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. 2014 Jun;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080

RADIATION ONCOLOGY

PMCID: PMC4046296
Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.1

RO-002. RADIOTHERAPY FOR ASTROCYTOMA DURING PREGNANCY: A CASE REPORT

Beena Kunheri 1, Asha Arjunan 2, Padmanabhan Krishnan 1, Bhaskara Pillai 1, Satheesh Prasad 3

Abstract

INTRODUCTION: There are only a few reports of brain irradiation during pregnancy. The probable effects of radiation exposure during foetal period include mental retardation, anatomical malformations, carcinogenesis and death of embryo or foetus.We report a method for reducing foetal dose while delivering radiotherapy for brain tumours during pregnancy. We modified the shielding techique described by Magne et al. MATERIALS AND METHODS: A young woman underwent craniotomy and decompression in May 2004 for left insular astrocytoma (WHO grade II) extending to temporal and frontal lobes and was referred for radiotherapy. She was at 20 weeks gestation and not willing for therapeutic abortion. 3-Dimensional Conformal treatment was planned on CT-MRI fusion image and was delivered by 4 fields (AP, PA Right and Left Lateral) in Linear Accelerator using 6MV photons. Total dose was 60Gy in 30 fractions (50Gy/ 25 fractions for initial CTV followed by boost of 10Gy/5 fractions). Precautions were taken to reduce foetal dose due to leakage radiation. AP/PA treatment was isocentric at 100cm SAD and lateral fields were treated at extended SSD of 115cm. Collimators were rotated to 90 degrees for all fields to provide maximum shielding from head leakage. Wedges were avoided in all fields. 5 cm thick lead shields were provided for lateral fields. RESULTS: Phantom measurements estimated foetal dose of 0.8cGy while delivering 60Gy and measurement on lower abdominal surface using survey meter showed total foetal dose of 0.63cGy for the entire treatment. A healthy female baby was delivered by caesarian section in August 2004.The patient developed recurrence in July 2005 for which a revision surgery was done and she expired in November 2005. The child showed normal growth and development at last follow up in September 2013.She is now 9 years old. CONCLUSION: Foetal dose was significantly reduced compared to published reports in literature.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.2

RO-003. AVARTHEC STUDY: CEREBROVASCULAR DISEASE FOLLOWING CHILDHOOD AND ADOLESCENCE CANCER RADIATION THERAPY

Valerie Bernier-Chastagner 1, Emmanuel Desandes 2, Christian Carrie 3, Claire Alapetite 4

Abstract

AIM: To describe clinical and imaging characteristics of cerebrovascular disease (CVD) in survivors after irradiation of brain tumors (BT) during childhood. To identify high-risk patients to develop CVD and to adapt their long-term follow-up (FU).The study could help elaborating recommendations on new radiation techniques considering potential risk factors of cerebrovascular morbidity. MATERIAL AND METHOD: This study was performed in 13 French centers. Patients alive at the time of the study were irradiated between 1990 and 2002, at the age 0 to 18 years, for a BT. Patients who signed the consent had to have a clinical exam, an angioMRI and fullfill a questionnaire about their quality of life (QOL). MRI images were reviewed independantly. Finally, a retrospective analysis of the dosimetry collected radiation criteria, and doses received by the abnormalities. RESULTS: Out of the 173 included patients, 165 are available for analysis because 6 finally refused the MRI after the inclusion. Median age at diagnosis and at the moment of the study are respectively 9 and 24 years, Median FU is 15 years. 198 CVD have been observed in 118 patients. Most of them are cavernoma (132 cases for 80 patients). 25 serious abnormalities as carotid stenosis and several second tumors have been detected, The average dose received by the site of cavernoma was 43 Gy. 106 QOL questionnaires are available. CONCLUSION: 71.5% of survivors irradiated for BT during childhood developed a CVD. Characteristics and correlation with dose will be discussed, as well as impact on QOL.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.3

RO-004. SHORT COURSE FRACTIONATED STEREOTACTIC RADIOSURGERY FOR CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA

Todd Hankinson 1, Dylan Jones 2, Michael Handler 1, Nicholas Foreman 1, Arthur Liu 2

Abstract

INTRODUCTION: Diffuse Intrinsic Pontine Glioma (DIPG) is associated with abysmal clinical outcomes, with reported median survival ranging from 7-11 months. Conventional fractionated radiation remains the standard treatment, requiring patients and families to commit substantial time and resources to receiving care. In order to reduce the temporal burden on patients and families, we employed a regimen of fractioned stereotactic radiosurgery (fSRS). METHODS: Single institution review of children with DIPG treated with fractionated stereotactic radiosurgery. Parameters assessed included patient demographics, treatment regimen, and survival outcomes. RESULTS: Seven children with lesions that were clinically and radiographically consistent with DIPG were treated. The regimen in all children included Linac-based fractionated stereotactic radiosurgery at a dose of 25Gy in 5 fractions. The median age at diagnosis was 4.5 years (range 2.6-7.7). Four patients (57.1%) had histologically confirmed high grade glioma, the remaining 3 did not undergo biopsy. The mean duration of treatment was 6.71 days (range 5-11d). The mean time from diagnosis to initiation of treatment was 11 days (range 6-14d). There were no severe complications attributed to fSRS. All patients completed the treatment regimen. All patients demonstrated initial clinical improvement. Two children underwent re-irradiation at the time of progression. Median overall survival from diagnosis was 6.57 months (range 3.73-13.3m). DISCUSSION: Short course fSRS appears to be safe and offers logistical benefits in the treatment of DIPG, as well as initial clinical benefit. Although our cohort was small and presented at a relatively young age, this preliminary evaluation indicates that a regimen of 25Gy in 5 fractions may not achieve equivalent survival outcomes as established regimens of conventional radiotherapy. Further studies with a more aggressive regimen should be considered.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.4

RO-005. SEVERE BRAINSTEM NECROSIS SUCCESSFULLY TREATED WITH BEVACIZUMAB IN AN INFANT WITH A LOW GRADE GLIOMA FOLLOWING RADIATION FOR INTRACTABLE TRIGEMINAL NEURALGIA

