Treatment of Cancer

Pat Price, Pat Price, Karol Sikora

• Publisher: CRC Press
• Year: 2014
• ISBN:
  9780429586040
• Edition: 6
• Topic: Medizin
• Subtopic: Medizinische Theorie, Praxis & Referenz

Treatment of Cancer, Sixth Edition is a multi-authored work based on a single theme-the optimal treatment of cancer. A comprehensive guide to modern cancer treatment, it supports an integrated approach to patient care including radiotherapy, chemotherapy and surgery. The sixth edition has been completely updated to create a useful, practical guide

1

Central nervous system

ANTHONY CHALMERS, ALLAN JAMES AND ROY RAMPLING

The central nervous system (CNS) is host to a remarkable variety of primary tumours that demonstrate an equal diversity of clinical behaviour, response to treatment and prognosis. Although most malignant tumours still carry a bleak prognosis, worthwhile extension of life can be achieved in many patients. For those with more responsive tumours, adequate management can provide prolonged survival or cure. An accurate diagnosis is required in almost all cases, and advances in neuro-imaging, neurosurgical technique and neuropathology now facilitate this. Molecular analysis is having an increasing impact on the management of brain tumours, with a number of useful prognostic and predictive markers having emerged over the past decade.

PATHOLOGY

Incidence

The overall incidence (see also Table 1.1) of primary CNS tumours in the United Kingdom is around 15 per 100,000, of which around half are malignant. In 2010, there were 9156 new cases in the United Kingdom, with equal numbers in men and women.

Table 1.1 Approximate incidence rates (worldwide) for brain tumour types (per 100,000/year)

Tumour type	Incidence
Astrocytoma	1.5
AA	1.0
GBM	3
Meningioma	3
CNS lymphoma: immune competent	0.3
CNS lymphoma: overall	0.8-6.8
Medulloblastoma	0.5
Germ cell tumours	0.2
Pinealoma/pineoblastoma	0.1
Metastases	8

Brain tumours account for approximately 1.6% of all primary tumours, but they account for nearly 7% of the number of years of life lost from cancer before the age of 70 years. The rate of brain tumour registration in the United Kingdom increased by 17% in the decade 1991–2000, but it has subsequently stabilized. Although some of this increase is due to improved diagnosis, there is evidence of an underlying increase in incidence, particularly among the elderly.¹

Age

Brain tumours occur at any age, from neonates to the elderly. The age-specific incidence shows a small peak in early childhood and a poorly defined minimum in teenage years, rising at an increasing rate to a second major peak at around 75 years. Most series report a decline in incidence after 75–80 years, but this may be an artefact of data collection. It is important to recognize that the brain is the most common site for solid tumours in childhood.

The tumour spectrum also varies with age. The majority of brain tumours in children (70%–80%) arise infratentorially (glial tumours and medulloblastoma) or in the midline (germ cell tumours and craniopharyngioma). Low-grade glial tumours are common, particularly pilocytic astrocytoma. In adults, most brain tumours are supratentorial. Gliomas, particularly glioblastomas (GBMs), and meningiomas predominate.

Sex

Most brain tumours occur more commonly in males than in females, particularly medulloblastomas, germ cell tumours, astrocytomas and oligodendrogliomas, and this difference is more marked above the age of 60 years. Some tumours, such as ependymomas and nerve sheath tumours, are equally distributed, and meningiomas are more common in females.

Aetiology

Ionizing radiation is the only environmental factor that is clearly associated with an increased risk of developing a brain tumour. Radiation-induced tumours include astrocytomas of all grades, benign and malignant meningiomas, sarcomas and nerve sheath tumours. A number of genetic syndromes is associated with an increased risk of brain tumour; these are described in Table 1.2. Immunosuppression (e.g., transplant recipients and AIDS) predisposes to primary CNS lymphoma (PCNSL), which is also associated with the Epstein–Barr virus genome in 95% of cases. There is no evidence that any other aetiological factor plays a role in brain tumour carcinogenesis. In particular, industrial chemicals, bacteria, head injury, exposure to non-ionizing radiation (e.g., power lines and mobile phones), diet and tobacco have all been studied but do not appear to be linked.²

