Hypofractionated re-irradiation for diffuse intrinsic pontine glioma.

BACKGROUND: Re-irradiation (reRT) increases survival in locally recurrent diffuse intrinsic pontine glioma (DIPG). There is no standard dose and fractionation for reRT, but conventional fractionation (CF) is typically used. We report our institutional experience of reRT for DIPG, which includes hypofractionation (HF). METHODS: We reviewed pediatric patients treated with brainstem reRT for DIPG at our institution from 2012 to 2022. Patients were grouped by HF or CF. Outcomes included steroid use, and overall survival (OS) was measured from both diagnosis and start of reRT. RESULTS: Of 22 patients who received reRT for DIPG, two did not complete their course due to clinical decline. Of the 20 who completed reRT, the dose was 20-30 Gy in 2-Gy fractions (n = 6) and 30-36 Gy in 3-Gy fractions (n = 14). Median age was 5 years (range: 3-14), median interval since initial RT was 8 months (range: 3-20), and 12 received concurrent bevacizumab. Median OS from diagnosis was 18 months [95% confidence interval: 17-24]. Median OS from start of reRT for HF versus CF was 8.2 and 7.5 months, respectively (p = .20). Thirteen (93%) in the HF group and three (75%) in the CF group tapered pre-treatment steroid dose down or off within 2 months after reRT due to clinical improvement. There was no significant difference in steroid taper between HF and CF (p = .4). No patients developed radionecrosis. CONCLUSION: reRT with HF achieved survival duration comparable to published outcomes and effectively palliated symptoms. Future investigation of this regimen in the context of new systemic therapies and upfront HF is warranted.

Rapid Peroxide Removal Limits the Radiosensitization of Diffuse Intrinsic Pontine Glioma (DIPG) Cells by Pharmacologic Ascorbate.

Diffuse intrinsic pontine gliomas (DIPG) are an aggressive type of pediatric brain tumor with a very high mortality rate. Surgery has a limited role given the tumor's location. Palliative radiation therapy alleviates symptoms and prolongs survival, but median survival remains less than 1 year. There is no clear role for chemotherapy in DIPGs as trials adding chemotherapy to palliative radiation therapy have failed to improve survival compared to radiation alone. Thus, there is a critical need to identify tissue-specific radiosensitizers to improve clinical outcomes for patients with DIPGs. Pharmacologic (high dose) ascorbate (P-AscH-) is a promising anticancer therapy that sensitizes human tumors, including adult high-grade gliomas, to radiation by acting selectively as a generator of hydrogen peroxide (H2O2) in cancer cells. In this study we demonstrate that in contrast to adult glioma models, P-AscH- does not radiosensitize DIPG. DIPG cells were sensitive to bolus of H2O2 but have faster H2O2 removal rates than GBM models which are radiosensitized by P-AscH-. These data support the hypothesis that P-AscH- does not enhance DIPG radiosensitivity, likely due to a robust capacity to detoxify and remove hydroperoxides.

Preliminary findings of German-sourced ONC201 treatment in H3K27 altered pediatric pontine diffuse midline gliomas.

PURPOSE: H3K27 altered pediatric pontine diffuse midline gliomas (pDMG) have a poor prognosis, and conventional treatments offer limited benefits. However, recent advancements in molecular evaluations and targeted therapies have shown promise. The aim of this retrospective analysis was to evaluate the effectiveness of German-sourced ONC201, a selective antagonist of dopamine receptor DRD2, for the treatment of pediatric H3K27 altered pDMGs. METHODS: Pediatric patients with H3K27 altered pDMG treated between January 2016 and July 2022 were included in this retrospective analysis. Tissue samples were acquired from all patients via stereotactic biopsy for immunohistochemistry and molecular profiling. All patients received radiation treatment with concurrent temozolomide, and those who could acquire GsONC201 received it as a single agent until progression. Patients who could not obtain GsONC201 received other chemotherapy protocols. RESULTS: Among 27 patients with a median age of 5.6 years old (range 3.4-17.9), 18 received GsONC201. During the follow-up period, 16 patients (59.3%) had progression, although not statistically significant, the incidence of progression tended to be lower in the GsONC201 group. The median overall survival (OS) of the GsONC201 group was considerably longer than of the non-GsONC201 group (19.9 vs. 10.9 months). Only two patients receiving GsONC201 experienced fatigue as a side effect. 4 out of 18 patients in the GsONC201 group underwent reirradiation after progression. CONCLUSION: In conclusion, this study suggests that GsONC201 may improve OS in pediatric H3K27-altered pDMG patients without significant side effects. However, caution is warranted due to retrospective design and biases, highlighting the need for further randomized clinical studies to validate these findings.