Natasha Pillay Smiley 1, Tord Alden 1, William Hartsell 1, Jason Fangusaro 1

Abstract

Radiation necrosis is well documented in patients with high grade brain tumors, but we present a case of severe radiation necrosis in a child treated for a low grade glioma and intractable trigeminal neuralgia. The patient presented at 14 months of age with repetitive pulling of her left face. Imaging revealed a large brain stem lesion, and a biopsy was consistent with Grade II pilomyxoid astrocytoma. Her therapy was complicated by severe facial pain and twitching with no tumor shrinkage after 10 weeks of induction carboplatin and vincristine chemotherapy. She was diagnosed with “central” trigeminal neuralgia caused by tumor compression of the trigeminal nerve root; extensive therapies including surgical decompression were pursued. Her severe pain necessitated prolonged sedation and intubation. As a final treatment option, she underwent proton beam radiation in attempt to improve her quality of life. The patient received 49 Gy to the tumor, brainstem and upper cervical cord. Radiation significantly reduced her trigeminal neuralgia pain, and the patient was extubated and discharged home. Approximately 4 months post-radiation, she presented with worsening irritability, head tilt and bradycardia. MRI demonstrated new hydrocephalus and a large area of radiation necrosis within the tumor bed and brainstem. Despite surgical correction of the hydrocephalus, the patient remained critically ill. She was emergently treated with dexamethasone and bevacizumab (10 mg/kg). The patient had a dramatic clinical improvement within 24-48 hours. An MRI performed 6 weeks after initiating bevacizumab revealed a significant decrease in the size of the tumor and almost complete resolution of the radiation necrosis. The bevacizumab was continued for a total of 12 doses given every 2 weeks. This case study illustrates the successful treatment of central trigeminal neuralgia with radiation. It also displays a rare case of radiation necrosis in a low grade glioma successfully treated with bevacizumab.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.5

RO-006. OUTCOMES AFTER PROTON RADIOTHERAPY (RT) FOR INFRATENTORIAL BRAIN TUMORS IN INFANTS AND VERY YOUNG CHILDREN

Christine E Hill-Kayser 1, Robert A Lustig 1, Jane E Minturn 2, Stefan Both 1, Angela J Waanders 2, Jean B Belasco 2, Carol Armstrong 2, Peter C Phillips 2, Michael J Fisher 2

Abstract

INTRODUCTION: Photon RT has a risk of unacceptable toxicity in most infants with a brain tumor. Proton RT has potential to reduce acute and late RT-related toxicity by reducing exposure of normal brain. METHODS: From 2010-2013, 21 consecutive patients age <4y with infratentorial brain tumors requiring focal RT (with daily general anesthesia) were enrolled on a prospective registry. All patients underwent tumor resection. RT was planned after CT simulation and fusion of pre and post-operative MRI scans. Eclipse treatment planning software was used to contour the tumor bed, clinical target volume (1 cm expansion), and organs at risk. Doses are reported in radiobiologic-equivalent-weighted absorbed dose (cGyRBE). Brainstem planning constraints: maximum dose 6000; only 5% > 5400. RESULTS: At time of RT, patients (13M:8F) ranged from 11m - 47.9m of age; tumor types included ependymoma (13), medulloblastoma (5), ATRT (2), and Ewing sarcoma (1). The non-ependymoma patients received pre-RT chemotherapy. RT was delivered using passive scattered proton beams (20) or pencil beam scanning (1). Median RT dose was 5400 (R 5040-5940); median duration of RT course was 44 days (R 40-50). RT was tolerated with minimal acute toxicity (none > grade 1): fatigue (2), nausea (5), anorexia (4), constipation (2), and dermatitis (15). No serious (grade 3-4), long-term, RT-related toxicity has been reported. At a median follow-up of 12 months (R 1.4-35), 19 patients are alive without evidence of disease, 1 patient is LTFU, and one is dead of disease. CONCLUSIONS: Proton RT for infratentorial brain tumors appears to be well-tolerated by very young children with minimal acute toxicity and excellent disease control. Thus far, there has been no serious long-term toxicity; however, longer follow-up is required to fully evaluate the risks.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.6

RO-007. PROTON RADIATION FOR TREATMENT OF LOCALIZED EPENDYMOMA IN CHILDREN

Christine E Hill-Kayser 1, Iris Paltin 2, Robert A Lustig 1, Michael J Fisher 2, Stefan Both 1, Jean B Belasco 2, Kristina A Cole 2, Angela J Waanders 2, Peter C Phillips 2, Jane E Minturn 2

Abstract

INTRODUCTION: Radiotherapy (RT) is an integral part of ependymoma (EP) treatment, contributing to improved local control and outcomes. Proton RT allows sparing of normal brain which may reduce RT-related toxicity. METHODS: 23 subjects with newly diagnosed EP (M0) were enrolled on a prospective registry from 2010-13. Following resection, focal RT was planned after CT simulation and fusion of pre and post-operative MRI scans. Eclipse treatment planning software was used to contour the tumor bed, clinical target volume (1 cm expansion), and organs at risk. Doses are reported in radiobiologic-equivalent-weighted absorbed dose (cGyRBE). Neurocognitive (NC) testing was performed. RESULTS: At time of RT, subjects (16M:7F) ranged from 1-15 years (median 4). Tumors were infratentorial in 18 (78%) and supratentorial in 5 subjects. Average RT dose was 5900 (range 5580-5940) for 11 subjects with anaplastic histology, and 5565 (range 5400-5940) for those without anaplastic disease. Median RT course duration was 44 days (range 37-50). No > grade 2 acute toxicity was noted [grade 1: fatigue (3), headache (3), dermatitis (12), nausea (5), vomiting (2), anorexia (2), dysphagia (1); grade 2: dermatitis (2)]. No serious (grade 3-4), long-term, RT-related toxicity has been reported. With median follow-up of 12.8 months (range 1-43), 18 subjects are alive without disease, 2 dead of disease, 3 AWD. 13 subjects underwent baseline NC testing; overall pre-RT NC abilities were low average to superior (median IQ = 105, range 88-127). Social-emotional, adaptive, and executive functioning were within normal limits. One year post-RT, 5 children completed follow up NC evaluations (IQ range: 96-118). Two years post-RT, IQ ranged from 99 to 121 (3 children). Performance was stronger on verbal than perceptual reasoning tasks. CONCLUSIONS: Proton RT appears well-tolerated by children with EP with minimal acute toxicity, excellent disease control, and no serious late toxicity, although longer follow-up is required for full evaluation.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.7

