Tumor Type – Location – Date€¦ · 26-year-old woman with refractory low - grade glioma...

$: Tumor Type – Location – Date€¦ · 26-year-old woman with refractory low - grade glioma Initial diagnosis Pilocitic Astrocytoma in 1994(aged 3 years) – Partial resection +$
ESMO Preceptorship Programme

Impact of targeted treatment in the management of Low-grade glioma

Maria Vieito MD, Msc Medical OncologistGU, Sarcoma and Neuroncology Unit

Vall d'Hebron University Hospital

Tumor Type – Location – Date

ESMO PRECEPTORSHIP PROGRAMME

Disclosures

Roche: Travel grant to ESMO meeting.


26-year-old woman with refractory low-grade glioma

Initial diagnosis Pilocitic Astrocytoma in 1994(aged 3 years)– Partial resection + adjuvant XRT (41 Gy)

First relapse: 1997- Observation until 2000:– Second (complete) resection + Adjuvant carboplatin+ vincristine CT

Second relapse: 2002– Third (complete) resection, no adjuvant treatment due to postsurgical LCR

fistula Third relapse: December 2015

– Fourth(partial) resection: the pathologist notes a change in morphology, compatible with neuroglial tumor/vs/G2 xantoastrocitoma

– Multiple postsurgical complications: bleeding, thrombosis, SIADH… Fourth relapse: June 2016

– Palliative treatment with Temozolomide + inclusion in molecular pre-screening program


Molecular prescreening in patients with low grade tumors: recurrent targetable mutations

Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas•TCGA nteworkNew England Journal of Medicine 2015 vol: 372 (26) pp: 2481-2498


Molecular prescreening program for patients with low grade tumors: some

targetable translocations

Emerging Gene Fusion Drivers in Primary and Metastatic Central Nervous System Malignancies: A Review of AvailableEvidence for Systemic Targeted Therapies. Brastianos P, Ippen F, Hafeez U, Gan H. The oncologist. 2018 pp: theoncologist.2017-0614


Molecular prescreening in patients with low grade tumors: xanthoastrocytomas vs neuroglial

tumors

Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas.Zhang J Wu G Miller C Tatevossian R Dalton J et. al. Nature genetics, 2013 vol: 45 (6) pp: 602-12


IDH wt, p53 wt, ATRX wt, IHQ for EGFR negative, PTEN conserved.

Mutation panel of 50 genes: negative.

Molecular prescrening results:

Translocation panel: FGFR1 E17-TACC1 E7


FGFR translocations in glioma

FGFR-TACC gene fusions in human glioma.Lasorella A, Sanson M, Iavarone ANeuro-Oncology 2017 vol: 19 (4) pp: 475-483 Whole-genome sequencing identifies genetic alterationsin pediatric low-grade gliomas.Zhang J Wu G Miller C Tatevossian R Dalton J et. al. Nature genetics, 2013 vol: 45 (6) pp: 602-12

HINT: IDH wt, low grade, benign tumor


Targeted vs standard treatment

Temozolomide: 6 cycles from July 2016 to January 2017. – Best response SD. Several episodes of thrombocitopenia.

Progression on October 2017: – Diffuse leptomeningeal infiltration + multiple subependimary

nodes Included in clinical trial with narrow-spectrum Pan-FGFR

inhibitor(not from Roche): Ten cycles from November 2017 to June 2018.

– Best response PR with -83% on target lessions and clinicalresponse.

– Significant toxicity: G4 hyperphosfatemia, G2 nausea, G2 palmoplantar disestesia, G2 fatigue…


June 2016 January 2017


Nov 2017 April 2018


Conclusions: Children are not small adults, treating relapsed

childhood tumors and tumors in AYA patients requiresspecific knowledge (and being willing to colaborate)

While the morphological appearance of a tumor maychange, this sometimes doesn´t reflect a change in driver mutations

Patients with “benign” tumors have many unmet needs The existence of molecular prescreening programs

offers hope for patients with low-grade gliomas


Update: therapeutic resistance is an issue..

April 2018 July 2018

ESMO Preceptorship Programme

Tumor Type – Location – Date€¦ · 26-year-old woman with refractory low - grade glioma...

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