plasms of the nervous system whose tumor type andof the optic nerves a - PDF document

158 plasms of the nervous system whose tumor type andof the optic nerves and chiasm are strongly associ-gamut from very benign astrocytomas, considered by 3601_e05_p158-170 2/15/02 4:31 PM Page 158 progress at all or progress over many years. Poste-virtually indistinguishable from a primary hypothala- 3601_e05_p158-170 2/15/02 4:31 PM Page 159 ing from rare reports of spontaneous tumor regres- Clinic at The University of Texas M. D. Anderson Cancer Center, 1980 to 1993* No.%Total60100Neurofibromatosis (NF)3154Male3457Female2643Decreased visual acuity or blindness2847Visual field deficit1220Nausea/vomiting1746Headache1932Failure to thrive and diencephalic syndrome610Behavioral problems (irritability, social1220No symptoms with NF127Endocrine complaints47Multilobular suprasellar-optic chiasmal masses3558Optic nerve and chiasmal swelling1732Isolated optic nerve610 Hydrocephalus2338 3601_e05_p158-170 2/15/02 4:31 PM Page 160 to 90%) for those with optic chiasmal tumors(Packer et al., 1983; Pierce et al., 1990; Horwichand Bloom, 1985; Tao et al., 1997). Upon carefulexamination, it can be observed that chiasmal in-volvement that is not extensive and not associatedwith a large exophytic mass may also carry an ex-cellent prognosis. The characteristics of tumors withthe worst prognosis include early onset in infancy,hypothalamic symptoms, signs of hydrocephalus,presence of diencephalic syndrome, third ventricu-lar involvement, and large chiasmal tumors extend-ing posteriorly. It is most difficult to determine thebest treatment for young children with these char-acterist

ics because aggressive treatment with sur-gery and irradiation do not necessarily lead to thebest survival rates or the best quality of life (Jan-noun and Bloom, 1990).In evaluating the effects of the tumor itself and thetreatment of optic chiasmal gliomas, the series fromSan Francisco (Hoyt and Baghdassarian, 1969; Imesand Hoyt, 1986) is useful because of its long-termfollow-up period and its evaluation of the actualcauses of death. In the original 1969 report, 8 of 28patients were dead, and at follow up 15 years later 8more had died, leaving only 12 (46%) of 28 surviv-ing at a median follow up of 20 years. Nine of the 16deaths occurred in patients with neurofibromatosis;only two of these patients had died of their chiasmaltumors. The remaining died of other malignantgliomas of the brain, neurofibrosarcomas of periph-eral nerves, or complications of management of cer-vical neurofibromas. Of the seven who died withoutneurofibromatosis, five died as a result of tumor andthree died of unrelated medical illnesses. Of those pa-tients treated with radiation, 4 of 14 patients died be-cause of their tumor, whereas only 5 of 14 who didnot receive radiation died, 1 from tumor and 4 fromother causes.On the basis of these data, no benefit from radio-therapy (RT) could be demonstrated. In addition, therisk of death from tumor was greatest in the early follow-up period. However, most other investigatorshave concluded that RT does improve survival anddoes prolong the interval before disease progression(Alvord and Lofton, 1988; Pierce et al., 1990; Hor-wich and Bloom, 1985; Tao et al.

, 1997). For exam-ple, in a series of 26 children with chiasmal gliomastreated with RT at the Joint Center for Radiation Ther-apy, 60% had objective tumor shrinkage that oc-curred gradually over a period of 5 years. Vision ei-ther improved or stabilized in 72.7% of the children.The 15 year overall survival rate was 85.1% and free-dom from progression was 82.1%, with median fol-low up of 108 months (Tao et al., 1997).Optic Nerve, Chiasmal, and Hypothalamic Tumors161 Age at onsetEarly childhood to adolescenceClinical featuresVisual loss with lateralitySlowly progressive or arrested courseRadiographic featuresIntrinsic optic nerve and/or chiasmal locationAge at onsetInfancy to early childhood and adulthoodClinical featureHypothalamic symptoms and/or signs of increasedRadiographic featuresLarge exophytic chiasmal tumor with posterior extension HydrocephalusAdapted from Kanamori et al. (1985) and Alvord and Lofton (1988). 3601_e05_p158-170 2/15/02 4:31 PM Page 161 for both hypopituitarism and endocrine-active syn- 3601_e05_p158-170 2/15/02 4:31 PM Page 162 gressive visual loss and progressive proptosis. Sur-chiasm produces obstructive hydrocephalus; in suchcious puberty.progression occur. For those who show unfavorable 3601_e05_p158-170 2/15/02 4:31 PM Page 163 age of the individual. For patients who have extensivetumors invading the hypothalamus, extending to thethird ventricular region, with massive infiltrationalong the optic tracts, or with clear-cut evidence ofrapidly progressive disease at the time of diagnosis,a delay in treatment is not recommended. However,

