Clinical Utility of Genomic Profiling Tests in Patients with Advanced Gastrointestinal Cancers.


Journal

Targeted oncology
ISSN: 1776-260X
Titre abrégé: Target Oncol
Pays: France
ID NLM: 101270595

Informations de publication

Date de publication:
03 2022
Historique:
accepted: 02 03 2022
pubmed: 3 4 2022
medline: 13 4 2022
entrez: 2 4 2022
Statut: ppublish

Résumé

Comprehensive analyses of cancer-related genomic alterations are expected to lead to increased availability of targeted therapies. However, in patients with gastrointestinal (GI) cancers, the utility of genomic profiling is unclear because of common non-druggable alterations and rapid disease progression that prevent a sufficient time period to seek targets. The aim of this study was to determine the utility of genomic profiling tests in patients with GI cancers. The subjects of this retrospective study were patients with GI cancers and patients with non-GI cancers who underwent tissue-based genomic profiling at a single institution from April 2017 to October 2020. The profile of gene alterations, frequency of tumor mutational burden-high (≥ 10 Muts/Mb), and accessibility of recommended molecular targeted therapy were compared between patients with GI cancers and patients with non-GI cancers. In all, 133 patients with GI cancers and 63 patients with non-GI cancers were included. The genomic profiles of GI cancers showed the highest frequencies of TP53, KRAS, and APC mutations and a significantly lower frequency of PIK3CA mutations than those of non-GI cancers. Tumor mutational burden-high was significantly less prevalent in GI cancers (4% vs 20%, p = 0.008). Twenty-nine patients with GI cancers (40%) and 35 patients with non-GI cancers (56%) were recommended for targeted therapies based on the findings. Among them, seven patients each with GI cancers and non-GI cancers received the recommended therapy on their genomic findings, which showed similar treatment accessibility between the GI and non-GI cancer groups (10% vs 11%, p = 0.791). HER2-targeted and BRAF-targeted therapies were the primary treatments administered to patients with GI cancers. Although their genomic profiles revealed fewer druggable sites, patients with GI cancers accessed targeted therapies similarly to patients with non-GI cancers. The utility of genomic profile testing in patients with GI cancers was highlighted to determine if patients can receive specific treatments, such as HER2-targeted and BRAF-targeted therapies.

Sections du résumé

BACKGROUND
Comprehensive analyses of cancer-related genomic alterations are expected to lead to increased availability of targeted therapies. However, in patients with gastrointestinal (GI) cancers, the utility of genomic profiling is unclear because of common non-druggable alterations and rapid disease progression that prevent a sufficient time period to seek targets.
OBJECTIVE
The aim of this study was to determine the utility of genomic profiling tests in patients with GI cancers.
METHODS
The subjects of this retrospective study were patients with GI cancers and patients with non-GI cancers who underwent tissue-based genomic profiling at a single institution from April 2017 to October 2020. The profile of gene alterations, frequency of tumor mutational burden-high (≥ 10 Muts/Mb), and accessibility of recommended molecular targeted therapy were compared between patients with GI cancers and patients with non-GI cancers.
RESULTS
In all, 133 patients with GI cancers and 63 patients with non-GI cancers were included. The genomic profiles of GI cancers showed the highest frequencies of TP53, KRAS, and APC mutations and a significantly lower frequency of PIK3CA mutations than those of non-GI cancers. Tumor mutational burden-high was significantly less prevalent in GI cancers (4% vs 20%, p = 0.008). Twenty-nine patients with GI cancers (40%) and 35 patients with non-GI cancers (56%) were recommended for targeted therapies based on the findings. Among them, seven patients each with GI cancers and non-GI cancers received the recommended therapy on their genomic findings, which showed similar treatment accessibility between the GI and non-GI cancer groups (10% vs 11%, p = 0.791). HER2-targeted and BRAF-targeted therapies were the primary treatments administered to patients with GI cancers.
CONCLUSIONS
Although their genomic profiles revealed fewer druggable sites, patients with GI cancers accessed targeted therapies similarly to patients with non-GI cancers. The utility of genomic profile testing in patients with GI cancers was highlighted to determine if patients can receive specific treatments, such as HER2-targeted and BRAF-targeted therapies.

Identifiants

pubmed: 35366174
doi: 10.1007/s11523-022-00871-4
pii: 10.1007/s11523-022-00871-4
doi:

Substances chimiques

Biomarkers, Tumor 0
Proto-Oncogene Proteins B-raf EC 2.7.11.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

177-185

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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Auteurs

Hiroyuki Takeda (H)

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.

Kiyomi Imoto (K)

Center for Genomic Medicine, St. Marianna University Hospital, Kawasaki, Japan.

Kumiko Umemoto (K)

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.

Ayako Doi (A)

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.

Hiroyuki Arai (H)

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.

Yoshiki Horie (Y)

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.

Takuro Mizukami (T)

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.

Tomoyo Oguri (T)

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.

Takashi Ogura (T)

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.

Naoki Izawa (N)

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.

Hiroyuki Yamamoto (H)

Department of Bioinformatics, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Yoshihisa Yamano (Y)

Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.

Yu Sunakawa (Y)

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan. y.sunakawa@marianna-u.ac.jp.
Center for Genomic Medicine, St. Marianna University Hospital, Kawasaki, Japan. y.sunakawa@marianna-u.ac.jp.

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Classifications MeSH