNS tumors were found to be expressing known tumor-associated antigens. Five patients also had an increase in tumor antigen-specific CD8-positive T cells with vaccination.

The relationship between response to tumor antigens and patient survival was somewhat disappointing. “In my opinion, there was not a strong correlation between the response to these defined tumor antigens and patient response,” Dr. Wong said.

In general there is a need for better surrogate markers to assess immune response. Perhaps the best may be the infiltration of T cells into the tumor, he added.

In terms of safety, no grade 3 or 4 adverse events were reported. The most frequent adverse events were low-grade fever, injection-site itching and pain, and arthralgia and myalgia. Seizures also occurred that were possibly related to the vaccines; however, seizures are also typical in GBM patients.

An important next step is to identify what the true tumor antigens are, in order to better refine the vaccine. Dr. Wong likened the current generation of dendritic cell vaccines to using foxglove to treat “x,” when it would really be better to extract and use the active component, digitalis.

Dr. Liau did not disclose any conflicts of interest. The study was sponsored in part by Northwest Biotherapeutics Inc., which is developing the technology behind the vaccines. A phase II clinical trial, sponsored by Northwest Biotherapeutics Inc., is underway.

CHICAGO — Combining dendritic cell vaccination with imiquimod for the treatment of glioblastoma more than doubled survival in an intervention group compared to a conventionally treated control group in a small phase I trial presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Two-year survival—the primary clinical end point—for 19 patients treated with the dendritic cell vaccines was 68%, and 3-year survival was 43%. In comparison, only 26% of control patients at the University of California, Los Angeles, survived to 2 years, and only 20% survived to 3 years.

To date, the median progression-free survival and median overall survival in the vaccinated group are 18 months and 34 months, respectively. This compared with 7 months and 15 months, respectively, for control patients from the published literature.

Dr. Linda Liau, a neurosurgeon at UCLA, and her colleagues presented immunologic response data for 13 patients with newly diagnosed glioblastoma multiforme (GBM). Patients underwent resection, followed by a 6-week course of radiation and chemotherapy with temozolomide. Two weeks prior to the first immunization, patients underwent MRI. One week before the first immunization, patients underwent leukapheresis and immunologic assays.

The vaccines were composed of autologous dendritic cells that have been pulsed with lysates from GBM tumor cells. Preclinical studies have demonstrated that dendritic cells are preferentially responsible for the sensitization of naive T cells in their first exposure to antigen.

Each patient initially received three vaccinations at 2-week intervals. Four patients received 1 million dendritic cells per immunization; four others received 5 million dendritic cells per immunization, and the remaining five received 10 million dendritic cells per immunization.

Patients without tumor progression subsequently received booster injections every 3 months combined with topical administration of imiquimod, which is a toll-like receptor-7 agonist that enhances both the innate and acquired immune response. Imiquimod (Aldara) is indicated for the treatment of actinic keratosis, superficial basal cell carcinoma, and external genital and perianal warts.

Immunologic responses to tumor antigens were monitored using several methods. Clinical tumor growth was monitored by MRI every 2 months.

The control group consisted of a total of 191 patients with GBM at UCLA, who received standard treatment. The average age of the patients in the vaccinated and control groups was 51 and 49 years, respectively.

“It appears that vaccination approaches in general are very successful,” said Dr. Albert Wong of Stanford University Palo Alto, Calif., who reviewed the poster during a discussion session.

Almost all of the patients had de novo infiltration of T lymphocytes into CNS tumors. In addition, CNS tumors were found to be expressing known tumor-associated antigens. Five patients also had an increase in tumor antigen-specific CD8-positive T cells with vaccination.

The relationship between response to tumor antigens and patient survival was somewhat disappointing. “In my opinion, there was not a strong correlation between the response to these defined tumor antigens and patient response,” Dr. Wong said.

In general there is a need for better surrogate markers to assess immune response. Perhaps the best may be the infiltration of T cells into the tumor, he added.

In terms of safety, no grade 3 or 4 adverse events were reported. The most frequent adverse events were low-grade fever, injection-site itching and pain, and arthralgia and myalgia. Seizures also occurred that were possibly related to the vaccines; however, seizures are also typical in GBM patients.

An important next step is to identify what the true tumor antigens are, in order to better refine the vaccine. Dr. Wong likened the current generation of dendritic cell vaccines to using foxglove to treat “x,” when it would really be better to extract and use the active component, digitalis.

Dr. Liau did not disclose any conflicts of interest. The study was sponsored in part by Northwest Biotherapeutics Inc., which is developing the technology behind the vaccines. A phase II clinical trial, sponsored by Northwest Biotherapeutics Inc., is underway.

CHICAGO — Measurement of cerebral blood flow volume in a patient with glioma is a sensitive predictor of disease stability or progression, according to Dr. Meng Law, who presented his findings at the annual meeting of the American Society of Neuroradiology.

Using dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI), Dr. Law found that gliomas with a high relative cerebral blood volume (rCBV) showed significantly more rapid time to progression than did gliomas with a low rCBV. This information gained at the time of diagnosis can impact treatment decisions, including the extent of neurosurgical resection, or the choice of postoperative radiation or chemotherapy protocols.

This 10-year, retrospective study included 189 patients with histologically proved gliomas: low-grade astrocytomas (28), low-grade oligodendrogliomas (14), low-grade oligoastrocytomas (11), anaplastic astrocytomas (72), anaplastic oligoastrocytomas (12), and glioblastoma multiforme (52).

