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This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
Incidence and Mortality
Estimated new cases and deaths from brain and other nervous system tumors in the United States in 2015:[1]
Brain tumors account for 85% to 90% of all primary central nervous system (CNS) tumors.[2] Available registry data from the Surveillance, Epidemiology, and End Results (SEER) database for 2007 indicate that the combined incidence of primary invasive CNS tumors in the United States is 6.36 per 100,000 persons per year with an estimated mortality of 4.22 per 100,000 persons per year.[3] Worldwide, approximately 238,000 new cases of brain and other CNS tumors were diagnosed in the year 2008, with an estimated 175,000 deaths.[4] In general, the incidence of primary brain tumors is higher in whites than in blacks, and mortality is higher in males than in females.[2]
Risk Factors
Few definitive observations on environmental or occupational causes of primary CNS tumors have been made.[2] Exposure to vinyl chloride may predispose to the development of glioma. Epstein-Barr virus infection has been implicated in the etiology of primary CNS lymphoma. Transplant recipients and patients with the acquired immunodeficiency syndrome have substantially increased risks for primary CNS lymphoma.[2,5] (Refer to the PDQ summary on Primary CNS Lymphoma Treatment for more information.)
Disease Overview
The glial cell tumors, anaplastic astrocytoma and glioblastoma, account for approximately 38% of primary brain tumors. Since anaplastic astrocytomas represent less than 10% of all CNS gliomas, phase III randomized trials restricted to the anaplastic astrocytomas are not practical. Meningiomas and other mesenchymal tumors account for approximately 27% of primary brain tumors.[2]
Other less-common primary brain tumors include the following in decreasing order of frequency:
Schwannomas, meningiomas, and ependymomas account for up to 79% of primary spinal tumors. Other less common primary spinal tumors include sarcomas, astrocytomas, vascular tumors, and chordomas, in decreasing order of frequency. The familial tumor syndromes (and respective chromosomal abnormalities that are associated with CNS neoplasms) include neurofibromatosis type I (17q11), neurofibromatosis type II (22q12), von Hippel-Lindau disease (3p25-26), tuberous sclerosis (9q34, 16p13), Li-Fraumeni syndrome (17p13), Turcot syndrome type 1 (3p21, 7p22), Turcot syndrome type 2 (5q21), and nevoid basal cell carcinoma syndrome (9q22.3).[6,7]
Clinical Presentation
The clinical presentation of various brain tumors is best appreciated by considering the relationship of signs and symptoms to anatomy.[2] General signs and symptoms include the following:
Whether primary, metastatic, malignant, or benign, brain tumors must be differentiated from other space-occupying lesions such as abscesses, arteriovenous malformations, and infarction, which can have a similar clinical presentation.[8] Other clinical presentations of brain tumors include focal cerebral syndromes such as seizures.[2] Seizures are a presenting symptom in approximately 20% of patients with supratentorial brain tumors and may antedate the clinical diagnosis by months to years in patients with slow-growing tumors. Among all patients with brain tumors, 70% with primary parenchymal tumors and 40% with metastatic brain tumors develop seizures at some time during the clinical course.[9]
Computed tomography (CT) and magnetic resonance imaging (MRI) have complementary roles in the diagnosis of CNS neoplasms.[8,10] The speed of CT is desirable for evaluating clinically unstable patients. CT is superior for detecting calcification, skull lesions, and hyperacute hemorrhage (bleeding less than 24-hours old) and helps direct differential diagnosis as well as immediate management. MRI has superior soft-tissue resolution. MRI can better detect isodense lesions, tumor enhancement, and associated findings such as edema, all phases of hemorrhagic states (except hyperacute), and infarction. High-quality MRI is the diagnostic study of choice in the evaluation of intramedullary and extramedullary spinal cord lesions.[2] In posttherapy imaging, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) may be useful in differentiating tumor recurrence from radiation necrosis.[8]
Biopsy confirmation to corroborate the suspected diagnosis of a primary brain tumor is critical, whether before surgery by needle biopsy or at the time of surgical resection, except in cases in which the clinical and radiologic picture clearly point to a benign tumor. Radiologic patterns may be misleading, and a definitive biopsy is needed to rule out other causes of space-occupying lesions, such as metastatic cancer or infection. CT- or MRI-guided stereotactic techniques can be used to place a needle safely and accurately into all but a very few inaccessible locations within the brain.
CNS abnormalities
Specific genetic or chromosomal abnormalities involving deletions of 1p and 19q have been identified for a subset of oligodendroglial tumors, which have a high response rate to chemotherapy.[2,7,11,12,13,14,15] Other CNS tumors are associated with characteristic patterns of altered oncogenes, altered tumor-suppressor genes, and chromosomal abnormalities. Familial tumor syndromes with defined chromosomal abnormalities are associated with gliomas. (Refer to the Classification section of this summary for more information.)
Metastatic Brain Tumors
Brain metastases outnumber primary neoplasms by at least 10 to 1, and they occur in 20% to 40% of cancer patients.[16] Because no national cancer registry documents brain metastases, the exact incidence is unknown, but it has been estimated that 98,000 to 170,000 new cases are diagnosed in the United States each year.[2,8] This number may be increasing because of the capacity of MRI to detect small metastases and because of prolonged survival resulting from improved systemic therapy.[2,16]
Origins of metastatic brain tumors
The most common primary cancers metastasizing to the brain are lung cancer (50%), breast cancer (15%–20%), unknown primary cancer (10%–15%), melanoma (10%), and colon cancer (5%).[2,16] Eighty percent of brain metastases occur in the cerebral hemispheres, 15% occur in the cerebellum, and 5% occur in the brain stem.[2] Metastases to the brain are multiple in more than 70% of cases, but solitary metastases also occur.[16] Brain involvement can occur with cancers of the nasopharyngeal region by direct extension along the cranial nerves or through the foramina at the base of the skull. Dural metastases may constitute as much as 9% of total CNS metastases.
Primary Brain Tumors
A lesion in the brain should not be assumed to be a metastasis just because a patient has had a previous cancer; such an assumption could result in overlooking appropriate treatment of a curable tumor. Primary brain tumors rarely spread to other areas of the body, but they can spread to other parts of the brain and to the spinal axis.
Clinical Features
The diagnosis of brain metastases in cancer patients is based on the following:
Patients may describe any of the following:
Often, family members or friends may notice the following:
A physical examination may show objective neurological findings or only minor cognitive changes. The presence of multiple lesions and a high predilection of primary tumor metastasis may be sufficient to make the diagnosis of brain metastasis. In the case of a solitary lesion or a questionable relationship to the primary tumor, a brain biopsy (via resection or stereotactic biopsy) may be necessary. CT scans with contrast or MRIs with gadolinium are quite sensitive in diagnosing the presence of metastases. PET scanning and spectroscopic evaluation are new strategies to diagnose cerebral metastases and to differentiate the metastases from other intracranial lesions.[17]
Related Summaries
Other PDQ summaries containing information related to adult and childhood brain cancer include the following:
This classification is based on the World Health Organization (WHO) classification of central nervous system (CNS) tumors.[1] The WHO approach incorporates and interrelates morphology, cytogenetics, molecular genetics, and immunologic markers in an attempt to construct a cellular classification that is universally applicable and prognostically valid. Earlier attempts to develop a TNM-based classification were dropped: tumor size (T) is less relevant than tumor histology and location, nodal status (N) does not apply because the brain and spinal cord have no lymphatics, and metastatic spread (M) rarely applies because most patients with CNS neoplasms do not live long enough to develop metastatic disease.[2]
The WHO grading of CNS tumors establishes a malignancy scale based on histologic features of the tumor.[3] The histologic grades are as follows:
WHO grade I includes lesions with low proliferative potential, a frequently discrete nature, and the possibility of cure following surgical resection alone.
WHO grade II includes lesions that are generally infiltrating and low in mitotic activity but recur more frequently than grade I malignant tumors after local therapy. Some tumor types tend to progress to higher grades of malignancy.
WHO grade III includes lesions with histologic evidence of malignancy, including nuclear atypia and increased mitotic activity. These lesions have anaplastic histology and infiltrative capacity. They are usually treated with aggressive adjuvant therapy.
WHO grade IV includes lesions that are mitotically active, necrosis-prone, and generally associated with a rapid preoperative and postoperative progression and fatal outcomes. The lesions are usually treated with aggressive adjuvant therapy.
The following table is from the WHO Classification of Tumours of the Central Nervous System and lists the tumor types and grades.[4] Tumors limited to the peripheral nervous system are not included. Detailed descriptions of histopathology, grading methods, incidence, and what is known about etiology specific to each tumor type can be found in the WHO classification book.[4]
Radiation therapy and chemotherapy options vary according to histology and anatomic site of the brain tumor. For glioblastoma, combined modality therapy with resection, radiation, and chemotherapy is standard. Since anaplastic astrocytomas, anaplastic oligodendrogliomas, and anaplastic oligoastrocytomas represent only a small proportion of central nervous system gliomas, phase III randomized trials restricted to them are not generally practical. The natural histories of these tumors are variable, depending on histological and molecular factors; therefore, treatment guidelines are evolving. Therapy involving surgically implanted carmustine-impregnated polymer wafers combined with postoperative external-beam radiation therapy (EBRT) may play a role in the treatment of high-grade gliomas (grade III and IV gliomas) in some patients.[1] Specific treatment options for tumor types are listed below under the tumor types and locations. This section covers general treatment principles.
