Implementation of “clinical sequencing” in cancer genome medicine in Japan

Kohno, Takashi

doi:10.1111/cas.13486

Cited by 35 publications

(34 citation statements)

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“…A recent prospective cohort study in the USA revealed that only 11% of patients receiving the MSK‐IMPACT gene panel test were subsequently enrolled on genomically matched clinical trials . The gaps between the number of patients with actionable mutations and those receiving genomically matched therapy indicate the need to develop drugs targeting new genes covering not only druggable kinase genes but also nonkinase genes such as epigenomic and transcriptional regulator genes, which are often mutated in a variety of tumors . Developing drugs that target such currently undruggable molecules will be of great help.…”

Section: Discussionmentioning

confidence: 99%

“…Gene panel tests have not yet been implemented in routine oncological practice in Japan; ie, they have not been reimbursed by the national insurance system run by the Japanese Ministry of Health, Labor, and Welfare (MHLW) . However, several academic institutions have examined the feasibility and utility of gene panel tests, and 3 major Japanese cancer‐related societies (the Japanese Society of Medical Oncology, the Japanese Society of Clinical Oncology, and the Japanese Cancer Association) have issued consensus clinical practice guidance for NGS‐based cancer tests (the Consensus Clinical Practice Guidelines for Next Generation Sequencing in Cancer Diagnosis and Treatment [Edition 1.0]; http://www.jsmo.or.jp/about/kanko.html#guideline) . Therefore, it is likely that implementation of gene panel tests in Japan will happen soon.…”

Section: Introductionmentioning

confidence: 99%

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Feasibility and utility of a panel testing for 114 cancer‐associated genes in a clinical setting: A hospital‐based study

Ichikawa²,

et al. 2019

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Next‐generation sequencing ( NGS ) of tumor tissue (ie, clinical sequencing) can guide clinical management by providing information about actionable gene aberrations that have diagnostic and therapeutic significance. Here, we undertook a hospital‐based prospective study ( TOP ‐ GEAR project, 2nd stage) to investigate the feasibility and utility of NGS ‐based analysis of 114 cancer‐associated genes (the NCC Oncopanel test). We examined 230 cases (comprising more than 30 tumor types) of advanced solid tumors, all of which were matched with nontumor samples. Gene profiling data were obtained for 187 cases (81.3%), 111 (59.4%) of which harbored actionable gene aberrations according to the Clinical Practice Guidelines for Next Generation Sequencing in Cancer Diagnosis and Treatment (Edition 1.0) issued by 3 major Japanese cancer‐related societies. Twenty‐five (13.3%) cases have since received molecular‐targeted therapy according to their gene aberrations. These results indicate the utility of tumor‐profiling multiplex gene panel testing in a clinical setting in Japan. This study is registered with UMIN Clinical Trials Registry ( UMIN 000011141).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Feasibility and utility of a panel testing for 114 cancer‐associated genes in a clinical setting: A hospital‐based study

Ichikawa²,

et al. 2019

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“…The MYB‐NFIB fusion results in an increased expression of the protein Myb . Myb is important for the growth of multiple solid tumors, and MYB protein overexpression in ACC is associated with a more aggressive clinical course . For example, Mitani et al reported that the level of MYB expression in identical histological subtypes of ACC is associated with a shorter survival time.…”

Section: Discussionmentioning

confidence: 99%

“…In 2015, the American Medical Association introduced specific NGS panel codes, and we calculated the overall reimbursement rate by dividing the total sum of obtained payments through the total sum of charges using CMS values as a reference. For comparison of our reimbursement rates with local, national, and international rates, we reviewed reimbursement data from selected publications [28][29][30][31][32][33][34][35][36].…”

Section: Economic Analysismentioning

confidence: 99%

“…4C). Notably, these comparison data are obtained in nonorphan disease settings and include multisite studies including large community centers or even national initiatives [28][29][30][31][32][33][34][35][36]. Nonetheless, obtaining reimbursement requires carefully designed workflows to account for prior authorization, policy tailoring, and appeals processes [45][46][47].…”

Section: Assessment Of Financial Sustainabilitymentioning

confidence: 99%

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Clinically Integrated Molecular Diagnostics in Adenoid Cystic Carcinoma