Patients underwent DSC-MRI, and measurements of rCBV were obtained by choosing the highest regional intratumoral rCBV after excluding large intratumoral vessels. Patients were followed up clinically and with MRI (median follow-up 3.2 years).

Dr. Law, currently of Mount Sinai Medical Center, New York, conducted this research while on the faculty of New York University.

Patients who progressed had a mean rCBV of 4.84 (n=130) and for patients who died the mean value was 3.82 (n=36), values that were much higher than in those who showed a complete response (1.41, n=4) or who had stable disease (2.36, n=41). P values from logistic regression demonstrated that age and rCBV were significant predictors of disease progression and death.

Patients with higher rCBV scores showed more rapid time to progression (TTP), as seen in the image, below. Those patients with an rCBV greater than 1.75 had a mean TTP of 265 days, compared with 3,585 days for those with an rCBV less than 1.75.

These values were derived from Kaplan-Meier Progression Free Survival curves. The 1.75 threshold for rCBV has a sensitivity of about 90% for distinguishing low-grade from high-grade tumors, said Dr. Law.

DSC-MRI is a technique that can provide physiologic information about vascular endothelial proliferation, vascular density, and angiogenesis. Since vascular proliferation is an important factor in the biology of gliomas, Dr. Law said, it is not surprising that DSC-MRI can provide an accurate means of characterizing tumor biology.

According to Dr. Law, while histopathology is the standard reference for determining glioma tumor biology and making prognostic decisions, histopathology has significant limitations. These include sampling errors, inter- and intraobserver variability, and dynamic changes as the tumor progresses.

Since patients with misclassified gliomas may not receive optimum treatment, Dr. Law suggested that measuring cerebral blood volume may be as sensitive, or even more sensitive, a predictor than pathology when assessing glioma outcomes.

He is investigating this further in a multicenter study using perfusion in predicting patient outcome; the study is being funded by the nonprofit Accelerate Brain Cancer Cure in Washington.

Imaging shows disease progression over a 6-month period in a man with a pathology-proven low-grade astrocytoma but a high baseline relative cerebral blood volume (rCBV). Dr. Law said that while histopathology is the standard reference for determining glioma biology and making prognostic decisions, it has limitations. Images courtesy Dr. Meng Law

CHICAGO — Measurement of cerebral blood flow volume in a patient with glioma is a sensitive predictor of disease stability or progression, according to Dr. Meng Law, who presented his findings at the annual meeting of the American Society of Neuroradiology.

Using dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI), Dr. Law found that gliomas with a high relative cerebral blood volume (rCBV) showed significantly more rapid time to progression than did gliomas with a low rCBV. This information gained at the time of diagnosis can impact treatment decisions, including the extent of neurosurgical resection, or the choice of postoperative radiation or chemotherapy protocols.

This 10-year, retrospective study included 189 patients with histologically proved gliomas: low-grade astrocytomas (28), low-grade oligodendrogliomas (14), low-grade oligoastrocytomas (11), anaplastic astrocytomas (72), anaplastic oligoastrocytomas (12), and glioblastoma multiforme (52).

Patients underwent DSC-MRI, and measurements of rCBV were obtained by choosing the highest regional intratumoral rCBV after excluding large intratumoral vessels. Patients were followed up clinically and with MRI (median follow-up 3.2 years).

Dr. Law, currently of Mount Sinai Medical Center, New York, conducted this research while on the faculty of New York University.

Patients who progressed had a mean rCBV of 4.84 (n=130) and for patients who died the mean value was 3.82 (n=36), values that were much higher than in those who showed a complete response (1.41, n=4) or who had stable disease (2.36, n=41). P values from logistic regression demonstrated that age and rCBV were significant predictors of disease progression and death.

Patients with higher rCBV scores showed more rapid time to progression (TTP), as seen in the image, below. Those patients with an rCBV greater than 1.75 had a mean TTP of 265 days, compared with 3,585 days for those with an rCBV less than 1.75.

These values were derived from Kaplan-Meier Progression Free Survival curves. The 1.75 threshold for rCBV has a sensitivity of about 90% for distinguishing low-grade from high-grade tumors, said Dr. Law.

DSC-MRI is a technique that can provide physiologic information about vascular endothelial proliferation, vascular density, and angiogenesis. Since vascular proliferation is an important factor in the biology of gliomas, Dr. Law said, it is not surprising that DSC-MRI can provide an accurate means of characterizing tumor biology.

According to Dr. Law, while histopathology is the standard reference for determining glioma tumor biology and making prognostic decisions, histopathology has significant limitations. These include sampling errors, inter- and intraobserver variability, and dynamic changes as the tumor progresses.

Since patients with misclassified gliomas may not receive optimum treatment, Dr. Law suggested that measuring cerebral blood volume may be as sensitive, or even more sensitive, a predictor than pathology when assessing glioma outcomes.

He is investigating this further in a multicenter study using perfusion in predicting patient outcome; the study is being funded by the nonprofit Accelerate Brain Cancer Cure in Washington.

Imaging shows disease progression over a 6-month period in a man with a pathology-proven low-grade astrocytoma but a high baseline relative cerebral blood volume (rCBV). Dr. Law said that while histopathology is the standard reference for determining glioma biology and making prognostic decisions, it has limitations. Images courtesy Dr. Meng Law

CHICAGO — Measurement of cerebral blood flow volume in a patient with glioma is a sensitive predictor of disease stability or progression, according to Dr. Meng Law, who presented his findings at the annual meeting of the American Society of Neuroradiology.

Using dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI), Dr. Law found that gliomas with a high relative cerebral blood volume (rCBV) showed significantly more rapid time to progression than did gliomas with a low rCBV. This information gained at the time of diagnosis can impact treatment decisions, including the extent of neurosurgical resection, or the choice of postoperative radiation or chemotherapy protocols.

