Reirradiation practices for children with diffuse intrinsic pontine glioma

Abstract

Background Diffuse intrinsic pontine gliomas (DIPGs) are a leading cause of brain tumor deaths in children. Current standard of care includes focal radiation therapy (RT). Despite clinical improvement in most patients, the effect is temporary and median survival is less than one year. The use and benefit of reirradiation has been reported in progressive DIPG, yet standardized approaches are lacking. We conducted a survey to assess reirradiation practices for DIPG in North America. Methods A 14-question REDCap survey was disseminated to 396 North American physicians who care for children with CNS tumors. Results Response rate was 35%. Participants included radiation-oncologists (63%; 85/135) and pediatric oncologists/neuro-oncologists (37%; 50/135). Most physicians (62%) treated 1-5 DIPG patients per year, with 10% treating >10 per year. Reirradiation was considered a treatment option by 88% of respondents. Progressive disease or worsening clinical status were the most common reasons to consider reirradiation. The majority (84%) surveyed considered reirradiation a minimum of six months following initial RT. Doses varied, with median total dose of 2400 cGy (range 1200-6000 cGy) and fraction size of 200 cGy (range 100-900 cGy). Concurrent use of systemic agents with reirradiation was considered in 46%, including targeted agents (37%), biologics (36%), or immunotherapy (25%). One-time reirradiation was the most common practice (71%). Conclusion Although the vast majority of physicians consider reirradiation as a treatment for DIPG, total doses and fractionation varied. Further clinical trials are needed to determine the optimal radiation dose and fractionation for reirradiation in children with progressive DIPG.

Hypofractionated re‐irradiation for diffuse intrinsic pontine glioma

“…Various fractionation regimens have been utilized, but CF of 1.8-2 Gy has predominated. 9 In initial treatment of DIPG, there does not appear to be a role for hyperfractionation. 25 However, interest in HF has emerged, given the value of decreased patient and caregiver burden with fewer treatments.…”

“…In a published survey, 30% of responding physicians reported symptomatic radiation necrosis and 43% reported asymptomatic radiation necrosis as complications of reRT in this setting. 9 In published series, this toxicity has been rare, but it remains an important risk to consider for dose escalation or HF, as consequences can be severe. In the dose escalation series in India, two patients who received 43.2 and 45 Gy developed sudden onset headache and neurologic dysfunction, and they were found to have intratumoral hemorrhage 7 and 77 days after reRT, respectively.…”

“…8 The tumors inevitably recur, often locally, and reirradiation (reRT) can offer further palliation and extend survival after clinical decline or exhaustion of investigational therapies. [8][9][10] Retrospective data first indicated safety and effectiveness of 20 Gy in 10 fractions for reRT. 11 Subsequently, when compared to best supportive care or systemic therapy, reRT at first progression appears to improve OS without severe toxicity and resulted in clinical improvement in most patients.…”

Pediatric Diffuse Midline Gliomas: An Unfinished Puzzle

“…Several other studies confirmed a statistically significant median survival benefit after re-irradiation for recurrent DIPG, ranging from 3 to 4 months. The maximum doses reported in the literature ranged from 30 to 36 Gy (1.8 Gy/day), according to the time passed since their first radiation therapy to permit some recovery of brainstem tolerance [ 57 ].…”

Pediatric diffuse midline glioma H3K27- altered: A complex clinical and biological landscape behind a neatly defined tumor type

“…Nonetheless, despite the various attempts at new treatment approaches described so far, the prognosis remains poor (8). Re-irradiation, which represents the only effective treatment for recurrent disease, can lead to symptom relief or neurological improvement in the majority of patients and slightly prolong survival after relapse but remains a palliative and not a curative option (17)(18)(19)(20)(21).…”