Central Nervous System Cancers

The incidence of primary malignant brain tumors is increasing, especially in the elderly, and metastatic disease to the central nervous system (CNS) occurs even more frequently (an incidence about 10 times that of primary brain tumors). In fact, estimates are that 20% to 40% of patients with systemic cancer will develop brain metastases. Primary and metastatic brain tumors are heterogeneous, with varied outcomes and management strategies. Primary brain tumors range from the rare but surgically curable pilocytic astrocytomas to the much more common and virtually incurable glioblastoma multiforme. Similarly, patients with metastatic brain disease may have one or dozens of brain metastases that are highly responsive or highly resistant to radiation or chemotherapy. This marked heterogeneity means that prognostic features and treatment options must be carefully reviewed for each patient. As these guidelines note, the involvement of an interdisciplinary team is key in the appropriate management of these patients. Important updates to the guidelines include the addition of systemic chemotherapy as a salvage therapy treatment option for local recurrence and limited metastatic lesions and it’s deletion as an option for multiple metastatic lesions.

Special Features

Fatigue is the Most Important Symptom for Advanced Cancer Patients Who Have Had Chemotherapy
Zeeshan Butt, PhD; Sarah K. Rosenbloom, PhD; Amy P. Abernethy, MD; Jennifer L. Beaumont, MS; Diane Paul, MS, RN; Debra Hampton; Paul B. Jacobsen, PhD; Karen L. Syrjala, PhD; Jamie H. Von Roenn, MD; and David Cella, PhD

Cancer-related fatigue has been described as an important problem, but few studies have assessed the relative importance of fatigue against other patient symptoms and concerns. To explore this issue, 534 patients and 91 physician experts were surveyed from 5 NCCN member institutions and community support agencies. Specifically, patients were asked about the “most important symptoms or concerns to monitor.” Across the entire sample and individually in some cancers, fatigue emerged as a top-ranked symptom. Expert ratings of the extent to which fatigue is attributable to disease versus treatment suggested in most cases that both causes play an important role, with disease-related cause most predominant in hepatobiliary and lung cancer, and treatment-related factors playing a stronger role particularly in head and neck cancer.

Featured Articles

Guidelines for the Initial Management of Metastatic Brain Tumors: The Role of Surgery, Radiosurgery, or Radiation Therapy
Matthew G. Ewend, MD; David E. Morris, MD; Lisa A. Carey, MD; Alim M. Ladha, MD;
and Steven Brem, MD

Brain metastases are an increasingly important determinant of survival and quality of life in patients with cancer. Current approaches to the management of brain metastases are driven by prognostic factors, including the Karnofsky Performance score, tumor histology, number of metastases, age, and status of systemic disease. Remarkable advances in computer-assisted neuronavigation have made neurosurgical removal of metastases safer, even in “eloquent areas” of the brain. Computerization has also enhanced the efficacy and safety of conformal radiosurgery planning using a variety of modern stereotactic radiosurgery (SRS) technologies, including newer frameless based systems. More controversial issues include 1) whether to defer whole brain radiotherapy (WBRT) in a patient receiving SRS or image guided surgery, and 2) when to use SRS “boost” in a patient receiving WBRT. The determination of how best to apply these treatments for an individual patient cannot be standardized to a single paradigm, but data from well-controlled studies helps physicians make informed decisions about the benefits and risks of each approach.

Antiangiogenesis Treatment for Glioblastoma Multiforme:  Challenges and Opportunities
Eric T. Wong, MD, and Steven Brem, MD

Angiogenesis is a major hallmark of cancer cells, and glioblastomas are one of the most angiogenic tumors known to man. The cascade of angiogenesis is probably initiated by hypoxia, leading to the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Both VEGF and bFGF have paracrine effects on endothelial cells, pericytes, or both. As a result, hyperpermeable tumor blood vessels are formed. Because a decrease in vascular permeability and perfusion can be detected after antiangiogenesis drug treatment, either with a monoclonal antibody or small molecule VEGF receptor tyrosine kinase inhibitors, these therapies are increasingly used to treat glioblastomas. This review summarizes 30 years of laboratory and clinical research on glioblastoma angiogenesis and discusses its underlying biology, clinical trial results, vascular neuroimaging, and the potential side effects of antiangiogenesis treatment.