Summary: care management for children receiving systemic therapy for pLGG

European standard clinical practice recommendations call for a multidisciplinary tumor board (neuro-oncology, neurosurgery, neurology, neuroradiology, radiotherapy, neuropathology) with involvement of ophthalmology, audiology, and endocrinology, and state that maintaining visual, endocrine, and neurological function is a key aspect of management. A 2026 Delphi consensus of 82 experts from 29 countries (funded by an educational grant from Day One Biopharmaceuticals) reached agreement on 50 of 129 statements, including that MAPK inhibitors should be prescribed and overseen by an oncology team in a multidisciplinary setting, that patient and caregiver education is essential, and that early prophylactic skin care is recommended; consensus was not reached for most cardiac, ophthalmologic, and endocrine statements. Recommended monitoring for MAPK inhibitors includes sodium and glucose in children with hypothalamic-pituitary lesions, echocardiography and ophthalmologic examination for MEK inhibitors, and height and growth velocity for tovorafenib. After discontinuation, structured imaging is recommended, particularly in the first 6 months, and Canadian consensus suggests MRI at least every 3 months for 1 year off therapy and slow tapering. Long-term visual monitoring and survivorship follow-up are supported by data showing that 26% of children with optic pathway glioma diagnosed before age 3 were bilaterally blind after a median of 11 years, and that adult survivors with bilateral blindness were more likely to be unemployed and to live with a caregiver.

Multidisciplinary tumor board and functional preservation

“Involvement of other specialties including ophthalmology, audiology and endocrinology is extremely important.” (opens the source at this quote in a new tab)
“There are therefore several strategies from different disciplines for tumour control for paediatric low grade glioma, and a key aspect of overall management is to maintain visual, endocrinological and neurological function. Management strategy should therefore always be planned in the multi-disciplinary team setting.” (opens the source at this quote in a new tab)

“All patients need comprehensive neuro-oncological care, the principles and details of which are summarized in the current guidelines. These represent standard of care for diagnostic work-up (including neuroimaging and neuropathology), and for therapeutic decisions (including the indications to non-surgical treatment) as well as concepts for neurosurgical intervention, chemotherapy and radiotherapy as well as surveillance and rehabilitation.” (opens the source at this quote in a new tab)

Delphi consensus on adverse event management with MAPK inhibitors

Consensus statement	Domain
“Ensuring appropriate education of patients and caregivers on the potential AEs is essential to improve patient outcomes, manage patient/caregiver expectations, and aid treatment adherence”	General management
“Additionally, patients/caregivers should be educated on the need for proactive AE management in order to control some AEs, particularly cutaneous toxicities”	General management
“Proactive management of pre-existing skin conditions, including topical treatments and close dermatologic monitoring, is essential in preventing severe AEs in high-risk patients”	Cutaneous AEs
“Early signs of hyponatremia, such as headache, lethargy, nausea, and confusion, should prompt immediate evaluation, and serum electrolytes should be checked promptly”	Endocrine-related AEs

“Of the 129 statements drafted, consensus (≥75% agreement) among 82 global experts in pLGG was reached for 50 statements, mostly pertaining to the general management of AEs occurring with MAPKi and the management of cutaneous AEs.” (opens the source at this quote in a new tab)
“It is also important that for all patients with pLGG in the suprasellar region, treatment should be started in consultation with the pediatric endocrinologist for adequate monitoring and guidance of growth and serum sodium values.” (opens the source at this quote in a new tab)

Endocrine monitoring during BRAF and MEK inhibitor therapy

“Clinicians using such treatments need to be aware of these potential effects, particularly the risk of hyponatraemia in patients with pre-existing central diabetes insipidus and monitor for these accordingly, including performing measurements of sodium and glucose prior to, during and after treatment.” (opens the source at this quote in a new tab)

Growth monitoring during tovorafenib therapy

“Reduced growth velocity has been reported with tovorafenib, and recovery of growth velocity may occur after treatment interruption; therefore, baseline and longitudinal monitoring of height/weight percentiles and growth velocity should be incorporated into routine care, with pubertal assessment and endocrine evaluation when clinically indicated [73].” (opens the source at this quote in a new tab)

Cardiac and ophthalmologic monitoring with MEK inhibitors

“While the rates of cardiac toxicity are low in children receiving MAPK pathway inhibitors in published reports, most guidelines recommend routine echocardiograms (ECHO) to monitor for asymptomatic diminishing ejection fraction (EF) while on MEK inhibitor therapy.” (opens the source at this quote in a new tab)

“Regular cardiac and ophthalmological review is mandatory to monitor for rare yet significant events including reduced ejection fraction and retinal detachment.” (opens the source at this quote in a new tab)

Imaging surveillance and discontinuation of targeted therapy

“Since discontinuation of treatment can be associated with rapid clinical and radiological progression, we suggest tapering one drug at a time, starting with MEKis by approximately 25% every 3 months, and the BRAFis by 25% every 6 months.” (opens the source at this quote in a new tab)
“We suggest continuing with surveillance MRI at least every 3 months once off drugs for 1 year then as per institutional standard.” (opens the source at this quote in a new tab)

“Importantly, approximately one-third of RR events (34.8%) were reported to be clinically symptomatic, whereas most were detected radiologically during routine surveillance. This finding underscores the importance of structured imaging follow-up, particularly during the first 6 months after MAPKi cessation.” (opens the source at this quote in a new tab)

