Long-term treatment outcomes of pediatric low-grade gliomas treated at a university-based hospital.

PURPOSE: A multimodality approach is generally considered for pediatric low-grade gliomas (LGG); however, the optimal management remains uncertain. The objective of the study was to evaluate treatment outcomes of pediatric LGG, focusing on long-term survival and factors related to outcomes. METHODS: A retrospective review of 77 pediatric LGG cases treated at Ramathibodi Hospital, Thailand between 2000 and 2018 was performed. The inclusion criteria were all pediatric LGG cases aged ≤ 15 years. Diffuse intrinsic pontine gliomas and spinal cord tumors were excluded. RESULTS: The median follow-up time was 8.2 years (range, 0.6-19.7). The median age at diagnosis was 6.2 years (interquartile range, 3.6-11.4). Treatments modality included tumor surgery (93%), chemotherapy (40%), and radiation therapy (14%). The 10-year overall survival (OS) and 10-year progression-free survival were 94% and 59%, respectively, for the entire cohort. The 10-year OS was 100% in three subgroups of patients: pilocytic subtype, WHO grade 1 tumors, and recipient of gross total resection. After multivariable analysis, no tumor surgery had a significantly unfavorable influence on overall survival. CONCLUSIONS: With a multimodality approach, pediatric LGGs had excellent outcome. Gross total resection is the standard primary treatment. Chemotherapy is the alternative standard treatment in incomplete resection cases, unresectable patients, or patients with progressive disease. Radiation therapy should be reserved as a salvage treatment option because of late complications that usually affect patients' quality of life.

Adaptive Proton Therapy of Pediatric Head and Neck Cases Using MRI-Based Synthetic CTs: Initial Experience of the Prospective KiAPT Study.

BACKGROUND AND PURPOSE: Interfractional anatomical changes might affect the outcome of proton therapy (PT). We aimed to prospectively evaluate the role of Magnetic Resonance Imaging (MRI) based adaptive PT for children with tumors of the head and neck and base of skull. METHODS: MRI verification images were acquired at half of the treatment course. A synthetic computed tomography (CT) image was created using this MRI and a deformable image registration (DIR) to the reference MRI. The methodology was verified with in-silico phantoms and validated using a clinical case with a shrinking cystic hygroma on the basis of dosimetric quantities of contoured structures. The dose distributions on the verification X-ray CT and on the synthetic CT were compared with a gamma-index test using global 2 mm/2% criteria. RESULTS: Regarding the clinical validation case, the gamma-index pass rate was 98.3%. Eleven patients were included in the clinical study. The most common diagnosis was rhabdomyosarcoma (73%). Craniofacial tumor site was predominant in 64% of patients, followed by base of skull (18%). For one individual case the synthetic CT showed an increase in the median D2 and Dmax dose on the spinal cord from 20.5 GyRBE to 24.8 GyRBE and 14.7 GyRBE to 25.1 GyRBE, respectively. Otherwise, doses received by OARs remained relatively stable. Similarly, the target volume coverage seen by D95% and V95% remained unchanged. CONCLUSIONS: The method of transferring anatomical changes from MRIs to a synthetic CTs was successfully implemented and validated with simple, commonly available tools. In the frame of our early results on a small cohort, no clinical relevant deterioration for neither PTV coverage nor an increased dose burden to OARs occurred. However, the study will be continued to identify a pediatric patient cohort, which benefits from adaptive treatment planning.

Proton Therapy for Primary Bone Malignancy of the Pelvic and Lumbar Region - Data From the Prospective Registries ProReg and KiProReg.

PURPOSE/OBJECTIVES: Multimodality treatments together with local proton therapy (PT) are commonly used in unresectable primary bone malignancies in order to provide better tumor control rate while maintaining good feasibility. The aim of this study is to provide data on outcome of PT for the challenging cohort of pelvic and lumbar bone tumors. METHODS AND MATERIALS: This retrospective study includes all patients with primary bone malignancy of the pelvis and lumbar spine receiving PT in our institution between May 2013 and December 2019 enrolled in the prospective registries KiProReg and ProReg collecting information on demographics, treatment, tumor characteristics, toxicities, and outcome. RESULTS: Eighty-one patients were enrolled with a median age of 19.7 years (1.3-85.8). The median follow-up time was 27.5 months (1.2-83.2). The majority of patients was male (64.2%), ECOG status of 0-1 (75.2%), underwent only biopsy (50.6%), received chemotherapy (69.1%) and was assigned for definite PT (70.4%). The predominant tumor characteristics were as follows: Ewing's sarcoma histology (58%), negative nodal involvement (97.5%) and no metastasis at diagnosis (81.5%). Median maximal diameter of tumor was 8 cm (1.4-20). LC, EFS and OS rate were 76.5, 60, and 88.1% at two years and 72.9, 45.7, and 68.9% at three years, respectively. Age over 20 years was a significant negative factor for LC, EFS, and OS. Metastatic disease at initial diagnosis affected OS and ECOG status of 2-4 affected EFS only. Regarding 17 relapsed cases (21%), isolated distant relapse was the most common failure (46.9%) followed by local failure (40.6%). Eleven out of 14 evaluable patients relapsed within high-dose region of radiotherapy. Acute grade 3-4 toxicity was found in 41 patients (50.6%) and all toxicities were manageable. Late grade 3 toxicity was reported in 7 patients (10.4%) without any of grade 4. Most common higher grade acute and late side effects concerned hematologic and musculoskeletal toxicity. CONCLUSION: Proton therapy resulted in good oncological outcomes when being part of the multimodality treatment for pelvic and lumbar primary bone malignancies. However, distant metastases and local failures within the high-dose region of radiotherapy are still a common issue. Acute and late toxicities of combined therapy were acceptable.

Carboplatin-based regimen in pediatric intracranial germ-cell tumors (IC-GCTs): effectiveness and ototoxicity.

BACKGROUND: Induction chemotherapy with carboplatin followed by radiotherapy has been used for many years for treating intracranial germ-cell tumors (IC-GCTs) in Thailand. The objective of this study was to assess treatment outcomes, focusing on survival and ototoxicity. METHODS: The outcomes of all patients with IC-GCT treated at Ramathibodi Hospital and the Prasat Neurological Institute between 2000 and 2017 were reviewed and analyzed, including all patient characteristics and treatment modalities. Five-year overall survival (OS) and event-free survival (EFS) were analyzed using the Kaplan-Meier method, and factors affecting survival were compared using the log-rank test. RESULTS: Fifty-three patients age 1-14 years (median, 11 years) were included in this study. The median follow-up time was 63 months. The 5-year EFS and OS rates were 94.3% and 96.2% for all patients, respectively. No statistical difference in OS or EFS was observed between the data of recipients in the carboplatin-based and historical cisplatin-based therapies in our institutes. Concerning radiotherapy, omission of radiotherapy or focal irradiation results in worse long-term survival outcomes, but reduction in dose of radiotherapy to less than 40 Gy did not cause any negative impact on survival rates. Furthermore, carboplatin was associated with lower rates of hearing loss than cisplatin (5.7% vs 87.5%). CONCLUSIONS: Induction chemotherapy with carboplatin-based regimens was associated with excellent survival rates and low ototoxicity in patients with IC-GCT. Radiotherapy should be given to all patients with a minimal volume equivalent to whole-ventricular radiotherapy, during which doses of lower than 40 Gy can be effectively used.