Dexamethasone, mannitol, and furosemide are used to treat the peritumoral edema associated with brain tumors. Use of anticonvulsants is mandatory for patients with seizures.[2]
Finally, active surveillance is appropriate in some circumstances. With the increasing use of sensitive neuroimaging tools, there has been increased detection of asymptomatic low-grade meningiomas. The majority appear to show minimal growth and can often be safely observed, with therapy deferred until the detection of tumor growth or the development of symptoms.[3,4]
For most types of brain tumors in most locations, an attempt at complete or near-complete surgical removal is generally recommended, if possible, within the constraints of preservation of neurologic function and underlying patient health. This recommendation is based on observational evidence that survival is better in patients who undergo tumor resection than in those who have closed biopsy alone.[5,6] However, the benefit of resection has not been tested in randomized trials.
Selection bias can enter into observational studies despite attempts to adjust for patient differences that guide the decision to operate. Therefore, the actual difference in outcome between radical surgery and biopsy alone may not be as large as noted in the retrospective studies.[6] An exception to the general recommendation for attempted resection is the case of deep-seated tumors such as pontine gliomas, which are diagnosed on clinical evidence and treated without initial surgery approximately 50% of the time. In most cases, however, diagnosis by biopsy is preferred. Stereotactic biopsy can be used for lesions that are difficult to reach and resect.
Two primary goals of surgery include:[2]
However, total elimination of primary malignant intraparenchymal tumors by surgery alone is rarely achievable. Therefore, intraoperative techniques have been developed to reach a balance between removing as much tumor as is practical and the preservation of functional status. For example, craniotomies with stereotactic resections of primary gliomas can be done in cooperative patients while they are awake, with real-time assessment of neurologic function.[7] Resection proceeds until either the magnetic resonance imaging (MRI) signal abnormality being used to monitor the extent of surgery is completely removed or subtle neurologic dysfunction appears (e.g., slight decrease in rapid alternating motor movement or anomia). Likewise, when the tumor is located in or near language centers in the cortex, intraoperative language mapping can be performed by electrode discharge-induced speech arrest while the patient is asked to count or read.[8]
As is the case with several other specialized operations [9,10] in which postoperative mortality has been associated with the number of procedures performed, postoperative mortality after surgery for primary brain tumors may be associated with hospital and/or surgeon volume.[11] Using the Nationwide Inpatient Sample hospital discharge database for the years 1988 to 2000, which represented 20% of inpatient admissions to nonfederal U.S. hospitals, investigators found that large-volume hospitals had lower in-hospital mortality rates after craniotomies for primary brain tumors (odds ratio [OR] = 0.75 for a tenfold higher caseload; 95% confidence interval [CI], 0.62–0.90) and after needle biopsies (OR = 0.54; 95% CI, 0.35–0.83). For example, although there was no specific sharp threshold in mortality outcomes between low-volume hospitals and high-volume hospitals, craniotomy-associated in-hospital mortality was 4.5% for hospitals with five or fewer procedures per year and 1.5% for hospitals with at least 42 procedures per year.
In-hospital mortality rates decreased over the study years (perhaps because the proportion of elective nonemergent operations increased from 45% to 57%), but the decrease was more rapid in high-volume hospitals than in low-volume hospitals. High-volume surgeons also had lower in-hospital patient mortality rates after craniotomy (OR= 0.60; 95% CI, 0.45–0.79).[11] As with any study of volume-outcome associations, these results may not be causal because they may be affected by residual confounding factors, such as referral patterns, private insurance, and patient selection, despite multivariable adjustment.
Radiation Therapy
High-grade tumors
Radiation therapy has a major role in the treatment of patients with high-grade gliomas. A systematic review and meta-analysis of five randomized trials (plus one trial with allocation by birth date) comparing postoperative radiation therapy (PORT) with no radiation therapy showed a statistically significant survival advantage with radiation (risk ratio (RR) = 0.81; 95% CI, 0.74–0.88).[12][Level of evidence: 1iiA] Based on a randomized trial comparing 60 Gy (in 30 fractions over 6 weeks) with 45 Gy (in 25 fractions over 4 weeks) that showed superior survival in the first group (12 months vs. 9 months median survival; hazard ratio [HR] = 0.81; 95% CI, 0.66–0.99), 60 Gy is the accepted standard dose of EBRT for malignant gliomas.[13][Level of evidence: 1iiA]
EBRT using either 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy is considered an acceptable technique in radiation therapy delivery. Typically 2- to 3-cm margins on the MRI-based volumes (T1-weighted and FLAIR [fluid-attenuated inversion recovery]) to create the planning target volume are used. Dose escalation using radiosurgery has not improved outcomes.
A randomized trial tested radiosurgery as a boost added to standard EBRT, but the trial found no improvement in survival, quality of life, or patterns of relapse compared with EBRT without the boost.[14,15]
For the same theoretical reasons, brachytherapy has been used to deliver high doses of radiation locally to the tumor while sparing normal brain tissue. However, this approach is technically demanding and has fallen out of favor with the advent of the above-mentioned techniques.
Low-grade tumors
The role of immediate PORT for low-grade gliomas (i.e., low-grade astrocytoma, oligodendroglioma, mixed oligoastrocytomas) is not as clear as in the case of high-grade tumors. The European Organisation for Research and Treatment of Cancer (EORTC) randomly assigned 311 patients with low-grade gliomas to radiation versus observation in the EORTC-22845 and MRC BR04 trials.[16,17] (On central pathology review, about 25% of the patients on the trial were reported to actually have high-grade tumors.) Most of the control patients received radiation at the time of progression. After a median follow-up of 93 months, median progression-free survival was 5.3 years in the radiation arm versus 3.4 years in the control arm (HR = 0.59; 95% CI, 0.45–0.77).[16,17][Level of evidence: 1iiDiii] However, there was no difference in the overall survival (OS) rate (median survival = 7.4 years vs. 7.2 years; HR = 0.97; 95% CI, 0.71–1.34; P = .87).[16,17][Level of evidence: 1iiA] This was caused by a longer survival after progression in the control arm (3.4 years) than in the radiation arm (1.0 years) (P < .0001). The investigators did not collect reliable quality-of-life measurements, so it is not clear whether the delay in initial relapse in the radiation therapy arm translated into improved function or quality of life.
Repeat radiation therapy (re-irradiation)
Because there are no randomized trials, the role of repeat radiation after disease progression or the development of radiation-induced cancers is also ill defined. The literature is limited to small retrospective case series, which makes interpretation difficult.[18] The decision to use repeat radiation must be made carefully because of the risk of neurocognitive deficits and radiation-induced necrosis. One advantage of radiosurgery is the ability to deliver therapeutic doses to recurrences that may require the re-irradiation of previously irradiated brain tissue beyond tolerable dose limits.
Systemic chemotherapy
For many years, the nitrosourea carmustine (BCNU) was the standard chemotherapy added to surgery and radiation for malignant gliomas. This was based upon a randomized trial (RTOG-8302) of 467 patients conducted by the Brain Tumor Study Group that compared four regimens after initial resection, including semustine (methyl-CCNU), radiation therapy, radiation therapy plus carmustine, and radiation therapy plus semustine.[19]
The radiation therapy plus carmustine arm had the best survival rate.[19][Level of evidence: 1iiA] A modest impact on survival using nitrosourea-containing chemotherapy regimens for malignant gliomas was confirmed in a patient-level meta-analysis of 12 randomized trials (combined HR death = 0.85; 95% CI, 0.78–0.91).[20]
However, the oral agent, temozolomide, has since replaced the nitrosoureas as the standard systemic chemotherapy for malignant gliomas based upon a large multicenter trial (NCT00006353) of glioblastoma patients conducted by the EORTC-National Cancer Institute of Canada that showed a survival advantage.[21,22][Level of evidence: 1iiA] (Refer to the Glioblastoma section of the Management of Specific Tumor Types and Locations section of this summary for more information.)
Localized chemotherapy
Because malignant glioma-related deaths are nearly always the result of an inability to control intracranial disease (rather than the result of distant metastases), the concept of delivering high doses of chemotherapy while avoiding systemic toxicity is attractive. A biodegradable carmustine wafer has been developed for that purpose. The wafers contain 3.85% carmustine, and up to eight wafers are implanted into the tumor bed lining at the time of open resection, with an intended total dose of about 7.7 mg per wafer (61.6 mg maximum per patient) over a period of 2 to 3 weeks. Two randomized, placebo-controlled trials of this focal drug-delivery method have shown an OS advantage associated with the carmustine wafers versus radiation therapy alone. Both trials had an upper age limit of 65 years. The first was a small trial closed because of a lack of continued availability of the carmustine wafers after 32 patients with high-grade gliomas had been entered.[23] Although OS was better in the carmustine-wafer group (median 58.1 vs. 39.9 weeks; P = .012), there was an imbalance in the study arms (only 11 of the16 patients in the carmustine-wafer group vs. 16 of the 16 patients in the placebo-wafer group had Grade IV glioblastoma tumors).
The second study was, therefore, more informative.[24,25] It was a multicenter study of 240 patients with primary malignant gliomas, 207 of whom had glioblastoma. At initial surgery, they received the carmustine versus placebo wafers, followed by radiation therapy (55 Gy–60 Gy). Systemic therapy was not allowed until recurrence, except in the case of anaplastic oligodendrogliomas, of which there were nine patients. Unlike the initial trial, patient characteristics were well balanced between the study arms. Median survival in the two groups was 13.8 months versus 11.6 months; P = .017 (HR = 0.73; 95% CI, 0.56–0.96). A systematic review combining both studies estimated a HR for overall mortality of 0.65; 95% CI, 0.48–0.86; P = .003.[26][Level of evidence: 1iA]
Treatment Options Under Clinical Evaluation
Patients who have brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials. Information about ongoing clinical trials is available from the NCI Web site.
