Comparison of ALK detection by FISH, IHC and NGS to predict benefit from crizotinib in advanced non-small-cell lung cancer

Chen, Lin; Shi, Xun; Shao, Yi; Zhao, Jun; He, Qi; Jin, Ying; Yu, Xinmin

doi:10.1016/j.lungcan.2019.03.018

Cited by 83 publications

(72 citation statements)

References 43 publications

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“…26,27 Similarly, these three kinds of fusion occur easily, predominantly in younger non-smokers, and in lung adenocarcinoma patients. 28,29 ALK gene rearrangement has been reported to be present in about 3%-8% of NSCLC patients, 4,30 and ROS1 and RET fusion reported to be present in about 1%-2% of patients with NSCLC. 11 In our study, the rate of occurrence of ALK, ROS1 and RET fusion was slightly lower.…”

Section: Discussionmentioning

confidence: 99%

Status of 10 targeted genes of non‐small cell lung cancer in eastern China: A study of 884 patients based on NGS in a single institution

Ran

et al. 2020

Thoracic Cancer

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Background The status of targeted genes and the association between targeted genes and clinicopathological features in Chinese lung cancer patients remains to be elucidated. Methods The status of 10 targeted genes was evaluated by next‐generation sequencing (NGS) in 884 non‐small cell lung cancer (NSCLC) patients. The relationship between gene alterations and clinicopathological characters was analyzed. Results Overall, 684 (77.4%) patients harbored gene alterations, and EGFR (510, 57.7%) was found to be the most common type of mutation followed by KRAS (91, 10.3%), HER2 (38, 4.3%), PIK3CA (32, 3.6%), ALK (21, 2.4%), BRAF (10, 1.1%), ROS1 (5, 0.6%), RET (5, 0.6%), MET (4, 0.5%) and NRAS (1, 0.1%). Gene alterations were more frequent in females, non‐smokers and adenocarcinoma (P < 0.001). EGFR mutations were associated with women, non‐smokers, normal level of serum tumor markers, and adenocarcinoma (P < 0.001). Patients without lymph node metastasis (P = 0.012), or early stage disease (P < 0.001) exhibited a higher EGFR mutation rate. KRAS mutations tended to arise in men (P < 0.001), smokers (P < 0.001) and patients with higher levels of serum tumor markers (P = 0.048). A mucus‐producing component was associated with KRAS (P < 0.001), ROS1 (P = 0.033) and ALK (P < 0.001) alterations. ALK and ROS1 rearrangements were more frequent in micropapillary structures (P = 0.004, P = 0.012). BRAF mutation was associated with advanced disease patients and micropapillary structure (P < 0.001). PIK3CA mutation was more likely to be found in elderly patients (P = 0.014). Some patients had synchronous gene alterations, including EGFR/PIK3CA, EGFR/HER2, HER2/KRAS, EGFR/KRAS, EGFR/ROS1, EGFR/NRAS, KRAS/PIK3CA, KRAS/PIK3CA/HER2. Conclusions Most patients had at least one genetic alteration, and individual patients harbored synchronous mutation. Each gene alteration had unique clinicopathological characteristics. Key points Significant findings of the study This study revealed the frequency and distribution of 10 targeted gene abnormalities and their association with clinicopathological parameters of Chinese non‐small cell lung cancer (NSCLC) patients in eastern China. What this study adds Some rare synchronous mutations were detected in our study by next‐generation sequencing (NGS).