This 10-year, retrospective study included 189 patients with histologically proved gliomas: low-grade astrocytomas (28), low-grade oligodendrogliomas (14), low-grade oligoastrocytomas (11), anaplastic astrocytomas (72), anaplastic oligoastrocytomas (12), and glioblastoma multiforme (52).

Patients underwent DSC-MRI, and measurements of rCBV were obtained by choosing the highest regional intratumoral rCBV after excluding large intratumoral vessels. Patients were followed up clinically and with MRI (median follow-up 3.2 years).

Dr. Law, currently of Mount Sinai Medical Center, New York, conducted this research while on the faculty of New York University.

Patients who progressed had a mean rCBV of 4.84 (n=130) and for patients who died the mean value was 3.82 (n=36), values that were much higher than in those who showed a complete response (1.41, n=4) or who had stable disease (2.36, n=41). P values from logistic regression demonstrated that age and rCBV were significant predictors of disease progression and death.

Patients with higher rCBV scores showed more rapid time to progression (TTP), as seen in the image, below. Those patients with an rCBV greater than 1.75 had a mean TTP of 265 days, compared with 3,585 days for those with an rCBV less than 1.75.

These values were derived from Kaplan-Meier Progression Free Survival curves. The 1.75 threshold for rCBV has a sensitivity of about 90% for distinguishing low-grade from high-grade tumors, said Dr. Law.

DSC-MRI is a technique that can provide physiologic information about vascular endothelial proliferation, vascular density, and angiogenesis. Since vascular proliferation is an important factor in the biology of gliomas, Dr. Law said, it is not surprising that DSC-MRI can provide an accurate means of characterizing tumor biology.

According to Dr. Law, while histopathology is the standard reference for determining glioma tumor biology and making prognostic decisions, histopathology has significant limitations. These include sampling errors, inter- and intraobserver variability, and dynamic changes as the tumor progresses.

Since patients with misclassified gliomas may not receive optimum treatment, Dr. Law suggested that measuring cerebral blood volume may be as sensitive, or even more sensitive, a predictor than pathology when assessing glioma outcomes.

He is investigating this further in a multicenter study using perfusion in predicting patient outcome; the study is being funded by the nonprofit Accelerate Brain Cancer Cure in Washington.

Imaging shows disease progression over a 6-month period in a man with a pathology-proven low-grade astrocytoma but a high baseline relative cerebral blood volume (rCBV). Dr. Law said that while histopathology is the standard reference for determining glioma biology and making prognostic decisions, it has limitations. Images courtesy Dr. Meng Law

Cancer Monthly publishes information about the side effects of hundreds of cancer treatments and is designed to help patients and their families make informed decisions about brain tumors as well as other types of cancer. This online resource lets patients see survival rates for each type of cancer as well as quality of life measures for different cancer therapies. It offers physicians' contact information and a list of 260 hospitals where new therapies have been performed. It also provides patients with access to cancer news, clinical trials, medical scientific reports, and alternative and integrative approaches. For additional information, visit the Cancer Monthly Web site at www.cancermonthly.com

Cancer Monthly publishes information about the side effects of hundreds of cancer treatments and is designed to help patients and their families make informed decisions about brain tumors as well as other types of cancer. This online resource lets patients see survival rates for each type of cancer as well as quality of life measures for different cancer therapies. It offers physicians' contact information and a list of 260 hospitals where new therapies have been performed. It also provides patients with access to cancer news, clinical trials, medical scientific reports, and alternative and integrative approaches. For additional information, visit the Cancer Monthly Web site at www.cancermonthly.com

Cancer Monthly publishes information about the side effects of hundreds of cancer treatments and is designed to help patients and their families make informed decisions about brain tumors as well as other types of cancer. This online resource lets patients see survival rates for each type of cancer as well as quality of life measures for different cancer therapies. It offers physicians' contact information and a list of 260 hospitals where new therapies have been performed. It also provides patients with access to cancer news, clinical trials, medical scientific reports, and alternative and integrative approaches. For additional information, visit the Cancer Monthly Web site at www.cancermonthly.com

A new guidebook directed at cancer patients and their families contains lists of the nation's top treatment facilities and medical specialists for different cancers, plus financial tips, drug trial information, and success stories. Entitled: “Patient Resource: A Cancer Treatment and Facilities Guide for Patients and Their Families,” the book is to physicians and costs patients $6.95 when bought online at www.patientresource.net/place-order.htm

A new guidebook directed at cancer patients and their families contains lists of the nation's top treatment facilities and medical specialists for different cancers, plus financial tips, drug trial information, and success stories. Entitled: “Patient Resource: A Cancer Treatment and Facilities Guide for Patients and Their Families,” the book is to physicians and costs patients $6.95 when bought online at www.patientresource.net/place-order.htm

A new guidebook directed at cancer patients and their families contains lists of the nation's top treatment facilities and medical specialists for different cancers, plus financial tips, drug trial information, and success stories. Entitled: “Patient Resource: A Cancer Treatment and Facilities Guide for Patients and Their Families,” the book is to physicians and costs patients $6.95 when bought online at www.patientresource.net/place-order.htm

SALT LAKE CITY — The unique challenges of providing palliative care to patients with lethal brain tumors can best be met by anticipating and preparing for functional decline and working with a pharmacist and neurologist to optimize the use of steroid and antiseizure medications, according to joint presentations at the annual meeting of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association.

