Clinical application of amplicon-based next-generation sequencing to therapeutic decision making in lung cancer

M. Takeda, K. Sakai, M. Terashima, H. Kaneda, H. Hayashi, K. Tanaka, K. Okamoto, T. Takahama, T. Yoshida, T. Iwasa, T. Shimizu, Y. Nonagase, K. Kudo, Shuta Tomida, T. Mitsudomi, K. Saigo, A. Ito, K. Nakagawa, K. Nishio

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background: The clinical implementation of genomic profiling for lung cancer with high-throughput, multiplex tests is warranted to allow prioritization of appropriate therapies for individual patients. We have now applied such testing to detect actionable mutations that may inform treatment recommendations in lung cancer. Patients and methods: We prospectively applied amplicon sequencing panels that cover both mutational hotspots in 22 genes related to lung and colon tumorigenesis as well as 72 major variants of ALK, RET, ROS1, and NTRK1 fusion transcripts. We then determined the proportion of patients who received genotype-directed therapy and their overall survival (OS). Results: Tumor specimens from 110 patients with lung cancer recruited between July 2013 and March 2015 were analyzed. The most common genetic alterations were TP53 mutations in 42 patients, followed by EGFR mutations in 25, STK11 mutations in 12, and KRAS mutations in 10. Potentially actionable mutations were identified in 44 patients including 50% of those with adenocarcinoma and 14% of those with squamous cell carcinoma. The OS of patients with advanced or recurrent cancer who had an actionable mutation and received targeted therapy (median OS not achieved) was significantly longer than that of those with no mutation (18.1 months, P = 0.041) or of those with a mutation not so treated (6.1 months, P = 0.0027). Conclusions: Multiplex genomic testing was performed on formalin-fixed, paraffin-embedded tumor specimens with a success rate of ≥95%. Such testing can assist physicians in matching patients with approved or experimental targeted treatments. Clinical trial registration: The University Medical Hospital Information Network (UMIN) Clinical Trials Registry under the identifier UMIN000014782.

Original languageEnglish
Pages (from-to)2477-2482
Number of pages6
JournalAnnals of Oncology
Volume26
Issue number12
DOIs
Publication statusPublished - Dec 1 2015
Externally publishedYes

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Lung Neoplasms
Decision Making
Mutation
Therapeutics
Survival
Clinical Trials
Neoplasms
Information Services
Paraffin
Formaldehyde
Registries
Squamous Cell Carcinoma
Colon
Carcinogenesis
Adenocarcinoma
Genotype
Physicians
Lung
Genes

Keywords

  • Driver mutation
  • Lung cancer
  • Next-generation sequencing
  • Targeted therapy
  • Transbronchial biopsy

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Takeda, M., Sakai, K., Terashima, M., Kaneda, H., Hayashi, H., Tanaka, K., ... Nishio, K. (2015). Clinical application of amplicon-based next-generation sequencing to therapeutic decision making in lung cancer. Annals of Oncology, 26(12), 2477-2482. https://doi.org/10.1093/annonc/mdv475

Clinical application of amplicon-based next-generation sequencing to therapeutic decision making in lung cancer. / Takeda, M.; Sakai, K.; Terashima, M.; Kaneda, H.; Hayashi, H.; Tanaka, K.; Okamoto, K.; Takahama, T.; Yoshida, T.; Iwasa, T.; Shimizu, T.; Nonagase, Y.; Kudo, K.; Tomida, Shuta; Mitsudomi, T.; Saigo, K.; Ito, A.; Nakagawa, K.; Nishio, K.

In: Annals of Oncology, Vol. 26, No. 12, 01.12.2015, p. 2477-2482.