in those few cases of tumors where surgical decom-pression and improvement of vision have occurred,especially in young children, very close follow upwithout intervention until objective signs of progres-sion occur is also an acceptable alternative.RadiationMost modern reports utilizing megavoltage RT docu-ment an advantage for patients who have progressivechiasmal gliomas (Pierce et al., 1990; Horwich andBloom, 1985; Wong et al., 1987; Tao et al., 1997).Radiation therapy is generally the treatment of choicefor symptomatic chiasmatic/hypothalamic gliomas inolder children. Many recent series report excellentsurvival after RTÑgenerally 90% at 10 years (Pierceet al., 1990; Horwich and Bloom, 1985; Tao et al.,1997). However, deaths can occur from disease pro-gression many years after treatment, and, thus, long-term follow up is critical in the management of thisdisease.Outcome in terms of vision is an important mea-sure of treatment success for chiasmal/hypothalamicgliomas. Following RT, vision is improved in approx-imately one-third of patients, with most patients ex-periencing visual stabilization (Pierce et al., 1990;Tao et al., 1997). This success in maintaining or im-proving vision is possible only if treatment is initiatedbefore severe visual damage has occurred. Therefore,documented visual deterioration is a major indica-tion for the prompt initiation of therapy.The overall survival rate for patients with optic sys-tem gliomas is excellent. However, conventional RThas been associated with significant morbidity. Mostradiation fields cover not only the tumor bed (tumorv

olume) but also tissues thought to be at risk for mi-croscopic disease to allow for uncertainty in tumordefinition and for inconsistencies in the daily treat-ment set-up (target volume). The tolerance of thenormal brain parenchyma and its vascular and sup-porting structures becomes, therefore, the limitingparameter of external-beam therapy, and the risks of acute and long-term sequelae are major dose-limiting factors. Permanent radiation injury can in-clude pituitary-hypothalamic dysfunction as well asmemory and intellectual deficits. Young children areat greater risk than adults (Glauser and Packer, 1991;Ellenberg et al., 1987; Ater et al., 1999). After irra-diation, 72% of children treated at the Joint Centerfor Radiation Therapy developed new onset of hy-popituitarism, most commonly growth hormone de-ficiency in 59%, with panhypopituitarism in 21% (Taoet al., 1997).With conventional fractionation schedules (1.8Gy/day), total doses of 50 to 54 Gy are consideredstandard for the treatment of optic gliomas. Late ef-fects appear in a predictable manner in terms of ra-diation dose, volume, and fractionation. Fractionationexploits the differences in response to irradiation be-tween normal brain and tumor tissue; normal tissuestolerate multiple small doses of irradiation much bet-ter than they tolerate a single, large fraction.Until recently, greater precision in the delivery ofconventional RT was limited by an incomplete diag-nostic definition of tumor volumes, unsophisticatedtreatment planning systems, and imprecise immobi-lization devices. Computed tomography and MRI nowp

