Current Status of Next-Generation Sequencing-Based Cancer Genome Profiling Tests in Japan and Prospects for Liquid Biopsy

Abstract

Next-generation sequencing-based comprehensive genome profiling (CGP) testing, OncoGuide NCC Oncopanel System, and FoundationOne CDx Cancer Genomic Profile have been covered by the Japanese national health insurance system since June 2019. Because CGP was initially developed to enroll patients into an early-phase clinical trial for solid tumors, its approved indications have been limited to patients who have completed the standard chemotherapy treatment. Approximately 14,000 cases have been registered with the Center for Cancer Genomics and Advanced Therapeutics as of March 2021. Measuring the drug access rate is not enough due to patients’ deteriorating condition during CGP analysis and due to the limited number of ongoing clinical trials available, although tumor-agnostic therapies, such as the use of pembrolizumab in high microsatellite-instable solid tumors and in conditions with a high tumor mutational burden (≥10 mut/Mb) as well as the use of entrectinib and larotrectinib in NTRK fusion-positive tumors have been approved in Japan. Moreover, since this analysis is performed using DNA derived from tumor tissue, it is difficult to perform CGP in cases in which an insufficient amount of tissue exists. Thus, noninvasive blood-based assays have been developed, and CGP panels using circulating tumor DNA from blood were approved in March 2021. However, cost, timing, and the number of tests allowed by the health system have not yet been determined. Therefore, in this review, we outline the current status and issues of CGP testing using tumor tissues as well as the expectations and limitations of liquid biopsy for use in Japanese clinical practice.

Human resources for administrative work to carry out a comprehensive genomic profiling test in Japan

“…Among the six steps, most time was spent preparing for Expert Of the nationally fixed rate of ¥560,000 for all CGP tests in Japan, 70%-90% is reimbursed by the national health-care system, while co-pay for patients is 10%-30%. 5 It is important to note that most of the ¥560,000 paid to hospitals are then used to pay the testing companies, and the remainder is considered fees for clinical practice such as informed consent and explanation of CGP test results, including disclosure of germline findings, if applicable. Because cancer genomic medicine requires significant administrative work outside of usual clinical practice, the actual labor cost is higher than a typical laboratory test.…”

“…[1][2][3][4] Currently, CGP tests have a fixed rate of 560,000 yen (¥560,000 = $4308 at ¥130/dollar and 4000 euros at ¥140/euro) in Japan, and 70%-90% is reimbursed. 5 For reimbursement under the national health insurance, the following conditions must be met: (1) the patient has a solid tumor in which standard therapy is expected to finish or is unavailable; (2) Health, Labour and Welfare (MHLW), 6 (4) a pre-specified informed consent procedure is followed, (5) every test result must be discussed at MTBs, which can only be hosted by Core or Designated Hospitals, and (6) clinical and genomic data from every patient must be submitted to C-CAT. 7,8 In an Expert Panel, specialists in clinical oncology, clinical genetics, genetic counseling, pathology, cancer genomic medicine, and bioinformatics are all required to participate and discuss each test result.…”

Metastasis of Hepatocellular Carcinoma in the Pouch of Douglas Successfully Treated by Radiation Therapy: A Case Report

“…Such new therapies may provide an effective treatment option for this case. In addition, since we obtained the tumor tissue by a percutaneous biopsy, we were able to identify another effective treatment using recently developed technologies, such as cancer genomic profiling [ 25 , 26 ]. Finally, our case report suggests that more precise and individualized approaches need to be tested in well-designed clinical trials.…”

Towards Personalized Management of Ovarian Cancer

“…Essential in aiding this transition towards “personalized oncology” is the development of validated, tumor-based companion diagnostic testing such as the FDA-approved Foundation One Ⓡ test 90 or the NCC Oncopanel Ⓡ test. 91 The former test can assess the tumor mutational burden and PD-L1 expression (predictive of immunotherapy response) as well as degree of LOH, HRD and BRCA1/2 expression (predictive of PARPi response). 90 Increasing the availability of companion testing and access to stratified precision therapies has the potential to change the face of ovarian cancer therapeutics.…”