Second course of re-irradiation in pediatric diffuse intrinsic pontine glioma : A case study.

PURPOSE: Concomitant chemoradiation followed by repeat (dose-deescalated) irradiation has become standard of care in treating childhood diffuse intrinsic pontine glioma (DIPG) during first line treatment and at first progression. Progression after re-irradiation (re-RT) is in most cases symptomatic and either treated systemically with chemotherapy or new innovative approaches including targeted therapy. Alternatively, the patient receives best supportive care. Data on second re-irradiation in DIPG patients with second progression and good performance status are sparse. This is a case report of second short-term re-irradiation to shed further light on this option. METHODS: Retrospective case report of a 6-year-old boy with DIPG receiving a second course of re-irradiation (with 21.6 Gy) as part of an individual multimodal approach in a patient with very low symptom burden. RESULTS: The second course of re-irradiation was feasible and well tolerated. No acute neurological symptoms or radiation-induced toxicity occurred. Overall survival was 24 months after initial diagnosis. CONCLUSION: A second course of re-irradiation can be an additional tool in patients with progressive disease after first- and second-line irradiation. It is unclear whether and to what extent it contributes to progression-free survival prolongation and if-since our patient was asymptomatic-progression-associated neurological deficits can be alleviated.

Suggestions for Escaping the Dark Ages for Pediatric Diffuse Intrinsic Pontine Glioma Treated with Radiotherapy: Analysis of Prognostic Factors from the National Multicenter Study.

PURPOSE: This multicenter retrospective study aimed to investigate clinical, radiologic, and treatment-related factors affecting survival in patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) treated with radiotherapy. MATERIALS AND METHODS: Patients aged <30 years who underwent radiotherapy as an initial treatment for DIPG between 2000 and 2018 were included; patients who did not undergo magnetic resonance imaging at diagnosis and those with pathologically diagnosed grade I glioma were excluded. We examined medical records of 162 patients collected from 10 participating centers in Korea. The patients' clinical, radiological, molecular, and histopathologic characteristics, and treatment responses were evaluated to identify the prognosticators for DIPG and estimate survival outcomes. RESULTS: The median follow-up period was 10.8 months (interquartile range, 7.5 to 18.1). The 1- and 2-year overall survival (OS) rates were 53.5% and 19.0%, respectively, with a median OS of 13.1 months. Long-term survival rate (≥ 2 years) was 16.7%, and median OS was 43.6 months. Age (< 10 years), poor performance status, treatment before 2010, and post-radiotherapy necrosis were independently associated with poor OS in multivariate analysis. In patients with increased post-radiotherapy necrosis, the median OS estimates were 13.3 months and 11.4 months with and without bevacizumab, respectively (p=0.138). CONCLUSION: Therapeutic strategy for DIPG has remained unchanged over time, and the associated prognosis remains poor. Our findings suggest that appropriate efforts are needed to reduce the occurrence of post-radiotherapy necrosis. Further well-designed clinical trials are recommended to improve the poor prognosis observed in DIPG patients.

[Formula: see text] The neuropsychological profile of children with Diffuse Intrinsic Pontine Glioma (DIPG) before and after radiation therapy: A prospective longitudinal study.

Children with Diffuse Intrinsic Pontine Gliomas (DIPG), a malignant brainstem tumor, experience poor prognosis. Because of the disease's rarity and highly aggressive course, there is a dearth of research on cognitive and psychosocial outcomes in this underserved, vulnerable population. However, evaluating effects of the disease and treatment on the cognitive and daily functioning of these patients is important to better understand their specific needs and improve their quality of life. The current longitudinal study administered prospective neuropsychological assessments to children diagnosed with CNS malignancies, including the largest sample of children with DIPG to date (n = 21, mean age = 7.86 years, range = 3-16) in neurocognitive, behavioral, social-emotional, and adaptive functioning at baseline, two weeks post-radiation, and six months later. The results describe population-based, cross-sectional characteristics and within-patient longitudinal changes. Prior to radiation, children with DIPG exhibited significant weaknesses compared to normative samples in both parent-report and performance-based measures of attention, and tests of processing speed and verbal learning/memory. Younger children demonstrated poorer inhibitory control on performance tests and worse parent-reported behavioral regulation, depression, and social withdrawal compared to older children. Six-months post-radiation, older children exhibited poorer socialization than younger children. Longitudinally, children with DIPG exhibited short-term improvements immediately post-radiation in performance-based attention tests and parent-reported behavior, including attention, hyperactivity, behavioral regulation, and executive function. However, these improvements did not persist and significant decline was documented on tests of attention by six months. Clinical implications for professionals working with children with DIPG and recommendations for cognitive remediation and quality of life interventions are provided.