RO-008. ACUTE BRAIN INJURY MAY BE MORE SEVERE FROM PROTON BEAM RADIATION (PBR) THAN FROM CONVENTIONAL RADIATION THERAPY (CRT) FOR YOUNG PEDIATRIC PATIENTS WITH POSTERIOR FOSSA TUMORS

Elizabeth Wells 1, Gilbert Vezina 1, Lindsay Kilburn 1, Brian Rood 1, Faith Crozier 1, Eugene Hwang 1, Roger Packer 1

Abstract

INTRODUCTION: Proton beam radiation (PBR) is employed to decrease toxicity to surrounding tissue. METHODS: We reviewed imaging from 30 consecutive pediatric patients with posterior fossa tumors between 2005 and 2013 irradiated at multiple institutions, without progressive disease 2 years post radiation. 16 were treated with PBR (mean age 6.1; range 1.4 - 16.3 years; 5 under 3 years) and 14 with CRT (mean age 8.0 years; range 1.1 - 15.8 years; 2 under 3 years). The PBR group included 1 AT/RT, 7 ependymomas, 1 low grade glioma, 3 medulloblastomas,1 brainstem PNET and 1 choroid plexus papilloma. The CRT group included 1 AT/RT, 10 medulloblastomas, and 3 ependymomas. MRI was reviewed at 3 month intervals to at least 12 months post-radiation. Radiation change was graded 1: focal increase T2 in brainstem, cerebellum and/or cerebral white matter (no enhancement or diffusion restriction); 2: extensive increase in T2 in brainstem, cerebellum, and/or cerebral white matter or focal abnormal enhancement without diffusion restriction; 3: extensive abnormal enhancement or diffusion restriction. RESULTS: The PBR group showed 2 grade 2, 4 grade 3 injuries, and 1 pseudoprogression. 3 patients with radiographic brainstem change, all less than 3 years of age and also treated with chemotherapy, died at 3,7, and 6 months post-PRB with autopsy-demonstrated multifocal necrotizing leukoencephalopathy and areas of demyelination. The CRT group had 1 grade 2 and no grade 3 injuries, and no brainstem injuries. Radiation injury was more severe in the PBR group (Chi-square 9.5, df 3, p < 0.05). CONCLUSION: PBR was associated with more severe acute brain injury on MRI than CRT, including 3 fatalities from brainstem necrosis. PBR is increasingly recommended to spare long term adverse effects, but further investigation is needed given these adverse outcomes.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.8

RO-009. VOLUME AND POSITION SHIFT OF THE FOURTH VENTRICLE: RELEVANT ISSUES DURING CONFORMAL IRRADIATION OF THE TUMORBED IN MEDULLOBLASTOMA

Geert O Janssens 1, Sven van den Bosch 1, Peter G van Kollenburg 1, Corrie E Gidding 1, Jolanda H Schieving 1, Johannes H Kaanders 1, Erik J van Lindert 1

Abstract

PURPOSE: After complete macroscopic removal of a medulloblastoma, the tumorbed is defined based on pre-operative tumor extent and anatomic shifts or changes visible on T1 ± gadolinium MR-images. In this era of image-guided radiation techniques, it is important to investigate the change in volume and position of the fourth ventricle and to implement this information in the target volume definition for high-precision radiotherapy. MATERIAL AND METHODS: Ten patients with medulloblastoma and complete macroscopic removal of the tumor were selected. Onset of radiotherapy within one month from surgery was required as well as MR-imaging repeated 6 weeks after the end of radiotherapy. Delineation of the fourth ventricle was performed in a standardized way based on post-surgery, pre-radiotherapy and post-radiotherapy imaging and registered to the treatment planning CT-scan. The Dice similarity coefficient was used to evaluate spatial overlap (0-1) of the fourth ventricle contours between CT- and MR-imaging after co-registration based on bony structures. RESULTS: Imaging was performed at a mean of 2 and 18 days post-surgery and repeated at a mean interval of 45 days after the end of radiotherapy. The mean post-operative, pre-radiotherapy and post-radiotherapy fourth ventricle volumes were 6.4 cm3 (2.5-11.6cm3), 4.3 cm3 (2.3-6.5cm3) and 4.0 cm3 (1.7-6.1cm3), respectively. Volume reduction more than 0.5 cm3 between pre- and post-radiotherapy imaging was limited to 3 patients (0.5-1.6cm3). Co-registration of the treatment planning CT-scan with post-radiotherapy MR based on bony anatomy resulted in a mean fourth ventricle shift of 4 mm (2-9mm), especially in the dorsal and cranio-caudal direction, resulting in a spatial overlap of 0.65 (0.50-0.84). CONCLUSION: During radiotherapy volume change of the fourth ventricle is limited. However, significant position shifts of the fourth ventricle up to 9 mm are observed, especially in the dorsal and cranio-caudal direction. To prevent geographic miss of radiotherapy, image-guidance is obligate.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.9

RO-010. RADIONECROSIS IN CHILDREN TREATED WITH CONVENTIONAL RADIATION THERAPY AND INTRATHECAL RADIOIMMUNOTHERAPY: IS IT A CONCERN?

Kim Kramer 1, Neeta Pandit-Taskar 1, Mark M Souweidane 1, Suzanne Wolden 1, Carl DeSelm 1, Nai-Kong V Cheung 1