Gliomas account for three-quarters of all malignant brain tumors, and half of all gliomas are glioblastomas, which have a 5-year survival rate of 3%, said Dr. Michael E. Salacz, a medical oncologist and board-certified palliative care physician at St. Luke's Cancer Institute in Kansas City, Mo.

Three-quarters of patients with metastatic brain tumors (which outnumber primary brain tumors 10 to 1) die from systemic disease progression and not from brain progression, he explained.

“We're making some preliminary inroads on the treatment of these tumors, but unfortunately what's more common is surgical resection and cancer resurgence,” he said, adding that management of seizures is a crucial part of palliative care in such cases.

“About half of these patients are going to have seizures as their initial presenting symptom, and the other half are going to have seizures sometime during the course of treatment,” Dr. Salacz said.

While traditional antiepileptic drugs such as Dilantin, Depakote, and Tegretol reduce the risk of subsequent seizures, they do not prevent initial seizures, he said, pointing to American Academy of Neurology Guidelines, which state that patients who have not had a seizure after surgery should not be on an antiseizure medication.

“The reality is that over half of physicians use antiepileptic drugs prophylactically. Even though the data show no benefit, many patients will come to palliative care and hospice with seizure prophylaxis. Neurosurgeons have been trained to give Dilantin. As a result, any patient who has had a craniotomy is on Dilantin, and a good portion of these patients are going to have side effects and toxicity as a result of these drugs,” Dr. Salacz said, adding that palliative care doctors treating brain tumor patients who no longer take anything by mouth and have no intravenous line must decide how and whether to give antiepileptic drugs.

“This is a common dilemma in this patient population because the alternative routes of dosing have relatively little data to support them. What I can tell you is that I used transdermal phenobarbital in an advanced patient who would not tolerate oral medications and had a history of seizure disorder,” Dr. Salacz said, adding that after application of the topical paste, the patient was seizure free for his remaining 2 weeks of life.

“While there are no data on use of transdermal phenobarbital, we do know how much of each milligram applied to the skin will get into the bloodstream,” he said.

Short-term corticosteroids, though they have no antitumor effect, can be beneficial at reducing symptoms caused by peritumoral edema.

However, steroids may produce gastrointestinal toxicity, steroid myopathy and, occasionally, lymphopenia or Pneumocystis carinii pneumonia, said Dr. Salacz.

Describing the use of dexamethasone as more art than science, Dr. Salacz said, “There are no magic doses when you're using dexamethasone to reduce brain edema. Oral absorption is rapid and excellent, so you don't need to do [intravenous] steroids when you have an oral rate that you can use.”

Dexamethasone is given every 6 hours, which requires that the patient be awakened at 2 a.m. to take his medication. Dr. Salacz uses a loading dose, though he conceded that doing so is not supported by research data.

“The half-life of dexamethasone is 36–50 hours and pharmacologically it takes about five half-lives for the drug to be out of your system, so the dose I give the patient is going to be gone 7–10 days later,” he said, adding that dexamethasone can be given daily or twice a day.

Steroid-induced insomnia can be minimized by dosing at 8 a.m. and 4 p.m., Dr. Salacz said, adding that neurologic changes follow 1–4 days after a dexamethasone dose change, which can be confusing to a patient on a steroid taper who suddenly develops symptoms.

Cognitive dysfunction occurs in half to three-quarters of brain tumor patients secondary to the disease or to treatment, and has been shown to predict radiographic progression and worse survival.

Although many trials use the Mini-Mental Status Exam (MMSE), Dr. Salacz said that by the time cognitive dysfunction shows up on this screening test, it already has become significant. An alternative is neuropsychiatric testing, which is not widely available or covered by Medicaid. “So I'm stuck trying to help these patients as best as I can out of our clinic,” he said.

Palliative care for brain tumor patients at the end of life also is preventive medicine that involves anticipating and getting the jump on functional decline, said Dr. Christian T. Sinclair, a palliative care and hospice physician.

“Our job is to maximize benefits for the patient and family by discussing alternative services that are available and getting physical or occupational therapy involved early to strengthen the patient as much as possible,” said Dr. Sinclair, with Kansas City Hospice and Palliative Care. Although little can be done to slow functional decline, supplementing a corticosteroid with short-term methyl-phenidate can help increase energy and help cognition, he said.

“Start methylphenidate at 5 mg in the morning and 5 mg at noon. You'll know within a day if it works. If it does, go to 10 mg b.i.d. and top out at 30 mg a day. If the patient gets jittery and anxious, you may want to discontinue the drug,” he said.

Dr. Sinclair's “simple medication regimen at the end of life” was presented as an example: Dexamethasone 4 mg by mouth b.i.d., valproic acid 500 mg by mouth b.i.d., subcutaneous Lovenox daily, morphine ER 15 mg by mouth b.i.d., and morphine 5 mg by mouth every 2 hours p.r.n. for pain. And, he emphasized, some of these doses exceed FDA's normal dosage recommendations, therefore always use the lowest effective dose.

Anticipating functional decline is the goal care for a brain tumor patient at the end of life. DR. SINCLAIR

SALT LAKE CITY — The unique challenges of providing palliative care to patients with lethal brain tumors can best be met by anticipating and preparing for functional decline and working with a pharmacist and neurologist to optimize the use of steroid and antiseizure medications, according to joint presentations at the annual meeting of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association.

Gliomas account for three-quarters of all malignant brain tumors, and half of all gliomas are glioblastomas, which have a 5-year survival rate of 3%, said Dr. Michael E. Salacz, a medical oncologist and board-certified palliative care physician at St. Luke's Cancer Institute in Kansas City, Mo.