Oncolytic Viral Therapy Is Feasible in Diffuse Intrinsic Pontine Glioma.

Infusion of an oncolytic virus followed by radiotherapy led to responses and prolonged survival in patients with DIPG.

Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma.

BACKGROUND: Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year. Oncolytic viral therapy has been evaluated in patients with pediatric gliomas elsewhere in the brain, but data regarding oncolytic viral therapy in patients with DIPG are lacking. METHODS: We conducted a single-center, dose-escalation study of DNX-2401, an oncolytic adenovirus that selectively replicates in tumor cells, in patients with newly diagnosed DIPG. The patients received a single virus infusion through a catheter placed in the cerebellar peduncle, followed by radiotherapy. The primary objective was to assess the safety and adverse-event profile of DNX-2401. The secondary objectives were to evaluate the effect of DNX-2401 on overall survival and quality of life, to determine the percentage of patients who have an objective response, and to collect tumor-biopsy and peripheral-blood samples for correlative studies of the molecular features of DIPG and antitumor immune responses. RESULTS: A total of 12 patients, 3 to 18 years of age, with newly diagnosed DIPG received 1×1010 (the first 4 patients) or 5×1010 (the subsequent 8 patients) viral particles of DNX-2401, and 11 received subsequent radiotherapy. Adverse events among the patients included headache, nausea, vomiting, and fatigue. Hemiparesis and tetraparesis developed in 1 patient each. Over a median follow-up of 17.8 months (range, 5.9 to 33.5), a reduction in tumor size, as assessed on magnetic resonance imaging, was reported in 9 patients, a partial response in 3 patients, and stable disease in 8 patients. The median survival was 17.8 months. Two patients were alive at the time of preparation of the current report, 1 of whom was free of tumor progression at 38 months. Examination of a tumor sample obtained during autopsy from 1 patient and peripheral-blood studies revealed alteration of the tumor microenvironment and T-cell repertoire. CONCLUSIONS: Intratumoral infusion of oncolytic virus DNX-2401 followed by radiotherapy in pediatric patients with DIPG resulted in changes in T-cell activity and a reduction in or stabilization of tumor size in some patients but was associated with adverse events. (Funded by the European Research Council under the European Union's Horizon 2020 Research and Innovation Program and others; EudraCT number, 2016-001577-33; ClinicalTrials.gov number, NCT03178032.).

Compassionate use of Quantum Magnetic Resonance Therapy for treatment of children with Diffuse Brainstem Glioma in Mexico City: a single institutional experience.

PURPOSE: Diffuse Brainstem Glioma (DBG) is a catastrophic brain tumor with a survival rate of less than 10% two years after diagnosis despite the existence of different treatment protocols. Among the devices that use magnetic fields generated by Magnetic Resonance Imaging is Quantum Magnetic Resonance Therapy (QMRT). METHODS: Five children diagnosed with DBG in our institution in Mexico City underwent treatment of compassionate use with QMRT between December 2018 and July 2019. A survival analysis was performed with previously reported historical data (n = 15). RESULTS: Two patients (40%) survived after three years of follow-up; the log-rank test showed a statistically significant difference in overall survival between both groups (p = 0.032). All patients tolerated the treatment adequately without reporting any severe clinical or neuroradiological adverse effects. Of the patients included, all showed a decrease in the tumor one month after the end of the treatment, although there was great variability in the response and the difference was not statistically significant (p = 0.06). CONCLUSIONS: Although future investigations are needed to confirm the findings reported in the present study, the improvement in survival is promising for a group of patients whose prognosis has been catastrophic over the years. Trial registration NCT03577600.

Leptomeningeal and subependymal seeding of diffuse intrinsic pontine glioma: a case report.

