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Genomic tumor correlates of clinical outcomes following organ-sparing chemoradiation therapy for bladder cancer

ABSTRACT: Genomic tumor correlates of clinical outcomes following organ-sparing chemoradiation therapy for bladder cancer

PROVIDER: PRJNA1009888 | ENA |

REPOSITORIES: ENA

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Genomic tumor correlates of clinical outcomes following organ-sparing chemoradiation therapy for bladder cancer

Project description:Genomic tumor correlates of clinical outcomes following organ-sparing chemoradiation therapy for bladder cancer

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Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer.

Project description:PurposeThere is an urgent need for biomarkers of radiation response in organ-sparing therapies. Bladder preservation with trimodality therapy (TMT), consisting of transurethral tumor resection followed by chemoradiation, is an alternative to radical cystectomy for muscle-invasive bladder cancer (MIBC), but molecular determinants of response are poorly understood.Experimental designWe characterized genomic and transcriptomic features correlated with long-term response in a single institution cohort of patients with MIBC homogeneously treated with TMT. Pretreatment tumors from 76 patients with MIBC underwent whole-exome sequencing; 67 underwent matched transcriptomic profiling. Molecular features were correlated with clinical outcomes including modified bladder-intact event-free survival (mBI-EFS), a composite endpoint that reflects long-term cancer control with bladder preservation.ResultsWith a median follow-up of 74.6 months in alive patients, 37 patients had favorable long-term response to TMT while 39 had unfavorable long-term response. Tumor mutational burden was not associated with outcomes after TMT. DNA damage response gene alterations were associated with improved locoregional control and mBI-EFS. Of these alterations, somatic ERCC2 mutations stood out as significantly associated with favorable long-term outcomes; patients with ERCC2 mutations had significantly improved mBI-EFS [HR, 0.15; 95% confidence interval (CI), 0.06-0.37; P = 0.030] and improved BI-EFS, an endpoint that includes all-cause mortality (HR, 0.33; 95% CI, 0.15-0.68; P = 0.044). ERCC2 mutant bladder cancer cell lines were significantly more sensitive to concurrent cisplatin and radiation treatment in vitro than isogenic ERCC2 wild-type cells.ConclusionsOur data identify ERCC2 mutation as a candidate biomarker associated with sensitivity and long-term response to chemoradiation in MIBC. These findings warrant validation in independent cohorts.

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Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer

Project description:Background: Bladder-sparing trimodality therapy (TMT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), and biomarkers to inform therapy selection are needed. Objective: To evaluate immune and stromal signatures in MIBC treated with TMT.

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Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer

Project description:Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer

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Genomic copy number variation correlates with survival outcomes in glioblastoma patients

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Will chemoradiation-based bladder-sparing therapy become a standard of care for muscle-invasive bladder cancer?

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Transcription profiling of untreated and cisplatin-based chemoradiation treated human squamous cell carcinomas to improve prediction of outcome after chemoradiation

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