Cancer Genomic Medicine Research Articles

Current Status and Future Prospects of Cancer Genomic Medicine

Current Status and Future Prospects of Cancer Genomic Medicine

Endoscopic Ultrasound-Guided Tissue Acquisition of Pancreaticobiliary Cancer Aiming for a Comprehensive Genome Profile

In recent years, cancer genomic medicine centered on comprehensive genome profile (CGP) analysis has become widely used in the field of pancreatic cancer. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has played an important role in pancreatic cancer, and recently, more EUS-TA tissue samples are considered for CGP analysis. Differences exist between the Oncoguide NCC Oncopanel System and Foundation One CDx Cancer Genome Profile, which are CGP tests approved by insurance programs in Japan, including the analysis criteria, optimal needle selection for meeting these criteria, and puncture target. It is important to understand not only the specimen collection factors, but also the specimen processing factors that can increase the success rate of CGP testing. Furthermore, cancer genome medicine is expected to enter an era of increasing turbulence in the future, and endoscopists need to respond flexibly to these changes. Herein, we review the current status of cancer genome medicine in pancreatic and biliary tract cancers and cancer gene panel testing using EUS-TA.

Adaptation to the Progress in Cancer Genomic Medicine by a Japanese Community Hospital

Background: Remarkable progress in cancer genomic medicine (CGM) has been made with the advent of next-generation sequencing and advanced computational data analysis approaches. In Japan gene panel testing has been covered by the National Health Insurance System since June 2019. Although Nagoya Memorial Hospital has been designated as a regional medical support hospital, their medical staff are unfamiliar with CGM and generally experience difficulty in explaining the genetic testing to cancer patients.
 Methods: A multi-disciplinary CGM team was created in July 2019 to adapt to the clinical application of gene panel testing. Hospital functions were then maintained focusing on the following three aspects: a pathology system for handling genetic information, human resource development related to CGM, and a patient support system, including genetic counseling.
 Results: Third party ISO15189 (International Organization for Standardization) certification was acquired for the Department of Pathology to establish a quality-assured laboratory. Here, we report on 21 cancer patients who consulted and received information from the CGM outpatient department of our hospital. Among them 14 patients were introduced into a group of certified hospitals by the Japanese Ministry of Health, Labour, and Welfare and 10 patients underwent gene panel tests.
 Conclusions: As a regional medical support hospital dealing with many cancer patients, we will further improve hospital functions to match the progress in CGM.

Clinical Outcomes of Comprehensive Genomic Profiling Tests for Gastrointestinal Cancers: Experience from Tokushima University Hospital

In Japan, cancer genome profiling (CGP) for cancer patients without standard treatment has been covered by public insurance since June 2019. This study analyzed data of 122 patients with gastrointestinal tumors who underwent CGP to clarify cancer genome medicine's current status and possible problems at the Tokushima University Hospital. The major types of cancer included pancreatic (n=30), colorectal (n=25), biliary tract (n=15), gastric (n=11), and hepatocellular carcinoma (n=8). CGP tests included F1CDx in 70 patients (57%), F1LCDx in 36 (30%), TSO500 in 14 (11%), and NCC Oncopanel in 2 (2%). Actionable gene alterations were identified in 72 patients (59%), but only 5 patients (4%) were treated for pancreatic (n=1), colorectal (n=3), and small bowel cancers (n=1). The main reasons for not receiving genotype-matched therapy included the lack of appropriate drugs or clinical trials that matched the actionable gene alterations (n=40) and the inability to participate in clinical trials (n=10). There is still not a sufficient number of patients receiving genotype-matched treatment for gastrointestinal cancers. To promote cancer genome medicine in regional areas, attempts to improve access to genotype-matched therapies are required, as well as to promote the development of new molecular-targeted drugs and clinical trials for these drugs. J. Med. Invest. 70 : 154-159, February, 2023.