DIPG (diffuse intrinsic pontine glioma) is a deadly cancerous tumor of the brainstem that spreads across the pons. The tumor's infiltrative nature, as well as the tumor's critical pathway and nuclei compression, contributes to the tumor's extremely poor prognosis and limited existing therapeutic options. A previous study revealed that in 40 patients with brainstem glioma, 13 (33%) patients had leptomeningeal spreading. In this paper, we reported a 7-year-old female patient who presented with a history of decreased consciousness and weakness of the right limb. Her magnetic resonance imaging (MRI) revealed a pontine mass. She was given 35 fractions of 54 Gy whole-brain radiotherapy. The post-radiotherapy MRI evaluation showed multiple nodules in periventricular region, and was suggestive of leptomeningeal and subependymal seeding of the pontine glioma in the lateral ventricles. This case report elucidated the leptomeningeal seeding in a pediatric patient with diffuse intrinsic pontine glioma.

Volumetric endpoints in diffuse intrinsic pontine glioma: comparison to cross-sectional measures and outcome correlations in the International DIPG/DMG Registry.

BACKGROUND: Cross-sectional tumor measures are traditional clinical trial endpoints; however volumetric measures may better assess tumor growth. We determined the correlation and compared the prognostic impact of cross-sectional and volumetric measures of progressive disease (PD) among patients with DIPG. METHODS: Imaging and clinical data were abstracted from the International DIPG Registry. Tumor volume and cross-sectional product (CP) were measured with mint Lesion™ software using manual contouring. Correlation between CP and volume (segmented and mathematical [ellipsoid] model) thresholds of PD were assessed by linear regression. Landmark analyses determined differences in survival (via log-rank) between patients classified as PD versus non-PD by CP and volumetric measurements at 1, 3, 5, 7, and 9 months postradiotherapy (RT). Hazard ratios (HR) for survival after these time points were calculated by Cox regression. RESULTS: A total of 312 MRIs (46 patients) were analyzed. Comparing change from the previous smallest measure, CP increase of 25% (PD) correlated with a segmented volume increase of 30% (R2 = 0.710), rather than 40% (spherical model extrapolation). CP-determined PD predicted survival at 1 month post-RT (HR = 2.77), but not other time points. Segmented volumetric-determined PD (40% threshold) predicted survival at all imaging timepoints (HRs = 2.57, 2.62, 3.35, 2.71, 16.29), and 30% volumetric PD threshold predicted survival at 1, 3, 5, and 9 month timepoints (HRs = 2.57, 2.62, 4.65, 5.54). Compared to ellipsoid volume, segmented volume demonstrated superior survival associations. CONCLUSIONS: Segmented volumetric assessments of PD correlated better with survival than CP or ellipsoid volume at most time points. Semiautomated tumor volume likely represents a more accurate, prognostically-relevant measure of disease burden in DIPG.

Chorioallantoic membrane (CAM) assay to study treatment effects in diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain tumor. While there are a number of in vivo rodent models for evaluating tumor biology and response to therapy, these models require significant time and resources. Here, we established the chick-embryo chorioallantoic (CAM) assay as an affordable and time efficient xenograft model for testing a variety of treatment approaches for DIPG. We found that patient-derived DIPG tumors develop in the CAM and maintain the same genetic and epigenetic characteristics of native DIPG tumors. We monitored tumor response to pharmaco- and radiation therapy by 3-D ultrasound volumetric and vasculature analysis. In this study, we established and validated the CAM model as a potential intermediate xenograft model for DIPG and its use for testing novel treatment approaches that include pharmacotherapy or radiation.

Hypofractionated Radiation Therapy For Diffuse Intrinsic Pontine Glioma: A Noninferiority Randomized Study Including 253 Children.

