lunes, 6 de noviembre de 2017

Prospective feasibility trial for genomics-informed treatment in recurrent and progressive glioblastoma. - PubMed - NCBI

2017 Oct 26. pii: clincanres.0963.2017. doi: 10.1158/1078-0432.CCR-17-0963. [Epub ahead of print]

Prospective feasibility trial for genomics-informed treatment in recurrent and progressive glioblastoma.

Byron SA1, Tran NL2, Halperin RF3, Phillips JJ4, Kuhn JG5, de Groot JF6, Colman H7, Ligon KL8, Wen PY9, Cloughesy TF10, Mellinghoff IK11, Butowski N12, Taylor J13, Clarke JL14, Chang SM4, Berger MS15, Molinaro AM16, Maggiora GM3, Peng S17, Nasser S18, Liang WS3, Trent JM19, Berens ME20, Carpten JD21, Craig DW21, Prados MD14.

Author information

Abstract

PURPOSE:

Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generation sequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma.

METHODS:

We conducted a prospective genomics-informed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome-sequencing and tumor RNA-sequencing was performed to identify molecular targets for potential matched therapy. A multi-disciplinary 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, three-times longer than the patient's previous time to progression. Analysis of matched non-enhancing tissue from 12 patients revealed overlapping as well as novel putatively actionable genomic alterations.

CONCLUSION:

Use of genome-wide molecular profiling is feasible and can be informative for guiding real-time, central nervous system (CNS)-penetrant, genomics-informed treatment recommendations for patients with recurrent glioblastoma.