Li-Fraumeni syndrome (LFS) is a highly penetrant, autosomal dominant disorder where affected individuals carry a 50% risk of developing cancer before 30 years of age. It is most commonly associated with mutations in the tumour suppressor gene, TP53. Adrenocortical carcinoma (ACC) is a very rare paediatric cancer, and up to 80% of affected children are found to carry germline TP53 mutations. Hence, we propose using childhood ACC incidence as selection criteria for referral for TP53 mutation testing, independent of familial cancer history. Under the auspices of the Malaysian Society of Paediatric Haematology-Oncology, four eligible children diagnosed with ACC over a 30-month study period were referred for mutation testing. Three had a germline TP53 mutation. Subsequent TP53 testing in relatives showed two inherited mutations and one de novo mutation. These findings strongly support paediatric ACC as a useful sentinel cancer for initiating a germline TP53/LFS detection programme, particularly in countries where the lack of structured oncogenetic practice precludes the identification of families with LFS features.

Chemoresistant B-ALL patients are associated with increased methylation in ADAMTSL5 and CDH11. These findings need to be validated in a larger group of patients, and the functional biological and prognostic significance of differential methylation needs to be studied further.

BACKGROUND: Radiation treatment of GCT brain, in particular germinomas which are highly radio-sensitive,over the years has evolved from the cranio-spinal irradiation(CSI) to more conformal treatment like whole ventricle radiation followed by tumor bed boost (WV + TB), without compromising the results. We report our experience of treatment outcome of patients treated consecutively over a period of more than ten years with both the methods. METHOD: Twelve consecutive patients registered and treated in radiotherapy department between 2000 and 2013 after surgery (biopsy/decompression) and chemotherapy, were analysed in December 2013. Total Number (Histo-pathology) 12 (Germinoma-9, Non-Germinoma-2, No histology-1); Median age (Years) 13 (Range 5-24 years); Gender-M/F (%) 10:2(83:17); Co-morbidities None; Pre-Surgery KPS .90 (92%); Surgery (n) Biopsy/Decompression+ VP shunt (11), No Surgery (1); Sub-site Pineal-7(58%), Supra-sellar-5(42%). TREATMENT: Ten patients received 3D-CRT, while two received IMRT. Three received CSI while nine received WV + TB. CSI dose ranged from 23.4 Gy -36 Gy in 13-20 fractions. For WV the intended dose was 36Gy/20 fractions followed by 9Gy/5 fractions to TB. Pre-radiation all received combination chemotherapy, cisplatin or carboplatin + etoposide + irinotecan. RESULTS: All the patients tolerated and completed treatment with no serious adverse effects. Follow-up was done with serial tumor markers, hormonal, visual, auditory assessment and MRI. Two patients,both non-germinomas treated with CSI progressed and died with-in one year of treatment. Ten patients (9-germinomas, 1-no histology) till date are doing fine,without any loco-regional or distant failures. Ten year overall survival is around 80%.Two patients have developed hormonal imbalance and are on treatment,while one of them developed progressive bilateral optic atrophy which was present prior to radiotherapy. CONCLUSION:Our results are comparable with the reported literature.The overall survival in Germinomas is 100%,Treatment related effects are minimal as a result of reduced dose and limited treatment volume,-contributing possibly to better outcome along with various other reasons. BACKGROUND: Intracranial germ cell tumor (ICGCT) represents 3-15% of pediatric brain tumors. According to the current WHO classification, ICGCTs are classified as germinomas and non-germinomatous germ cell tumors. Germinomas are exquisitely radiosensitive, and chemo-radiotherapy is equally effective. Non-germinomatous germ cell tumors, though more aggressive than germinomas, can be treated effectively with intensive chemo-radiotherapy. ICGCTs in infants and very young children are typically mature teratomas which have excellent outcome after gross total resection. ICGCTs excluding mature teratomas, in this young age group, are extremely rare. There is also no published series or reported incidence of ICGCTs which excludes mature teratomas in children younger than 3 years of age. METHODS AND MATERIALS: We describe a series of 15 ICGCTs excluding mature ter...

INTRODUCTION Patients with high risk medulloblastoma are treated either with high dose chemotherapy or hyperfractionated radiotherapy. Both approaches are not feasible in resource-limited countries. POG9031 trial has reported favourable outcome for high risk medulloblastoma using standard chemotherapy and radiotherapy only. Hence, we have adopted the protocol using chemotherapy first approach due to logistical reasons. OBJECTIVE To review the outcome of children diagnosed with high risk medulloblastoma in Hospital Kuala Lumpur. METHODS Patients diagnosed with high risk medulloblastoma between January 2015 and June 2018 treated using the chemotherapy first approach as per POG9031 protocol were identified. Data was then extracted and analysed. RESULTS Nine patients were identified, 3 boys and 9 girls. Median age was 9.3 years (range 2.6 – 15.9 years). Median follow up for survivors are 3.6 years. Five patients (55.6%) had macroscopic metastatic disease at diagnosis. All patients had significant residual disease post-op. Only 3 patients are disease free till last follow up, giving a 3 years event free survival of 16%. Of the 6 patients who had relapsed, 4 have died, giving a 3 years overall survival of 46%. Patients with no metastasis at diagnosis (M0) fared better with 3 years event free survival of 38%, but 3 years event free survival for patients with macroscopic metastatic disease (M+) was 0%. CONCLUSION Outcome of children with high risk medulloblastoma treated with chemotherapy first approach was dismal.