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Section: Discussionmentioning

confidence: 99%

Status of 10 targeted genes of non‐small cell lung cancer in eastern China: A study of 884 patients based on NGS in a single institution

Ran

et al. 2020

Thoracic Cancer

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“…Several other studies have also reported the possibility of false results from FISH assays and have strongly suggested that NGS be used to resolve IHC-FISH discordant cases [20][21][22][23][24]. In addition, the re-validation of molecular testing would be useful in the treatment of tumors that are unresponsive to target agents.…”

Section: Discussionmentioning

confidence: 99%

Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing

Park

Shim

2020

Cancer Res Treat

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PurposeEpidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) are ‘must-test’ biomarkers in the molecular diagnostics of advanced-stage lung cancer patients. Although single-gene assays are currently considered the gold standard for these genes, next-generation sequencing (NGS) tests are being introduced to clinical practices. We compared the results of current diagnostics and aimed to suggest timely effective guidance for their clinical use. Materials and MethodsPatients with lung cancer who received both conventional single-gene assays and subsequent targeted NGS testing were enrolled, and the results of their tests were compared. ResultsA total of 241 patients were enrolled, and the EGFR real-time polymerase chain reaction, ALK fluorescence in situ hybridization (FISH), and ROS1 FISH assays exhibited 92.9%, 99.6%, and 99.5% concordance with the NGS tests, respectively. The discordant cases were mostly false-negatives of the single-gene assays, probably due to technical limitation. Of 158 cases previously designated as wild-type, EGFR, ALK, and ROS1 alterations were identified in 10.1%, 1.9%, and 1.3%, respectively, and other targetable alterations were identified in 36.1% of the cases. Of patients with additionally identified actionable alterations, 32.6% (31/95) received matched therapy with a clinical benefit of 48.4% (15/31). ConclusionEven though the conventional and NGS methods were concordant in the majority of cases, NGS testing still revealed a considerable number of additional EGFR, ALK, and ROS1 alterations, as well as other targetable alterations, in Korean advanced-stage lung cancer patients. Given the high frequency of EGFR and other targetable mutations identified in the present study, NGS testing is highly recommended in the diagnosis of Korean lung cancer patients.

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“…IHC had the greatest sensitivity (94.5%), followed by NGS (92.7%), then FISH (82.4%), with the greatest concordance between IHC and NGS (87.3%). 203 Note ctDNA NGS is principally being developed in monitoring for response and resistance to treatment given a lower sensitivity (77%) in detecting ALK rearrangements. 204,205 An additional consideration for NGS in diagnostic evaluation of ALK rearrangement is the ability to evaluate for other mutations concurrently.…”

Section: Diagnosismentioning

confidence: 99%

“…206 Lin and colleagues independently noted worse outcomes with TP53 comutations in ALK-rearranged NSCLC treated with crizotinib. 203 Biomarker development will likely continue to evolve in the targeted mutation space, and clinically relevant comutations may identify those who will benefit from combination therapy.…”

Section: Diagnosismentioning

confidence: 99%

Targeted Therapy for Non-Small Cell Lung Cancer

Noor

Cummings

Johnson

et al. 2020

Semin Respir Crit Care Med

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Lung cancer is a heterogeneous disease, and the availability of comprehensive genomic profiling has allowed for the characterization of its molecular subtypes. This has increased the ability to deliver “personalized medicines” by tailoring therapies to target driver mutations in a patient's cancer. The development of targeted therapies for non-small cell lung cancer (NSCLC) has helped define the era of precision medicine throughout oncology. This article aims to contextualize recent research and provide an updated summary of targeted therapies available for patients with NSCLC. With practitioners and clinical researchers in mind, we note standard of care therapies, important approvals, practice guidelines, and treatments in development. The first section discusses mutations in the epidermal growth factor receptor (EGFR) gene, and the second section examines rearrangements in the anaplastic lymphoma kinase (ALK) and ROS1 fusions. Finally, we explore the rarer molecular alterations in BRAF, RET, MET, HER2, and KRAS. Given the many available therapies, it is important to understand the molecular alterations in NSCLC, and how to target them.

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Comparison of ALK detection by FISH, IHC and NGS to predict benefit from crizotinib in advanced non-small-cell lung cancer

Cited by 83 publications

References 43 publications

Status of 10 targeted genes of non‐small cell lung cancer in eastern China: A study of 884 patients based on NGS in a single institution

Status of 10 targeted genes of non‐small cell lung cancer in eastern China: A study of 884 patients based on NGS in a single institution

Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing

Targeted Therapy for Non-Small Cell Lung Cancer

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