Three-quarters of patients with metastatic brain tumors (which outnumber primary brain tumors 10 to 1) die from systemic disease progression and not from brain progression, he explained.

“We're making some preliminary inroads on the treatment of these tumors, but unfortunately what's more common is surgical resection and cancer resurgence,” he said, adding that management of seizures is a crucial part of palliative care in such cases.

“About half of these patients are going to have seizures as their initial presenting symptom, and the other half are going to have seizures sometime during the course of treatment,” Dr. Salacz said.

While traditional antiepileptic drugs such as Dilantin, Depakote, and Tegretol reduce the risk of subsequent seizures, they do not prevent initial seizures, he said, pointing to American Academy of Neurology Guidelines, which state that patients who have not had a seizure after surgery should not be on an antiseizure medication.

“The reality is that over half of physicians use antiepileptic drugs prophylactically. Even though the data show no benefit, many patients will come to palliative care and hospice with seizure prophylaxis. Neurosurgeons have been trained to give Dilantin. As a result, any patient who has had a craniotomy is on Dilantin, and a good portion of these patients are going to have side effects and toxicity as a result of these drugs,” Dr. Salacz said, adding that palliative care doctors treating brain tumor patients who no longer take anything by mouth and have no intravenous line must decide how and whether to give antiepileptic drugs.

“This is a common dilemma in this patient population because the alternative routes of dosing have relatively little data to support them. What I can tell you is that I used transdermal phenobarbital in an advanced patient who would not tolerate oral medications and had a history of seizure disorder,” Dr. Salacz said, adding that after application of the topical paste, the patient was seizure free for his remaining 2 weeks of life.

“While there are no data on use of transdermal phenobarbital, we do know how much of each milligram applied to the skin will get into the bloodstream,” he said.

Short-term corticosteroids, though they have no antitumor effect, can be beneficial at reducing symptoms caused by peritumoral edema.

However, steroids may produce gastrointestinal toxicity, steroid myopathy and, occasionally, lymphopenia or Pneumocystis carinii pneumonia, said Dr. Salacz.

Describing the use of dexamethasone as more art than science, Dr. Salacz said, “There are no magic doses when you're using dexamethasone to reduce brain edema. Oral absorption is rapid and excellent, so you don't need to do [intravenous] steroids when you have an oral rate that you can use.”

Dexamethasone is given every 6 hours, which requires that the patient be awakened at 2 a.m. to take his medication. Dr. Salacz uses a loading dose, though he conceded that doing so is not supported by research data.

“The half-life of dexamethasone is 36–50 hours and pharmacologically it takes about five half-lives for the drug to be out of your system, so the dose I give the patient is going to be gone 7–10 days later,” he said, adding that dexamethasone can be given daily or twice a day.

Steroid-induced insomnia can be minimized by dosing at 8 a.m. and 4 p.m., Dr. Salacz said, adding that neurologic changes follow 1–4 days after a dexamethasone dose change, which can be confusing to a patient on a steroid taper who suddenly develops symptoms.

Cognitive dysfunction occurs in half to three-quarters of brain tumor patients secondary to the disease or to treatment, and has been shown to predict radiographic progression and worse survival.

Although many trials use the Mini-Mental Status Exam (MMSE), Dr. Salacz said that by the time cognitive dysfunction shows up on this screening test, it already has become significant. An alternative is neuropsychiatric testing, which is not widely available or covered by Medicaid. “So I'm stuck trying to help these patients as best as I can out of our clinic,” he said.

Palliative care for brain tumor patients at the end of life also is preventive medicine that involves anticipating and getting the jump on functional decline, said Dr. Christian T. Sinclair, a palliative care and hospice physician.

“Our job is to maximize benefits for the patient and family by discussing alternative services that are available and getting physical or occupational therapy involved early to strengthen the patient as much as possible,” said Dr. Sinclair, with Kansas City Hospice and Palliative Care. Although little can be done to slow functional decline, supplementing a corticosteroid with short-term methyl-phenidate can help increase energy and help cognition, he said.

“Start methylphenidate at 5 mg in the morning and 5 mg at noon. You'll know within a day if it works. If it does, go to 10 mg b.i.d. and top out at 30 mg a day. If the patient gets jittery and anxious, you may want to discontinue the drug,” he said.

Dr. Sinclair's “simple medication regimen at the end of life” was presented as an example: Dexamethasone 4 mg by mouth b.i.d., valproic acid 500 mg by mouth b.i.d., subcutaneous Lovenox daily, morphine ER 15 mg by mouth b.i.d., and morphine 5 mg by mouth every 2 hours p.r.n. for pain. And, he emphasized, some of these doses exceed FDA's normal dosage recommendations, therefore always use the lowest effective dose.

Anticipating functional decline is the goal care for a brain tumor patient at the end of life. DR. SINCLAIR

SALT LAKE CITY — The unique challenges of providing palliative care to patients with lethal brain tumors can best be met by anticipating and preparing for functional decline and working with a pharmacist and neurologist to optimize the use of steroid and antiseizure medications, according to joint presentations at the annual meeting of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association.

Gliomas account for three-quarters of all malignant brain tumors, and half of all gliomas are glioblastomas, which have a 5-year survival rate of 3%, said Dr. Michael E. Salacz, a medical oncologist and board-certified palliative care physician at St. Luke's Cancer Institute in Kansas City, Mo.

Three-quarters of patients with metastatic brain tumors (which outnumber primary brain tumors 10 to 1) die from systemic disease progression and not from brain progression, he explained.