Concordance Between Recommendations From Multidisciplinary Molecular Tumor Boards and Central Consensus for Cancer Treatment in Japan

Quality assurance of molecular tumor boards (MTBs) is crucial in cancer genome medicine. To evaluate the concordance of recommendations by MTBs and centrally developed consensus treatment recommendations at all 12 leading institutions for cancer genomic medicine in Japan using 50 simulated cases. This was a prospective quality improvement study of 50 simulated cancer cases. Molecular tumor boards from 12 core hospitals independently recommended treatment for 50 cases blinded to the centrally developed consensus treatment recommendations. The study's central committee consisted of representatives from all 12 core hospitals in Japan who selected the 50 simulated cases from The Cancer Genome Atlas database, including frequently observed genomic alterations. The central committee recommended centrally developed consensus treatment. The concordance rate for genomically matched treatments between MTBs and centrally developed consensus treatment recommendations was evaluated. Data analysis was conducted from January 22 to March 3, 2021. Simulated cases of cancer. The primary outcome was concordance, defined as the proportion of recommendations by MTBs concordant with centrally developed consensus treatment recommendations. A mixed-effects logistic regression model, adjusted for institutes as a random intercept, was applied. High evidence levels were defined as established biomarkers for which the treatment was ready for routine use in clinical practice, and low evidence levels were defined as biomarkers for genomically matched treatment that were under investigation. The Clinical Practice Guidance for Next-Generation Sequencing in Cancer Diagnosis and Treatment (edition 2.1) was used for evidence-level definition. The mean concordance between MTBs and centrally developed consensus treatment recommendations was 62% (95% CI, 57%-65%). Each MTB concordance varied from 48% to 86%. The concordance rate was higher in the subset of patients with colorectal cancer (100%; 95% CI, 94.0%-100%), ROS1 fusion (100%; 95% CI, 85.5%-100%), and high evidence level A/R (A: 88%; 95% CI, 81.8%-93.0%; R:100%; 95% CI, 92.6%-100%). Conversely, the concordance rate was lower in cases of cervical cancer (11%; 95% CI, 3.1%-26.1%), TP53 mutation (16%; 95% CI, 12.5%-19.9%), and low evidence level C/D/E (C: 30%; 95% CI, 24.7%-35.9%; D: 25%; 95% CI, 5.5%-57.2%; and E: 18%; 95% CI, 13.8%-23.0%). Multivariate analysis showed that evidence level (high [A/R] vs low [C/D/E]: odds ratio, 4.4; 95% CI, 1.8-10.8) and TP53 alteration (yes vs no: odds ratio, 0.06; 95% CI, 0.03-0.10) were significantly associated with concordance. The findings of this study suggest that genomically matched treatment recommendations differ among MTBs, particularly in genomic alterations with low evidence levels wherein treatment is being investigated. Sharing information on matched therapy for low evidence levels may be needed to improve the quality of MTBs.

PEDT-12 NATIONWIDE LANDSCAPE OF GENOMIC ANALYSIS OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS

Abstract Background and Purpose In Japan, cancer-gene profiling (CGP) tests, such as the OncoGuide NCC Oncopanel System, FoundationOne CDx Cancer Genome Profile (F-one), and FoundationOne Liquid CDx Cancer Genome Profile, are covered by insurance and clinically applied to promote cancer genomic medicine. Information from CGP tests is managed at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) and shared with clinicians after discussions at the Expert Panel (EP). We provide an overview of the registered pediatric CNS tumors. Methods We extracted and analyzed CNS/brain data from the C-CAT registry from June 2019 to June 2022 for ages 0–19 years. Variables such as age, gender, histopathological diagnosis, CGP test type, ECOG Performance Status (PS), registration status, genetic abnormalities, and treatments were analyzed. Results Among 1133 patients of all ages with CNS tumors, 361 (31.9%) were aged 0–19 years; Of the 918 patients aged 0-19 years with any type of cancer, those with CNS tumors accounted for 34.2%; 188 patients were aged under 10 years, 173 patients were teenagers, 174 patients were males, 187 patients were females; PS was 0 in 47.9% of patients. The most common histopathological diagnoses were medulloblastoma, diffuse midline glioma and glioblastoma. Genetic abnormalities included TP53 mutations in 85 cases, H3F3A mutations in 38 cases, STK11 mutations in 36 cases, BRAF mutations in 33 cases, BRAF-KIAA1549 fusions in 24 cases, and TMB high in 16 cases. Seventy-six patients (21.1%) were offered treatment options in the EP, and 26 patients (7.2%) received the recommended treatment, including two in physician-initiated trials, four in company trials, eleven in treatments within insurance coverage, and eleven in others. Discussion This is the first report of genetic analysis of pediatric CNS tumors on a nationwide scale. Pediatric CNS tumors have a large number of registered cases; thus, drug development for them is urgently needed.