Heavy-particle radiation, such as proton-beam therapy, carries the theoretical advantage of delivering high doses of ionizing radiation to the tumor bed while sparing surrounding brain tissue. The data are preliminary for this investigational technique, and are not widely available.
Novel biologic therapies under clinical evaluation for patients with brain tumors include the following:[27]
Primary Tumors of the Spinal Axis
Surgery and radiation therapy are the primary modalities used to treat tumors of the spinal axis; therapeutic options vary according to the histology of the tumor.[2] The experience with chemotherapy for primary spinal cord tumors is limited; no reports of controlled clinical trials are available for these types of tumors.[2,32] Chemotherapy is indicated for most patients with leptomeningeal involvement (from a primary or metastatic tumor) and positive cerebrospinal fluid (CSF) cytology.[2] Most patients require treatment with corticosteroids, particularly if they are receiving radiation therapy.
Patients who have spinal axis tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials. Information about ongoing clinical trials is available from the NCI Web site.
Leptomeningeal carcinomatosis (LC)
The management of LC includes the following:
LC occurs in about 5% of all cancer patients. The most common types include breast tumors (35%), lung tumors (24%), and hematologic malignancies (16%). Diagnosis includes a combination of neurospinal axis imaging and CSF cytology. Median OS is in the range of 10 to 12 weeks.
In a series of 149 patients with metastatic non-small cell lung carcinoma, cytologically proven LC, poor performance status, high protein level in the CSF, and a high initial CSF white blood cell count were significant poor prognostic factors for survival.[33] Patients received active treatment including intrathecal chemotherapy, whole-brain radiation therapy (WBRT), or epidermal growth factor receptor-thymidine kinase-1, or underwent a ventriculoperitoneal shunt procedure.
In a retrospective series of 38 patients with metastatic breast cancer and LC, the proportion of luminal A, B, human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer subtype was 18.4%, 31.6%, 26.3% and 23.7%, respectively.[34] Patients with triple-negative breast cancer had a shorter interval between metastatic breast cancer diagnosis and the development of LC. Median survival did not differ across breast cancer subtypes. Consideration of intrathecal administration of trastuzumab in patients with HER2-positive LC has also been reported in case reports.[35]
Approximately 20% to 40% of cancer patients develop brain metastases, with a subsequent median survival generally less than 6 months. Common primary tumors with brain metastases include the following cancers:
The optimal therapy for patients with brain metastases continues to evolve.[32,36,37] Corticosteroids, anticonvulsants, radiation therapy, radiosurgery, and, possibly, surgical resection have roles in management. Because most cases of brain metastases involve multiple metastases, a mainstay of therapy has historically been WBRT, but stereotactic radiosurgery (SRS) has come into increasingly common use. The role of radiosurgery continues to be defined. Chemotherapy is usually not the primary therapy for most patients; however, it may have a role in the treatment of patients with brain metastases from chemosensitive tumors and can even be curative when combined with radiation for metastatic testicular germ cell tumors.[36,38] Intrathecal chemotherapy is also used for meningeal spread of metastatic tumors.
Treatment for patients with a single metastasis
About 10% to 15% of patients with cancer will have a single brain metastasis. Radiation therapy is the mainstay of palliation for these patients. The extent of extracranial disease can influence treatment of the brain lesions. In the presence of extensive active systemic disease, surgery provides little benefit for OS. In patients with stable minimal extracranial disease, combined modality treatment may be considered, using surgical resection followed by radiation therapy. However, the published literature does not provide clear guidance.
There have been three randomized trials of resection of solitary brain metastases followed by WBRT versus WBRT alone, totaling 195 randomly assigned patients.[39,40,41] The process that necessarily goes into selecting appropriate patients for surgical resection may account for the small numbers in each trial. In the first trial, performed at a single center, all patients were selected and operated upon by one surgeon. The first two trials showed an improvement in survival in the surgery group, but the third showed a trend in favor of the WBRT-only group. The three trials were combined in a trial-level meta-analysis.[26] The combined analysis did not show a statistically significant difference in OS (HR = 0.72; 95% CI, 0.34–1.53; P = .4); nor was there a statistically significant difference in death from neurologic causes (RRdeath = 0.68; 95% CI, 0.43–1.09; P = .11). None of the trials assessed or reported quality of life. One of the trials reported that combined therapy increased the duration of functionally independent survival.[39][Level of evidence: 1iiD]
The need for WBRT after resection of solitary brain metastases has been tested.[42] Patients in the WBRT group were less likely to have tumor progression in the brain and were significantly less likely to die of neurological causes, but OS was the same, and there was no difference in duration of functional independence.[42] One additional randomized study of observation versus WBRT after either surgery or SRS for solitary brain metastases was closed because of slow accrual after 19 patients had been entered, so little can be deduced from the trial.[43] (Refer to the Treatment for patients with oligometastases (1–3 or 4 brain metastases) section of this summary for more information.)
Treatment for patients with oligometastases (1–3 or 4 brain metastases)
A Radiation Therapy Oncology Group (RTOG) study (RTOG-9508) randomly assigned 333 patients with one to three metastases with a maximum diameter of 4 cm to WBRT (37.5 Gy over 3 weeks) with or without a stereotactic boost.[44] Patients with active systemic disease requiring therapy were excluded. The primary endpoint was OS with predefined hypotheses in both the full study population and the 186 patients with a solitary metastasis (and no statistical adjustment of P values for the two separate hypotheses). Mean OS in the combined-therapy and WBRT-alone groups was 5.7 months and 6.5 months, respectively (P = .14). In the subgroup with solitary metastases, OS was better in the combined-therapy group (6.5 months vs. 4.9 months; P =.039 in univariate analysis; P = .053 in a multivariable analysis adjusting for baseline prognostic factors); in patients with multiple metastases, survival was 5.8 months in the combined-therapy group versus 6.7 months in the WBRT-only group (P = .98). (The combined-treatment group had a survival advantage of 2½ months in patients with a single metastasis but not in patients with multiple lesions.) Local control was better in the full population with combined therapy.
At the 6-month follow-up, Karnofsky Performance status (considered a soft endpoint because of its imprecision and subjectivity) was better in the combined-therapy group, but there was no difference in mental status between the treatment groups. Acute and late toxicities were similar in both treatment arms. Quality of life was not assessed.[44][Levels of evidence: 1iiDii for the full study population and 1iiA for patients with solitary metastases]
The converse question has also been addressed—whether WBRT is necessary after focal treatment (i.e., resection or SRS) of oligometastases. Several randomized trials have been performed that were designed with varying primary endpoints.[45,46,47] However, the results can be summarized as follows:
A phase III randomized trial compared adjuvant WBRT with observation after surgery or radiosurgery for a limited number of brain metastases in patients with stable solid tumors.[48] Health-related quality of life was improved in the observation-only arm compared with WBRT. Patients in the observation arm had better mean scores in physical, role, and cognitive functioning at 9 months. In an exploratory analysis, statistically significant worse scores for bladder control, communication deficit, drowsiness, hair loss, motor dysfunction, leg weakness, appetite loss, constipation, nausea/vomiting, pain, and social functioning were observed in patients who underwent WBRT compared with those who underwent observation only.[48][Level of evidence: 1iiC]
The study that had a primary endpoint of learning and neurocognition, using a standardized test for total recall, was stopped by the data and safety monitoring committee because of worse outcomes in the WBRT group.[46]
Given this body of information, focal therapy plus WBRT or focal therapy alone, with close follow-up with serial MRIs and initiation of salvage therapy when clinically indicated, appear to be reasonable treatment options. The pros and cons of each approach should be discussed with the patient.[46][Level of evidence: 1iiD]
Treatment for patients with multiple metastases
Patients with multiple brain metastases may be treated with WBRT. Surgery is indicated to obtain tissue from a metastasis with an unknown primary tumor or to decompress a symptomatic dominant lesion that is causing significant mass effect. SRS in combination with WBRT has been assessed. A meta-analysis of two trials with a total of 358 participants found no statistically significant difference in OS between the WBRT plus SRS and WBRT alone groups (HR, 0.82; 95% CI, 0.65–1.02). Patients in the WBRT plus SRS group had decreased local failure compared with patients who received WBRT alone (HR, 0.27; 95% CI, 0.14–0.52). Unchanged or improved Karnofsky Performance Scale at 6 months was seen in 43% of patients in the combined therapy group versus only 28% in the WBRT group (P = .03).[49][Level of evidence: 1iiDiii]
Brain Stem Gliomas
Standard treatment options:
Patients with brain stem gliomas have relatively poor prognoses that correlate with histology (when biopsies are performed), location, and extent of tumor. The overall median survival time of patients in studies has been 44 to 74 weeks.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult brain stem glioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Pineal Astrocytic Tumors
Depending on the degree of anaplasia, patients with pineal astrocytomas vary in prognoses. Higher grades have worse prognoses.
Pilocytic Astrocytomas
This astrocytic tumor is classified as a World Health Organization (WHO) grade I tumor and is often curable.