“We're making some preliminary inroads on the treatment of these tumors, but unfortunately what's more common is surgical resection and cancer resurgence,” he said, adding that management of seizures is a crucial part of palliative care in such cases.

“About half of these patients are going to have seizures as their initial presenting symptom, and the other half are going to have seizures sometime during the course of treatment,” Dr. Salacz said.

While traditional antiepileptic drugs such as Dilantin, Depakote, and Tegretol reduce the risk of subsequent seizures, they do not prevent initial seizures, he said, pointing to American Academy of Neurology Guidelines, which state that patients who have not had a seizure after surgery should not be on an antiseizure medication.

“The reality is that over half of physicians use antiepileptic drugs prophylactically. Even though the data show no benefit, many patients will come to palliative care and hospice with seizure prophylaxis. Neurosurgeons have been trained to give Dilantin. As a result, any patient who has had a craniotomy is on Dilantin, and a good portion of these patients are going to have side effects and toxicity as a result of these drugs,” Dr. Salacz said, adding that palliative care doctors treating brain tumor patients who no longer take anything by mouth and have no intravenous line must decide how and whether to give antiepileptic drugs.

“This is a common dilemma in this patient population because the alternative routes of dosing have relatively little data to support them. What I can tell you is that I used transdermal phenobarbital in an advanced patient who would not tolerate oral medications and had a history of seizure disorder,” Dr. Salacz said, adding that after application of the topical paste, the patient was seizure free for his remaining 2 weeks of life.

“While there are no data on use of transdermal phenobarbital, we do know how much of each milligram applied to the skin will get into the bloodstream,” he said.

Short-term corticosteroids, though they have no antitumor effect, can be beneficial at reducing symptoms caused by peritumoral edema.

However, steroids may produce gastrointestinal toxicity, steroid myopathy and, occasionally, lymphopenia or Pneumocystis carinii pneumonia, said Dr. Salacz.

Describing the use of dexamethasone as more art than science, Dr. Salacz said, “There are no magic doses when you're using dexamethasone to reduce brain edema. Oral absorption is rapid and excellent, so you don't need to do [intravenous] steroids when you have an oral rate that you can use.”

Dexamethasone is given every 6 hours, which requires that the patient be awakened at 2 a.m. to take his medication. Dr. Salacz uses a loading dose, though he conceded that doing so is not supported by research data.

“The half-life of dexamethasone is 36–50 hours and pharmacologically it takes about five half-lives for the drug to be out of your system, so the dose I give the patient is going to be gone 7–10 days later,” he said, adding that dexamethasone can be given daily or twice a day.

Steroid-induced insomnia can be minimized by dosing at 8 a.m. and 4 p.m., Dr. Salacz said, adding that neurologic changes follow 1–4 days after a dexamethasone dose change, which can be confusing to a patient on a steroid taper who suddenly develops symptoms.

Cognitive dysfunction occurs in half to three-quarters of brain tumor patients secondary to the disease or to treatment, and has been shown to predict radiographic progression and worse survival.

Although many trials use the Mini-Mental Status Exam (MMSE), Dr. Salacz said that by the time cognitive dysfunction shows up on this screening test, it already has become significant. An alternative is neuropsychiatric testing, which is not widely available or covered by Medicaid. “So I'm stuck trying to help these patients as best as I can out of our clinic,” he said.

Palliative care for brain tumor patients at the end of life also is preventive medicine that involves anticipating and getting the jump on functional decline, said Dr. Christian T. Sinclair, a palliative care and hospice physician.

“Our job is to maximize benefits for the patient and family by discussing alternative services that are available and getting physical or occupational therapy involved early to strengthen the patient as much as possible,” said Dr. Sinclair, with Kansas City Hospice and Palliative Care. Although little can be done to slow functional decline, supplementing a corticosteroid with short-term methyl-phenidate can help increase energy and help cognition, he said.

“Start methylphenidate at 5 mg in the morning and 5 mg at noon. You'll know within a day if it works. If it does, go to 10 mg b.i.d. and top out at 30 mg a day. If the patient gets jittery and anxious, you may want to discontinue the drug,” he said.

Dr. Sinclair's “simple medication regimen at the end of life” was presented as an example: Dexamethasone 4 mg by mouth b.i.d., valproic acid 500 mg by mouth b.i.d., subcutaneous Lovenox daily, morphine ER 15 mg by mouth b.i.d., and morphine 5 mg by mouth every 2 hours p.r.n. for pain. And, he emphasized, some of these doses exceed FDA's normal dosage recommendations, therefore always use the lowest effective dose.

Anticipating functional decline is the goal care for a brain tumor patient at the end of life. DR. SINCLAIR

Long-term or heavy use of mobile phones does not increase the risk of developing one type of brain tumor, although exclusive long-term use on one side of the head appears to increase the risk slightly.

The case-control study examined mobile phone use among 1,521 glioma patients and 3,301 controls in Denmark, England, Finland, Norway, and Sweden. Mobile phones emit radio waves that some believe play a role in tumor development, although a carcinogenic link has not been established, wrote Anna Lahkola of the Finnish Radiation and Nuclear Safety Authority, Helsinki (Int. J. Cancer 2007 Jan. 17 [Epub doi:10.1002/ijc.22503]).

Researchers conducted interviews with all study participants to identify patterns of mobile phone use among glioma patients and controls. Of the cases, 58% said they had used a mobile phone regularly—at least once weekly for at least 6 months—in the year before diagnosis. A total of 59% of controls reported regular use. Regular mobile phone users had a lower risk of developing gliomas, compared with those who never or seldom used mobile phones (odds ratio 0.78).