Abstract

BACKGROUND: Radionecrosis is a potentially devastating long-term complication of external beam radiotherapy (XRT) including craniospinal radiation therapy (CSI). Intraventricular compartmental radioimmunotherapy (cRIT) using 131I-3F8 or 131I-8H9 has been used to eradicate malignant cells in the cerebrospinal fluid (CSF) space. The incidence of radionecrosis following both CSI-XRT and cRIT is unknown. PATIENTS AND METHODS: We retrospectively analyzed the incidence of radionecrosis in patients treated with CSI-XRT and cRIT at MSKCC since 2003. Patients had prior CSI-XRT 1800-3600 cGy with tumor boost 3060-5400 cGy, followed by cRIT, 10-70 mCi 131I-3F8 or 131I-8H9. CSF dosimetry by cRIT was based on post-injection serial intraventricular samplings over 48 hours. To avoid the risk of radiation toxicity in patients with medulloblastoma (MB), cRIT CSF doses were administered to a maximum of 2400 cGy. RESULTS: 96 patients (58 CNS neuroblastoma (NB); 38 MB) received both CSI-XRT and cRIT, median follow up 41.5 months (6.5-124.8 months). Within the MB cohort, overall mean CSI dose was 28 Gy (boost to 51.3 Gy); 20% had re-irradiation at a later date, mean re-XRT dose was 29.1 Gy. 5 pts with NB had addition stereotactic XRT. Median CSF dose by cRIT was 2595 cGy (1038-13143 cGy) -NB cohort and 1347 (124-2303 cGy) -MB cohort. Only 1 asymptomatic patient underwent resection of 0.6 cm hemorrhagic periventricular white matter lesion confirmed to be necrosis and granuation tissue, 2.5 years after XRT. CONCLUSIONS: The risk of radionecrosis in children treated with XRT and cRIT appears minimal (<1%). No neurologic deficits secondary to radionecrosis have been observed in long term survivors treated with both modalities, including patients who underwent re-XRT. Administration of cRIT may safely proceed in patients with CSI-XRT without increasing the risk of radionecrosis.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.10

RO-011. RISK OF DEVELOPING RADIATION INDUCED SECONDARY MALIGNANCIES IN THE THYROID, BREAST AND OVARIES AFTER RADIOTHERAPY FOR A PEDIATRIC BRAIN TUMOUR

Yasmin Lassen-Ramshad 1, Jolanta Hansen 2, Klaus Seiersen 2, Jørgen BB Petersen 2

Abstract

INTRODUCTION: Although often indispensible for cure of childhood brain cancer, radiation therapy can also induce secondary cancer. Conebeam-CT-scans (CBCT) for treatment positioning increase the ionizing irradiation. We investigated the risk of secondary cancer for the thyroid, breasts and ovaries after radiation treatment for a childhood brain tumour. MATERIAL AND METHODS: A four year old boy with an infratentorial ependymoma was treated postoperatively in the tumour bed with photon multiple field IMRT radiotherapy, that included noncoplanar fields, with 54 Gy/30 fx. CBCT positioning was used for each fraction. The delivered thyroid dose was measured. On a 5 year old female phantom a similar IMRT and a coplanar VMAT plan were calculated. Radiation doses given by the two plans in the thyroid, the breasts and the ovaries were measured. The risk of secondary cancer in these organs was estimated in accordance to the BEIR VII report. RESULTS: The estimated risk of secondary cancer by the original treatment to the thyroid was 3.61 %. In the phantom study, the risk with IMRT in the thyroid was 1.67% for males and 9.20% for females, 1.49% for the breast and 0.02% for the ovaries. With VMAT, the risk for the thyroid was 0.25% for males and 1.38% for females, 1.22% for the breast and 0.02% for the ovaries. CBCT added only 0.01% to the risk. CONCLUSION: The estimated risk of secondary cancer for the thyroid, breasts and ovaries after radiotherapy for a pediatric brain tumour was highest in the thyroid gland and especially if calculated for girls. Coplanar VMAT treatment had a lower risk than IMRT with non coplanar fields. CBCT had only a minor contribution to the risk of secondary cancer. Studies are necessary to facilitate the estimation of risk of secondary cancer in the routine evaluation of pediatric radiotherapy treatment plans.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.11

RO-012. NEUROCOGNITIVE OUTCOMES IN RELATIONSHIP TO HIPPOCAMPAL AND BRAIN DOSES AFTER PARTIAL BRAIN PROTON RADIOTHERAPY IN CHILDREN

Anita Mahajan 1, David Grosshans 1, Douglas Ris 2, Murali Chintagumpala 2, Fatih Okcu 2, Mary Frances McAleer 1, Bartlett Moore 1, Heather Stancel 2, Charles Minard 2, Danielle Guffey 2, Lisa Kahalley 1

Abstract

BACKGROUND: We evaluated the relationship between IQ and hippocampal RT doses in pediatric patients with brain tumors treated with proton radiotherapy (PRT). METHODS: IQ scores were abstracted for patients treated with partial brain PRT who underwent serial neurocognitive testing. Hippocampal delineation was performed according to RTOG guidelines. The PRT dosimetric data were compiled. The relationships between IQ and 1)median hippocampal doses and 2)percentage of hippocampus receiving 50, 30 and 10GyRBE were evaluated using general linear mixed models while controlling for mean brain-GTV dose, CTV volume, tumor location, and age-at-RT. RESULTS: Data were collected for 25 patients (13 males, 12 females) receiving PRT from 2007-2012. The mean interval between first-last IQ testing was 2.1 years (range 0.9-6.0). The median age-at-PRT was 9.4y (range 1.7-15.4y). Tumors were supratentorial in 17 patients (9 glial, 5 craniopharyngioma, 2 germinoma, 1 meningeal tumors) and infratentorial in 7 patients (3 anaplastic ependymoma, 2 medulloblastoma, 2 glial tumor). 17, 2 and 6 tumors were midline, right and left, respectively. The median dose was 50.4GyRBE (range 45.0-60.0GyRBE). The median CTV volume was 43.3cc (range 12.3-234.4cc). The median mean brain-GTV dose was 9.4GyRBE (range 3.9-19.7GyRBE). The median mean right and left hippocampal doses were 17.0 and 16.3GyRBE (range 0.2-54.8 and 0.0-46.2GyRBE), respectively. After controlling for the factors mentioned above, patients who received any right hippocampal dose >50GyRBE exhibited significant IQ decline (6.4 points/year, p = 0.01), while patients who received <50GyRBE exhibited stable IQ over time (p = 0.62). Patients who received > 30GyRBE to ≥10% of the right hippocampal volume also experienced significant IQ decline (4.0 points/year, p < 0.01), while patients with less right hippocampal dose/volume maintained stable IQ over time (p = 0.67). Left hippocampal dose/volume was not associated with IQ decline in this cohort. CONCLUSIONS: Preliminary findings suggest right hippocampal dose is associated with steeper IQ decline post-PRT in this cohort of patients.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.12