Diffuse Astrocytomas (WHO grade II)
This WHO grade II astrocytic tumor is less often curable than is a pilocytic astrocytoma.
Anaplastic Astrocytomas (WHO grade III)
Patients with anaplastic astrocytomas (WHO grade III) have a low cure rate with standard local treatment. Because anaplastic astrocytomas represent less than 10% of all central nervous system gliomas, phase III randomized trials restricted to patients with them are not practical. However, because these tumors are often aggressive, they are frequently managed the same way as glioblastomas, with surgery and radiation, and often with chemotherapy, even though it is not known whether the improved survival with chemotherapy in glioblastoma can be extrapolated to anaplastic astrocytomas.
Postoperative radiation alone has been compared with postoperative chemotherapy alone in patients with anaplastic gliomas (i.e., 144 astrocytomas, 91 oligoastrocytomas, and 39 oligodendrogliomas) with crossover to the other modality at the time of tumor progression. Of the 139 patients randomly assigned to radiation therapy, 135 were randomly assigned to chemotherapy with a 32-week course of either procarbazine + lomustine + vincristine (PCV) or single-agent temozolomide (2:1:1 randomization). The order of the modalities did not affect time to treatment failure (TTF) or overall survival (OS).[2][Levels of evidence: 1iiA and 1iiD] Neither TTF nor OS differed across the treatment arms.
Patients with anaplastic astrocytomas are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment. Information about ongoing clinical trials is available from the NCI Web site.
Standard treatment options for patients with newly diagnosed disease:
The standard-of-care treatment for patients with newly diagnosed glioblastoma is surgery followed by concurrent radiation therapy and daily temozolomide, and then followed by six cycles of temozolomide. This standard therapy is based on a large, multicenter, randomized trial (NCT00006353) conducted by the European Organization for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada (NCIC), which reported a survival benefit with concurrent radiation therapy and temozolomide compared with radiation therapy alone.[3,4][Level of evidence: 1iiA] In that study, 573 patients with glioblastoma were randomly assigned to receive standard radiation to the tumor volume with a 2- to 3-cm margin (60 Gy, 2 Gy per fraction, over 6 weeks) alone or with temozolomide (75 mg/m2 orally per day during radiation therapy for up to 49 days, followed by a 4-week break and then up to six cycles of five daily doses every 28 days at a dose of 150 mg/m2, increasing to 200 mg/m2 after the first cycle). Patients in the combined therapy group were given prophylactic therapy for pneumocystis carinii during the period of concomitant radiation therapy and temozolomide. OS was statistically significantly better in the combined radiation therapy–temozolomide group (hazard ratio [HR]death, 0.6; 95% confidence interval [CI], 0.5–0.7; OS at 3 years was 16.0% vs. 4.4%).
O6-methylguanine–DNA methyltransferase (MGMT) promoter DNA methylation
A companion molecular, correlation subset study to the EORTC-NCIC trial provided strong evidence that epigenetic silencing of the MGMT DNA-repair gene by promoter DNA methylation was associated with increased OS in patients with newly diagnosed glioblastoma.[5] MGMT promoter methylation was an independent favorable prognostic factor (P < .001 by the log-rank test; HR, 0.45; 95% CI, 0.32–0.61). The median OS for MGMT-methylated patients was 18.2 months (95% CI, 15.5–22.0), compared with 12.2 months (95% CI, 11.4–13.5) for MGMT-unmethylated patients.
Dose-dense temozolomide
MGMT DNA-repair activity has been proposed as a major mechanism of resistance to alkylating agents. Intracellular depletion of MGMT has been hypothesized to enhance treatment response, and protracted temozolomide schedules have been shown to deplete intracellular MGMT in peripheral blood mononuclear cells. To test whether protracted temozolomide enhances treatment response in patients with newly diagnosed glioblastoma, a multicenter, randomized, phase III trial conducted by the Radiation Therapy Oncology Group (RTOG), EORTC, and the North Central Cancer Therapy Group, RTOG 0525 (NCT00304031), compared standard adjuvant temozolomide treatment (days 1–5 of a 28-day cycle) with a dose-dense schedule (days 1–21 of a 28-day cycle). All patients were treated with surgery followed by radiation therapy and concurrent daily temozolomide. Patients were then randomly assigned to receive either standard adjuvant temozolomide or dose-dense temozolomide.[6][Level of evidence: 1iiA]
Among 833 randomly assigned patients, no statistically significant difference between standard and dose-dense temozolomide was observed for median OS (16.6 months for standard temozolomide vs. 14.9 months for dose-dense temozolomide; HR, 1.03; P = .63) or median progression-free survival (PFS) (5.5 vs. 6.7 months; HR, 0.87; P = .06). MGMT status was determined in 86% of randomly assigned patients, and no difference in efficacy was observed in either the MGMT-methylated or MGMT-unmethylated subsets. However, this study confirmed the strong prognostic effect of MGMT methylation because the median OS was 21.2 months (95% CI, 17.9–24.8) for methylated patients versus 14 months (95% CI, 12.9–14.7) (HR, 1.74; P < .001) for unmethylated patients.
In summary, there was no survival advantage for the use of dose-dense temozolomide versus standard-dose temozolomide in newly diagnosed glioblastoma patients, regardless of MGMT status. The efficacy of dose-dense temozolomide for patients who have recurrent glioblastoma, however, is yet to be determined.
Bevacizumab in newly diagnosed glioblastoma
In 2013, final data from two multicenter, phase III, randomized, double-blind, placebo-controlled trials of bevacizumab in patients who have newly diagnosed glioblastoma were reported: RTOG 0825 (NCT00884741) and the Roche-sponsored AVAglio (NCT00943826).[7,8][Level of evidence: 1iA] Patients in both studies were randomly assigned to receive standard therapy (chemoradiation with temozolomide) or standard therapy plus bevacizumab. OS and PFS were coprimary endpoints in both trials, and these outcomes were similar. Bevacizumab did not improve OS in either study (median OS was 16–17 months for each arm in both studies); however, it increased median PFS to a similar degree (AVAglio study: 10.6 vs. 6.2 months; HR, 0.64; P < .0001; RTOG 0825 study: 10.7 vs. 7.3 months; HR, 0.79; P = .007). The PFS result in the AVAglio study was statistically significant and associated with clinical benefit because bevacizumab-treated patients remained functionally independent for longer (9.0 months vs. 6.0 months) and went longer before their Karnofsky Performance scale deteriorated (HR, 0.65; P < .0001). Furthermore, bevacizumab-treated patients went longer before corticosteroids were initiated (12.3 vs. 3.7 months; HR, 0.71; P = .002), and a larger proportion of patients was able to discontinue corticosteroids if they were already taking them (66% vs. 47%). However, the PFS result in the RTOG 0825 trial did not meet the prespecified significance level (P = .004). Of note, there was significant crossover in both trials (approximately 40% of RTOG 0825 patients and approximately 30% of AVAglio patients received bevacizumab at the first sign of disease progression).
The two trials had contradictory results in health-related quality of life (HRQoL) and neurocognitive outcomes studies. In the mandatory HRQoL studies in the AVAglio trial, bevacizumab-treated patients experienced improved HRQoL, but bevacizumab-treated patients in the elective RTOG 0825 studies showed more decline in patient-reported HRQoL and neurocognitive function. The reasons for these discrepancies are unclear.
On the basis of these results, there is no definite evidence that the addition of bevacizumab to standard therapy is beneficial for all newly diagnosed glioblastoma patients. It is yet to be determined whether certain subgroups may benefit from the addition of bevacizumab.
For patients with glioblastoma (WHO grade IV), the cure rate is very low with standard local treatment. These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment. Information about ongoing clinical trials is available from the NCI Web site.
Oligodendroglial Tumors
Patients who have oligodendrogliomas (WHO grade II) generally have better prognoses than do patients who have diffuse astrocytomas; however, most of the oligodendrogliomas eventually progress.
Anaplastic oligodendrogliomas
Mature results from the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group Study 26951 (NCT00002840), a phase III, randomized study with 11.7 years of follow up demonstrated increased OS and progression-free survival in patients with anaplastic oligodendroglial tumors with six cycles of adjuvant PCV chemotherapy after radiation therapy compared with radiation therapy alone.[11] The OS was significantly longer in the radiation therapy and PCV arm (42.3 months vs. 30.6 months; HR, 0.75; 95% CI, 0.60–0.95). 1p/19q-codeleted tumors derived more benefit from adjuvant PCV chemotherapy compared with non-1p/19q-deleted tumors.[11][Level of evidence: 1iiA]
In contrast, the Radiation Therapy Oncology Group (RTOG) trial (RTOG-9402 [NCT00002569]) demonstrated no differences in median survival by treatment arm between an 8-week, intensive PCV chemotherapy regimen followed by immediate involved-field-plus-radiation therapy and radiation therapy alone.[12] However, in an unplanned subgroup analysis, patients with 1p/19q codeleted anaplastic oligodendroglioma and mixed anaplastic astrocytoma demonstrated a median survival of 14.7 years versus 7.3 years (HR, 0.59; 95% CI, 0.37–0.95; P = .03). For patients with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 vs. 2.7 years; HR, 0.85; 95% CI, 0.58–1.23; P = .39).[12][Level of evidence: 1iiA]
On the basis of these data, CODEL, a study that randomly assigned patients to radiation therapy alone (control arm), radiation therapy with temozolomide, and temozolomide alone (exploratory arm), was halted because radiation therapy alone was no longer considered adequate treatment in patients with anaplastic oligodendroglioma with 1p/19q codeletion.[13] A comparison between temozolomide and PCV chemotherapy in anaplastic oligodendroglioma has not been done, although in the setting of grade 3 anaplastic gliomas, no survival difference was seen between PCV chemotherapy and temozolomide.[2,14]
Patients with anaplastic oligodendrogliomas (WHO grade III) have a low cure rate with standard local treatment, but their prognoses are generally better than are the prognoses of patients with anaplastic astrocytomas. Since anaplastic oligodendrogliomas are uncommon, phase III randomized trials restricted to patients with them are not practical. Patients with these tumors are generally managed with the following:
PORT alone has been compared with postoperative chemotherapy alone in patients with anaplastic gliomas (i.e., 144 astrocytomas, 91 oligoastrocytomas, and 39 oligodendrogliomas) with crossover to the other modality at the time of tumor progression. Of the 139 patients randomly assigned to radiation therapy, 135 were randomly assigned to chemotherapy with a 32-week course of either PCV or single-agent temozolomide (2:1:1 randomization). The order of the modalities did not affect TTF or OS.[2][Levels of evidence: 1iiA and 1iiD]. Neither TTF nor OS differed across the treatment arms.
