A Literature Review of the Recent Radiotherapy Clinical Trials in Pediatric Brain Tumors

Abstract

Primary central nervous system neoplasms are the second malignancy in children following leukemia. Despite developments in neurosurgery and new drugs in chemotherapy, irradiation is an essential part of the management in most of pediatric brain tumors. A good treatment strategy should consider not only survival but also the quality of life. The new approach of radiotherapy and importance of new drugs in combined treatment are recently considered. This article summarizes the recent clinical trials conducted in pediatric brain tumors management. Results of randomized study of pre-irradiation chemotherapy versus radiotherapy alone for medulloblastoma were presented by SIOP/UKCCSG PNET-3. The French M-SFOP 98 protocol considered hyper-fractionated radiotherapy with reduced boost volume, without chemotherapy and estimated impact on early relapses and intellectual function. The influence of radiotherapy quality on survival in high-risk medulloblastoma patients was evaluated in POG Trial 9031. In the treatment of low-grade glioma in children the effectiveness of novel combination chemotherapy was considered. Role of new drugs as temozolamid, topotecan and RMP-7 was investigated in pediatric high grade glioma and brain stem tumors. Impact of combined treatment on outcome of intracranial germ-cell tumors was investigated as well.

The application of radiation therapy to the pediatric preclinical testing program (PPTP): Results of a pilot study in rhabdomyosarcoma

“…These consequences include impairments in IQ, growth retardation, organ dysfunction and the development of secondary malignancies; all of which hold a direct correlation to the integral and maximal radiation doses received [24,25]. Because of its late toxicity potential, attempts to scale back radiation dose or the removal of this modality entirely, based on population or clinical characteristics, has been met with increased treatment failures, especially when gross/measurable disease is present [26]. Only by incorporating radiotherapy into robust in vivo models, like the PPTP, can there be discovery of relevant radio-resistance mechanisms and their predictive biomarkers, as well as the comprehensive preclinical testing within the context of novel agents.…”

Institutional experience of paediatric high-grade central nervous system tumours: An analysis of 74 patients and review of the literature

“…Conformal RT techniques are performed using multiple treatment fields, allowing for a high homogeneous dose of irradiation to be delivered to the tumour region while minimizing the doses to normal tissue [31, 32]. The development of conformal radiation techniques has also opened the possibility for re-irradiation in the setting of failure after conventional treatment.…”

“…Children with HGG carry a little better prognosis than in adults, but outcomes for these patients also remain poor [31, 33]. These tumours are locally invasive and rarely present with signs of leptomeningeal or distant spread.…”

“…The standard adjuvant treatment consists of a combination of focal RT and CT in children > 3 years of age and CT alone for younger children. Some new drugs such as TMZ were well tolerated and somewhat effective in children with recurrent high-grade glioma but it is still unclear whether TMZ plus irradiation offers improved survival as compared to irradiation alone [31, 33, 38, 39]. We have a small number of patients treated with TMZ yielding limited information for an objective comment.…”

“…Concurrent RMP-7 and carboplatin with radiation therapy can be a feasible option, requiring more studies to prove the efficacy. Very little is known about the genetic and molecular biology of diffuse intrinsic pontine glioma, and if stereotactic biopsies can be performed at diagnosis, biological and molecular data will help to direct future targeted therapies [31, 33, 41–44]. We have used no CT in the majority of our patients with diffuse infiltrating pons glioma and used low dose or metronomic CT in the others.…”