Radiation dose response of neurologic symptoms during conformal radiotherapy for diffuse intrinsic pontine glioma

Tinkle, Christopher L.; Campbell, Kristen; Han, Yuanyuan; Li, Yimei; Bianski, Brandon; Broniscer, Alberto; Khan, Raja B.; Merchant, Thomas E.

doi:10.1007/s11060-020-03415-w

Cited by 8 publications

(12 citation statements)

References 19 publications

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“…However, Tinkle et al assessed the evolution of neurological triad symptoms of DIPG patients undergoing upfront RT. At the end of the upfront RT, 87.9% (n = 73/83), 85.4% (n = 88/103), and 80.8% (n = 63/78) of patients had improvement in CB, CN, and LT signs, respectively (2). Focusing on neurological improvement after re-RT, we demonstrated that 44% (n = 11/25), 40% (n = 10/25), and 44% (n = 11/25) of patients had improvement in CN, LT, and CB signs, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Comparison of these two studies is limited by several differences. The study of Tinkle et al reported on a larger and prospective study about RT-naive DIPG patients, investigating the impact of a median cumulative upfront RT dose of 54 Gy on neurological triad improvement (2).…”

Section: Discussionmentioning

confidence: 99%

“…The same study extensively investigated the influence of neurologic symptom change during RT on survival outcomes ( 2 ). Survival was longer in patients who experienced an improvement in cranial nerve deficits, as compared to patients who did not experience such an improvement ( 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…Radiotherapy (RT) is still considered as the cornerstone of treatment for patients with diffuse intrinsic pontine glioma (DIPG) (1)(2)(3)(4). Current standard of care for newly diagnosed DIPG patients includes at least focal RT up to a dose of 54 Gy, or a low-burden alternative up to 39 Gy (1,5).…”

Section: Introductionmentioning

confidence: 99%

“…Among 108 patients, 57% of the patients had the classical triad ( 6 ), composed of cerebellar signs (CB) (e.g., ataxia, dysmetria, and dysarthria), cranial neuropathy (CN) (e.g., diplopia), and long-tract (LT) signs (e.g., paraplegia, Babinski sign, and hyperreflexia) at diagnosis. Neurological improvement in CB, CN, and LT signs at the end of upfront RT is 87.9%, 85.4%, and 80.8%, respectively ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Neurological Symptom Improvement After Re-Irradiation in Patients With Diffuse Intrinsic Pontine Glioma: A Retrospective Analysis of the SIOP-E-HGG/DIPG Project

et al. 2022

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PurposeThe aim of this study is to investigate the spectrum of neurological triad improvement in patients with diffuse intrinsic pontine glioma (DIPG) treated by re-irradiation (re-RT) at first progression.MethodsWe carried out a re-analysis of the SIOP-E retrospective DIPG cohort by investigating the clinical benefits after re-RT with a focus on the neurological triad (cranial nerve deficits, ataxia, and long tract signs). Patients were categorized as “responding” or “non-responding” to re-RT. To assess the interdependence between patients’ characteristics and clinical benefits, we used a chi-square or Fisher’s exact test. Survival according to clinical response to re-RT was calculated by the Kaplan–Meier method.ResultsAs earlier reported, 77% (n = 24/31) of patients had any clinical benefit after re-RT. Among 25/31 well-documented patients, 44% (n = 11/25) had improvement in cranial nerve palsies, 40% (n = 10/25) had improvement in long-tract signs, and 44% (11/25) had improvement in cerebellar signs. Clinical benefits were observed in at least 1, 2, or 3 out of 3 symptoms of the DIPG triad, in 64%, 40%, and 24%, respectively. Patients irradiated with a dose ≥20 Gy versus <20 Gy may improve slightly better with regard to ataxia (67% versus 23%; p-value = 0.028). The survival from the start of re-RT to death was not different between responding and non-responding DIPG patients (p-value = 0.871).ConclusionA median re-irradiation dose of 20 Gy provides a neurological benefit in two-thirds of patients with an improvement of at least one symptom of the triad. DIPG patients receiving ≥20 Gy appear to improve slightly better with regard to ataxia; however, we need more data to determine whether dose escalation up to 30 Gy provides additional benefits.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neurological Symptom Improvement After Re-Irradiation in Patients With Diffuse Intrinsic Pontine Glioma: A Retrospective Analysis of the SIOP-E-HGG/DIPG Project

et al. 2022

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Interdisciplinary care of children with diffuse midline glioma

Coleman

Chen

et al. 2023

Neoplasia

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A review of current therapeutics targeting the mitochondrial protease ClpP in diffuse midline glioma, H3 K27-altered

Jackson,

Persson,

Fish

et al. 2023

Neuro-Oncology

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Diffuse midline gliomas (DMGs) are devastating pediatric brain tumors recognized as the leading cause of cancer-related death in children. DMGs are high-grade gliomas (HGGs) diagnosed along the brain’s midline. Euchromatin is the hallmark feature of DMG, caused by global hypomethylation of H3K27 either through point mutations in histone H3 genes (H3K27M), or by overexpression of the enhancer of zeste homolog inhibitory protein (EZHIP). In a clinical trial for adults with progressive HGGs, a 22-year-old patient with a thalamic H3K27-altered DMG, showed remarkable clinical and radiological responses to dordaviprone (ONC201). This response in a H3K27-altered HGG patient, coupled with the lack of response of patients harboring wildtype-H3 tumors, has increased the clinical interest in dordaviprone for the treatment of DMG. Additional reports of clinical benefit have emerged, but research defining mechanisms of action (MOA) fall behind dordaviprone’s clinical use, with biomarkers of response unresolved. Here, we summarize dordaviprone’s safety, interrogate its preclinical MOA- identifying the mitochondrial protease ‘ClpP’ as a biomarker of response, and discuss other ClpP-agonists, expanding the arsenal of potential weapons in the fight against DMG. Finally, we discuss combination strategies including ClpP-agonists, and its immunomodulatory effects suggestive of a role for the tumor microenvironment in DMG patients’ response.

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Radiation dose response of neurologic symptoms during conformal radiotherapy for diffuse intrinsic pontine glioma

Cited by 8 publications

References 19 publications

Neurological Symptom Improvement After Re-Irradiation in Patients With Diffuse Intrinsic Pontine Glioma: A Retrospective Analysis of the SIOP-E-HGG/DIPG Project

Neurological Symptom Improvement After Re-Irradiation in Patients With Diffuse Intrinsic Pontine Glioma: A Retrospective Analysis of the SIOP-E-HGG/DIPG Project

Interdisciplinary care of children with diffuse midline glioma

A review of current therapeutics targeting the mitochondrial protease ClpP in diffuse midline glioma, H3 K27-altered

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