RO-013. LITHIUM REDUCED HIPPOCAMPAL PROGENITOR CELL DEATH, INFLAMMATION, CENTRAL HYPOTHYROIDISM AND COGNITIVE DYSFUNCTION AFTER IRRADIATION TO THE YOUNG RAT BRAIN

Klas Blomgren 1, Kai Zhou 1, Ciuciu Xie 1, Changlian Zhu 2

Abstract

Cranial radiotherapy in children often results in cognitive impairment and pituitary dysfunction. We evaluated short- and long-term effects of lithium (Li) in the juvenile brain after irradiation (IR). Male Wistar rats received 2 mmol/kg LiCl i.p. on postnatal day 7 (P7) and additional lithium injections, 1 mmol/kg, were administered at 24 h intervals for up to 14 days (until P20). On P11 the whole brain received a single IR dose of 6 Gy. Body weight gain was identical in all groups from P7 until P25. After P25 growth rate increased, but irradiated rats now followed a lower growth trajectory. Li did not affect growth rate, neither in controls, nor in irradiated rats. Serum creatinine was not different in Li-treated rats at any age. IR-induced progenitor cell death in the subgranular zone of the hippocampus was reduced by Li treatment. Neurogenesis was reduced by IR, but increased by Li, both in control rats and after IR. IR-induced inflammation (CCL2, IL-1α, IL-1β, and GRO/KC in the hippocampus 6 h after IR) was reduced by Li. Thyroid-Stimulating Hormone (TSH) tripled when the growth rate increased. The normal, growth-related TSH increase was abolished in irradiated rats, but Li treatment restored TSH levels and hence prevented the central hypothyroidism that otherwise would have developed. Novel object recognition was used to test memory and learning. Recognition index at P60 was reduced 50% by IR, but normalized by Li treatment. Together, these results demonstrate that Li can be safely administered to young rats during the second and third weeks of life and prevent both short- and long-term damage to the brain caused by ionizing radiation.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.13

RO-014. STEREOTACTIC RADIOSURGERY FOR RADIATION-RESISTANT BRAIN METASTASES IN PEDIATRIC PATIENTS

Mary Frances McAleer 1, Zhongxiang Zhao 1, Jeffrey Weinberg 1, David Sandberg 1, Dennis Hughes 1, Anita Mahajan 1, Peter Anderson 2, Nandita Guha-Thakurta 1

Abstract

BACKGROUND: In contradistinction to adult patients with solid tumors, brain metastases in pediatric malignancies are rare, with incidence <5% in most series. As local control of pediatric tumors improves, this incidence is anticipated to rise. Treatment of brain metastases, particularly from radiation-resistant tumors, includes surgery, radiotherapy and/or systemic therapy, alone or in combination, but outcomes are poor. Here we report feasibility and outcomes of stereotactic radiosurgery (SRS) for pediatric patients with radiation-resistant brain metastases. MATERIALS AND METHODS: Retrospective analysis of 16 patients, median age 17.3 y (range, 3.1-24.8) treated between 2002-2014 with SRS for brain metastases from radiation-resistant primary tumors was conducted on an institutional, IRB-approved protocol. SRS was delivered using frame-based, linear accelerator (linac) x-ray or Gamma Knife (GK) 60Co-based external beam radiotherapy. Descriptive statistics were used to evaluate treatment, local control, adverse reactions and survival. Toxicity was graded using Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Median marginal dose 20 Gy (range, 12-20) was delivered by single-fraction SRS to 69 lesions (range, 1-8 per treatment, 1-11 per patient). Six patients (37.5%) were treated with linac, and 10 by GK. Histologies included melanoma (31.3%), soft tissue sarcoma (STS, 31.3%), osteosarcoma (18.8%), chondrosarcoma (12.5%), and alveolar soft part sarcoma (6.3%). The number of treatments per patient was one for 81.3%, two for 12.5% and three for 6.3%. Of 11 patients with at least one month follow-up, local failure was detected in three (27.3%; one each with melanoma, osteosarcoma and STS) at a mean 16 weeks (range, 6-30) after SRS. No grade 3+ toxicities were observed. Two patients remain alive, and mean survival of 15 assessable patients was 10.9 months (range, 1-47) from SRS. CONCLUSIONS: SRS is an effective and well-tolerated treatment for improved local control and palliation of brain metastases in pediatric patients with radiation-resistant brain metastases.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.14

RO-015. SALVAGE TREATMENT OF PROGRESSIVE NON-PONTINE PEDIATRIC HIGH-GRADE GLIOMAS BY RE-IRRADIATION: PRELIMINARY EXPERIENCES FROM THE GERMAN HIT-HGG STUDY GROUP

Klaus Müller 1, Marion Hoffmann 2, Clemens Seidel 1, Monika Warmuth-Metz 3, Torsten Pietsch 4, Uwe Kordes 5, Annette Sander 6, Jochen Rössler 7, Norbert Graf 8, Heike Scheithauer 9, Rolf-Dieter Kortmann 1, Christof M Kramm 2, André O von Bueren 2

Abstract

BACKGROUND: Whereas several retrospective studies have meanwhile evaluated the role of re-irradiation in progressive adult high-grade gliomas (HGG), reports relating to pediatric HGG patients are still missing. The aim of this analysis was to evaluate the treatment and outcome in a small cohort of children with progressive HGG who underwent re-irradiation. PATIENTS AND METHODS: We performed a retrospective study and screened the data base of the reference center for radio-oncology of the German Pediatric Brain Tumor Network between April 2006 - July 2012 in order to identify children who received re-irradiation for their progressive non-pontine HGG. RESULTS: We report on eight children (3 females, 5 males) with progressive HGG (WHO grade III, n = 5, WHO grade IV, n = 3). Median age at primary diagnosis was 13.5 years (range: 10.3-16.7 years), and 14.8 years (range: 11.0-17.5 years) at first relapse or progression, respectively. All patients had initially received combined first-line treatment (surgery [incomplete resection, n = 7, biopsy, n = 1], radiochemotherapy [n = 8, four with concurrent temozolomide]). Relapses occurred outside (n = 3) and within or at the borders of the previous radiation fields (n = 5). The median time interval between initial radiotherapy and (first) re-irradiation was 9.0 months (range, 3.8 - 52.1 months). There were no major unexpected toxicities, and no treatment-related deaths were reported. All patients have died due to disease progression with a median survival of 26.2 months (range: 13.1-61.4 months) since initial diagnosis and 11.4 months (range: 4.9-39.5 months) after the first relapse/progression, respectively. CONCLUSION: These results, which are based on a limited patient number, suggest that re-irradiation might be feasible in progressive pediatric non-pontine HGG. Further documentation of such cases is necessary in order to better delineate feasibility, toxicity, and impact on outcome of this new treatment in pediatric non-pontine HGG patients in the relapse situation. Supported by Deutsche Kinderkrebsstiftung.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.15

