A Prospective Validation Study of Lung Cancer Gene Panel Testing Using Cytological Specimens

Morikawa, Kei; Kida, Hirotaka; Handa, Hiroshi; Inoue, Tatsuya; Saji, Hisashi; Koike, Junki; Nakamura, Seiji; Sato, Yoshiharu; Ueda, Yumi; Suzuki, Fujio; Matoba, Ryo; Mineshita, Masamichi

doi:10.3390/cancers14153784

Cited by 18 publications

(10 citation statements)

References 31 publications

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“…Although initially designed for the Japanese medical environment, the high-sensitivity NGS panel can also benefit other medical environments. Studies using cytological samples have demonstrated the stable performance of the compact panel in a real clinical setting [ 26 , 27 , 28 ], which was not possible with conventional NGS panels.…”

Section: Discussionmentioning

confidence: 99%

Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics

et al. 2023

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The recent increase in the number of molecular targeted agents for lung cancer has led to the demand for the simultaneous testing of multiple genes. Although gene panels using next-generation sequencing (NGS) are ideal, conventional panels require a high tumor content, and biopsy samples often do not meet this requirement. We developed a new NGS panel, called compact panel, characterized by high sensitivity, with detection limits for mutations of 0.14%, 0.20%, 0.48%, 0.24%, and 0.20% for EGFR exon 19 deletion, L858R, T790M, BRAF V600E, and KRAS G12C, respectively. Mutation detection also had a high quantitative ability, with correlation coefficients ranging from 0.966 to 0.992. The threshold for fusion detection was 1%. The panel exhibited good concordance with the approved tests. The identity rates were as follows: EGFR positive, 100% (95% confidence interval, 95.5–100); EGFR negative, 90.9 (82.2–96.3); BRAF positive, 100 (59.0–100); BRAF negative, 100 (94.9–100); KRAS G12C positive, 100 (92.7–100); KRAS G12C negative, 100 (93.0–100); ALK positive, 96.7 (83.8–99.9); ALK negative, 98.4 (97.2–99.2); ROS1 positive, 100 (66.4–100); ROS1 negative, 99.0 (94.6–100); MET positive, 98.0 (89.0–99.9); MET negative 100 (92.8–100); RET positive, 93.8 (69.8–100); RET negative, 100 (94.9–100). The analytical performance showed that the panel could handle various types of biopsy samples obtained by routine clinical practice without requiring strict pathological monitoring, as in the case of conventional NGS panels.

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Section: Discussionmentioning

confidence: 99%

Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics

et al. 2023

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“…Selpercatinib with a dose reduction (160 mg/day) for grade 2 elevated liver enzymes was continued. A high sensitivity next generation sequencing (NGS) panel system: lung cancer compact panel, with RNA assay using cytological brushing solution ( 6 , 7 ), confirmed the fusion gene KIF5B exon 15; RET exon 12 ( K15RET12 ). We could further confirm RET from formalin-fixed paraffin-embedded (FFPE) specimens from 7-year-old pleural effusion cell blocks ( Figures 3A, B ), which were morphologically similar to re-biopsy sample in terms of malignant cells with large nucleoli ( Figures 3C, D ).…”

Section: Case Reportmentioning

confidence: 97%

RET fusion mutation detected by re-biopsy 7 years after initial cytotoxic chemotherapy: A case report

et al. 2022

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Personalized medicine using molecular-targeted drugs to achieve better therapeutic response and long-term prognosis is common practice for lung cancer treatment. However, in cases before gene batch tests were available, medical treatment continued without the detection of rare mutations. We report a sixty-seven-old year man diagnosed with adenocarcinoma T1cN3M1a, stage IVA. Initial screening performed 7 years earlier using EGFR mutation and ALK immunohistochemical tests were negative. Although first-line cytotoxic combination chemotherapy was remarkably effective, a gradual regression of the primary lesion was noted. After a recent bronchoscopic re-biopsy, RET fusion was detected by gene panel test. In addition, we were able to confirm RET from FFPE specimens obtained from 7-year-old pleural effusion cell blocks. Subsequent administration of the molecular-targeted drug selpercatinib, was highly effective for the primary lesion and all metastatic lesions including brain metastases. We describe a case of RET fusion-positive lung cancer where molecular targeted therapy and cytotoxic drug showed a drastic response and long-term therapy was well maintained. Next generation sequencing was able to correctly diagnose RET fusion mutation using re-biopsy specimen after going undiagnosed for 7 years.

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“…The lung cancer compact panel (LCCP), which was recently approved as a new multi-companion diagnostic method, uses cytology pellet specimens and has very high sensitivity for detecting genetic mutations [ 15 ]. Another report showed that cytology pellet specimens from the fixative medium of transbronchial lung biopsy can exfoliate tumor cells with good cellularity [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Utility of bronchoscopically obtained frozen cytology pellets for next-generation sequencing

Mimura,

Takamiya,

Fujimoto

et al. 2024

BMC Cancer

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Background Next-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay. Methods We retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine. We investigated the amount of extracted DNA and RNA and determined the NGS success rates. We also compared the amount of DNA and RNA by bronchoscopy methods. To create the frozen cytology pellets, we first effectively collected the cells and then quickly centrifuged and cryopreserved them. Results A total of 132 patients were enrolled in this study between May 2016 and December 2022; of them, 75 were subjected to frozen cytology pellet examinations and 57 were subjected to frozen tissue examinations. The amount of DNA and RNA obtained by frozen cytology pellets was nearly equivalent to frozen tissues. Frozen cytology pellets collected by endobronchial ultrasound-guided transbronchial needle aspiration yielded significantly more DNA than those collected by transbronchial biopsy methods. (P < 0.01) In RNA content, cytology pellets were not inferior to frozen tissue. The success rate of NGS analysis with frozen cytology pellet specimens was comparable to the success rate of NGS analysis with frozen tissue specimens. Conclusions Our study showed that frozen cytology pellets may have equivalent diagnostic value to frozen tissue for NGS analyses. Bronchial cytology specimens are usually used only for cytology, but NGS analysis is possible if enough cells are collected to create pellet specimens. In particular, the frozen cytology pellets obtained by endobronchial ultrasound-guided transbronchial needle aspiration yielded sufficient amounts of DNA. Trial registration This was registered with the University Medical Hospital Information Network in Japan (UMINCTR registration no. UMIN000052050).

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A Prospective Validation Study of Lung Cancer Gene Panel Testing Using Cytological Specimens

Cited by 18 publications

References 31 publications

Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics

Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics

RET fusion mutation detected by re-biopsy 7 years after initial cytotoxic chemotherapy: A case report

Utility of bronchoscopically obtained frozen cytology pellets for next-generation sequencing

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