<i>NTRK</i> gene fusions in biliary tract cancers.

Demols, A.; Rocq, Laureen; Charry, Manon; Nève, Nancy De; Verrellen, Audrey; Ramadhan, Ali A; Campenhout, Claude Van; Clercq, Sarah De; Salmon, Isabelle; D’Haene, Nicky

doi:10.1200/jco.2020.38.4_suppl.574

Cited by 22 publications

(9 citation statements)

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“…The comprehensive genomic profiling of Chinese BTC patients has not been well elucidated and is needed to be investigated in large cohorts. Furthermore, NTRK fusions occurring in 0.75% of patients with BTC, 34 were not observed in this cohort. Somatic mutations were detected in 71.4% of bile cfDNA samples, whereas these were identified in only 53.6% of plasma cfDNA samples in this study.…”

Section: Discussionmentioning

confidence: 57%

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Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer

et al. 2021

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Background: Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile as a liquid biopsy medium in patients with BTC. Patients and methods: Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes. Results: Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P ¼ 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis. Conclusion: We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 57%

Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer

et al. 2021

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“…NTRK fusions have recently emerged as interesting driver mutations for cancer treatment, which have been detected in adult and pediatric cancers [ 113 ]. In BTC, the reported percentage of NTRK fusions was 0.75% [ 114 ]. Larotrectinib (LOXO-101) and entrectinib (RDX-101) are first-generation, potent and highly selective pan-TRK inhibitors that were approved by the FDA, for pediatric and adult patients with refractory solid tumors harboring NTRK gene that progressed after standard treatments without suitable alternative treatments [ 115 ].…”

Section: Ntrkmentioning

confidence: 99%

Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials

et al. 2021

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Biliary tract cancer (BTC) compromises a heterogenous group of tumors with poor prognoses. Curative surgery remains the first choice for localized disease; however, most BTC patients have had unresectable or metastatic disease. The gold standard therapy for these patients is chemotherapy with gemcitabine and cisplatin. There are no consensus guidelines for standard treatment in a second-line setting, although the data of the ABC-06 trial showed a slight survival benefit from oxaliplatin and 5-fluorouracil combination chemotherapy. Recent progress in comprehensive genomic profiling for advanced BTC (ABTC) has helped to clarify tumorigenesis and facilitate the coming era of precision medicine. Generally, targeted agents fail to show significant clinical benefits in unselected populations. Only fibroblast growth factor receptor 2 (FGFR2) fusion and isocitrate dehydrogenase (IDH)- and BRAF mutation-enriched populations have survival benefits from the corresponding inhibitors. Several interesting targeted agents for monotherapies or combination therapies with other compounds are currently ongoing or recruiting. Here, we review the published data from clinical trials of second-line therapies after the failure of gemcitabine-based chemotherapy in ABTC. The results were stratified by different genetic alternations, as well as by chemotherapy, targeted therapy and immunotherapy.

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“…It has also been reported that these fusion genes tend to be found in younger patients. There are some case reports showing the effects of inhibitors targeting these genetic abnormalities [117][118][119][120][121].…”

Section: Rare Fusion Genesmentioning

confidence: 99%

Tumour-Agnostic Therapy for Pancreatic Cancer and Biliary Tract Cancer

Kato

2021

Diagnostics

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The prognosis of patients with solid tumours has remarkably improved with the development of molecular-targeted drugs and immune checkpoint inhibitors. However, the improvements in the prognosis of pancreatic cancer and biliary tract cancer is delayed compared to other carcinomas, and the 5-year survival rates of distal-stage disease are approximately 10 and 20%, respectively. However, a comprehensive analysis of tumour cells using The Cancer Genome Atlas (TCGA) project has led to the identification of various driver mutations. Evidently, few mutations exist across organs, and basket trials targeting driver mutations regardless of the primary organ are being actively conducted. Such basket trials not only focus on the gate keeper-type oncogene mutations, such as HER2 and BRAF, but also focus on the caretaker-type tumour suppressor genes, such as BRCA1/2, mismatch repair-related genes, which cause hereditary cancer syndrome. As oncogene panel testing is a vital approach in routine practice, clinicians should devise a strategy for improved understanding of the cancer genome. Here, the gene mutation profiles of pancreatic cancer and biliary tract cancer have been outlined and the current status of tumour-agnostic therapy in these cancers has been reported.

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NTRK gene fusions in biliary tract cancers.

Cited by 22 publications

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Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer

Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer

Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials

Tumour-Agnostic Therapy for Pancreatic Cancer and Biliary Tract Cancer

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