**1. Introduction**

In North America and Europe, cancer involving the central nervous system (CNS) ranks second as the most common malignancy seen in infancy through adolescence, second only to leukaemia [1-7]. Consistent with this are figures on cancer-related mortality. In the year 2004, for example, there were 566 confirmed cases of leukemia-related death among children in the United States, followed by 555 CNS cancer-related deaths; these numbers accounted for 25.5% and 25.0% of the total number of cancer deaths in individuals less than 20 years old, respec‐ tively [4].

In general, survival from cancer has improved dramatically over the past forty years, pre‐ sumably due to a combination of improved treatments and earlier detection. This is especially true in the paediatric population, among whom the overall long-term survival rate across all cancers has risen from under 50% to roughly 70% [4;8;9]. Even with brain cancer, the prognosis in children has improved, such that long-term survival is now achieved in more than half of patients [10]. This being said, the neoplasm originates in the brainstem in roughly 10-20% of children with CNS cancer [7;11-13], accounting for 150 to 300 new cases per year in the U.S. [11;13] and thus rendering it more common in children and adolescents than in adults [14;15]. And in this subset of children, the prognosis generally is considered extremely bleak, akin to that of glioblastoma multiforme [1;4;14;16-19].

Despite a continued poor prognosis, much has changed over the past several decades — like how paediatric brainstem tumours are diagnosed and classified, if and when surgery is considered, approaches to surgery, the use of adjunct therapies like radiation and chemother‐ apy, and the evolution of several new therapeutic options. Once lumped together as a single

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entity that was considered inoperable and, hence, completely incurable, recent developments in imaging and surgical techniques have led to the classification of several different types of brainstem tumour; and, for some of these, surgical resection is considered the treatment of choice [16;18;20].

tended to be lumped together as a single clinical entity and considered uniformly inoperable [30]. Since they were presumed gliomas and surgery was deemed contraindicated, there was no call even to biopsy them, except in certain instances in which the diagnosis was in doubt. For example, in 1969, Matson wrote: "brainstem gliomas must be classified as malignant tumors since their location in itself renders them inoperable" [21]. And as late as 1984, Tomita et al. [31] wrote: "Since biopsy specimens often misrepresent the true pathology... surgery undertaken to obtain precise histological verification of brain stem gliomas is futile." Instead, these latter authors recommended computed tomography (CT) with high-resolution metriza‐ mide CT cisternography to distinguish surgically resectable extra-axial tumors adjacent to the brain stem from non-resectable intrinsic brain stem gliomas. Such sentiments — that tumours only were worth a biopsy if they were either completely exterior to brainstem tissue or, at worst, on the surface — were echoed by others [32]. Consequently, early classification of brainstem tumours often subdivided lesions into those that were exclusively or primarily intraaxial, and those that were exclusively or primarily extra-axial. Meanwhile, brainstem tumours were collectively contrasted against those involving the midbrain or thalamus, both of which

Paediatric Brainstem Cancers — Where We Have Been; Where We Are; Where We Are Going

http://dx.doi.org/10.5772/58297

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This being said, there were early reports of certain patients with brainstem tumours who survived long-term. For example, in 1971, Lassiter et al. reported on 37 patients with presumed brainstem gliomas (22 of them children), among whom there were four children with large, surgically-drained neoplastic cysts who achieved long-term survival: two of these children died 7½ and 13 years later, and two still were alive 8½ and 9 years post diagnosis, one of them going on to graduate from college and the other with residual hemiparesis and mental retardation [34]. In 1975, Hara et al. reviewed the cases of 24 brainstem gliomas, and found that the median survival was 9 months, except for one patient who survived beyond 4½ years and another who lived for 14 years and 10 months before succumbing to the disease [35]. Similar isolated cases of long-term survival with brainstem gliomas, especially cystic lesions, were reported as far back as 1937 and 1940 through the mid nineteen seventies and early eighties [36-42]. And, contrary to conventional wisdom, even then, some neurosurgeons were routinely performing biopsies and surgery on select patients with brainstem gliomas

In the nineteen sixties and early nineteen seventies, angiography and pneumoencephalograms were largely used to identify brain and brainstem tumours [47-50]. These imaging modalities were replaced in the mid nineteen seventies as computed tomography (CT) emerged as the imaging tool of choice for the detection and diagnosis of both supra-and infra-tentorial lesions, including brainstem tumours [51-54]. By this point, some surgeons were starting to distinguish outcomes between different subsets of patient who were able to undergo either partial or radical resection of brainstem cancers [27;40;41;43-45]. The first to propose what he termed a staging system for brainstem gliomas was Epstein, in 1985, who first categorized tumours as intrinsic, exophytic and disseminated; and then subcategorized intrinsic (actual brainstem) tumours as either diffuse, focal or cervico-medullary [43]. In 1986 and again in 1988, Epstein et al. published series of paediatric patients undergoing surgery for brainstem cancer, again classifying patients as focal, diffuse or cervico-medullary; in the latter report, they added a

exhibited considerably superior prognoses [33].

[27;40;41;43-46].

This chapter reviews the historical progression of understanding of paediatric brainstem tumours, including evolving beliefs regarding their classification, diagnosis, management, prognosis and prognosticators, dating from the 1970s to current times. It then describes current diagnostic and management protocols for these tumours, ending with a glance forwards towards potentially promising treatments and technologies and how they might, hopefully within the near future, favourably alter outcomes in these patients, both in terms of their survival and quality of life.