RO-016. IMAGING CHANGES IN PEDIATRIC PATIENTS TREATED WITH PROTON BEAM RADIATION THERAPY COMPARED TO INTENSITY MODULATED RADIATION THERAPY FOR INTRACRANIAL EPENDYMOMA

J Gunther 1, M Sato 2, M Chintagumpala 2, E Jo 2, A Paulino 1, A Adesina 2, L Ketonen 1, J Jones 2, J Su 2, F Okcu 2, S Khatua 2, R Dauser 2, W Whitehead 2, J Weinberg 1, A Mahajan 1

Abstract

PURPOSE: MRI changes after radiotherapy (RT) in children with ependymoma are not well-defined. We compared imaging changes following proton beam (PBRT) to intensity-modulated radiation therapy (IMRT) in these patients. MATERIALS/METHODS: Sixty-seven pediatric patients with non-metastatic intracranial ependymoma who received RT at two institutions were identified: 32 PBRT and 35 IMRT were treated at mean age 4.3 and 6.9 years, respectively. Two neuroradiologists, blinded to RT modality, reviewed initial, pre-RT, and post-RT MRI images. RESULTS: Seventeen of 32 PBRT patients (53%) developed post-RT MRI changes at an average time of 4.1 months with resolution at an average of 5.8 months. Seven of 35 IMRT patients (20%) developed changes at an average time of 5.2 months with an average of 8.7 months to resolution. Relative risk (PBRT:IMRT) of change was 2.66 (95% CI 1.27 to 5.56). For patients with infratentorial tumors, 4 of 21 IMRT patients (19%) developed changes compared to 15 of 24 (63%) PBRT (p = 0.003). Of the 19 infratentorial tumors with changes, 10 (53%) had changes involving brainstem (7 PBRT, 3 IMRT). The total radiation dose was not higher in patients who developed changes for either the IMRT (56.6 Gy vs 55.7 Gy, p = 0.48) or PBRT (56.8 Gy vs 57.2 Gy, p = 0.65) groups. The use of chemotherapy was not more frequent in the group with changes compared to those without (16% vs 21%, p = 0.59). Six (3 IMRT, 3 PBRT) of 25 patients had symptomatic changes requiring interventions such as steroids and/or bevacizumab (4/6 involved brainstem). One developed permanent deficits due to brainstem radiation necrosis including hemiparesis, incontinence, cranial nerve deficits, and speech impairment. CONCLUSIONS: In this study, post-RT MRI changes are more common after PBRT compared to IMRT in children with infratentorial ependymoma. These changes are usually self-limited but may require medical intervention if the brainstem is involved.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.16

RO-017. REIRRADIATION OF RECURRENT INTRACRANIAL EPENDYMOMA IN PEDIATRIC PATIENTS: A SINGLE INSTITUTION LEARNING CURVE

Lorenza Gandola 1, Emilia Pecori 1, Veronica Biassoni 1, Chiara Chiruzzi 1, Elisabetta Schiavello 1, Silvia Meroni 1, Filippo Spreafico 1, Emanuele Pignoli 1, Maura Massimino 1

Abstract

This is a retrospective study on reirradiation in pediatric patients with Ependymoma relapsing after first line surgery, local radiotherapy at doses of 70.4 Gy, hyperfractionated (first AIEOP, Associazione Italiana Ematologia Oncologia Pediatrica, protocol) or 59.4 Gy conventionally fractionated + 8 Gy boost in 2 fractions in case of measurable residue (second AIEOP protocol) ± chemotherapy based on grading and possible residual disease. From 1997 to 2013, 30 patients, median age 4.11 at diagnosis, 24 grade 3 tumors, 21 infratentorial sites, underwent reirradiation after a median of 3.9 years. Radiotherapy dose, volume, and fractionation were selected based on type of relapse, local (Group1), single distant lesion (Group2), local + single distant (Group3), and disseminated (Group4). 7 children underwent 2 or 3 reirradiation procedure. Group1: 16 patients, 8 Gy in 2 fractions if completely resected or 16 Gy in 4 fractions in case of incomplete or no resection, 8 alive 5-106 months after reirradiation. Group2: 3 patients, full dose radiotherapy to the distant site, 1 alive at 105 months after reirradiation. Group3: 3 patients, 12 Gy/3 fractions or surgery locally and full dose radiotherapy to the distant site, none alive. Group4: 4 patients, 30-36 Gy to the spine± local boost, none alive;4 patients, 30-36 Gy CSI ± local boost, 1 alive 20 months after reirradiation. Median survival after reirradiation was 11 and 21.5 months in patients with a first PFS < or > to 24 months respectively. No clinically significant acute or late side effects were documented, including the 7 children receiving 2 or 3 reirradiations, all alive (4-46 months after last reirradiation) and well despite the high local doses (75.5-94.4 Gy) In our series, reirradiation offered a survival benefit to children with recurrent ependimoma with durable local tumor control in case of local recurrence. Disseminated relapses should receive also a full dose CSI.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.17

RO-018. LONG-TERM PROSPECTIVE NEURO-PSYCHOLOGICAL OUTCOMES AND SURVIVAL IN CHILDREN WITH PROGRESSIVE BENIGN/LOW-GRADE BRAIN TUMOURS TREATED WITH HIGH-PRECISION STEREOTACTIC CONFORMAL RADIATION THERAPY

Rakesh Jalali 1, Uday Krishna 1, Tejpal Gupta 1, Savita Goswami 1, Joyita Deodhar 1, Debnarayan Dutta 1, Sadhana Kannan 1, Atul Goel 2, Rajiv Sarin 1