Tumour types

A robust pathological classification system that can be used by clinicians to predict tumour behaviour and inform management is essential. The World Health Organization (WHO) classification for CNS tumours was updated in 2007³ and is almost universally accepted for this purpose. A modestly abridged version is shown in Box 1.1. The classification separates tumour types according to tissue of origin and subsequently cell of origin. Further classification recognizes features of the tumour and assigns a ‘grade’ to each tumour according to its degree of malignancy. Care must be taken when comparing modern studies with older clinical series that may have used different classification schemes.

Conventional light microscopy provides the backbone of pathological analysis but is often insufficient to produce a complete diagnosis, and the discriminatory role of immunohistochemistry is now indispensable. Glial fibrillary acidic protein (GFAP) is valuable in identifying normal astrocytes and tumour cells of astrocytic origin, but non-astrocytic and even some non-glial tumours may be positive. Diagnosis of lymphomas, germ cell tumours, sarcomas and metastases is often confirmed by immunostaining (see entry under each tumour type later in this chapter.).

A major change over the past decade has been the growing role of molecular and genetic diagnostic tools, in identifying and classifying tumours, in providing prognostic information and in some cases predicting response to treatment.

Molecular biology of brain tumours

Increasing data describe the molecular and genetic landscape of primary brain tumours (see also Table 1.3^{3, 4}).In the context of glial tumours, it is sometimes possible to document evolving genetic changes that correlate with and may drive the process of transformation from low-grade to high-grade tumours. Some common abnormalities have been identified that have diagnostic and prognostic value and influence treatment. In the context of medulloblastoma, a number of genetic and molecular markers have been described that provide useful prognostic information and are increasingly being used to determine treatment approaches. However, many adult brain tumours exhibit a bewildering array of mutations and chromosomal rearrangements that reflect severe genomic instability and render the interpretation of gene expression data very difficult and potentially misleading. To cover this important and rapidly evolving area, the key histological tumour types are considered individually.

Table 1.2 Genetic syndromes associated with an increased risk of brain tumour

Syndrome	Brain tumour	Other associations	Genetics
Neurofibromatosis I	Neurofibromas Gliomas Sarcomas	Pigmentation Peripheral neurofibromas Osseous and vascular lesions	NF1 on 17q11 Autosomal dominant
NF2	Schwannomas (acoustic neuromas) Meningiomas, Gliomas (especially spinal)	Cerebral calcification Lens opacities	NF2 on 22q12 Autosomal dominant
Von Hippel-Lindau	Haemangioblastoma	Retinal haemangioblastoma Renal carcinoma Phaeochromocytoma Visceral cysts	VHL on 3p25-26 Autosomal dominant
Cowden's	Dysplastic gangliocytoma of cerebellum	Peripheral hamartomas Breast cancer Thyroid neoplasia	PTEN/MMAC1 on 10q23 Autosomal dominant
Turcot's	GBMs Medulloblastomas	Colorectal tumours	MLH1 or PMS2 APC Inheritance unclear
Tuberose sclerosis	Subependymal giant-cell astrocytoma Hamartomas	Angiofibromas Hypomelanotic patches	TSC1 on 9q34 TSC2 on16p13 Autosomal Dominant
Li Fraumeni	Gliomas PNETs	Sarcomas Breast cancer	TP53 on 17p13 Autosomal dominant
Basal naevus	Medulloblastomas	Basal-cell carcinomas Bone abnormalities Palmer pits	PTCH on 9q22 Autosomal dominant

PNET, primitive neuro-ectodermal tumour; PTCH, patched gene.

