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Reirradiation and PD-1 inhibition with nivolumab for the treatment of recurrent diffuse intrinsic pontine glioma: a single-institution experience

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Abstract

Background

Diffuse intrinsic pontine glioma (DIPG) is a rare, aggressive brain tumor with no known cure. Reirradiation (reRT) at recurrence can prolong survival. The impact of irradiation may be heightened when combined with PD-1 inhibition. We describe our experience using reRT, with or without PD-1 inhibition, in a cohort of patients with recurrent DIPG.

Methods

We performed a retrospective cohort analysis of children who received reRT with or without concomitant PD-1 inhibition for recurrent DIPG at a single institution between 2005 and 2016. We compared progression-free (PFS) and overall survival (OS) between those who received reRT alone or in combination with PD-1 inhibition. We then compared reRT to a cohort of patients who did not receive reRT.

Results

Thirty-one patients were included (8—reRT with nivolumab; 4—reRT alone; 19—no reRT). Patients who received reRT had prolonged OS compared to no reRT (22.9 months—reRT with nivolumab; 20.4 months—reRT alone; 8.3 months—no reRT; p < 0.0001). Patients who received reRT with nivolumab vs. reRT only had slightly prolonged OS from diagnosis and from reRT (22.9 vs. 20.4 months for time from diagnosis; 6.8 vs. 6.0 months for time from reRT). All patients receiving reRT with or without nivolumab tolerated the therapy without acute or late toxicity.

Conclusions

Our experience demonstrates the tolerability of reRT with concurrent PD-1 inhibition for recurrent DIPG and suggests that combination therapy may offer survival benefit. Future prospective studies are needed to confirm the benefits of this combination therapy.

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Funding

C.N.K. is supported by Frank A. Campini Foundation, Cannonball Kids’ Cancer [A129749], and National Institutes of Health National Center for Advancing Translational Sciences [KL2TR001870-This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH]. The research was supported in part by the William M. Wood Foundation (D.H.K).

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Author notes

  1. Cassie Kline and S. John Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, University of California, San Francisco, CA, USA

    Cassie Kline, Anuradha Banerjee, Shannon Raber, Nalin Gupta & Sabine Mueller

  2. School of Medicine, University of California, San Francisco, CA, USA

    S. John Liu

  3. Department of Radiation Oncology, Washington University in Saint Louis, St Louis, MO, USA

    Sai Duriseti

  4. Department of Neurology, University of California, San Francisco, CA, USA

    Cassie Kline & Sabine Mueller

  5. Department of Neurological Surgery, University of California, San Francisco, CA, USA

    Anuradha Banerjee, Theodore Nicolaides, Nalin Gupta & Sabine Mueller

  6. Department of Pediatrics, New York University, New York, NY, USA

    Theodore Nicolaides

  7. Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, USA

    Daphne Haas-Kogan

  8. Department of Radiation Oncology, University of California, San Francisco, CA, USA

    Steve Braunstein

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  1. Cassie Kline
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Correspondence to Cassie Kline or Sabine Mueller.

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Kline, C., Liu, S.J., Duriseti, S. et al. Reirradiation and PD-1 inhibition with nivolumab for the treatment of recurrent diffuse intrinsic pontine glioma: a single-institution experience. J Neurooncol 140, 629–638 (2018). https://doi.org/10.1007/s11060-018-2991-5

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  • DOI: https://doi.org/10.1007/s11060-018-2991-5

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