Abstract

BACKGROUND: To report longitudinal detailed neuro-psychological outcomes in children and young adults with progressive/ residual benign and low-grade brain tumours treated with stereotactic conformal radiotherapy (SCRT). METHODS: Between 2001-10, 98 patients (55 males, 32 females; median age 13 years) with residual or progressive low-grade and benign brain tumours treated with high-precision SCRT to 54 Gy/30 fractions were accrued on a prospective protocol. Neuropsychological age-appropriate test battery included full-scale IQ (FSIQ), verbal-quotient (VQ), performance-quotient (PQ), memory-quotient (>16 years) by Wechsler scores and Lowenstein-Occupational-Therapy-Cognitive-Assessment (LOTCA). Serial longitudinal evaluations were performed at baseline (pre-RT), 6-months and 2, 3, 4, and 5-years post-RT and analyzed using generalized linear mixed model (GLMM). RESULTS: At a median follow-up of 44months, 7 year overall survival was 90%. 68 patients had tumours located close to the hypothalamic-pituitary axis. The most common histology was craniopharyngioma (n = 41), followed by optic pathway/hypothalamic glioma (n = 22), pilocytic astrocytomas (n = 21), cortical low-grade gliomas (n = 12) and other histology (n = 9). Baseline mean FSIQ was 80, of which 17% had low intelligence (FSIQ <69) even before starting RT. At post-RT 5 years, mean FSIQ of the entire cohort was 92 (87-97, 95% CI), MQ was 114, PQ was 108 and VQ was 80. GLMM for repeated measures demonstrated significant preservation of FSIQ over time at 3 year and 5 year post-RT assessments. Baseline LOTCA score was 13 with improvement in mean scores over time to 15.5 at 5 years (p = 0.002). Anxiety and depression scores in either age groups did not show any difference by serial evaluations over time (p = 0.18) (p = 0.17) respectively. CONCLUSIONS: Children with low grade and benign brain tumours have relatively low IQ before starting RT. There is improvement in IQ over time and is maintained at long term follow up with the use of modern high precision radiotherapy techniques.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.18

RO-019. BRAINSTEM TOXICITY FOLLOWING PROTON THERAPY: A CASE REPORT

Jairam Sastry 1, Milind Ronghe 1, Dermot Murphy 1, Kirsten Forbes 1, Richard Jones 1, Fiona Cowie 1, Jennifer Brown 1, Danny Indelicato 2

Abstract

Due to poor prognosis, younger patients are increasingly receiving radiotherapy for malignant brain tumours such as medulloblastoma and ependymoma. Proton therapy, for these group of patients, reduces the amount of radiation outside of the target volume (posterior fossa) and thus is associated with a reduction in auditory, neuroendocrine, neurocognitive toxicity and second malignancy risk. However, the dose to the tissues within the target volume is equivalent which includes brainstem. CASE REPORT: A 2.5 year old Caucasian girl presented with increasing unsteadiness, squinting of left eye, and hydrocephalus. She had near total resection of an anaplastic ependymoma followed by chemotherapy according to CCG9921 until she was 3 years old. She experienced vincristine related neurologic toxicity including vocal cord palsy. This was followed by proton therapy to the tumor bed to a total dose of 54 Gy. Approximately 4 months following treatment, she developed new unsteadiness and an MRI Scan showed abnormal T2 hyperintensity and patchy contrast enhancement within the pons, medulla, and upper cervical spinal cord. This was concerning for treatment effect versus disease recurrence. She was empirically treated with prolonged course of steroids for a presumptive grade II (CTCAE) brainstem necrosis. She made a good clinical and radiological improvement. Two years from diagnosis, she remains free of disease. DISCUSSION: Approximately 3.8% of children experience brainstem toxicity following proton therapy, comparable to published data following conventional radiation. This case report describes a patient with a number of known risk factors for brainstem toxicity. It serves as an important reminder that infants who present with hydrocephalus and undergo aggressive resection of posterior fossa lesions followed by neurotoxic chemotherapy may be less tolerant of radiation to the brainstem. In these vulnerable patients, we must strike a careful balance between the aggressive therapy required for cure and the risk of treatment toxicity.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.19

RO-020. DOSIMETRIC COMPARISON OF VMAT, IMRT AND FinF TECHNIQUES FOR CRANIO-SPINAL IRRADIATION

Evren Ozan Goksel 1, Evrim Tezcanli 2, Hatice Bilge 3, Yasemin, Yildiz Yarar 4

Abstract

PURPOSE: We compared the doses to target volume and OARs for VMAT, IMRT and FinF techniques, in the setting of craniospinal radiotherapy for medulloblastoma. MATERIALS: The OARs and PTV were generated on the Rando phantom on supine CT images. Eclipse (version 8.6) AAA algorithm was used to create plans for VMAT, IMRT and FinF techniques. The prescription dose was 36Gy in 1.8Gy/frx. Lateral craniocervical opposed fields adjoined by 2 posterior spinal fields were used for FinF. For IMRT, cranial fields were created with FinF and the spinal component was planned using inverse planning IMRT with 5 posterior oblique fields. Upper spinal (US) field was overlapped by 3cm with cranial and lower spinal (LS) fields. Cranial plan was used as a base plan during optimization to provide dose homogeneity at junctions. VMAT plan consisted of cranial, US and LS regions that were optimized in same plan. Dose–volume parameters for target volumes and OARs were compared. RESULTS: Mean values for V95 and V2 PTV doses for VMAT, IMRT and FinF techniques were 3619-3883cGy, 3689-3948cGy, 3188-3741cGy, respectively. Maximum and mean dose values for OARs, were given in Table1. Absolute volume of body-PTV receiving prescription doses were 121cc (VMAT), 1553cc (IMRT) and 1031cc (FinF). FinF failed to obtain adequate dose distribution for US, while VMAT and IMRT provided appropriate dose coverage for PTV. The most homogenous dose distribution at field junctions were obtained with VMAT(Figure1). Although heart, thyroid, intestine, lung, liver and testicular maximum doses were lower for VMAT, mean doses were higher except for heart and thyroid. Body-PTV mean doses were similar but absolute volumes receiving prescription doses were significantly lower for VMAT. CONCLUSION: Craniospinal planning with VMAT provides homogenous dose distribution at field junctions and reduces OAR maximum doses satisfactorily. This study was supported by Yildiz Technical University Scientific Research project coordinatorship.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.20