rovide much improved delineation of CNS neo-plasms, and three-dimensional treatment planningsystems are currently available. These technologicaladvances allow for accurate focal administration of adose to the target area and have thus promoted thewidespread use of radiosurgery techniques.Stereotactic RadiosurgeryStereotactic radiosurgery is a highly accurate andprecise technique that utilizes stereotactically di-rected convergent beams of ionizing radiation to treata small and distinct volume of tissue with a single radiation dose. The multiple-beam approach of ra-diosurgery results in sharp dose fall-off beyond thetarget, thus sparing adjacent normal tissue. The tech-nique must, however, be reserved for select small le-sions because it ablates both normal and abnormaltissue within the treatment volume. Some investiga-tors have advocated using stereotactic radiosurgeryto reduce the treatment volumes of discrete, well-circumscribed lesions, although certain parameters,including the size and location of the target volume,are associated with complications from radiosurgery(Marks and Spencer, 1991; Loeffler and Alexander,1993; Tishler et al., 1993). Certain intracranial le-sions cannot be treated safely or effectively with ra-164PRIMARY CENTRAL NERVOUS SYSTEM TUMORS 3601_e05_p158-170 2/15/02 4:31 PM Page 164 are noninvasive or non- 3601_e05_p158-170 2/15/02 4:31 PM Page 165 median of 12 points from baseline (Janss et al., 3601_e05_p158-170 2/15/02 4:31 PM Page 166 visual loss, compressing the optic nerves from abovetype visual loss. 3601_e05_p158-170 2/15/02 4:31

PM Page 167 have a very firm consistency. 3601_e05_p158-170 2/15/02 4:31 PM Page 168 SurgeryThe surgical principles utilized in the management ofcraniopharyngioma are a subject of some contro-versy. It is clear that a proportion of these lesions,particularly cystic lesions in children, can be totallyexcised. Ordinarily this is accomplished using a cran-iotomy for those lesions that are suprasellar. Thecraniotomy procedure utilized to attack a cranio-pharyngioma can be tailored to the position and ex-tent of the lesion. Subfrontal, frontotemporal (pteri-onal), and a variety of skull base approaches can beutilized to approach and effectively remove these le-sions. A scrupulous microsurgical technique is es-sential and can provide good results in both extent oftumor removal and preservation or restoration of vi-sion. If a craniopharyngioma is associated with sig-nificant enlargement of the sella, then the tumor mayhave had its origin below the diaphragma sella andmay be amenable to total removal using thetranssphenoidal approach. For these lesions, the sizeof the sella, whether the tumor is primarily cystic orprimarily solid, and whether calcifications are pres-ent can be important factors in determining the ex-tent of debulking. Many suprasellar craniopharyn-giomas, particularly in older patients, are intimatelyassociated with the floor of the third ventricle, the hy-pothalamus, and the optic chiasm. In such cases, at-tempts at total removal can produce significant neu-rologic damage; thus the surgeon must use goodjudgment in attempting complete tumor removal. Of-ten

, it is better to remove the bulk of the tumor andto treat the small remnants adherent to vital struc-tures with postoperative irradiation.RadiotherapyConventional RT has been effective for craniopharyn-giomas (Hetelekidis et al., 1993). For the reasonsstated previously, however, conventional RT is notrecommended for the immature brain (generally,children 3 years of age or younger). Stereotactic tech-niques include radiosurgery, stereotactic RT, and di-rect colloid instillation into cystic craniopharyn-giomas. Radiosurgery has been utilized for adjunctivemanagement of craniopharyngiomas. However, be-cause the chiasm is often in close proximity, the sameconstraints as discussed earlier apply for cranio-pharyngiomas (Tarbell et al., 1994).Radiosurgery should only be considered whenthere is a very small area (less than 2 cm) of resid-ual/recurrent tumor that is away from the optic chi-asm. Direct instillation of colloidal radioisotopes intothe cysts of primarily cystic tumors appears effectivewhen appropriately applied. This technique has beenwidely used in Europe with limited experience in theUnited States. Stereotactic radiation or conformal ra-diation treatments using conventional fractionationmay be the safest mode of treatment for patients witha solid component of residual disease.REFERENCESAlvord EC Jr, Lofton S. 1988. Gliomas of the optic nerve orchiasm: outcome by patientsÕ age, tumor site, and treat-ment. J Neurosurg 68:85Ð98.Ater JL, Moore BD, Slopis J, Copeland D. 1999. Neuropsy-chological effects of focal cranial radiation therapy on chil-dren treated for brain

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