PATH-30 - Gliomas with FGFR Oncogenic alterations: Clinico-pathological features, management and outcomes in pediatric, adolescent and young adult patients.

Friday, November 17, 2023

7:30 PM – 9:30 PM PT

Location: Exhibit Hall A/B

Poster Presenter(s)

Magimairajan Issai Vanan

Cancer Care Manitoba, University of Manitoba
Winnipeg, Manitoba, Canada

Author(s)

SK

Saranya Kakumanu

Cancer Care Manitoba
Winnipeg, Manitoba, Canada
MP

Marshall Pitz

Cancer Care Manitoba
Winnipeg, Manitoba, Canada
CH

Craig Harlos

Cancer Care Manitoba
Winnipeg, Manitoba, Canada
CK

Colin Kazina

Health Sciences Center, Winnipeg Children's Hospital
Winnipeg, Manitoba, Canada
PM

Patrick McDonald

Health Sciences Center, University of Manitoba
Winnipeg, Manitoba, Canada
AD

Annie Drapeau

Health Sciences Center, University of Manitoba
Winnipeg, Manitoba, Canada
AK

Anthony Kaufmann

Health Sciences Center, University of Manitoba
Winnipeg, Manitoba, Canada
AO

Aoife O'Carroll

Winnipeg Children's Hospital, University of Manitoba
Winnipeg, Manitoba, Canada
QX

Qi Xu

Winnipeg Childrens Hospital, Health Sciences Center, University of Manitoba
Winnipeg, Manitoba, Canada
TD

Tina Drimes

Cancer Care Manitoba
Winnipeg, Manitoba, Canada
CB

Cathy Bourne

Cancer Care Manitoba
Winnipeg, Manitoba, Canada
JS

Jessica Streilein

Cancer Care Manitoba
Winnipeg, Manitoba, Canada
NS

Namita Sinha

Health Sciences Center, University of Manitoba
Winnipeg, Manitoba, Canada

Introduction: Fibroblast growth factor receptor (FGFR1-4) pathway alterations are rare in pediatric cancers (1-3%) but are enriched in certain specific subtypes of difficult to treat pediatric and AYA brain tumors. Some of the common oncogenic alterations include structural variants (fusions, duplications), mutations and amplifications.

Methods: We describe here the clinico-pathological features and therapeutic outcomes of pediatric and AYA patients (ages 0-39yrs) with FGFR pathway altered gliomas diagnosed in the past 10yrs (2013-2023). Data was collected from review of patient charts.

Results: We identified 13 patients with gliomas harboring an oncogenic FGFR alteration. Median age at diagnosis was 16yrs (range, 6-30yrs) and was more common in males (M: F-3:1). Seizures were the most common presenting symptom (N=5/13, 38%); all of these patients had cortical tumors, which were resected and seizures were adequately controlled. A biopsy only approach was done in more than half (N=7/13, 54%) of the patients. Pathological diagnosis included low grade glio-neuronal tumors in all but one of the patients, who had a high-grade glioma (Pilocytic astrocytoma N=6, Diffuse astrocytoma N=2, glio-neuronal tumors N=2, PLNTY N=2). FGFR alterations included oncogenic fusions (FGFR1-TACC1=1, FGFR2-TACC1=1, FGFR2-CTNNA3=2, FGFR3-TACC3=1), tandem duplications (FGFR1-TKD-ITD=3) and mutations (FGFR1- N546K=2, K654E=1, K656E=2). Co-occurring mutations were seen in 4 patients (H3.3-K27M=1, PIK3CA-E545K=1, PTPN11-G503V=1, PTPN11-E69K=1). Patients with symptomatic residual tumors (N=6, 46%) were treated with targeted therapies (Erdafitinib=3, Trametinib=1, Ponatinib / Everolimus=1, Dasatinib=1) and two patients received Radiation therapy. Erdafitinib was discontinued in one patient due to intra-tumoral bleed. Rest of the patients are tolerating the targeted therapy well and all of the patients are alive.

Conclusion: In summary, cortical tumors bearing FGFR alterations present with refractory seizures and are eminently treatable with surgical resection. Targeted therapy with FGFR specific inhibitors is tolerated well and updated response assessment of our patients will be presented in the meeting.