Dataset Information

Precision oncology for gallbladder cancer: insights from genetic alterations and clinical practice.

ABSTRACT: Background:Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy, with limited adjuvant therapy. The present study aims to explore the actionable alterations and precision oncology for GBC patients. Methods:Patients with pathologically confirmed GBC who progressed after first-line systemic treatment were enrolled. Genomic alterations were captured by ultra-deep targeted next-generation sequencing (tNGS). The actionabilities of alterations and the therapeutic regimens were evaluated by a multidisciplinary tumor board (MDTB). Results:Sixty patients with GBC were enrolled and analyzed. tNGS was successfully achieved in all patients. The median tumor mutation burden for GBC patients was 5.4 (range: 0.8-36.74) mutations/Mb, and the most common mutations were in TP53 (73%), CDKN2A (25%) and PIK3CA (20%). The most frequently copy-number altered genes were CDKN2A deletion (11.7%) and ERBB2 amplification (13.3%). 23% of the patients displayed gene fusion; 17 fusion events were identified, and 14 of the 17 fusion events co-occurred with mutations in driver genes. In total, 46 of the 60 (76%) patients were identified as possessing at least one actionable target to proceed precision oncology. Conclusions:The present study revealed the mutational profile for the clinical practice of precision oncology in GBC patients.

SUBMITTER: Lin J

PROVIDER: S-EPMC6803238 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Precision oncology for gallbladder cancer: insights from genetic alterations and clinical practice.

Lin Jianzhen J Dong Kun K Bai Yi Y Zhao Songhui S Dong Yonghong Y Shi Junping J Shi Weiwei W Long Junyu J Yang Xu X Wang Dongxu D Yang Xiaobo X Zhao Lin L Hu Ke K Pan Jie J Sang Xinting X Wang Kai K Zhao Haitao H

Annals of translational medicine 20190901 18

<h4>Background</h4>Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy, with limited adjuvant therapy. The present study aims to explore the actionable alterations and precision oncology for GBC patients.<h4>Methods</h4>Patients with pathologically confirmed GBC who progressed after first-line systemic treatment were enrolled. Genomic alterations were captured by ultra-deep targeted next-generation sequencing (tNGS). The actionabilities of alterations and the therapeutic regimens ...[more]

PMID: 31700903

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Project description:PURPOSE:Precision oncology is hindered by the lack of decision support for determining the functional and therapeutic significance of genomic alterations in tumors and relevant clinically available options. To bridge this knowledge gap, we established a Precision Oncology Decision Support (PODS) team that provides annotations at the alteration-level and subsequently determined if clinical decision-making was influenced. METHODS:Genomic alterations were annotated to determine actionability based on a variant's known or potential functional and/or therapeutic significance. The medical records of a subset of patients annotated in 2015 were manually reviewed to assess trial enrollment. A web-based survey was implemented to capture the reasons why genotype-matched therapies were not pursued. RESULTS:PODS processed 1,669 requests for annotation of 4,084 alterations (2,254 unique) across 49 tumor types for 1,197 patients. 2,444 annotations for 669 patients included an actionable variant call: 32.5% actionable, 9.4% potentially, 29.7% unknown, 28.4% non-actionable. 66% of patients had at least one actionable/potentially actionable alteration. 20.6% (110/535) patients annotated enrolled on a genotype-matched trial. Trial enrolment was significantly higher for patients with actionable/potentially actionable alterations (92/333, 27.6%) than those with unknown (16/136, 11.8%) and non-actionable (2/66, 3%) alterations (p=0.00004). Actionable alterations in PTEN, PIK3CA, and ERBB2 most frequently led to enrollment on genotype-matched trials. Clinicians cited a variety of reasons why patients with actionable alterations did not enroll on trials. CONCLUSION:Over half of alterations annotated were of unknown significance or non-actionable. Physicians were more likely to enroll a patient on a genotype-matched trial when an annotation supported actionability. Future studies are needed to demonstrate the impact of decision support on trial enrollment and oncologic outcomes.

Dataset Information

Precision oncology for gallbladder cancer: insights from genetic alterations and clinical practice.

Publications

Precision oncology for gallbladder cancer: insights from genetic alterations and clinical practice.

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