A pilot precision medicine trial for children with diffuse intrinsic pontine glioma—PNOC003

A report from the Pacific Pediatric Neuro-Oncology Consortium

Sabine Mueller, Payal Jain, Winnie S. Liang, Lindsay Kilburn, Cassie Kline, Nalin Gupta, Eshini Panditharatna, Suresh N. Magge, Bo Zhang, Yuankun Zhu, John R. Crawford, Anu Banerjee, Kellie Nazemi, Roger J. Packer, Claudia K. Petritsch, Nathalene Truffaux, Alison Roos, Sara Nasser, Joanna J. Phillips, David Solomon & 8 others Annette Molinaro, Angela J. Waanders, Sara A. Byron, Michael E. Berens, John Kuhn, Javad Nazarian, Michael Prados, Adam C. Resnick

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

This clinical trial evaluated whether whole exome sequencing (WES) and RNA sequencing (RNAseq) of paired normal and tumor tissues could be incorporated into a personalized treatment plan for newly diagnosed patients (<25 years of age) with diffuse intrinsic pontine glioma (DIPG). Additionally, whole genome sequencing (WGS) was compared to WES to determine if WGS would further inform treatment decisions, and whether circulating tumor DNA (ctDNA) could detect the H3K27M mutation to allow assessment of therapy response. Patients were selected across three Pacific Pediatric Neuro-Oncology Consortium member institutions between September 2014 and January 2016. WES and RNAseq were performed at diagnosis and recurrence when possible in a CLIA-certified laboratory. Patient-derived cell line development was attempted for each subject. Collection of blood for ctDNA was done prior to treatment and with each MRI. A specialized tumor board generated a treatment recommendation including up to four FDA-approved agents based upon the genomic alterations detected. A treatment plan was successfully issued within 21 business days from tissue collection for all 15 subjects, with 14 of the 15 subjects fulfilling the feasibility criteria. WGS results did not significantly deviate from WES-based therapy recommendations; however, WGS data provided further insight into tumor evolution and fidelity of patient-derived cell models. Detection of the H3F3A or HIST1H3B K27M (H3K27M) mutation using ctDNA was successful in 92% of H3K27M mutant cases. A personalized treatment recommendation for DIPG can be rendered within a multicenter setting using comprehensive next-generation sequencing technology in a clinically relevant timeframe.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StatePublished - Jan 1 2019

Fingerprint

Precision Medicine
Pediatrics
Exome
Genome
RNA Sequence Analysis
Neoplasms
Therapeutics
Glioma
DNA
Mutation
Clinical Trials
Technology
Recurrence
Cell Line

