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. 2020 Mar;147(1):195-203.
doi: 10.1007/s11060-020-03415-w. Epub 2020 Feb 3.

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

Christopher L Tinkle  1 , Kristen Campbell  2   3 , Yuanyuan Han  4 , Yimei Li  4 , Brandon Bianski  2 , Alberto Broniscer  5   6 , Raja B Khan  5   7 , Thomas E Merchant  2
Affiliations

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

Christopher L Tinkle et al. J Neurooncol. 2020 Mar.

Abstract

Purpose: To estimate the rate and magnitude of neurologic symptom change during radiation therapy (RT) and impact of symptom change on survival outcomes in patients with diffuse intrinsic pontine glioma (DIPG).

Methods: From 2006 to 2014, 108 patients with newly diagnosed DIPG were treated with conventionally fractionated radiation therapy (RT) to 54 Gy (median) at our institution. The presence and severity of neurologic symptoms related to cranial neuropathy (CN) and cerebellar (CB) and long-tract (LT) signs was reviewed before and weekly during RT for each patient. The rate and magnitude of change for each symptom category was evaluated according to accumulated RT dose. The impact of clinical factors and radiation dose-volume parameters was determined using Cox proportional hazards models.

Results: Median dose to first sign of symptomatic improvement was 16.2 Gy (CN), 19.8 Gy (LT) and 21.6 Gy (CB). Most patients showed an improvement by 20 Gy. Larger uninvolved brainstem volume, alone or normalized to total brain (TB) or posterior fossa volume (PF), was associated with shorter time to LT sign improvement (P = 0.044, P = 0.033, and P = 0.05, respectively). Patients with any improvement in CN experienced significantly, yet modestly, prolonged progression-free survival (PFS) and overall survival (OS) (P = 0.002 and P = 0.008, respectively). Tumor volume, with or without normalization to TB or PF, was not significantly associated with PFS or OS.

Conclusions: Low cumulative RT doses resulted in neurologic improvement in most patients with DIPG. The volume of brainstem spared by tumor influenced time to symptomatic improvement. Neurologic improvement during RT was associated with superior survival.

Keywords: Diffuse intrinsic pontine glioma; Diffuse midline glioma; Dose response; Neurologic symptoms; Radiation therapy.

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Conflict of interest statement

Conflict of interest: The authors declare that they have no conflict of interest.

Figures

Fig 1
Fig 1
Study CONSORT diagram and neurologic symptom course
Fig 2
Fig 2
Distribution of first neurologic symptom category improvement by RT dose and dexamethasone dose during RT with smoothed median dose (red line) and dose distribution (black dots) (far right).
Fig 3
Fig 3
Kaplan–Meier estimates of improvement in neurologic deficit with cumulative RT dose
See this image and copyright information in PMC

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