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Radiotherapy


Endocrine Complications in Children Treated for Medulloblastoma or Ependymoma using Radiation Therapy – Outcomes in the Computed Tomography Planning Era


Stacey L Urbach,1 Normand Laperriere2 and Ute Bartels3


1. Assistant Professor, Department of Paediatrics, Division of Endocrinology, The Hospital for Sick Children; 2. Associate Professor, Department of Radiation Oncology, Princess Margaret Hospital, Toronto; 3. Assistant Professor, Department of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children


Abstract


Radiation therapy is an integral part of the treatment of paediatric patients with medulloblastoma and ependymoma. With newer surgical techniques and adjuvant chemotherapy regimens, recurrence-free survival rates have improved dramatically. Unfortunately, improved survival has come at the cost of significant late effects, including endocrine dysfunction. Prior to the 1990s, radiation fields were planned using 2D X-rays, exposing large volumes of healthy tissue to harmful radiation. Over the past two decades, radiation oncologists have increasingly applied 3D computed tomography scans to radiation therapy planning. By shaping target fields more precisely, higher doses of radiation may be delivered directly to the tumour while limiting exposure to healthy tissues and reducing side effects. The objective of this article is to review recent evidence about late endocrine effects among survivors of childhood medulloblastoma and ependymoma who received radiation therapy and to assess whether the introduction of 3D radiation planning techniques has affected the prevalence of these effects. Patients treated for medulloblastoma with current doses of craniospinal radiation continue to be at high risk of growth hormone deficiency and primary hypothyroidism, even when conformal radiation is used to deliver posterior fossa radiation. Patients with ependymoma who are treated with focal radiation alone, however, demonstrate fewer late endocrine effects.


Keywords


Brain tumour, radiation therapy, computed tomography (CT) planning, growth hormone, thyroid hormone, adrenocorticotropin hormone (ACTH), endocrine, paediatrics, late effects, cancer


Disclosure: Stacey L Urbach and Ute Bartels have no conflicts of interest to declare. Normand Laperriere is a consultant and serves on the speaker’s bureau and advisory boards for Schering Plough/Merck. Received: 19 March 2010 Accepted: 14 January 2011 Citation: European Oncology & Haematology, 2011;7(1):48–52 Correspondence: Stacey L Urbach, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. E: stacey.urbach@sickkids.ca


Radiation therapy as a means to improve outcome for a patient suffering from medulloblastoma was first used by Cushing in the 1920s. In 1953 Patterson and Farr reported their success on 27 medulloblastoma patients treated with craniospinal irradiation.1


As


technology has improved, radiation oncologists have developed techniques to deliver higher-energy radiation beams that are more effective at destroying malignant cells. Newer table designs and the advent of the linear accelerator have allowed beams to be delivered from various angles. With the introduction of computed tomography (CT) in 1971, radiologists and radiation oncologists were able to visualise anatomy in 3D. It was not until the 1990s, however, that CT was applied to radiation therapy planning, allowing radiation oncologists to shape their target fields in a more precise manner.2


By


limiting exposure of the healthy tissues, higher doses of radiation could be delivered to the tumour while reducing side effects.


Radiation therapy is an integral part of the treatment of paediatric patients with medulloblastoma and ependymoma. In general, patients with medulloblastoma are treated with surgical resection followed by radiation given to the craniospinal axis (craniospinal irradiation [CSI]) with an additional boost to the posterior fossa or tumour bed


48


followed by chemotherapy.3


Implementation of chemotherapy into the


treatment of medulloblastoma has increased the chances of cure while allowing irradiation dose reduction.4


Despite this, conventional


chemotherapy is considered of limited effectiveness in ependymoma. In North America, patients with gross total resected (GTR) M0 ependymoma (except GTR of supratentorial WHO II ependymoma) are currently treated with conformal radiation to the tumour site with or without adjuvant chemotherapy.


With newer surgical techniques and adjuvant chemotherapy regimens, recurrence-free survival rates have exceeded 85% for average-risk medulloblastoma.4


Most recent publications report a seven-year overall survival of 81% for ependymoma patients treated with focal irradiation.5 Unfortunately, improved survival has come at a cost, especially when whole-brain irradiation is required. Many patients experience significant late side effects, including neurocognitive and endocrine dysfunction.6


Radiation oncologists have worked to develop techniques that enhance the delivery of radiation therapy to malignant areas while limiting the exposure of healthy tissues, including the cerebral cortex and hypothalamic pituitary axis. Over the past decade, they have


© TOUCH BRIEFINGS 2011


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