These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment. Information about ongoing clinical trials is available from the NCI Web site.
Mixed Gliomas
Patients with mixed glial tumors, which include oligoastrocytoma (WHO grade II) and anaplastic oligoastrocytoma (WHO grade III), have prognoses similar to that for astrocytic tumors of corresponding grades and are often treated as such.
Ependymal Tumors
Grade I and II ependymal tumors
Ependymomas (WHO grade II) and ependymal tumors (WHO grade I), i.e., subependymoma and myxopapillary ependymomas, are often curable.
Anaplastic ependymomas
Patients with anaplastic ependymomas (WHO grade III) have variable prognoses that depend on the location and extent of disease. Frequently, but not invariably, patients with anaplastic ependymomas have worse prognoses than do those patients with lower-grade ependymal tumors.
Embryonal Cell Tumors: Medulloblastomas
Treatment options under clinical evaluation:
Medulloblastoma occurs primarily in children, but it also occurs with some frequency in adults.[17] Other embryonal tumors are pediatric conditions. (Refer to the PDQ summary on Childhood Central Nervous System Embryonal Tumors Treatment for more information.)
Pineal Parenchymal Tumors
Pineocytoma (WHO grade II), pineoblastoma (WHO grade IV), and pineal parenchymal tumors of intermediate differentiation are diverse tumors that require special consideration. Pineocytomas are slow-growing tumors, and patients with them carry variable prognoses for cure. Pineoblastomas are more rapidly growing tumors, and patients with them have worse prognoses. Pineal parenchymal tumors of intermediate differentiation have unpredictable growth and clinical behavior.
Meningeal Tumors
Grade I meningiomas
WHO grade I meningiomas are usually curable when the mengiomas are resectable. With the increasing use of sensitive neuroimaging tools, there has been greater detection of asymptomatic low-grade meningiomas. The majority appear to show minimal growth and can often be safely observed while therapy is deferred until growth or the development of symptoms.[18,19]
Grade II and III meningiomas and hemangiopericytomas
The prognoses for patients with meningiomas (WHO grade II) (i.e., atypical, clear cell, and chordoid), meningiomas (WHO grade III) (i.e., anaplastic/malignant, rhabdoid, and papillary), and hemangiopericytomas are worse than are those for patients with low-grade meningiomas because complete resections are less commonly feasible, and the proliferative capacity is greater.
Germ Cell Tumors
The prognoses and treatment of patients with germ cell tumors—which include germinoma, embryonal carcinoma, choriocarcinoma, and teratoma—depend on tumor histology, tumor location, presence and amount of biological markers, and surgical resectability.
Tumors of the Sellar Region: Craniopharyngiomas
Craniopharyngiomas (WHO grade I) are often curable.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult brain tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Re-resection of recurrent brain tumors is used in some patients. However, the majority of patients do not qualify because of a deteriorating condition or technically inoperable tumors. The evidence is limited to noncontrolled studies and case series on patients who are healthy enough and have small enough tumors to technically debulk. The impact of reoperation versus patient selection on survival is not known.
Localized Chemotherapy
Carmustine wafers have been investigated in the setting of recurrent malignant gliomas, but the impact on survival is less clear than at the time of initial diagnosis and resection. In a multicenter randomized, placebo-controlled trial, 222 patients with recurrent malignant primary brain tumors requiring reoperation were randomly assigned to receive implanted carmustine wafers or placebo biodegradable wafers.[1] Approximately half of the patients had received prior systemic chemotherapy. The two treatment groups were well balanced at baseline. Median survival was 31 versus 23 weeks in the two groups. The statistical significance between the two overall survival (OS) curves depended upon the method of analysis. The hazard ratio (HR) for risk of dying in the direct intention-to-treat comparison between the two groups was 0.83 (95% confidence interval [CI], 0.63–1.10; P = .19). The baseline characteristics were similar in the two groups, but the investigators did an additional analysis, adjusting for prognostic factors, because they felt that even small differences in baseline characteristics could have a powerful influence on outcomes. In the adjusted proportional hazards model, the HR for risk of death was 0.67 (95% CI, 0.51–0.90, P = .006). The investigators put their emphasis on this latter analysis and reported this as a positive trial.[1][Level of evidence: 1iA] However, a Cochrane Collaboration systematic review of chemotherapeutic wafers for high-grade glioma focused on the unadjusted analysis and reported the same trial as negative.[2]
Systemic Chemotherapy
In 2009, the U.S. Food and Drug Administration (FDA) granted accelerated approval of bevacizumab monotherapy for patients with progressive glioblastoma. The indication was granted under the FDA's accelerated approval program that permits the use of certain surrogate endpoints or an effect on a clinical endpoint other than survival or irreversible morbidity as bases for approvals of products intended for serious or life-threatening illnesses or conditions. The approval was based on the demonstration of improved objective response rates observed in two historically controlled, single-arm, or noncomparative phase II trials.[3,4][Level of evidence: 3iiiDiv]
The FDA independently reviewed an open-label, multicenter, noncomparative phase II study that randomly assigned 167 recurrent glioblastoma multiforme (GBM) patients to receive bevacizumab alone or bevacizumab in combination with irinotecan,[3] although only efficacy data from the bevacizumab monotherapy arm (n = 85) were used to support drug approval. According to the FDA analysis of this study, tumor responses were observed in 26% of patients treated with bevacizumab alone, and the median duration of response in these patients was 4.2 months. On the basis of this externally controlled trial, the incidence of adverse events associated with bevacizumab did not appear to be significantly increased in GBM patients. The FDA independently assessed another single-arm, single-institution trial in which 56 recurrent glioblastoma patients were treated with bevacizumab alone.[4] Responses were observed in 20% of patients, and the median duration of response was 3.9 months.
Currently, however, no data are available from prospective, randomized controlled trials demonstrating improvement in health outcomes, such as disease-related symptoms or increased survival with the use of bevacizumab to treat glioblastoma. On the basis of these data and FDA approval, bevacizumab monotherapy has become standard therapy for recurrent glioblastoma.
Systemic therapy (e.g., temozolomide, lomustine, or the combination of procarbazine, a nitrosourea, and vincristine in patients who have not previously received the drugs) has been used at the time of recurrence of primary malignant brain tumors. However, it has not been tested in controlled studies. Patient-selection factors likely play a strong role in determining outcomes, so the impact of therapy on survival is not clear.
Because there are no randomized trials, the role of repeat radiation after disease progression or the development of radiation-induced cancers is also ill defined. Interpretation is difficult because the literature is limited to small retrospective case series.[5] The decision must be made carefully because of the risk of neurocognitive deficits and radiation necrosis.
Patients who have recurrent brain tumors are rarely curable and should be considered candidates for clinical trials when they have exhausted standard therapy. Information about ongoing clinical trials is available from the NCI Web site.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult brain tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information About Adult Brain Tumors
Editorial changes were made to this section.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult brain tumors. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Adult Brain Tumors Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
National Cancer Institute: PDQ® Adult Brain Tumors Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/adultbrain/HealthProfessional. Accessed <MM/DD/YYYY>.
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.
Contact Us
More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site's Contact Form.
Call 1-800-4-CANCER
For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.
Chat online
The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.
Write to us
For more information from the NCI, please write to this address:
Search the NCI Web site
The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.
There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.
Find Publications
The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).
Last Revised: 2015-02-25
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Press Room
Go Swim, Georgia: Cool off, swim safely in Georgia waters
Atlanta, May 20, 2010 – As the heat of summer approaches and more people head outside, the Georgia Department of Natural Resources (DNR) encourages families to get outdoors and "Go Swim!" Whether you are splashing in a creek, jumping off a dock or swimming at a state park beach, Georgia has plenty of places for you to cool off.
"Swimming has always been a popular way for families to enjoy summertime," said DNR Commissioner Chris Clark. "There are many swimming opportunities in our state parks and on Georgia lakes and rivers. But we encourage everyone to make sure they're safe when they're in the water."
Stay cool and save money
Georgia's state parks have more than 20 swimming beaches and pools where visitors can cool off this summer. For just a $5 parking fee, visitors can spend the entire day at a sandy lakeside beach while soaking in some of the state's most relaxing scenery. Beaches have no lifeguards, so swimmers are strongly urged to stay within boundary ropes marking off the swimming areas. Some of the most popular lakeside beaches are at Vogel, John Tanner, Seminole, Unicoi, Hard Labor Creek, Fort Mountain and Richard B. Russell state parks.