Box 1.1 World Health Organization grading of tumours of the central nervous system (2007)

Tumours of neuroepithelial tissue	WHO grade
Astrocytic tumours
Pilocytic astrocytoma	1
Pilomyxoid astrocytoma	2
Subependymal giant cell astrocytoma	1
Pleomorphic xanthoastrocytoma	2
Diffuse astrocytoma (variants: fibrillary, gemistocytic and protoplasmic)	2
Anaplastic astrocytoma	3
Glioblastoma (variants: giant cell and gliosarcoma)	4
Gliomatosis cerebri
Oligodendroglial tumours
Oligodendroglioma	2
Anaplastic oligodendroglioma	3
Oligoastrocytomas
Oligoastrocytoma	2
Anaplastic oligoastrocytoma	3
Ependymal tumours
Subependymoma (variant: myxopapillary ependymoma)	1
Ependymoma (variants: cellular, papillary, clear cell and tanyctic)	2
Anaplastic ependymoma	3
Choroid plexus tumours
Choroid plexus papilloma	1
Atypical choroid plexus carcinoma	2
Choroid plexus carcinoma	3
Other neuroepithelial tumours
Astroblastoma	1
Angiocentric glioma	1
Chordoid glioma of the third ventricle	2
Neuronal and mixed neuronal-glial tumours
Gangliocytoma	1
Ganglioglioma	1
Anaplastic ganglioglioma	3
Desmoplastic infantile astrocytoma and ganglioglioma	1
Dysembryoplastic neuroepithelial tumour	1
Neurocytoma (central or extraventricular)	1
Cerebellar liponeurocytoma	2
Paraganglioma of the spinal cord	1
Papillary glioneuronal tumour	1
Rosette-forming glioneuronal tumour of the fourth ventricle	1
Pineal tumours
Pineocytoma	1
Pineal parenchymal tumour of intermediate differentiation	2, 3
Pineoblastoma	4
Papillary tumour of the pineal region	2, 3
Embryonal tumours
Medulloblastoma	4
CNS primitive neuro-ectodermal tumours	4
Atypical teratoid/rhabdoid tumour	4
Tumours of the cranial and paraspinal nerves
Schwannoma (variants: cellular, plexiform and melanotic)	1
Neurofibroma (variant: plexiform)	1
Perineurioma	1, 2
Malignant perineurioma	3
Malignant peripheral nerve sheath tumour	2, 3, 4
Tumours of the meninges
Meningiomas
Meningioma (several variants)	1
Atypical meningioma	2
Anaplastic (malignant) meningioma	3
Mesenchymal tumours
Haemangiopericytoma	2
Anaplastic haemangiopericytoma	3
Haemangioblastoma	1
Lymphomas and haematopoeitic neoplasms
Malignant lymphomas
Plasmacytoma
Granulocytic sarcoma
Germ cell tumours
Germinoma
Embryonal carcinoma
Yolk sac tumour
Choriocarcinoma
Teratoma (matu...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• Foreword
• Preface
• An overview of cancer care
• Contributors
• List of abbreviations used
• Evidence scoring
• Reference annotation
• 1 Central nervous system
• 2 Ocular and adnexal tumours
• 3 Head and neck cancer
• 4 Thyroid
• 5 Endocrine and neuroendocrine tumours
• 6 Breast cancer
• 7 Lung cancer
• 8 Oesophageal cancer
• 9 Hepatocellular carcinoma
• 10 Pancreas
• 11 Biliary tract cancer
• 12 Gastric cancer
• 13 Bladder cancer
• 14 Prostate cancer
• 15 Colorectal cancer
• 16 Anal cancer
• 17 Germ-cell cancer of the testis and related neoplasms
• 18 Renal cell cancer
• 19 Ovarian and fallopian tube cancer
• 20 Endometrial cancer
• 21 Cervical cancer
• 22 Carcinoma of the vagina and vulva
• 23 Gestational trophoblastic neoplasia
• 24 Non-melanoma skin cancer
• 25 Malignant melanoma
• 26 Primary bone tumours
• 27 Soft tissue sarcomas
• 28 Leukaemias
• 29 Hodgkin lymphoma
• 30 Non-Hodgkin lymphoma
• 31 Multiple myeloma
• 32 Paediatric oncology
• 33 AIDS-related malignancy
• 34 Clinical cancer genetics
• 35 Lifestyle factors in cancer survivorship