Mobile customers who used the phone only on the same side of the head as the location of their tumor had a significantly increased risk of glioma if they started using the phone at least 10 years ago (OR 1.39).

Even among heavy and long-term users, the researchers found no link. “The most exposed group (the highest 10% based on the exposure distribution among controls) did not show an elevated risk of glioma,” they wrote. “Neither did the dose-response analyses reveal a clear trend in relation to the overall duration of mobile phone use, number of calls, or hours of use.” The authors acknowledge that “selection bias may have produced an apparent protective effect of mobile phone use.”

Long-term or heavy use of mobile phones does not increase the risk of developing one type of brain tumor, although exclusive long-term use on one side of the head appears to increase the risk slightly.

The case-control study examined mobile phone use among 1,521 glioma patients and 3,301 controls in Denmark, England, Finland, Norway, and Sweden. Mobile phones emit radio waves that some believe play a role in tumor development, although a carcinogenic link has not been established, wrote Anna Lahkola of the Finnish Radiation and Nuclear Safety Authority, Helsinki (Int. J. Cancer 2007 Jan. 17 [Epub doi:10.1002/ijc.22503]).

Researchers conducted interviews with all study participants to identify patterns of mobile phone use among glioma patients and controls. Of the cases, 58% said they had used a mobile phone regularly—at least once weekly for at least 6 months—in the year before diagnosis. A total of 59% of controls reported regular use. Regular mobile phone users had a lower risk of developing gliomas, compared with those who never or seldom used mobile phones (odds ratio 0.78).

Mobile customers who used the phone only on the same side of the head as the location of their tumor had a significantly increased risk of glioma if they started using the phone at least 10 years ago (OR 1.39).

Even among heavy and long-term users, the researchers found no link. “The most exposed group (the highest 10% based on the exposure distribution among controls) did not show an elevated risk of glioma,” they wrote. “Neither did the dose-response analyses reveal a clear trend in relation to the overall duration of mobile phone use, number of calls, or hours of use.” The authors acknowledge that “selection bias may have produced an apparent protective effect of mobile phone use.”

Long-term or heavy use of mobile phones does not increase the risk of developing one type of brain tumor, although exclusive long-term use on one side of the head appears to increase the risk slightly.

The case-control study examined mobile phone use among 1,521 glioma patients and 3,301 controls in Denmark, England, Finland, Norway, and Sweden. Mobile phones emit radio waves that some believe play a role in tumor development, although a carcinogenic link has not been established, wrote Anna Lahkola of the Finnish Radiation and Nuclear Safety Authority, Helsinki (Int. J. Cancer 2007 Jan. 17 [Epub doi:10.1002/ijc.22503]).

Researchers conducted interviews with all study participants to identify patterns of mobile phone use among glioma patients and controls. Of the cases, 58% said they had used a mobile phone regularly—at least once weekly for at least 6 months—in the year before diagnosis. A total of 59% of controls reported regular use. Regular mobile phone users had a lower risk of developing gliomas, compared with those who never or seldom used mobile phones (odds ratio 0.78).

Mobile customers who used the phone only on the same side of the head as the location of their tumor had a significantly increased risk of glioma if they started using the phone at least 10 years ago (OR 1.39).

Even among heavy and long-term users, the researchers found no link. “The most exposed group (the highest 10% based on the exposure distribution among controls) did not show an elevated risk of glioma,” they wrote. “Neither did the dose-response analyses reveal a clear trend in relation to the overall duration of mobile phone use, number of calls, or hours of use.” The authors acknowledge that “selection bias may have produced an apparent protective effect of mobile phone use.”

MANCHESTER, ENGLAND — A 56-year-old man, who had experienced a skin eruption 6 years earlier and received a diagnosis of early-stage mycosis fungoides, which has a good prognosis, was hospitalized following a car accident and episodes of confusion.

He died 3 weeks later of a T-cell lymphoma involving the central nervous system, Dr. Aoife Lally said at the annual meeting of the British Association of Dermatologists.

Although there have been reports of CNS involvement in mycosis fungoides, it usually occurs in the setting of advanced and histologically transformed cutaneous disease. Isolated CNS involvement in stage 1B mycosis fungoides is “remarkably rare,” said Dr. Lally of the department of dermatology, Oxford (England) Radcliffe Hospitals.

When the patient originally was examined in the dermatology department, his skin findings included annular, erythematous, scaly patches and only a few plaques. There was no scalp or nail involvement and no lymphadenopathy.

Blood count, erythrocyte sedimentation rate, and renal and hepatic profiles were all normal.

The patient did not respond to treatment with potent topical steroids, and relapsed following a course of UVB treatment. Biopsies showed folliculotropic mycosis fungoides. Treatment with photochemotherapy (PUVA) was commenced, and the patient responded well, according to Dr. Lally.

“At no point did he develop lymphadenopathy or systemic symptoms. But 5 years after initial presentation, a nodule appeared on the left ankle,” she said. This responded to radiotherapy, and the skin disease remained quiescent thereafter.

When he was admitted after the car accident, CT scan of the head revealed a frontal tumor. A craniotomy was performed, and histologic analysis confirmed the presence of a T-cell lymphoma.

“T-cell receptor gene analysis on DNA extracted from this tumor showed an identical T-cell clone to that of skin biopsies taken a year earlier,” Dr. Lally said.

Bone marrow examination was normal and staging CT found no nodal or extranodal disease.