Swimmers who prefer an aqua-blue pool can visit High Falls, Victoria Bryant and Magnolia Springs state parks, and those who love history can take a chilly dip in the spring-fed Liberty Bell Pool at F.D. Roosevelt State Park. A small fee is charged and lifeguards are provided. Most pools are open Memorial Day weekend through Labor Day weekend. However, days of operation vary, so swimmers should call ahead before visiting. Overnight lodge guests at George T. Bagby and Little Ocmulgee state parks can enjoy the lodge pools for no additional fee. These pools do not have lifeguards.
To quickly see which state parks have swimming beaches or pools, visit
Remember Safety First When Swimming
Accidents happen all too often, so DNR encourages everyone to practice safety at all times when in and around the water. Some swimming safety tips include:
- Take a swimming course.
- Never swim alone. If you are a marginal swimmer, wear a flotation device.
- Don't mix alcohol or drugs when swimming.
- Never let children swim unsupervised.
- Keep life jackets accessible and never make someone feel uncomfortable if they choose to wear a life jacket.
- Don't swim when you are too tired, too cold or too far from safety.
- Don't swim beyond marked boundaries at swimming beaches.
- Always be aware of the possibilities of hidden dangers such as underwater obstacles, changing currents and underwater drop-offs.
- When you find yourself in a stressful situation, don't panic. If in non-flowing water, float or "dog-paddle" to safety. If in flowing water, float with the current and don't fight against it.
Prevention and common sense can help prevent water-related tragedies. To learn more about water safety, visit the Red Cross at
"Go Swim, Georgia" is the latest in a series of outdoor adventure tips from DNR Commissioner Clark that highlight affordable getaways, outdoor activities close to home, and creative ways to support conservation in Georgia. The series is part of DNR's "Get Outdoors, Georgia" initiative, which encourages citizens to lead healthy, active lifestyles in the great outdoors and includes hiking, biking and paddling clubs, as well as outdoor events.
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© 2017 - Georgia Department of Natural Resources

subset: commoncrawl


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This week's post is from Marcelo Andrieu, who is the Product Manager for our new activEcho Enterprise File Sharing solution. Marcelo, thanks for the post! – Anders
For some reason in the software business people think about dot releases as if they are not that relevant. After all, what's in it? they say. Maybe some minor improvements and bug fixes?
Well, that is certainly not true anymore. Several years ago we embraced the Agile development process. This means we are releasing versions all the time and we have a great deal of flexibility. We can rapidly change the scope and features of release to respond to what our customers need. Instead of 1 release every 12-18 months, we may have 4 to 6 in the same period within a year.
This brings us to activEcho 2.1, which we are releasing today. We have had numerous conversations with our customers from many diverse markets including healthcare, financial services, education, publishing, advertising, government, and legal. In addition we talked to the VAR and service provide community. And, as you can imagine, they are impatient! So we have rolled out some new features which we believe are important. :
• IT wanted more infrastructure and storage management and control. In activEcho, when a user deletes a document it's actually "marked as deleted" but remains in the system to recover in case it is needed. With 2.1, IT can implement policies to purge deleted content after a period of time of their choosing. This helps keep storage under control. In addition, activEcho now has policies to define how many revisions of a document must be kept in the system. This not only helps with storage costs, but more importantly, it addresses key to compliance needs.
• Exporting event logs. IT needs to be able to not only view the event logs, but also be able to do something useful with it. With our new export capability, IT can click a button in their browser, save the log on to their desktop, and load it into Excel. Quick, easy, useful.
• Skinning and branding for the organization. Organizations like to "blend" solutions like activEcho with the look and feel of the corporate brand, etc. other elements. We already had "skinning", customization and branding capabilities, so we added more of it plus a sophisticated interface to completely customize email notifications and alerts for users and administrators, embedding images, signatures, legal disclaimers and such. T
• And something for the endusers – very powerful and easy to use 1 and 2 way sync for mobile devices. We have also added a bookmarking capability, enhanced notification subscription options and easier access for Windows, Mac and web browser users.
This is just the beginning of the many new features we are bringing to activEcho and you can expect to see us roll out a significant number of new features as we continue to evolve our Enterprise File Sharing solution.


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Buy-back guns melted at ArcelorMittal
(Cleveland) - ArcelorMittal Cleveland melted 352 guns Wednesday that were surrendered at the 2013 City of Cleveland Gun Buy-Back.
On June 15, citizens exchanged firearms for gift cards in addition to tickets to an upcoming Cleveland Cavaliers and Monsters game and an entry into a raffle for a chance to win up to $1,000.
"This gun melt will take guns surrendered by their owners, recycle them into steel and prevent them from ever being used in an act of violence," said Mayor Frank Jackson. "I'd like to thank ArcelorMittal for being a good partner in the City's efforts to improve safety and reduce gun violence."
(Mayor Frank Jackson looks over the surrendered weapons. Photo by Carmen Angelo/WTAM 1100)
"This year, ArcelorMittal Cleveland is celebrating one hundred years of steelmaking in the industrial valley. For a century, the steel industry has had deep roots in the Cleveland community, and we share a common goal for a healthy, safe, sustainable city. We are pleased to continue our partnership with the City of Cleveland and Cleveland Police Foundation," said Eric Hauge, Vice President & General Manager, ArcelorMittal Cleveland.
The guns are placed into the No. 1 Basic Oxygen Furnace iron ladle and melted by approximately 200 tons of molten iron, at temperatures of about 2,400 degrees Fahrenheit.
The molten iron, along with scrap, is then charged in the basic oxygen furnace to make steel which will eventually be used to manufacture cars, household appliances and other goods.
(Photo by Carmen Angelo/WTAM 1100)
Get breaking news sent to your mobile phone. Text "news" to 21095.
(Copyright © 2013 by Clear Channel, all rights reserved.)


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GSA Announces New Per Diem Rates for Federal Travelers
November 21, 1996
Contact: Steve Guiheen
(202) 501-1231
Acting Administrator David J. Barram of the U.S. General Services Administration (GSA) today announced updated per diem rates for federal employees on official travel in the 48 contiguous states and the District of Columbia. The rates, scheduled to appear in today's Federal Register, take effect Jan. 1, 1997.
Barram said federal per diem rates are based on a lodgings-plus system, whereby employees are reimbursed for the actual cost of lodging up to a set limit. In addition, they receive a fixed amount for meals and incidental expenses.
The lodging limit plus the meal and incidental expenses rate for a given destination equal the maximum per diem rate employees can be paid for official travel.
Barram said GSA periodically reviews the travel per diem rates based on independent surveys of lodging and meal costs. Where survey results warrant, rates are adjusted so federal workers may obtain lodging in moderate, business-class accommodations.
"For the first time in eight years," Barram said, "the standard rate has been increased -- from $66 to $80 -- for all locations not specifically listed as higher-cost areas by the Federal Travel Regulations."
The new standard rate allows a maximum of $50 for lodging and $30 for meals and incidental expenses.
Individual rates have been set for 497 higher-cost U.S. cities. Lodging in these locations is paid by the government up to a set limit; reimbursement for meals and incidental expenses is $30, $34, $38 or $42 depending on the location.
In addition to setting domestic per diem rates, GSA also negotiates discount rates with U.S. air carriers and with hotels and motels nationwide. For fiscal year 1997, GSA unrestricted air fares, on average, are 62 percent less than commercial rates.
GSA's per diem rates also apply to employees of certain government vendors when traveling in connection with federal contracts.
Travel per diem rates for locations outside the continental United States -- Alaska, Hawaii, and the U.S. territories and possessions are set by the Department of Defense. Rates for international travel are set by the State Department.
The complete list of GSA's new rates is on the World Wide Web at http://policyworks.gov/perdiem. The rates also are available from Federal Information Centers at 1-800-688-9889 or, for the hearing impaired (TDD/TTY users), at 1-800-326-2996.
Examples of New Rates for Some Frequently-Visited Cities
New Rates Current Rates
City Lodging Meals Total Lodging Meals Total
Atlanta $ 96 $ 38 $ 134 $ 85 $ 34 $ 119
Chicago 119 42 161 119 38 157
Dallas 84 42 126 84 38 122
Denver 92 34 126 92 34 126
Los Angeles 97 42 139 97 38 135
New York 153 42 195 142 38 180
San Diego 84 38 122 122 34 115
Washington, DC 124 42 166 124 38 162


text:
Minnesota Geocaching Association
User list
Log in to check your private messages
Log in
March 2004 Cache of the Month - VOTE HERE
MnGCA Forum Index
Cache of the Month
View previous topic
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Your choice for March's Cache of the Month is. . .
When Darkness Falls... by Candy Apple Green
[ 5 ]
Wild Side by Duch and Appsspec
[ 2 ]
GPS Knowledge Challenge by Arcticabn
[ 4 ]
The Suspense Is Killing Me by Bogeyboy
[ 3 ]
Total Votes : 14
Past MnGCA Board
Joined: 26 Nov 2002
Posts: 1270
Posted: Sun Feb 15, 2004 10:26 am
Post subject: March 2004 Cache of the Month - VOTE HERE
It's time to vote! In this post you will find the caches which have been nominated to be the MnGCA March Cache of the Month.
Voting ends on February 29th. Rules for nominations
. Thanks to nomination submitters!