Keywords

  • circulating tumor DNA
  • diffuse intrinsic pontine glioma
  • genomics-guided clinical trial
  • next generation sequencing
  • precision medicine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A pilot precision medicine trial for children with diffuse intrinsic pontine glioma—PNOC003 : A report from the Pacific Pediatric Neuro-Oncology Consortium. / Mueller, Sabine; Jain, Payal; Liang, Winnie S.; Kilburn, Lindsay; Kline, Cassie; Gupta, Nalin; Panditharatna, Eshini; Magge, Suresh N.; Zhang, Bo; Zhu, Yuankun; Crawford, John R.; Banerjee, Anu; Nazemi, Kellie; Packer, Roger J.; Petritsch, Claudia K.; Truffaux, Nathalene; Roos, Alison; Nasser, Sara; Phillips, Joanna J.; Solomon, David; Molinaro, Annette; Waanders, Angela J.; Byron, Sara A.; Berens, Michael E.; Kuhn, John; Nazarian, Javad; Prados, Michael; Resnick, Adam C.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Mueller, S, Jain, P, Liang, WS, Kilburn, L, Kline, C, Gupta, N, Panditharatna, E, Magge, SN, Zhang, B, Zhu, Y, Crawford, JR, Banerjee, A, Nazemi, K, Packer, RJ, Petritsch, CK, Truffaux, N, Roos, A, Nasser, S, Phillips, JJ, Solomon, D, Molinaro, A, Waanders, AJ, Byron, SA, Berens, ME, Kuhn, J, Nazarian, J, Prados, M & Resnick, AC 2019, 'A pilot precision medicine trial for children with diffuse intrinsic pontine glioma—PNOC003: A report from the Pacific Pediatric Neuro-Oncology Consortium', International Journal of Cancer. https://doi.org/10.1002/ijc.32258
Mueller, Sabine ; Jain, Payal ; Liang, Winnie S. ; Kilburn, Lindsay ; Kline, Cassie ; Gupta, Nalin ; Panditharatna, Eshini ; Magge, Suresh N. ; Zhang, Bo ; Zhu, Yuankun ; Crawford, John R. ; Banerjee, Anu ; Nazemi, Kellie ; Packer, Roger J. ; Petritsch, Claudia K. ; Truffaux, Nathalene ; Roos, Alison ; Nasser, Sara ; Phillips, Joanna J. ; Solomon, David ; Molinaro, Annette ; Waanders, Angela J. ; Byron, Sara A. ; Berens, Michael E. ; Kuhn, John ; Nazarian, Javad ; Prados, Michael ; Resnick, Adam C. / A pilot precision medicine trial for children with diffuse intrinsic pontine glioma—PNOC003 : A report from the Pacific Pediatric Neuro-Oncology Consortium. In: International Journal of Cancer. 2019.
@article{8e11679f06a94299970942f351f4169c,
title = "A pilot precision medicine trial for children with diffuse intrinsic pontine glioma—PNOC003: A report from the Pacific Pediatric Neuro-Oncology Consortium",
abstract = "This clinical trial evaluated whether whole exome sequencing (WES) and RNA sequencing (RNAseq) of paired normal and tumor tissues could be incorporated into a personalized treatment plan for newly diagnosed patients (<25 years of age) with diffuse intrinsic pontine glioma (DIPG). Additionally, whole genome sequencing (WGS) was compared to WES to determine if WGS would further inform treatment decisions, and whether circulating tumor DNA (ctDNA) could detect the H3K27M mutation to allow assessment of therapy response. Patients were selected across three Pacific Pediatric Neuro-Oncology Consortium member institutions between September 2014 and January 2016. WES and RNAseq were performed at diagnosis and recurrence when possible in a CLIA-certified laboratory. Patient-derived cell line development was attempted for each subject. Collection of blood for ctDNA was done prior to treatment and with each MRI. A specialized tumor board generated a treatment recommendation including up to four FDA-approved agents based upon the genomic alterations detected. A treatment plan was successfully issued within 21 business days from tissue collection for all 15 subjects, with 14 of the 15 subjects fulfilling the feasibility criteria. WGS results did not significantly deviate from WES-based therapy recommendations; however, WGS data provided further insight into tumor evolution and fidelity of patient-derived cell models. Detection of the H3F3A or HIST1H3B K27M (H3K27M) mutation using ctDNA was successful in 92{\%} of H3K27M mutant cases. A personalized treatment recommendation for DIPG can be rendered within a multicenter setting using comprehensive next-generation sequencing technology in a clinically relevant timeframe.",
keywords = "circulating tumor DNA, diffuse intrinsic pontine glioma, genomics-guided clinical trial, next generation sequencing, precision medicine",
author = "Sabine Mueller and Payal Jain and Liang, {Winnie S.} and Lindsay Kilburn and Cassie Kline and Nalin Gupta and Eshini Panditharatna and Magge, {Suresh N.} and Bo Zhang and Yuankun Zhu and Crawford, {John R.} and Anu Banerjee and Kellie Nazemi and Packer, {Roger J.} and Petritsch, {Claudia K.} and Nathalene Truffaux and Alison Roos and Sara Nasser and Phillips, {Joanna J.} and David Solomon and Annette Molinaro and Waanders, {Angela J.} and Byron, {Sara A.} and Berens, {Michael E.} and John Kuhn and Javad Nazarian and Michael Prados and Resnick, {Adam C.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/ijc.32258",
language = "English (US)",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - A pilot precision medicine trial for children with diffuse intrinsic pontine glioma—PNOC003

T2 - A report from the Pacific Pediatric Neuro-Oncology Consortium

AU - Mueller, Sabine

AU - Jain, Payal

AU - Liang, Winnie S.