Research output: Contribution to journalArticle

Takeda, M, Sakai, K, Terashima, M, Kaneda, H, Hayashi, H, Tanaka, K, Okamoto, K, Takahama, T, Yoshida, T, Iwasa, T, Shimizu, T, Nonagase, Y, Kudo, K, Tomida, S, Mitsudomi, T, Saigo, K, Ito, A, Nakagawa, K & Nishio, K 2015, 'Clinical application of amplicon-based next-generation sequencing to therapeutic decision making in lung cancer', Annals of Oncology, vol. 26, no. 12, pp. 2477-2482. https://doi.org/10.1093/annonc/mdv475
Takeda, M. ; Sakai, K. ; Terashima, M. ; Kaneda, H. ; Hayashi, H. ; Tanaka, K. ; Okamoto, K. ; Takahama, T. ; Yoshida, T. ; Iwasa, T. ; Shimizu, T. ; Nonagase, Y. ; Kudo, K. ; Tomida, Shuta ; Mitsudomi, T. ; Saigo, K. ; Ito, A. ; Nakagawa, K. ; Nishio, K. / Clinical application of amplicon-based next-generation sequencing to therapeutic decision making in lung cancer. In: Annals of Oncology. 2015 ; Vol. 26, No. 12. pp. 2477-2482.
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abstract = "Background: The clinical implementation of genomic profiling for lung cancer with high-throughput, multiplex tests is warranted to allow prioritization of appropriate therapies for individual patients. We have now applied such testing to detect actionable mutations that may inform treatment recommendations in lung cancer. Patients and methods: We prospectively applied amplicon sequencing panels that cover both mutational hotspots in 22 genes related to lung and colon tumorigenesis as well as 72 major variants of ALK, RET, ROS1, and NTRK1 fusion transcripts. We then determined the proportion of patients who received genotype-directed therapy and their overall survival (OS). Results: Tumor specimens from 110 patients with lung cancer recruited between July 2013 and March 2015 were analyzed. The most common genetic alterations were TP53 mutations in 42 patients, followed by EGFR mutations in 25, STK11 mutations in 12, and KRAS mutations in 10. Potentially actionable mutations were identified in 44 patients including 50{\%} of those with adenocarcinoma and 14{\%} of those with squamous cell carcinoma. The OS of patients with advanced or recurrent cancer who had an actionable mutation and received targeted therapy (median OS not achieved) was significantly longer than that of those with no mutation (18.1 months, P = 0.041) or of those with a mutation not so treated (6.1 months, P = 0.0027). Conclusions: Multiplex genomic testing was performed on formalin-fixed, paraffin-embedded tumor specimens with a success rate of ≥95{\%}. Such testing can assist physicians in matching patients with approved or experimental targeted treatments. Clinical trial registration: The University Medical Hospital Information Network (UMIN) Clinical Trials Registry under the identifier UMIN000014782.",
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AU - Terashima, M.

AU - Kaneda, H.

AU - Hayashi, H.

AU - Tanaka, K.

AU - Okamoto, K.

AU - Takahama, T.

AU - Yoshida, T.

AU - Iwasa, T.

AU - Shimizu, T.

AU - Nonagase, Y.

AU - Kudo, K.

AU - Tomida, Shuta

AU - Mitsudomi, T.

AU - Saigo, K.

AU - Ito, A.

AU - Nakagawa, K.

AU - Nishio, K.

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N2 - Background: The clinical implementation of genomic profiling for lung cancer with high-throughput, multiplex tests is warranted to allow prioritization of appropriate therapies for individual patients. We have now applied such testing to detect actionable mutations that may inform treatment recommendations in lung cancer. Patients and methods: We prospectively applied amplicon sequencing panels that cover both mutational hotspots in 22 genes related to lung and colon tumorigenesis as well as 72 major variants of ALK, RET, ROS1, and NTRK1 fusion transcripts. We then determined the proportion of patients who received genotype-directed therapy and their overall survival (OS). Results: Tumor specimens from 110 patients with lung cancer recruited between July 2013 and March 2015 were analyzed. The most common genetic alterations were TP53 mutations in 42 patients, followed by EGFR mutations in 25, STK11 mutations in 12, and KRAS mutations in 10. Potentially actionable mutations were identified in 44 patients including 50% of those with adenocarcinoma and 14% of those with squamous cell carcinoma. The OS of patients with advanced or recurrent cancer who had an actionable mutation and received targeted therapy (median OS not achieved) was significantly longer than that of those with no mutation (18.1 months, P = 0.041) or of those with a mutation not so treated (6.1 months, P = 0.0027). Conclusions: Multiplex genomic testing was performed on formalin-fixed, paraffin-embedded tumor specimens with a success rate of ≥95%. Such testing can assist physicians in matching patients with approved or experimental targeted treatments. Clinical trial registration: The University Medical Hospital Information Network (UMIN) Clinical Trials Registry under the identifier UMIN000014782.

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KW - Driver mutation

KW - Lung cancer

KW - Next-generation sequencing

KW - Targeted therapy

KW - Transbronchial biopsy

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