Sadaaki Nishimura1,2,3,4, Atsushi Sugimoto1,2,3, Shuhei Kushiyama1,2,3, Shingo Togano1,2,3, Kenji Kuroda1,2,3, Yurie Yamamoto2,3, Makoto Yamauchi5, Toshiyuki Sumi5,6, Hiroyasu Kaneda7, Tomoya Kawaguchi8, Minoru Kato9, Mizuki Tagami10, Naoto Oebisu11, Manabu Hoshi11, Kenjiro Kimura1,4, Shoji Kubo4, Kazuya Muguruma1, Tsutomu Takashima1,12, Masaichi Ohira1,12, Masakazu Yashiro1,2,3,6. 1. Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. 2. Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan. 3. Cancer Center for Translational Research, Osaka City University Graduate School of Medicine, Osaka, Japan. 4. Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. 5. Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka, Japan. 6. Cancer Genomic Center, Osaka City University Graduate School of Medicine, Osaka, Japan. 7. Department of Clinical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. 8. Department of Respiratory Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan. 9. Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan. 10. Department of Ophthalmology and Visual Sciences, Osaka City University Graduate School of Medicine, Osaka, Japan. 11. Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. 12. Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Abstract
BACKGROUND: Clinical sequencing using a panel of genes has recently been applied worldwide for patients with refractory solid tumors, but the significance of clinical sequencing using gene panel testing remains uncertain. Here we sought to clarify the feasibility and utility of clinical sequencing in the treatment of refractory tumors at our hospital. METHODS: A total of 39 patients with advanced solid tumors treated at our hospital between 2018 and 2020 were enrolled in the clinical sequencing. Among them, we identified 36 patients whose tissue samples were of suitable quality for clinical sequencing, and we analyzed the genomic profiles of these tumors. RESULTS: Pathogenic alterations were detected in 28 (78%) of the 36 patients. The most common mutation was TP53 (55%), followed by KRAS (22%), and the highest frequency of gene amplification was ERBB2 (17%). Nine of the 36 patients were identified as candidates for novel molecular-targeted therapy based on their actionable gene alterations, but only one case ended up receiving novel targeted therapy following the genetic tests. CONCLUSIONS: Our current results suggested that clinical sequencing might be useful for the detection of pathogenic alterations and the management of additional cancer treatment. However, molecular target based on actionable genomic alteration does not always bridge to subsequent therapy due to clinical deterioration, refusal for unapproved drug, and complexity of clinical trial access. Both improved optimal timing of clinical sequencing and a consensus about its off-label use might help patients receive greater benefit from clinical sequencing.
BACKGROUND: Clinical sequencing using a panel of genes has recently been applied worldwide for patients with refractory solid tumors, but the significance of clinical sequencing using gene panel testing remains uncertain. Here we sought to clarify the feasibility and utility of clinical sequencing in the treatment of refractory tumors at our hospital. METHODS: A total of 39 patients with advanced solid tumors treated at our hospital between 2018 and 2020 were enrolled in the clinical sequencing. Among them, we identified 36 patients whose tissue samples were of suitable quality for clinical sequencing, and we analyzed the genomic profiles of these tumors. RESULTS: Pathogenic alterations were detected in 28 (78%) of the 36 patients. The most common mutation was TP53 (55%), followed by KRAS (22%), and the highest frequency of gene amplification was ERBB2 (17%). Nine of the 36 patients were identified as candidates for novel molecular-targeted therapy based on their actionable gene alterations, but only one case ended up receiving novel targeted therapy following the genetic tests. CONCLUSIONS: Our current results suggested that clinical sequencing might be useful for the detection of pathogenic alterations and the management of additional cancer treatment. However, molecular target based on actionable genomic alteration does not always bridge to subsequent therapy due to clinical deterioration, refusal for unapproved drug, and complexity of clinical trial access. Both improved optimal timing of clinical sequencing and a consensus about its off-label use might help patients receive greater benefit from clinical sequencing.
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Authors: Tracy L Stockley; Amit M Oza; Hal K Berman; Natasha B Leighl; Jennifer J Knox; Frances A Shepherd; Eric X Chen; Monika K Krzyzanowska; Neesha Dhani; Anthony M Joshua; Ming-Sound Tsao; Stefano Serra; Blaise Clarke; Michael H Roehrl; Tong Zhang; Mahadeo A Sukhai; Nadia Califaretti; Mateya Trinkaus; Patricia Shaw; Theodorus van der Kwast; Lisa Wang; Carl Virtanen; Raymond H Kim; Albiruni R A Razak; Aaron R Hansen; Celeste Yu; Trevor J Pugh; Suzanne Kamel-Reid; Lillian L Siu; Philippe L Bedard Journal: Genome Med Date: 2016-10-25 Impact factor: 11.117