“Recommend scan sequences and slice thickness plus interpretation as per RAPNO pediatric low-grade glioma criteria (RAPNO pLGG)” (opens the source at this quote in a new tab)

Visual acuity monitoring

“In addition, screening for visual acuity is required for all patients; baseline assessments will be taken during screening.” (opens the source at this quote in a new tab)

“Our findings underscore the urgent need for earlier, vision-directed interventions and long-term visual monitoring.” (opens the source at this quote in a new tab)

Survivorship: vision loss and socioeconomic outcomes in adult survivors

“Among 1,233 survivors of childhood astroglial tumor ≥ 5 years post-diagnosis, 277 (22.5%) had visual impairment. In multivariable analysis, survivors with bilateral blindness were more likely to be unmarried (adjusted odds ratio [95% confidence interval]: 4.7 [1.5, 15.0]), live with a caregiver (3.1 [1.3, 7.5]), and be unemployed (2.2 [1.1, 4.5]) compared to those without visual impairment.” (opens the source at this quote in a new tab)

Survivorship: occupation, income, and education after radiotherapy

“On the long term, younger age at diagnosis and treatment with radiotherapy in LGG patients resulted in sevenfold lower occupation scores, more sheltered work, lower income, and less education in adulthood” (opens the source at this quote in a new tab)
“This lower occupation score was also related to vision, hearing, and motor impairments.” (opens the source at this quote in a new tab)

Detection of hemorrhage and biology-informed surveillance in pediatric low-grade glioma

“Five of the twelve hemorrhages were symptomatic at presentation (three with headache alone, one with nausea and vomiting, and one with headache and vision impairment); the remaining seven were detected incidentally on surveillance imaging.” (opens the source at this quote in a new tab)
“Patients with KIAA1549::BRAF fusion, particularly those receiving MAPK inhibitors or requiring CSF diversion in high-risk locations, warrant heightened surveillance and careful procedural planning. Patients with genetic syndromes, BRAF V600E mutations, or tumors in non-eloquent locations without fusion carry substantially lower risk and may follow standard imaging protocols.” (opens the source at this quote in a new tab)
“CSF diversion was independently associated with hemorrhage exclusively in high-risk anatomic locations (brainstem, optic pathway, hypothalamus), where it increased hemorrhage incidence sevenfold.” (opens the source at this quote in a new tab)

Management after carboplatin hypersensitivity: prophylaxis, discontinuation, and switching regimens

“Five of 15 patients who received prophylactic premedication developed Cb HSR (2 patients developed grade I Cb HSR, 1 patient developed grade II Cb HSR, and 2 patients developed grade III Cb HSR).” (opens the source at this quote in a new tab)
“Four patients were observed without further chemotherapy, 2 patients underwent surgical resection, and 14 received another noncarboplatin-containing chemotherapy regimen, including 7 patients who received weekly vinblastine; 4 patients who received either combined thioguanine, procarbazine, and CCNU or combined thioguanine and PCV; and 3 patients who received another line of chemotherapy.” (opens the source at this quote in a new tab)
“In patients with carboplatin allergy, the current International Society of Pediatric Oncology LGG protocol discourages attempts to continue therapy by means of desensitization and suggests alternative combinations, such as vincristine plus cyclophosphamide or vincristine plus cisplatin.” (opens the source at this quote in a new tab)
“For patients with an early onset allergic reaction, alternative chemotherapy regimens that offer a good efficacy rate without evidence of long-term toxicity should be considered instead.” (opens the source at this quote in a new tab)

Premedication and desensitization procedure used for carboplatin rechallenge

“All patients received premedication with dexamethasone (between 0.05 and 0.15 mg/kg delivered intravenously 1 hr prior to carboplatin) and cetirizine (approximately 0.2 mg/kg delivered orally 1 hr prior to carboplatin) and nine patients received a desensitization protocol with successive infusions of increasing doses as described by Confino-Cohen et al.” (opens the source at this quote in a new tab)
“This protocol begins with premedication followed by infusion of 1/1000 of the total dose over 90 min followed by 1/100 of the total dose over 90 min followed by 1/10 of the total dose over 90 min followed by the remainder of the dose over 90 min.” (opens the source at this quote in a new tab)
“Two of the patients with grade I reactions required no treatment; the other patient with a grade I reaction and the patients with grade II reactions responded promptly to steroid and antihistamine; and the patients with grade III anaphylaxis required adrenaline and responded promptly.” (opens the source at this quote in a new tab)

Senescence-associated secretory phenotype score as a possible guide to follow-up intensity

“These results could potentially have an impact on the therapeutic management and follow-up (FU) of these patient groups: (i) patients with a high or intermediate SASP sum score and GTR could potentially have longer FU intervals or even a shorter FU period overall; (ii) patients with initially subtotal resection and low or intermediate SASP sum score could benefit from a complete re-resection or possibly adjuvant therapy, to improve their PFS.” (opens the source at this quote in a new tab)
“The prognostic significance of the SASP sum score of course needs to be validated first in a prospective manner in upcoming clinical trials.” (opens the source at this quote in a new tab)

Tovorafenib (DAY101)

Care management intervention strategies