AU - Kilburn, Lindsay

AU - Kline, Cassie

AU - Gupta, Nalin

AU - Panditharatna, Eshini

AU - Magge, Suresh N.

AU - Zhang, Bo

AU - Zhu, Yuankun

AU - Crawford, John R.

AU - Banerjee, Anu

AU - Nazemi, Kellie

AU - Packer, Roger J.

AU - Petritsch, Claudia K.

AU - Truffaux, Nathalene

AU - Roos, Alison

AU - Nasser, Sara

AU - Phillips, Joanna J.

AU - Solomon, David

AU - Molinaro, Annette

AU - Waanders, Angela J.

AU - Byron, Sara A.

AU - Berens, Michael E.

AU - Kuhn, John

AU - Nazarian, Javad

AU - Prados, Michael

AU - Resnick, Adam C.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - This clinical trial evaluated whether whole exome sequencing (WES) and RNA sequencing (RNAseq) of paired normal and tumor tissues could be incorporated into a personalized treatment plan for newly diagnosed patients (<25 years of age) with diffuse intrinsic pontine glioma (DIPG). Additionally, whole genome sequencing (WGS) was compared to WES to determine if WGS would further inform treatment decisions, and whether circulating tumor DNA (ctDNA) could detect the H3K27M mutation to allow assessment of therapy response. Patients were selected across three Pacific Pediatric Neuro-Oncology Consortium member institutions between September 2014 and January 2016. WES and RNAseq were performed at diagnosis and recurrence when possible in a CLIA-certified laboratory. Patient-derived cell line development was attempted for each subject. Collection of blood for ctDNA was done prior to treatment and with each MRI. A specialized tumor board generated a treatment recommendation including up to four FDA-approved agents based upon the genomic alterations detected. A treatment plan was successfully issued within 21 business days from tissue collection for all 15 subjects, with 14 of the 15 subjects fulfilling the feasibility criteria. WGS results did not significantly deviate from WES-based therapy recommendations; however, WGS data provided further insight into tumor evolution and fidelity of patient-derived cell models. Detection of the H3F3A or HIST1H3B K27M (H3K27M) mutation using ctDNA was successful in 92% of H3K27M mutant cases. A personalized treatment recommendation for DIPG can be rendered within a multicenter setting using comprehensive next-generation sequencing technology in a clinically relevant timeframe.

AB - This clinical trial evaluated whether whole exome sequencing (WES) and RNA sequencing (RNAseq) of paired normal and tumor tissues could be incorporated into a personalized treatment plan for newly diagnosed patients (<25 years of age) with diffuse intrinsic pontine glioma (DIPG). Additionally, whole genome sequencing (WGS) was compared to WES to determine if WGS would further inform treatment decisions, and whether circulating tumor DNA (ctDNA) could detect the H3K27M mutation to allow assessment of therapy response. Patients were selected across three Pacific Pediatric Neuro-Oncology Consortium member institutions between September 2014 and January 2016. WES and RNAseq were performed at diagnosis and recurrence when possible in a CLIA-certified laboratory. Patient-derived cell line development was attempted for each subject. Collection of blood for ctDNA was done prior to treatment and with each MRI. A specialized tumor board generated a treatment recommendation including up to four FDA-approved agents based upon the genomic alterations detected. A treatment plan was successfully issued within 21 business days from tissue collection for all 15 subjects, with 14 of the 15 subjects fulfilling the feasibility criteria. WGS results did not significantly deviate from WES-based therapy recommendations; however, WGS data provided further insight into tumor evolution and fidelity of patient-derived cell models. Detection of the H3F3A or HIST1H3B K27M (H3K27M) mutation using ctDNA was successful in 92% of H3K27M mutant cases. A personalized treatment recommendation for DIPG can be rendered within a multicenter setting using comprehensive next-generation sequencing technology in a clinically relevant timeframe.

KW - circulating tumor DNA

KW - diffuse intrinsic pontine glioma

KW - genomics-guided clinical trial

KW - next generation sequencing

KW - precision medicine

UR - http://www.scopus.com/inward/record.url?scp=85063768662&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063768662&partnerID=8YFLogxK

U2 - 10.1002/ijc.32258

DO - 10.1002/ijc.32258

M3 - Article

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

ER -