RO-021. PROGRESSION-FREE SURVIVAL OF CHILDREN WITH LOCALIZED EPENDYMOMA TREATED WITH INTENSITY-MODULATED RADIATION THERAPY (IMRT) OR PROTON BEAM RADIATION THERAPY (PBRT)

Mariko Sato 1, Jillian Gunther 2, Anita Mahajan 2, Eunji Jo 1, Arnold Paulino 2, Adekunle Adesina 1, Jeremy Jones 1, Leena Ketonen 2, Jack Su 1, Mehmet Okcu 1, Souman Khatua 2, Robert Dauser 1, William Whitehead 1, Jeffrey Weinberg 2, Murali Chintagumpala 1

Abstract

BACKGROUND: Treatment for ependymoma includes maximal surgical resection followed by focal radiotherapy. Proton beam radiation therapy (PBRT) has been recently utilized in place of intensity-modulated radiation therapy (IMRT). Efficacy of PBRT in local control is largely unknown. PURPOSE: To assess 3 year progression-free survival (PFS) of patients with localized intracranial ependymoma treated with either IMRT or PBRT after surgical resection. METHOD: Retrospective review of medical records from September 2000 to April 2013 of children with localized intracranial ependymoma treated with IMRT or PBRT. RESULTS: 78 consecutive children were diagnosed with either supratentorial (n = 23) or infratentorial (n = 55) ependymomas. The median age at diagnosis was 3.7 years (range 0.4-18.7) and median follow up was 3.3 years (range 0.6-11.7). Pathology review revealed 15 grade II tumors and 63 anaplastic ependymomas including those with focal anaplasia. IMRT was used in 38 and PBRT in 40 patients after surgical resection. Patients treated with PBRT were younger at diagnosis (median age PBRT: 2.5 vs IMRT: 5.7 years, p = 0.001) and had shorter median follow up (PBRT 2.6 vs IMRT 4.9 years, p < 0.0001). Gross total resection (GTR) prior to radiation therapy was achieved in 67 patients (86%) and GTR was more frequently achieved in PBRT group compared to IMRT (95% vs 76%, p = 0.017). Those who started radiation therapy 90 days or later after surgery had a poorer PFS (p = 0.029). The 3-year PFS was 70% for all patients. The 3-year PFS were 60% and 82% for IMRT and PBRT respectively (p = 0.031). On multivariate analysis, extent of resection (p < 0.0001) and tumor location (p = 0.033) were the only prognostic factors. CONCLUSION: Children with localized ependymoma treated with PBRT have a 3-year PFS that compares favorably with IMRT. This analysis suggests that local control is not compromised with the use of PBRT.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.21

RO-022. OUTCOME AND PATTERNS OF FAILURE IN CHILDREN WITH RELAPSED EPENDYMOMA

Arnold Paulino 1, Eunji Jo 3, Mariko Sato 2, Jack Su 2, M Fatih Okcu 2, Anita Mahajan 1, Robert Dauser 2, William Whitehead 2, Adekunle Adesina 2, Murali Chintagumpala 2

Abstract

PURPPOSE: To determine the outcome and patterns of failure in children with relapsed ependymoma. PATIENTS AND METHODS: From 2000-2013, 27 children were seen with relapsed ependymoma. There were 14 boys (52%). Tumors were infratentorial in 16 (59.3%) and anaplastic in 22 (81.5%). Median time to relapse was 24 months (range, 2 to 93 months). Nine (33.3%) relapses occurred >54 months after initial surgery. The most common site of relapse was at the primary site alone in 21 (77.8%). For these 21 patients with local recurrence, treatment was surgery only in 5, surgery and radiotherapy (RT) in 11, chemotherapy in 4 and RT only in 1. For 6 patients with distant disease, treatment was surgery and RT in 2, RT alone in 3 and chemotherapy alone in 1. Median follow-up was 38 months (range: 4-85) from initial relapse for surviving patients. RESULTS: The 3-year progression-free (PFS) and overall survival (OS) for all patients was 30% and 63%. Patients receiving chemotherapy alone at relapse had the worst overall survival (p = 0.0023). There was no significant difference in PFS (p = 0.7) or OS (p = 0.92) in patients receiving surgery alone vs. RT +/- surgery. For the 21 patients who had initial local relapse, 14 relapsed a second time (10 local only, 1 distant only and 3 local and distant). In patients who received RT for the first relapse, time interval to develop a second relapse was not longer than the initial time interval to develop the first recurrence. CONCLUSION: Chemotherapy alone for first relapse was associated with worse OS. There was no difference in PFS or OS in patients receiving surgery alone vs. RT +/- surgery. Local recurrence remains the predominant pattern of treatment failure in children with relapsed ependymoma.

Neuro Oncol. 2014;16(Suppl 1):i117–i122. doi: 10.1093/neuonc/nou080.22

RO-023. CHARACTERIZING THE RADIORESPONSE OF PEDIATRIC BRAIN TUMOR STEM CELLS CULTURED IN VITRO

Anna Danielsson 1, Magnus Tisell 2, Bertil Rydenhag 2, Helena Caren 3

Abstract

Radiation is an important therapeutic tool for children diagnosed with brain tumours. Radiotherapy intentionally causes damage to tumour cells, but also exerts short- and long-term effects in normal tissues. Neurogenesis is severely affected by radiotherapy and neural stem cells have been linked to brain tumour development. Using a panel of paediatric and adult CNS tumour in vitro cultures and neural stem cell lines we explored the radiation response, measured by cellular and molecular endpoints, in these different cells. Cells were assayed after receiving X ray radiation doses from 1 Gy up to 6 Gy and followed up to 28 days. Genomic and phenotypic characteristics of surviving cells following radiation are being evaluated. Using live cell imaging and high content image analysis tools we were able to demonstrate differences in cellular radioresponse among cell types with regard to fraction of cells retaining their reproductive integrity, cell proliferation rates and frequencies of cells with a non-proliferating morphology.

Articles from Neuro-Oncology are provided here courtesy of Society for Neuro-Oncology and Oxford University Press

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