Treatment Challenges

Challenges and evolving treatment paradigms in managing pLGG16-18

Ayiden, lives with pLGG.
Lives for basketball.

Patients with pediatric low-grade gliomas (pLGG) experience significant and persistent long-term consequences16,17

While standard treatment approaches may control tumor growth, they have unique toxicity profiles that may impact the daily lives of patients with pLGG.16,18

Short- and long-term effects associated with surgery, chemotherapy, and targeted therapies*

Chemotherapy19-21

  • Chemotherapy can result in acute effects (eg, neutropenia, alopecia [hair loss], vomiting, and anemia) for patients

  • There are also long-term side effects (eg, cardiovasuclar diseases, fertility problems, and heart failure) that may persist indefinitely

Type 1 BRAF inhibitors and/or MEK inhibitors

Toxicity profiles for BRAF/MEK inhibitors, when used as a monotherapy or in combination with each other:

  • BRAF inhibitors, when used as a monotherapy, may cause rash and fever22

  • MEK inhibitors, when used as a monotherapy, may cause CPK elevation, maculopapular rash, truncal weakness, diarrhea, and paronychia (infection around the nail)23

  • BRAF/MEK inhibitor combination therapy may cause pyrexia, rash, vomiting, abdominal pain, and diarrhea24

*Not a comprehensive list.

Additionally, certain tumors require faster response time than others due to an unfavorable location.2,25,26

Evolving response assessment criteria in pLGG clinical trials

The Response Assessment in Neuro-Oncology (RANO) working group looked to improve and standardize response assessment in neuro-oncology.27

Historically, RANO HGG have been used to assess pLGG, focusing primarily on T1 contrast. Recent advances in the understanding of LGGs influenced the RANO working group to propose revised criteria, specific to LGGs.27

The Radiologic Assessment in Pediatric Neuro-Oncology (RAPNO) Working Group was established in 2020 to develop consensus recommendations for response criteria for pLGG.28

Response criteria guildelines in neuro‑oncology27-29

RANO HGGRANO LGGRAPNO LGG

Modality

T1-Gd +, T2/FLAIR

T2/FLAIR

T2/FLAIR

Response types†

  • Complete response, partial response, stable disease
  • Partial response, minor response, progressive disease, stable disease
  • Major response, partial response, minor response, progressive disease, stable disease

Additional factors

  • New lesions, corticosteroids, clinical status
  • T2/FLAIR imaging is more relevant for tumor changes in pLGG
  • Introduced "minor response" criteria
  • T1 contrast enhancement, clinical status, cyst assessment

Limitations

  • LGGs have minimal evidence of contrast enhancement
  • Designed with adult LGGs in mind, which are different from pLGGs
  • No focus on functional outcomes
  • RAPNO LGG continues to emerge as its uptake in clinical studies rises

†Any qualitative increase in nonenhancing disease constitutes progression.

Aligning with the needs for treating pLGG

RAPNO LGG combines radiographic assessment in RANO LGG response categories with functional assessments that are key component of response assessment in pLGG

Because patients with pLGG have good overall survival yet have neurological deficits, a shift toward radiographic and functional assessment is vital for treatment selection.27

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