Thierauf

Ramamurthy

et al. 2019

The Oncologist

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Background Adenoid cystic carcinoma (ACC) is an aggressive salivary gland malignancy without effective systemic therapies. Delineation of molecular profiles in ACC has led to an increased number of biomarker‐stratified clinical trials; however, the clinical utility and U.S.‐centric financial sustainability of integrated next‐generation sequencing (NGS) in routine practice has, to our knowledge, not been assessed. Materials and Methods In our practice, NGS genotyping was implemented at the discretion of the primary clinician. We combined NGS‐based mutation and fusion detection, with MYB break‐apart fluorescent in situ hybridization (FISH) and MYB immunohistochemistry. Utility was defined as the fraction of patients with tumors harboring alterations that are potentially amenable to targeted therapies. Financial sustainability was assessed using the fraction of global reimbursement. Results Among 181 consecutive ACC cases (2011–2018), prospective genotyping was performed in 11% (n = 20/181; n = 8 nonresectable). Testing identified 5/20 (25%) NOTCH1 aberrations, 6/20 (30%) MYB‐NFIB fusions (all confirmed by FISH), and 2/20 (10%) MYBL1‐NFIB fusions. Overall, these three alterations (MYB/MYBL1/NOTCH1) made up 65% of patients, and this subset had a more aggressive course with significantly shorter progression‐free survival. In 75% (n = 6/8) of nonresectable patients, we detected potentially actionable alterations. Financial analysis of the global charges, including NGS codes, indicated 63% reimbursement, which is in line with national (U.S.‐based) and international levels of reimbursement. Conclusion Prospective routine clinical genotyping in ACC can identify clinically relevant subsets of patients and is approaching financial sustainability. Demonstrating clinical utility and financial sustainability in an orphan disease (ACC) requires a multiyear and multidimensional program. Implications for Practice Delineation of molecular profiles in adenoid cystic carcinoma (ACC) has been accomplished in the research setting; however, the ability to identify relevant patient subsets in clinical practice has not been assessed. This work presents an approach to perform integrated molecular genotyping of patients with ACC with nonresectable, recurrent, or systemic disease. It was determined that 75% of nonresectable patients harbor potentially actionable alterations and that 63% of charges are reimbursed. This report outlines that orphan diseases such as ACC require a multiyear, multidimensional program to demonstrate utility in clinical practice.

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Molecular Genetics of Thymic Carcinoma

Saito

Kono

2019

Encyclopedia of Life Sciences

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Thymic carcinoma (TC) is a rare cancer with poor survival. Therapeutic regimen and drug clinical efficacy after failure of first‐line chemotherapy have not fully developed yet. Next‐generation sequencing studies were recently performed in patients with TC from Asian and Europe/US cohorts and reported genomic and epigenomic aberrations, including actionable aberrations for developing targeted personalised therapies. Some somatic variants, such as CYLD , TP53 , HRAS and RB1 , were commonly identified in both Asian and Europe/US cohorts, suggesting their contribution to thymic carcinogenesis. In addition to somatic mutations, epigenomic aberrations and gene rearrangements have been identified in TC. Mutational signature analysis revealed an accumulation of age‐related variants and DNA mismatch repair deficiency derived from TC development. The efforts to find novel actionable targets are continuing and immunotherapy for TC is investigated. Several clinical trials are currently underway to evaluate the therapeutic utility of immunotherapy for TC. Key Concepts Genomic and epigenomic aberrations in thymic carcinoma have been revealed. Targeted therapy and immunotherapy for thymic carcinoma have been developed. Thymic carcinoma is a rare cancer with poor survival. Efficient therapeutic drugs after failure of the first‐line chemotherapy are required. Genomic and epigenomic aberrations in thymic carcinoma have been revealed. Targeted therapies for thymic carcinoma is being developed. Efficacy of immunotherapy is expected for thymic carcinoma.

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Implementation of “clinical sequencing” in cancer genome medicine in Japan

Cited by 35 publications

References 34 publications

Feasibility and utility of a panel testing for 114 cancer‐associated genes in a clinical setting: A hospital‐based study

Feasibility and utility of a panel testing for 114 cancer‐associated genes in a clinical setting: A hospital‐based study

Clinically Integrated Molecular Diagnostics in Adenoid Cystic Carcinoma

Molecular Genetics of Thymic Carcinoma

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