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

Author:

Naito Yoichi1,Sunami Kuniko2,Kage Hidenori34,Komine Keigo5,Amano Toraji6,Imai Mitsuho78,Koyama Takafumi9,Ennishi Daisuke10,Kanai Masashi11,Kenmotsu Hirotsugu12,Maeda Takahiro13,Morita Sachi14,Sakai Daisuke15,Watanabe Kousuke16,Shirota Hidekazu5,Kinoshita Ichiro6,Yoshioka Masashiro11,Mamesaya Nobuaki12,Ito Mamoru13,Kohsaka Shinji17,Saigusa Yusuke18,Yamamoto Kouji18,Hirata Makoto19,Tsuchihara Katsuya20,Yoshino Takayuki21

Affiliation:

1. Department of General Internal Medicine, National Cancer Center Hospital East, Kashiwa, Japan

2. Department of Laboratory Medicine, National Cancer Center Hospital, Tokyo, Japan

3. Department of Next-Generation Precision Medicine Development Laboratory, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4. Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan

5. Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan

6. Division of Clinical Cancer Genomics, Hokkaido University Hospital, Sapporo, Japan

7. Genomics Unit, Keio University School of Medicine, Tokyo, Japan

8. Translational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan

9. Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan

10. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan

11. Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

12. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan

13. Division of Precision Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

14. Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan

15. Center for Cancer Genomics and Personalized Medicine, Osaka University, Suita, Japan

16. Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan

17. Section of Knowledge Integration, Center for Cancer Genomics and Advanced Therapeutics, National Cancer Center, Tokyo, Japan

18. Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan

19. Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan

20. Division of Translational Informatics, National Cancer Center Exploratory Oncology Research and Clinical Trial Center, Tokyo, Japan

21. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

Abstract

ImportanceQuality assurance of molecular tumor boards (MTBs) is crucial in cancer genome medicine.ObjectiveTo 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.Design, Setting, and ParticipantsThis 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.ExposuresSimulated cases of cancer.Main Outcomes and MeasuresThe 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.ResultsThe 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.Conclusions and RelevanceThe 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.

Publisher

American Medical Association (AMA)

Subject

General Medicine

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