がんゲノム診療における組織・細胞・血漿検体の取扱いと使い分け

がんゲノム診療における組織・細胞・血漿検体の取扱いと使い分け

Human genetics education as part of the Japanese Cancer Education Comprehensive Support Project.

In Japan, cancer education has been initiated with children as a measure against cancer. Cancer genome medicine, which is a social implementation, includes aspects of genetic medicine. For this reason, it is assumed that content related to "genetics" is also necessary in cancer education. To investigate the actual situation regarding the teaching of genetics in cancer education, we conducted a questionnaire survey of schoolteachers involved in cancer education; these schoolteachers belonged to the model school of the Cancer Education Comprehensive Support Project. Regarding genetic content, we asked questions related to two aspects: "the molecular genetic mechanisms of cancer" and "the phenomenon of sharing cancer in the family." The results showed that about 60% of the teachers had experience teaching content related to the molecular genetic mechanisms of cancer and the phenomenon of sharing cancer in the family. While many teachers felt that teaching genetics in cancer education was necessary, they also felt that there were difficulties in doing so: 65.2% for content related to the molecular genetic mechanisms of cancer and 70.8% for that related to the phenomenon of sharing cancer in the family. It is important to properly treat cancer as a genetic disease, and it is necessary to examine government curriculum guidelines and establish a collaborative system among other subjects. In addition, the involvement of specialists in genetic medicine and psychosocial support is expected to improve teachers' genetic literacy as well as to communicate with students with consideration for their family history.

C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan.

Since June 2019, under the umbrella of the national health insurance system, Japan has started cancer genomic medicine (CGM) with comprehensive genomic profiling (CGP) tests. The Ministry of Health, Labour and Welfare (MHLW) of Japan constructed a network of CGM hospitals (a total of 233 institutes as of July 1, 2022) and established the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national datacenter for CGM. Clinical information and genomic data from the CGP tests are securely transferred to C-CAT, which then generates "C-CAT Findings" reports containing information of clinical annotation and matched clinical trials based on the CGP data. As of June 30, 2022, a total of 36,340 datapoints of clinical/genomic information are aggregated in C-CAT, and the number is expected to increase swiftly. The data are now open for sharing with not only the CGM hospitals but also other academic institutions and industries.

Current Clinical Practice of Precision Medicine Using Comprehensive Genomic Profiling Tests in Biliary Tract Cancer in Japan.

With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests, which are designed to measure more than hundreds of cancer-related genes at a time, have now been widely introduced into daily clinical practice. For the patients whose tumor samples are not fit for tissue-based CGP tests, a blood-based CGP test (liquid biopsy) is available as an alternative option. Three CGP tests, “OncoGuide NCC™Oncopanel System (124 genes)”, “FoundationOne®CDx (324 genes)”, and “Founda-tionOne®CDx Liquid (324 genes)”, are now reimbursed by public insurance in 233 hospitals designated for cancer genomic medicine in Japan. In biliary tract cancer, the prevalence of druggable variants is relatively higher compared to other cancer types and the European Society for Medical Oncology recommends routine use of CGP tests for advanced biliary tract cancer to guide treatment options. The latest National Cancer Center Network guideline lists eight druggable markers (NTRK fusion, MSI-H, TMB-H, BRAF V600E, FGFR2 fusions/rearrangement, IDH1 mutations, RET fusion, and HER2 overexpression) and matched therapies. In Japan, matched therapies for four markers (NTRK, MSI-H, TMB-H, and FGFR2) are reimbursed by public insurance (as of September 2022). The progress of genomic profiling technology will contribute to the improvement of the dismal clinical outcomes of this disease in the future.

Expert panel consensus recommendations on the use of circulating tumor DNA assays for patients with advanced solid tumors.

