Subsequent Quality of Life for Children Irradiated for a Brain Tumor Before Age Four Years
Jenkin D, Danjoux C, Greenberg M
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 1 de noviembre del 2001
Reviewers: John Han-Chih Chang, MD
Source: Medical and Pediatric Oncology 1998; Volume 31: pages 506 - 511.
Primary brain tumors are among the most common malignancy in the pediatric population. Historically, the patients have been treated withsurgery followed by postoperative radiation therapy (RT). The RT fields would encompass no less than the preoperative tumor (postoperativetumor bed) with a 2 cm margin. Most of the time, fields are initially larger to encompass the area of surrounding edema. This leads to anextensive amount of brain parenchyma being irradiated. It has also been recognized that the younger the pediatric patient is at the time of his orher RT, the higher the incidence of this morbidity. With that being stated, long term toxicity of cognitive and other neurological dysfunction insurvivors has become a significant issue. Attempts have been made to delay RT until the child is at least 36 months of age. Efforts have beenmade to omit RT and utilize other postoperative modalities, such as chemotherapy (ChT). This seems to be a promising avenue of treatmentthough not completely established, despite its new found prevalence in many pediatric centers.
This article attempts to review the experience of the primary brain tumor patients treated with surgery and RT at the University of TorontoCentres. Focus was mainly on quality of life, in particular neurocognitive sequelae of treatment.
Materials and Methods
This retrospective review focused on patients who were less than 4 years of age when diagnosed with a primary brain tumor. The populationconsisted of 222 children diagnosed between 1958 - 1995. All the RT was givenwith megavoltage equipment with a dose range of 45 - 55 Gy at a 1.8 - 2 Gy/fraction rate. Median survival was 12 months in the 96 survivors. Follow up status of the patients was made by evaluations at officevisits, from questionnaires and/or phone conversations. Factors evaluated were focal neurological deficits, ambulation, vision, hearing andschooling. Only 23 of the survivors were over the age of 21. Tumor type was found to be low grade astrocytomas in approximately 1/4th andmedulloblastomas in another 1/4th. Seventeen percent were ependymomas and 7% were high grade astrocytomas. Twenty eight percent werelisted as other types. Survival data were according to the Kaplan-Meier method.
Overall Survival (OS) was found to be 40% at 10 years which was not much different when compared to a larger cohort children aged older than4 years (45% at 10 years for 776 patients). This is depicted graphically on figure 1. As expected, there was a discrepancy in the OS at 10 yearsbased on tumor type: low grade astrocytoma 52%, medulloblastoma 44%, high grade astrocytoma 23% and ependymoma 18%. The OS at 10years was better in the completly resected patients than in the incompletely resected patients (60% versus 36%, respectively).Let us proceed to the main issue, which is the quality of life results. Approximately 90% of the patients were able to be evaluated for all of thefactors that were listed the materials and methods section. Major focal neurological deficits were found in 1/3rd of the patients who were lessthan 2 years old at the time of diagnosis. This is in contrast to only 22% of those who were 2 - 4 years old at the time of diagnosis developingdeficits. They further elaborated on specific findings listed below:
|Neurocognitive Deficit||Age less than 2 years old||Aged 2 - 4 years|
|Major Ambulation Difficulty||21%||10%|
|Major Visual Defect||35%||18%|
|Moderate to Severe Hearing Loss||11%||15%|
|In Regular School System||48%||46%|
|In Special or Blind Education||52%||51%|
Table 1 has a breakdown by age and neurocognitive deficit, which I have condensed above. Data on the 23 that had survived and were olderthan 21 yielded only 3 having acquired a university and 2 a community college degree. Fourteen had not received a "higher education." This isnot too far from the national average in Canada, which has an 11% rate of university graduates in its adult population.
Surgical/tumor complications were also seen in 28% of 93 patients currently alive. These may have had an effect on the deficits seen. Thecomplications include shunt revisions, meningitis, subdural effusions and re-exploration.
The authors state that over 80% of the adult survivors are capable of independent living. One third are able to live a normal life and compete forgainful employment at a normal level. But, nearly 40% will have some major neurocognitive deficit.
Discussion and Conclusion
Despite the lack of difference in the rate of hearing loss, regular school system attendance and rate of college education, it appears thatradiation after the age of 2 years is better than earlier radiation for preservation of neurocognitive function. At present, studies have shownsome promise in the area of postoperative ChT for primary brain tumors in the pediatric population with RT reserved for salvage. Most have notquite duplicated the same OS rates as immediate postoperative RT. Is it worth limiting the RT when it compromises the long term survival?
One drawback of this article and of most reviews on neurocognitive sequelae of treatment in children is the lack of standardized testing beforesurgery and/or RT. That testing could have been truly revealing as to whether the tumor, surgery or the RT was the culprit behind the deficit.On the other hand, such tests performed in younger children may be inherently inaccurate. Another criticism is that some of the data wereobtained from questionnaires and phone calls. Finally, little was made about a comparison to those with primary brain tumors who did notreceive RT. Hopefully, future and current randomized trials will answer not only OS data, but quality of life on those who do and those thatnever receive RT.
Overall, this article did suggest that not all survivors of childhood primary brain tumors perform poorly in neurocognitive functioning. Asignificant proportion can function normally in society. But, it does make us aware of the critical issue of neurologic toxicity from definitivetreatment. Limiting this morbidity without compromising survival outcome is the necessary next step.
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