PURPOSE: Pediatric diffuse intrinsic pontine glioma is an orphen disease. This study aimed to confirm the noninferiority of hypofractionated (HF) radiation therapy. Identification of the prognostic factors that determine the overall survival (OS) and progression-free survival (PFS) was the secondary objective. METHODS AND MATERIALS: We randomized 253 patients into 3 arms of radiation therapy regimens: HF1, receiving 39 Gy in 13 fractions; HF2, receiving 45 Gy in 15 fractions; and conventional fractionation (CF), receiving 54 Gy in 30 fractions. The OS and PFS were calculated using Kaplan-Meier methods, and the noninferiority was estimated against the CF arm. RESULTS: The median OS for the HF1, HF2, and CF were 9.6, 8.2, and 8.7 months, respectively. The 1-, 1.5-, and 2-year OS were 34.6%, 17.9%, and 10.7% for HF1; 26.2%, 13.1%, and 4.8% for HF2; and 25.3%, 12.1%, and 8.4% for CF, respectively (P = .3). The hazard ratio was 0.776 and 1.124 for HF1 and HF2, respectively. Considering the noninferiority margin (Δ) of 15% and a power of 90%, the lower inferiority confidence interval for HF1 was -14.34% and for HF2 it was 11.37% (both below Δ), confirming its noninferiority at 18-months OS. Younger patients (2-5 years of age) had better median OS in the whole cohort (11.6 months), HF1 (13.5), and CF (12.1) but not HF2 (6.2) (P = .003). Furthermore, the OS rates at 1, 1.5, and 2 years for children 2 to 5 years of age in the HF2 arm were lower than those in the HF1 and CF arms. However, similar acute and late side effects were reported in the 3 arms. CONCLUSIONS: Two hypofractionated radiation therapy proved to be noninferior to conventional fractionation. Young age (2-5 years) is the only prognostic factor determining both OS and PFS. The young age superiority was lost with a higher hypofractionated radiation therapy dose, necessitating more caution in applying 45 Gy in 15 fractions in younger children (2-5 years of age).

Phase I/II trial of vorinostat and radiation and maintenance vorinostat in children with diffuse intrinsic pontine glioma: A Children's Oncology Group report.

BACKGROUND: A phase I/II trial of vorinostat (suberoylanilide hydroxamic acid), an oral histone deacetylase inhibitor, was conducted in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) through the Children's Oncology Group (COG) to: 1) determine the recommended phase II dose (RP2D) of vorinostat given concurrently with radiation therapy; 2) document the toxicities of continuing vorinostat as maintenance therapy after radiation; and 3) to determine the efficacy of this regimen by comparing the risk of progression or death with a historical model from past COG trials. METHODS: Vorinostat was given once daily, Monday through Friday, during radiation therapy (54 Gy in 30 fractions), and then continued at 230 mg/m2 daily for a maximum of twelve 28-day cycles. RESULTS: Twelve patients enrolled in the phase I study; the RP2D of vorinostat given concurrently with radiation was 230 mg/m2/day, Monday through Friday weekly. The six patients enrolled at the RP2D and an additional 64 patients enrolled in the phase II study contributed to the efficacy assessment. Although vorinostat was well-tolerated, did not interrupt radiation therapy, and was permanently discontinued in only 8.6% of patients due to toxicities, risk for EFS-event was not significantly reduced compared with the target risk derived from historical COG data (P = 0.32; 1-sided). The 1-year EFS was 5.85% (95% CI 1.89-13.1%) and 1-year OS was 39.2% (27.8-50.5%). CONCLUSIONS: Vorinostat given concurrently with radiation followed by vorinostat monotherapy was well tolerated in children with newly diagnosed DIPG but failed to improve outcome.

Radiosensitizing the Vasculature of Primary Brainstem Gliomas Fails to Improve Tumor Response to Radiation Therapy.

PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) arise in the pons and are the leading cause of death from brain tumors in children. DIPGs are routinely treated with radiation therapy, which temporarily improves neurological symptoms but generally fails to achieve local control. Because numerous clinical trials have not improved survival from DIPG over standard radiation therapy alone, there is a pressing need to evaluate new therapeutic strategies for this devastating disease. Vascular damage caused by radiation therapy can increase the permeability of tumor blood vessels and promote tumor cell death. METHODS AND MATERIALS: To investigate the impact of endothelial cell death on tumor response to radiation therapy in DIPG, we used dual recombinase (Cre + FlpO) technology to generate primary brainstem gliomas which lack ataxia telangiectasia mutated (Atm) in the vasculature. RESULTS: Here, we show that Atm-deficient tumor endothelial cells are sensitized to radiation therapy. Furthermore, radiosensitization of the vasculature in primary gliomas triggered an increase in total tumor cell death. Despite the observed increase in cell killing, in mice with autochthonous DIPGs treated with radiation therapy, deletion of Atm specifically in tumor endothelial cells failed to improve survival. CONCLUSIONS: These results suggest that targeting the tumor cells, rather than endothelial cells, during radiation therapy will be necessary to improve survival among children with DIPG.

Gamma Knife radiosurgery as primary treatment of low-grade brainstem gliomas: A systematic review and metanalysis of current evidence and predictive factors.