Comprehensive genomic profiling is increasingly used to facilitate precision oncology based on molecular stratification. In addition to conventional tissue comprehensive genomic profiling, comprehensive genomic profiling of circulating tumor DNA has become widely utilized in cancer care owing on its advantages, including less invasiveness, rapid turnaround time, and capturing heterogeneity. However, circulating tumor DNA comprehensive genomic profiling has some limitations, mainly false negatives due to low levels of plasma circulating tumor deoxyribonucleic acid and false positives caused by clonal hematopoiesis. Nevertheless, no guidelines and recommendations fully address these issues. Here, an expert panel committee involving representatives from 12 Designated Core Hospitals for Cancer Genomic Medicine in Japan was organized to develop expert consensus recommendations for the use of circulating tumor deoxyribonucleic acid-based comprehensive genomic profiling. The aim was to generate guidelines for clinicians and allied healthcare professionals on the optimal use of the circulating tumor DNA assays in advanced solid tumors and to aid the design of future clinical trials that utilize and develop circulating tumor DNA assays to refine precision oncology. Fourteen clinical questions regarding circulating tumor deoxyribonucleic acid comprehensive genomic profiling including the timing of testing and considerations for interpreting results were established by searching and curating associated literatures, and corresponding recommendations were prepared based on the literature for each clinical question. Final consensus recommendations were developed by voting to determine the level of each recommendation by the Committee members.

SY03-1 Multidisciplinary approach for optimal care in cancer genomic medicine

In Japan, cancer genomic medicine (GCM) has been started by the approval of cancer gene panel tests covered by the national health insurance system since June 2019. The number of institutes that can perfume cancer gene panel tests has increased from 167 at the beginning to 228 in October 2021, making GCM more accessible. Moreover, FoundationOne®Liquid CDx, which is a type of cancer gene panel test for ctDNA analysis, has been available from August 2021. The environment related to cancer gene panel tests is improving, and GCM opens its door to more and more patients.

SY03-3 The role of nurses in the genomic medicine from the viewpoint of CNS in genetics nursing

The establishment of the cancer genome medicine system has given us an opportunity to think about what the relevant specialists should do. In situations where cancer treatments and genomic medicine overlap, multidisciplinary cooperation is very important. In our experience, this leads to supporting the best possible medical care for cancer patients and their families.

SY07-1 New guidelines for clinical evaluation of anti-cancer drugs in Japan

The clinical benefits of an anti-cancer drug need to be demonstrated by clinical studies before they are approved by a regulatory agency. Recent progress in the development of drugs acting on the immune system and in using cancer genomic medicine to target rare molecular subtypes has significantly altered the approach for the clinical development of anti-cancer drugs. Drugs acting on the immune system have different characteristics from those of cytotoxic agents and molecular targeted drugs. For example, the anti-tumor effects of immune checkpoint inhibitors may be delayed, and new adverse events may occur several months after the start of treatment.

PSY4-2 Prospective of patient-proposal healthcare services with multiple targeted agents

Since June 2019, 3 comprehensive genomic profiling (CGP) tests have been covered by public medical insurance in Japan, and a body of cancer genomic medicine has been establishing such 12 designate core hospitals throughout Japan. However, when genomic abnormalities are detected by CGP tests, some patients can't receive treatments due to the lack of molecular targeted drugs to be covered by public medical insurance for the diseases. It has been our urgent issue. In October 2019, we started a basket/umbrella-type clinical trial based on the result of CGP test (NCCH1901).

P38-6 Evaluation of annotations for cancer gene panel testing using a genome-guided system

In Japan, oncogene panel testing is covered by public insurance since June 2019, and it is now mandatory to explain to the patients the results of testing, after interpretation by an Expert Panel (EP) at cancer genomic medicine hospitals. Therefore, the work burden of interpreting genomic data and proposing treatment based on the results is very heavy on clinicians, making an automated annotation system desirable.

Cancer genomic medicine in Japan and the roles of pharmacists.

Cancer genomic medicine (CGM) is a medical service that provides optimized treatment for each patient based on genes, biomarkers, environment, and lifestyle. In Japan, the approval of designed core hospitals for CGM started in 2017. In June 2019, two types of cancer gene panel tests became available in the national health insurance system, and CGM was socially implemented. While CGM is still in its infancy and there are some issues that need to be resolved, there are cases where the treatment has shown dramatic results. The present review highlights the CGM system in Japan, the issues it faces, and the role of pharmacists in this system.

7. The Role and Efforts of Clinical Research Coordinators in Cancer Genomic Medicine

7. The Role and Efforts of Clinical Research Coordinators in Cancer Genomic Medicine

頭頸部領域のゲノム医療の現状

頭頸部領域のゲノム医療の現状

Current Status and Future Prospects of Molecular Diagnostics for Lung Cancer Genomic Medicine

Current Status and Future Prospects of Molecular Diagnostics for Lung Cancer Genomic Medicine