Nomination articles: (in the order they were nominated)
When Darkness Falls... (GCHAYC)
Candy Apple Green
(nominated by s4xton)
This is one of the most inventive multi-caches in the Twin Cities area. Located in Lilydale Park in Saint Paul, this one likely cannot be accomplished during daylight. Thankfully, the park stays open until 11:00pm. While being winter friendly, it gives you a nice stroll around the shore of the Mississippi. Paved trails can be used for some of the walking. While the 3 options (you'll want to do them all) for the second part of the multi are likely a different style of caching that you've ever done before, the first stage is still rather tricky in it's own right. Finding the first stage of this multi gives you all the tools you need to complete the rest, but I also recommend bringing a flashlight and a partner. This one is definitely fun for two people.
Wild Side (GCHOPN)
Duch and Appsspec
(nominated by 15Tango)
This cache is in a great part of a great park that I
commute past on my way to work, but would have never
known about if it wasn't for geocaching. Alimagnet
Lake Park is tucked between Cedar Ave. and 35E, South
of where they cross each other. There are ball fields
at one end of the park, as well as a dog park, and
some of the trail network is groomed in the winter for
X-C skiing. Aside from a couple of large houses
visible on the opposite side of the lake from the
park, one can easily forget that they are smack dab in
the middle of suburbia. The only real shortfall is
that this cache is a PVC container, and the lid can
sometimes be difficult to remove. There is also
another cache in the same park, around the lake from
this one, Alimagnet Ski Trail by Catering Chef.
(click on images to see larger versions)
GPS Knowledge Challenge (GCHB6R)
(nominated by Silent Bob)
GPS Knowledge Challenge brings together several great aspects of geocaching into one fantastic multi-cache. Arcticabn was able to roll a history lesson, some great hides, a lengthy hike, and great terrain all into one 2.5+ hour long adventure through the middle of Lebanon Hills Park with a single ten-stage multi-cache.
Depending on your vehicle's abilities you may or may not have a lengthy hike to the first stage. From here you begin your adventure through the gorgeous rolling terrain of Lebanon Hills. Arcticabn's time and effort really shows through in the cache containers, the questions, and the stage locations. I would never have made it to some of these areas if it were not for this cache.
If you plan on attempting this cache *please* brush up on your GPS history, bring plenty of water (especially in the summer as Lebanon Hills is unforgiving at that time of year), bugspray, wear clothes that will protect your arms and legs as some of the areas will likely be full of vegetation that your arms and legs will not appreciate, and of course... Bring a friend. Long caches are always more fun when you have someone to pass the time with between stages!
The final cache is certainly worth the effort as it was originally stocked full of items from the geocaching.com store. It is frequently harboring several bugs and it is a great container in itself. As always, if you decide to make a trade please keep the trades even.
The Suspense Is Killing Me (GCAE44)
(nominated by KC0QEG)
Located in beautiful Plymouth, right off the 494 Circuit. I found this one in late summer, which made it a good hunt as there is quite a bit of canopy cover. The reason I like this one so much was the cleaver hiding equipment. Also, this "park" is tucked nicely in a neighborhood. I choose the short walk when I went for the hunt, by doing so, his statement is correct, you very likely can miss the entrance from this side of the park. It is a nice park, with a good hide, well worth a nomination for Cache of the month.
Last edited by towlebooth on Sun Feb 29, 2004 7:34 am; edited 1 time in total
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Past MnGCA Board
Joined: 26 Nov 2002
Posts: 1270
Posted: Wed Feb 18, 2004 9:11 am
Post subject:
Hi all,
Scott Johnson just sent in a nomination for next month which reinforces one already nominated this month. Since we can't nominate the same cache two months in a row I wanted to post his text here.
3 cont.)
I nominate GPS Knowledge Cache.
This cache is without a doubt the most accurately placed one I have ever seen. Very few of the caches were off more than 6-12 from posted coordinates. The game aspect of having to answer a GPS related question to direct you to your next cache was not only physically enjoyable, but mentally as well. This is an excellent cache to learn about Geocaching or to teach others with. The park is easy to find and to get around in.
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Brevard, N.C. - Brevard College women's soccer player Bailey Varley has been named Tornado Athlete of the Week for week two of the 2009-10 athletic season. The sophomore received 37.1% of the votes.
Varley scored three goals against Lees-McRae on Tuesday, September 1, including the game winner in doule over time to lift the Tornados to a victory and a 3-0 record.
Varley's first goal tied the game 1-1 in the first period. She took a pass from Allie Hovis and muscled past the goalkeeper to knock one in for Brevard. Her second goal came in the second period with the Tornados down 3-1 when she scored off of a pass from Alyssa Caracena. Nikki Peacock's goal then tied the game up allowing the Tornados to play into a double overtime when Varley completed her hat trick two minutes into that second overtime.
Other nominees for Athlete of the Week were Michael Crumbaker for football, who recieved 29% of the votes with 20 carries, 112 yards, 1 TD, 4-6 through the air for 37 yards as Brevard downs Pikeville on the road, 40-3 Prince Simunyu for football, who got 26% of the votes, with seven tackles, four tackles for loss and a sack as the Tornados defense swarmed the Bears offense, holding them to 75 total yards as BC defeated Pikeville, 40-3, Chelsea Larsen, for volleyball had 6% of the votes, with 26 kills, hitting 30.3% of her attacks, as well as recording seven digs and a block assist as the Tornados went 1-1 on the week, and Jo Tuttle for cycling who finished with 2% of the votes, winning the downhill and dual slalom events last weekend at ETSU.
The Tornado Athlete of the Week Poll comes out every Monday morning and will run until Tuesday at noon. For more information on the poll, contact the Brevard Sport Information Department.
2009-2010 Brevard Tornado Athlete of the Week Winners
Week 1 - Brooke Seaman, Volleyball (34 kills, 41.3% hitting percentage, 13 total blocks, six service aces as Tornados go 3-0 on the week)
Week 2 - Bailey Varley, Women's Soccer (Three goals, including the game winner in double overtime as the Tornados advanced to 3-0)
Week 3- TBA, September 15, 2009


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text:
Alicia - from Harlingen, TX
Replacing oil in baked products with applesauce can be a bit tricky to get the right taste and texture. It is recommended that when you replace the applesauce for oil in cakes that you can do a 1 to 1 ratio (example, 1/2 cup applesauce for 1/2 cup oil); however, some find the cake to be a little bit chewier so you can also replace half the oil with applesauce and still add some oil (example 1/4 cup applesauce and 1/4 cup oil). It takes some experimenting to get the right product for you.


text:
'Miller stopped 30 shots overall, his best coming on Miroslav Satan with 12 seconds left. Satan cut across the crease and had Miller beat before the goalie spun around and stuck out his glove hand, getting enough of Satan's shot to turn it aside. Miller than scrambled to the side of the net to prevent Alexei Yashin from wrapping in the rebound.'
Buffalo 4, NY Islanders 3
April 21, 2007 Submitted by
Via: AP


text: Video: Catching a cold? These diet tips can help you fight it off Add to ... The Globe and Mail Published Tuesday, Oct. 16, 2012 4:13PM EDT Last updated Wednesday, Oct. 24, 2012 7:41PM EDT When cold weather hits, your immune system is often the first thing to fail you. Dietitian Leslie Beck has tips on how a healthy diet can give your system a boost Watch More Video: Cola overdose: Woman dies after drinking 10 litres per day Hate shift work? Try these nutrition tips to stay healthy on the clock Video: You don't need meat: What are the top proteins for vegetarians? What are the healthiest snacks for your kids? What to eat – and what to avoid – to lower your blood pressure Stop right there! Tips on how to avoid overeating Healthy foods to fuel your child's brain Am I drinking enough water each day? The scoop on ice cream: Which treats are worth the calories Time to fire up the grill - but how do you keep BBQ'd food healthy? Are you breaking these food-safety rules? Comments Share via email Share on facebook Share on twitter Share on LinkedIn Print More Related to this Story Video: 4 foods to keep your mind sharp Video: 4 dietitian tips to help you read nutrition labels Video: 5 ways to get enough fibre in your diet


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Rent The Land of Little Rain 1st edition today, or search our site for other textbooks by Mary H. Austin. Every textbook comes with a 21-day "Any Reason" guarantee. Published by Penguin Classics.
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Roland Deschain and his "ka-tet" are bearing southeast through the forests of Mid-World, the almost timeless landscape that seems to stretch from the wreckage of civility that defined Roland's youth to the crimson chaos that seems the future's only promise. Readers of Stephen King's epic series know Roland well, or as well as this enigmatic hero can be known. They also know the companions who have been drawn to his quest for the Dark Tower: Eddie Dean and his wife, Susannah; Jake Chambers, the boy who has come twice through the doorway of death into Roland's world; and Oy, the Billy-Bumbler.In this long-awaited fifth novel in the saga, their path takes them to the outskirts of Calla Bryn Sturgis, a tranquil valley community of farmers and ranchers on Mid-World's borderlands. Beyond the town, the rocky ground rises toward the hulking darkness of Thunderclap, the source of a terrible affliction that is slowly stealing the community's soul. One of the town's residents is Pere Callahan, a ruined priest who, like Susannah, Eddie, and Jake, passed through one of the portals that lead both into and out of Roland's world.As Father Callahan tells the "ka-tet" the astonishing story of what happened following his shamed departure from Maine in 1977, his connection to the Dark Tower becomes clear, as does the danger facing a single red rose in a vacant lot off Second Avenue in midtown Manhattan. For Calla Bryn Sturgis, danger gathers in the east like a storm cloud. The Wolves of Thunderclap and their unspeakable depredation are coming. To resist them is to risk all, but these are odds the gunslingers are used to, and they can give the "Calla-folken" both courage and cunning. Their guns, however, will not be enough.
