Report of the Brain Tumor Progress

INTRODUCTION

Brain tumors represent a unique challenge in that they affect the organ that is the essence of the "self." Furthermore, because each area of the brain serves a different but vital function, the therapy that is most effective for other cancers--surgical removal of either the entire organ or the tumor with a generous surround of normal tissue--cannot be used to cure brain tumors. Unfortunately, most brain tumors are relatively insensitive to other cancer treatment, including radiation and chemotherapy.

Coupled with the difficulty in treating brain tumors is the unique biology of the brain:

• Brain tumors occur in an organ that is enclosed in a bony canal that allows little room for growth of the tumor without compressing and damaging normal brain.

• Many brain tumors extensively invade normally functioning brain, making complete surgical removal impossible.

• In their early stages, brain tumors are protected behind a blood-brain barrier; even when this barrier is disrupted in the bulk of the tumor, infiltrating tumor cells at the growing edge remain protected.

• Disruption of the blood-brain barrier leads to edema, which the brain tolerates poorly because of the limited intracranial space and the lack of lymphatics to rid itself of the products of edema and other debris.

• The brain itself is rich in expressed genes and therefore is a fertile field for the growth of both primary tumors and metastases.

• The brain and brain tumors appear to be less susceptible to attack by the immune system than are tumors in other organs. Even the term brain tumor, which suggests a single type of tumor, can be misleading. There are a bewildering variety of central nervous system tumors; the World Health Organization lists 126. Many of these tumors are not, strictly speaking, in the brain but arise from structures intimately associated with that organ, such as tumors of the covering membranes (meningiomas) and adjacent cranial and paraspinal nerves (schwannomas). Brain tumors range from benign (most meningiomas) to highly aggressive (glioblastomas). They affect both adults and children (although the distribution of tumors varies) and are often highly resistant to treatment.

The term brain cancer is also misleading. Most cancers that arise elsewhere in the body cause damage by metastasizing to other organs (including the brain). Primary brain tumors, however, rarely metastasize, although they may widely infiltrate the nervous system. Conversely, many cancers metastasize to the brain, making metastatic brain tumors much more common than primary brain tumors.

Throughout this document, the term brain tumor is used to refer to all tumors that grow inside the skull. The issues discussed in this document, however, also extend to tumors growing within the spinal canal.