The unusual nature of this disease course was echoed in a recent report of 10 cases of CNS involvement in mycosis fungoides. In that series, CNS involvement most commonly appeared within a few years of the initial diagnosis of mycosis fungoides, in the context of active skin disease, and with other visceral involvement (Cancer J. 2006;12:55–62). Stage at diagnosis also was significant: Only one patient had stage 1B disease, with all others having stages 2B or greater. Mean survival following the onset of CNS symptoms in this cohort was approximately 5 months.

The patient's progressive erythematous facial rash was diagnosed as early mycosis fungoides (left). CT image shows frontal T-cell lymphoma that evolved from the MF within 6 years (right). Photos courtesy Dr. Aoife Lally

MANCHESTER, ENGLAND — A 56-year-old man, who had experienced a skin eruption 6 years earlier and received a diagnosis of early-stage mycosis fungoides, which has a good prognosis, was hospitalized following a car accident and episodes of confusion.

He died 3 weeks later of a T-cell lymphoma involving the central nervous system, Dr. Aoife Lally said at the annual meeting of the British Association of Dermatologists.

Although there have been reports of CNS involvement in mycosis fungoides, it usually occurs in the setting of advanced and histologically transformed cutaneous disease. Isolated CNS involvement in stage 1B mycosis fungoides is “remarkably rare,” said Dr. Lally of the department of dermatology, Oxford (England) Radcliffe Hospitals.

When the patient originally was examined in the dermatology department, his skin findings included annular, erythematous, scaly patches and only a few plaques. There was no scalp or nail involvement and no lymphadenopathy.

Blood count, erythrocyte sedimentation rate, and renal and hepatic profiles were all normal.

The patient did not respond to treatment with potent topical steroids, and relapsed following a course of UVB treatment. Biopsies showed folliculotropic mycosis fungoides. Treatment with photochemotherapy (PUVA) was commenced, and the patient responded well, according to Dr. Lally.

“At no point did he develop lymphadenopathy or systemic symptoms. But 5 years after initial presentation, a nodule appeared on the left ankle,” she said. This responded to radiotherapy, and the skin disease remained quiescent thereafter.

When he was admitted after the car accident, CT scan of the head revealed a frontal tumor. A craniotomy was performed, and histologic analysis confirmed the presence of a T-cell lymphoma.

“T-cell receptor gene analysis on DNA extracted from this tumor showed an identical T-cell clone to that of skin biopsies taken a year earlier,” Dr. Lally said.

Bone marrow examination was normal and staging CT found no nodal or extranodal disease.

The unusual nature of this disease course was echoed in a recent report of 10 cases of CNS involvement in mycosis fungoides. In that series, CNS involvement most commonly appeared within a few years of the initial diagnosis of mycosis fungoides, in the context of active skin disease, and with other visceral involvement (Cancer J. 2006;12:55–62). Stage at diagnosis also was significant: Only one patient had stage 1B disease, with all others having stages 2B or greater. Mean survival following the onset of CNS symptoms in this cohort was approximately 5 months.

The patient's progressive erythematous facial rash was diagnosed as early mycosis fungoides (left). CT image shows frontal T-cell lymphoma that evolved from the MF within 6 years (right). Photos courtesy Dr. Aoife Lally

MANCHESTER, ENGLAND — A 56-year-old man, who had experienced a skin eruption 6 years earlier and received a diagnosis of early-stage mycosis fungoides, which has a good prognosis, was hospitalized following a car accident and episodes of confusion.

He died 3 weeks later of a T-cell lymphoma involving the central nervous system, Dr. Aoife Lally said at the annual meeting of the British Association of Dermatologists.

Although there have been reports of CNS involvement in mycosis fungoides, it usually occurs in the setting of advanced and histologically transformed cutaneous disease. Isolated CNS involvement in stage 1B mycosis fungoides is “remarkably rare,” said Dr. Lally of the department of dermatology, Oxford (England) Radcliffe Hospitals.

When the patient originally was examined in the dermatology department, his skin findings included annular, erythematous, scaly patches and only a few plaques. There was no scalp or nail involvement and no lymphadenopathy.

Blood count, erythrocyte sedimentation rate, and renal and hepatic profiles were all normal.

The patient did not respond to treatment with potent topical steroids, and relapsed following a course of UVB treatment. Biopsies showed folliculotropic mycosis fungoides. Treatment with photochemotherapy (PUVA) was commenced, and the patient responded well, according to Dr. Lally.

“At no point did he develop lymphadenopathy or systemic symptoms. But 5 years after initial presentation, a nodule appeared on the left ankle,” she said. This responded to radiotherapy, and the skin disease remained quiescent thereafter.

When he was admitted after the car accident, CT scan of the head revealed a frontal tumor. A craniotomy was performed, and histologic analysis confirmed the presence of a T-cell lymphoma.

“T-cell receptor gene analysis on DNA extracted from this tumor showed an identical T-cell clone to that of skin biopsies taken a year earlier,” Dr. Lally said.

Bone marrow examination was normal and staging CT found no nodal or extranodal disease.

The unusual nature of this disease course was echoed in a recent report of 10 cases of CNS involvement in mycosis fungoides. In that series, CNS involvement most commonly appeared within a few years of the initial diagnosis of mycosis fungoides, in the context of active skin disease, and with other visceral involvement (Cancer J. 2006;12:55–62). Stage at diagnosis also was significant: Only one patient had stage 1B disease, with all others having stages 2B or greater. Mean survival following the onset of CNS symptoms in this cohort was approximately 5 months.

The patient's progressive erythematous facial rash was diagnosed as early mycosis fungoides (left). CT image shows frontal T-cell lymphoma that evolved from the MF within 6 years (right). Photos courtesy Dr. Aoife Lally

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.”