Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma

Sara A. Byron, Nhan Tran, Rebecca F. Halperin, Joanna J. Phillips, John G. Kuhn, John F. De Groot, Howard Colman, Keith L. Ligon, Patrick Y. Wen, Timothy F. Cloughesy, Ingo K. Mellinghoff, Nicholas A. Butowski, Jennie W. Taylor, Jennifer L. Clarke, Susan M. Chang, Mitchel S. Berger, Annette M. Molinaro, Gerald M. Maggiora, Sen Peng, Sara NasserWinnie S. Liang, Jeffrey M. Trent, Michael E. Berens, John D. Carpten, David W. Craig, Michael D. Prados

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generationsequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma. Experimental Design: We conducted a prospective genomicsinformed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome sequencing and tumor RNA sequencing were performed to identify molecular targets for potential matched therapy. A multidisciplinary molecular tumor board issued treatment recommendations based on the genomic results, blood-brain barrier penetration of the indicated therapies, drug-drug interactions, and drug safety profiles. Feasibility of generating genomics-informed treatment recommendations within 35 days of surgery was assessed. Results: Of the 20 patients enrolled in the study, 16 patients had sufficient tumor tissue for analysis. Exome sequencing was completed for all patients, and RNA sequencing was completed for 14 patients. Treatment recommendations were provided within the study's feasibility time frame for 15 of 16 (94%) patients. Seven patients received treatment based on the tumor board recommendations. Two patients reached 12-month progression-free survival, both adhering to treatments based on the molecular profiling results. One patient remained on treatment and progression free 21 months after surgery, 3 times longer than the patient's previous time to progression. Analysis of matched nonenhancing tissue from 12 patients revealed overlapping as well as novel putatively actionable genomic alterations. Conclusions: Use of genome-wide molecular profiling is feasible and can be informative for guiding real-time, central nervous system-penetrant, genomics-informed treatment recommendations for patients with recurrent glioblastoma.

Original languageEnglish (US)
Pages (from-to)295-305
Number of pages11
JournalClinical Cancer Research
Volume24
Issue number2
DOIs
StatePublished - Jan 15 2018

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Glioblastoma
Genomics
Therapeutics
Exome
RNA Sequence Analysis
Neoplasms
Genome
Feasibility Studies
Blood-Brain Barrier
Ambulatory Surgical Procedures
Drug Interactions
Disease-Free Survival
Research Design
Central Nervous System
Safety
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Byron, S. A., Tran, N., Halperin, R. F., Phillips, J. J., Kuhn, J. G., De Groot, J. F., ... Prados, M. D. (2018). Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma. Clinical Cancer Research, 24(2), 295-305. https://doi.org/10.1158/1078-0432.CCR-17-0963

Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma. / Byron, Sara A.; Tran, Nhan; Halperin, Rebecca F.; Phillips, Joanna J.; Kuhn, John G.; De Groot, John F.; Colman, Howard; Ligon, Keith L.; Wen, Patrick Y.; Cloughesy, Timothy F.; Mellinghoff, Ingo K.; Butowski, Nicholas A.; Taylor, Jennie W.; Clarke, Jennifer L.; Chang, Susan M.; Berger, Mitchel S.; Molinaro, Annette M.; Maggiora, Gerald M.; Peng, Sen; Nasser, Sara; Liang, Winnie S.; Trent, Jeffrey M.; Berens, Michael E.; Carpten, John D.; Craig, David W.; Prados, Michael D.

In: Clinical Cancer Research, Vol. 24, No. 2, 15.01.2018, p. 295-305.

Research output: Contribution to journalArticle

Byron, SA, Tran, N, Halperin, RF, Phillips, JJ, Kuhn, JG, De Groot, JF, Colman, H, Ligon, KL, Wen, PY, Cloughesy, TF, Mellinghoff, IK, Butowski, NA, Taylor, JW, Clarke, JL, Chang, SM, Berger, MS, Molinaro, AM, Maggiora, GM, Peng, S, Nasser, S, Liang, WS, Trent, JM, Berens, ME, Carpten, JD, Craig, DW & Prados, MD 2018, 'Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma', Clinical Cancer Research, vol. 24, no. 2, pp. 295-305. https://doi.org/10.1158/1078-0432.CCR-17-0963
Byron, Sara A. ; Tran, Nhan ; Halperin, Rebecca F. ; Phillips, Joanna J. ; Kuhn, John G. ; De Groot, John F. ; Colman, Howard ; Ligon, Keith L. ; Wen, Patrick Y. ; Cloughesy, Timothy F. ; Mellinghoff, Ingo K. ; Butowski, Nicholas A. ; Taylor, Jennie W. ; Clarke, Jennifer L. ; Chang, Susan M. ; Berger, Mitchel S. ; Molinaro, Annette M. ; Maggiora, Gerald M. ; Peng, Sen ; Nasser, Sara ; Liang, Winnie S. ; Trent, Jeffrey M. ; Berens, Michael E. ; Carpten, John D. ; Craig, David W. ; Prados, Michael D. / Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 2. pp. 295-305.
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T1 - Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma

AU - Byron, Sara A.

AU - Tran, Nhan

AU - Halperin, Rebecca F.

AU - Phillips, Joanna J.

AU - Kuhn, John G.

AU - De Groot, John F.

AU - Colman, Howard

AU - Ligon, Keith L.

AU - Wen, Patrick Y.

AU - Cloughesy, Timothy F.

AU - Mellinghoff, Ingo K.

AU - Butowski, Nicholas A.

AU - Taylor, Jennie W.

AU - Clarke, Jennifer L.

AU - Chang, Susan M.

AU - Berger, Mitchel S.

AU - Molinaro, Annette M.

AU - Maggiora, Gerald M.

AU - Peng, Sen

AU - Nasser, Sara

AU - Liang, Winnie S.

AU - Trent, Jeffrey M.

AU - Berens, Michael E.

AU - Carpten, John D.

AU - Craig, David W.

AU - Prados, Michael D.

PY - 2018/1/15

Y1 - 2018/1/15

N2 - Purpose: Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generationsequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma. Experimental Design: We conducted a prospective genomicsinformed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome sequencing and tumor RNA sequencing were performed to identify molecular targets for potential matched therapy. A multidisciplinary molecular tumor board issued treatment recommendations based on the genomic results, blood-brain barrier penetration of the indicated therapies, drug-drug interactions, and drug safety profiles. Feasibility of generating genomics-informed treatment recommendations within 35 days of surgery was assessed. Results: Of the 20 patients enrolled in the study, 16 patients had sufficient tumor tissue for analysis. Exome sequencing was completed for all patients, and RNA sequencing was completed for 14 patients. Treatment recommendations were provided within the study's feasibility time frame for 15 of 16 (94%) patients. Seven patients received treatment based on the tumor board recommendations. Two patients reached 12-month progression-free survival, both adhering to treatments based on the molecular profiling results. One patient remained on treatment and progression free 21 months after surgery, 3 times longer than the patient's previous time to progression. Analysis of matched nonenhancing tissue from 12 patients revealed overlapping as well as novel putatively actionable genomic alterations. Conclusions: Use of genome-wide molecular profiling is feasible and can be informative for guiding real-time, central nervous system-penetrant, genomics-informed treatment recommendations for patients with recurrent glioblastoma.

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