The current standard of care for surgically inaccessible low-grade brainstem gliomas (BS-LLGs) is external-beam radiotherapy (RT). Developments toward more innovative conformal techniques have focused on decreasing morbidity, by limiting radiation to surrounding tissues. Among these Gamma Knife radiosurgery (SRS-GK) has recently gained an increasingly important role in the treatment of these tumors. Although SRS-GK has not yet been compared with conventional RT in patients harboring focal BS-LGGs, clinical practice has been deeply influenced by trials performed on other tumors. This is the first meta-analysis on the topic, systematically reviewing the most relevant available evidence, comparing RT and SRS-GK as primary treatments of BS-LGGs, focusing on survival, clinical outcome, oncological control, and complications. Predictive factors have been systematically evaluated and analyzed according to statistical significance and clinical relevance.

Molecularly targeted treatment of recurrent anaplastic astrocytoma - a case report.

High-grade astrocytomas are malignant and aggressive, with limited treatment options. Treatment is geared not only toward increasing patient's overall survival but also in delaying or preventing neurological disability, a cause of significant morbidity. Increasingly, targeted and customized treatment approaches, especially for recurrent disease, are being explored. Here we present a successful outcome in a young patient with rapidly progressive disease who responded to targeted treatment based on genetic sequencing and circulating tumor DNA markers, given the inaccessibility of the tissue to biopsy. Molecular testing on tissue, serum or CSF may be helpful in identifying unique targets in these complex patients.

Model-based evaluation of image-guided fractionated whole-brain radiation therapy in pediatric diffuse intrinsic pontine glioma xenografts.

Radiation therapy (RT) is currently the standard treatment for diffuse intrinsic pontine glioma (DIPG), the most common cause of death in children with brain cancer. A pharmacodynamic model was developed to describe the radiation-induced tumor shrinkage and overall survival in mice bearing DIPG. CD1-nude mice were implanted in the brain cortex with luciferase-labeled patient-derived orthotopic xenografts of DIPG (SJDIPGx7 H3F3AWT / K27 M and SJDIPGx37 H3F3AK27M / K27M ). Mice were treated with image-guided whole-brain RT at 1 or 2 Gy/fraction 5-days-on 2-days-off for a cumulative dose of 20 or 54 Gy. Tumor progression was monitored with bioluminescent imaging (BLI). A mathematical model describing BLI and overall survival was developed with data from mice receiving 2 Gy/fraction and validated using data from mice receiving 1 Gy/fraction. BLI data were adequately fitted with a logistic tumor growth function and a signal distribution model with linear radiation-induced killing effect. A higher tumor growth rate in SJDIPGx37 versus SJDIPGx7 xenografts and a killing effect decreasing with higher tumor baseline (p < 0.0001) were identified. Cumulative radiation dose was suggested to inhibit the tumor growth rate according to a Hill function. Survival distribution was best described with a Weibull hazard function in which the hazard baseline was a continuous function of tumor BLI. Significant differences were further identified between DIPG cell lines and untreated versus treated mice. The model was adequately validated with mice receiving 1 Gy/fraction and will be useful in guiding future preclinical trials incorporating radiation and to support systemic combination therapies with RT.

Single institution experience in re-irradiation of biopsy-proven diffuse intrinsic pontine gliomas.

OBJECTIVES: Diffuse intrinsic pontine glioma (DIPG) is the leading cause of death from CNS tumors in children. Multiple clinical trials have failed to show any benefit from systemic therapy in DIPG, and radiation therapy (RT) alone remains the standard of care. Re-irradiation (rRT) for symptomatic relief is an option at disease progression. However, published data on treatment details and outcomes are limited. The objective of this study was to review and report our institutional experience with re-irradiation of patients with biopsy-proven DIPG. METHODS: We identified a cohort of pediatric patients with biopsy-proven DIPG with clinical disease progression after initial radiotherapy who received a second course of radiotherapy at our institution. We reviewed patient and treatment characteristics and outcomes. RESULTS: Between January 2014 and July 2018, we identified five patients with progressive DIPG who received re-irradiation. Re-irradiation was well tolerated with no serious adverse events reported and all patients experiencing stable to improved neurologic function during treatment. Median survival from completion of re-irradiation was 116 days (range 62 to 159 days). Median overall survival from time of diagnosis was 16.3 months (range 13.0 to 18.0 months), which is longer than the historical average of less than 12 months. In patients with available postmortem neuropathology, common findings were Wallerian degeneration and necrosis. CONCLUSIONS: In our experience, re-irradiation is safe and feasible for patients with DIPG with symptomatic disease progression following initial radiotherapy treatment.