"synopsis" may belong to another edition of this title.
Stephen King, since writing the opening sentence of The Gunslinger, has written more than forty novels and two hundred short stories. He has won the World Fantasy Award, several Bram Stoker Awards, the O. Henry Award for his story "The Man in the Black Suit," and the National Book Foundation Medal for Distinguished Contribution to American Letters.Excerpt. © Reprinted by permission. All rights reserved.:
Tian was blessed (though few farmers would have used such a word) with three patches: River Field, where his family had grown rice since time out of mind; Roadside Field, where ka-Jaffords had grown sharproot, pumpkin, and corn for those same long years and generations; and Son of a Bitch, a thankless tract which mostly grew rocks, blisters, and busted hopes. Tian wasn't the first Jaffords determined to make something of the twenty acres behind the home place; his Gran-pere, perfectly sane in most other respects, had been convinced there was gold there. Tian's Ma had been equally positive it would grow porin, a spice of great worth. Tian's particular insanity was madrigal. Of course madrigal would grow in Son of a Bitch. Must grow there. He'd gotten hold of a thousand seeds (and a dear penny they had cost him) that were now hidden beneath the floorboards of his bedroom. All that remained before planting next year was to break ground in Son of a Bitch. This chore was easier spoken of than accomplished.
Clan Jaffords was blessed with livestock, including three mules, but a man would be mad to try using a mule out in Son of a Bitch; the beast unlucky enough to draw such duty would likely be lying legbroke or stung to death by noon of the first day. One of Tian's uncles had almost met this latter fate some years before. He had come running back to the home place, screaming at the top of his lungs and pursued by huge mutie wasps with stingers the size of nails.
They had found the nest (well, Andy had found it; Andy wasn't bothered by wasps no matter how big they were) and burned it with kerosene, but there might be others. And there were holes. Yer-bugger, plenty o' them, and you couldn't burn holes, could you? No. Son of a Bitch sat on what the old folks called "loose ground." It was consequently possessed of almost as many holes as rocks, not to mention at least one cave that puffed out draughts of nasty, decay-smelling air. Who knew what boggarts and speakies might lurk down its dark throat?
And the worst holes weren't out where a man (or a mule) could see them. Not at all, sir, never think so. The leg-breakers were always concealed in innocent-seeming nestles of weeds and high grass. Your mule would step in, there would come a bitter crack like a snapping branch, and then the damned thing would be lying there on the ground, teeth bared, eyes rolling, braying its agony at the sky. Until you put it out of its misery, that was, and stock was valuable in Calla Bryn Sturgis, even stock that wasn't precisely threaded.
Tian therefore plowed with his sister in the traces. No reason not to. Tia was roont, hence good for little else. She was a big girl -- the roont ones often grew to prodigious size -- and she was willing, Man Jesus love her. The Old Fella had made her a Jesus-tree, what he called a crusie-fix, and she wore it everywhere. It swung back and forth now, thumping against her sweating skin as she pulled.
The plow was attached to her shoulders by a rawhide harness. Behind her, alternately guiding the plow by its old ironwood handles and his sister by the hame-traces, Tian grunted and yanked and pushed when the blade of the plow dropped down and verged on becoming stuck. It was the end of Full Earth but as hot as midsummer here in Son of a Bitch; Tia's overalls were dark and damp and stuck to her long and meaty thighs. Each time Tian tossed his head to get his hair out of his eyes, sweat flew out of the mop in a spray.
"Gee, ye bitch!" he cried. "Yon rock's a plow-breaker, are ye blind?"
Not blind; not deaf, either; just roont. She heaved to the left, and hard. Behind her, Tian stumbled forward with a neck-snapping jerk and barked his shin on another rock, one he hadn't seen and the plow had, for a wonder, missed. As he felt the first warm trickles of blood running down to his ankle, he wondered (and not for the first time) what madness it was that always got the Jaffordses out here. In his deepest heart he had an idea that madrigal would sow no more than the porin had before it, although you could grow devil-grass; yar, he could've bloomed all twenty acres with that shit, had he wanted. The trick was to keep it out, and it was always New Earth's first chore. It --
The plow rocked to the right and then jerked forward, almost pulling his arms out of their sockets. "Arr!" he cried. "Go easy, girl! I can't grow em back if you pull em out, can I?"
Tia turned her broad, sweaty, empty face up to a sky full of low-hanging clouds and honked laughter. Man Jesus, but she even sounded like a donkey. Yet it was laughter, human laughter. Tian wondered, as he sometimes couldn't help doing, if that laughter meant anything. Did she understand some of what he was saying, or did she only respond to his tone of voice? Did any of the roont ones --
"Good day, sai," said a loud and almost completely toneless voice from behind him. The owner of the voice ignored Tian's scream of surprise. "Pleasant days, and may they be long upon the earth. I am here from a goodish wander and at your service."
Tian whirled around, saw Andy standing there -- all seven feet of him -- and was then almost jerked flat as his sister took another of her large lurching steps forward. The plow's hame-traces were pulled from his hands and flew around his throat with an audible snap. Tia, unaware of this potential disaster, took another sturdy step forward. When she did, Tian's wind was cut off. He gave a whooping, gagging gasp and clawed at the straps. All of this Andy watched with his usual large and meaningless smile.
Tia jerked forward again and Tian was pulled off his feet. He landed on a rock that dug savagely into the cleft of his buttocks, but at least he could breathe again. For the moment, anyway. Damned unlucky field! Always had been! Always would be!
Tian snatched hold of the leather strap before it could pull tight around his throat again and yelled, "Hold, ye bitch! Whoa up if you don't want me to twist yer great and useless tits right off the front of yer!"
Tia halted agreeably enough and looked back to see what was what. Her smile broadened. She lifted one heavily muscled arm -- it glowed with sweat -- and pointed. "Andy!" she said. "Andy's come!"
"I ain't blind," Tian said and got to his feet, rubbing his bottom. Was that part of him also bleeding? Good Man Jesus, he had an idea it was.
"Good day, sai," Andy said to her, and tapped his metal throat three times with his three metal fingers. "Long days and pleasant nights."
Although Tia had surely heard the standard response to this -- And may you have twice the number -- a thousand times or more, all she could do was once more raise her broad idiot's face to the sky and honk her donkey laugh. Tian felt a surprising moment of pain, not in his arms or throat or outraged ass but in his heart. He vaguely remembered her as a little girl: as pretty and quick as a dragonfly, as smart as ever you could wish. Then --
But before he could finish the thought, a premonition came. He felt a sinking in his heart. The news would come while I'm out here, he thought. Out in this godforsaken patch where nothing is well and all luck is bad. It was time, wasn't it? Overtime.
"Andy," he said.
"Yes!" Andy said, smiling. "Andy, your friend! Back from a goodish wander and at your service. Would you like your horoscope, sai Tian? It is Full Earth. The moon is red, what is called the Huntress Moon in Mid-World that was. A friend will call! Business affairs prosper! You will have two ideas, one good and one bad -- "
"The bad one was coming out here to turn this field," Tian said. "Never mind my goddam horoscope, Andy. Why are you here?"
Andy's smile probably could not become troubled -- he was a robot, after all, the last one in Calla Bryn Sturgis or for miles and wheels around -- but to Tian it seemed to grow troubled, just the same. The robot looked like a young child's stick-figure of an adult, impossibly tall and impossibly thin. His legs and arms were silvery. His head was a stainless-steel barrel with electric eyes. His body, no more than a cylinder, was gold. Stamped in the middle -- what would have been a man's chest -- was this legend:
in association with
LaMERK INDUSTRIES
Design: MESSENGER (Many Other Functions)
Serial # DNF-44821-V63
Why or how this silly thing had survived when all the rest of the robots were gone -- gone for generations -- Tian neither knew nor cared. You were apt to see him anywhere in the Calla (he would not venture beyond its borders) striding on his impossibly thin silver legs, looking everywhere, occasionally clicking to himself as he stored (or perhaps purged -- who knew?) information. He sang songs, passed on gossip and rumor from one end of town to the other -- a tireless walker was Andy the Messenger Robot -- and seemed to enjoy the giving of horoscopes above all things, although there was general agreement in the village that they meant little.
He had one other function, however, and that meant much.
"Why are ye here, ye bag of bolts and beams? Answer me! Is it the Wolves? Are they coming from Thunderclap?"
Tian stood there looking up into Andy's stupid smiling metal face, the sweat growing cold on his skin, praying with all his might that the foolish thing would say no, then offer to tell his horoscope again, or perhaps to sing "The Green Corn A-Dayo," all twenty or thirty verses.
But all Andy said, still smiling, was: "Yes, sai."
"Christ and the Man Jesus," Tian said (he'd gotten an idea from the Old Fella that those were two names for the same thing, but had never bothered pursuing the question). "How long?"
"One moon of days before they arrive," Andy replied, still smiling.
"From full to full?"
"Close enough, sai."
Thirty days, then, give or take one. Thirty days to the Wolves. And there was no sense hoping Andy was wrong. No one kenned how the robot could know they were coming out of Thunderclap so...
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