Annual Report 2017

Taro Shibata, Aya Kuchiba

Introduction

 Biostatisticians at the National Cancer Center (NCC) have two key roles. The first is to contribute to providing the best evidence through planning and implementing statistical designs and methods and providing statistical considerations in every stage of a subject-matter research project as a scientist. The second is to develop novel statistical and mathematical methods, motivated by methodological issues that arise in various scientific disciplines. While the Biostatistics Division at the Center for Research Administration and Support (Section directed by the NCC President) makes comprehensive efforts to work on both roles, the Division of Biostatistical Research at the Center for Public Health Sciences particularly focuses on the second role along with responsibility.

Research activities

 Investigators in the Division of Biostatistical Research are actively working on identifying and solving statistical problems, and developing novel methodology in various research areas.

1. Epidemiologic Research Area

1) Risk prediction models

Cohort sampling designs are often used for epidemiologic studies with biomarkers, such as SNPs (single nucleotide polymorphisms). We review the methods to estimate prediction performance in those study designs and apply

them to the study data from nested case-

control design to develop and evaluate the risk prediction model of colorectal cancer.

In addition, we are working on developing the methods to assess prediction performance for outcome with more than two categories (e.g., breast cancer with ER+, breast cancer with ER-, no cancer). Comparing the situations with binary outcome, evaluating prediction performance for multi-category outcome would not be so straightforward. We propose a new index for prediction performance on multi-

category outcome. The preliminary results of examining characteristics of the proposed index were presented at the international statistical conference (ENAR 2018).

2) Evaluation of risk factors with cancer subtypes

We are working on developing statistical methods to evaluate etiologic heterogeneity among cancer subtypes. The proposed method was applied to data from the cohort study to evaluate the difference in the associations of smoking between solitary and synchronous colorectal cancers.

3) Decomposition of population attributable fraction

Attributable fraction (AF) is interpreted as the fractional reduction of disease events that would occur if exposures were eliminated. We proposed a decomposition of the overall AF for two exposures into AFs for each of two exposures and AF for their interaction, using potential outcomes framework.

2. Clinical Research Area

1) Immunotherapy single arm trials with response

We are developing a single arm trial design to capture a potential delayed response, which is a unique pattern of response to immunotherapy. We presented preliminary results of the proposed design performance under potential scenarios at the cancer biostatistics workshop (2nd Pacific Rim Cancer Biostatistics Workshop).

2) Development and utilization of clinical trial database

Pre-registration system of clinical trials was originally institutionalized to avoid publication bias. On the other hand, the roles of clinical trials include the implementation of their results in clinical practice, as well as scientific and academic development. Also, participating clinical trials is increasingly considered as a treatment option. Considering these circumstances, the role of the clinical trial database is now changing. For the purpose of finding a way of utilizing the clinical trial database more effectively, we are working on establishing collaborative relationship with the other measures of providing cancer information and the project teams of cancer research.

Future prospects

 Biostatistics has a close connection with real applications. Working on both methodological projects and real applications is important for future developments of biostatistical research. In 2017, we started to be involved in the new research area of evaluating medical devices with artificial intelligence, besides the above. We are now working on identifying the statistical and study methodological issues.

 We endeavor to establish a powerful collaborative relationship with researchers throughout the NCC and to identify critical issues that the NCC needs to tackle.

List of papers published in January 2017 - March 2018

Journal

 1. Aokage K, Saji H, Suzuki K, Mizutani T, Katayama H, Shibata T, Watanabe S, Asamura H. A non-randomized confirmatory trial of segmentectomy for clinical T1N0 lung cancer with dominant ground glass opacity based on thin-section computed tomography (JCOG1211). Gen Thorac Cardiovasc Surg, 65:267-272, 2017

 2. Namikawa K, Tsutsumida A, Mizutani T, Shibata T, Takenouchi T, Yoshikawa S, Kiyohara Y, Uchi H, Furue M, Ogata D, Tsuchida T, Yamazaki N. Randomized phase III trial of adjuvant therapy with locoregional interferon beta versus surgery alone in stage II/III cutaneous melanoma: Japan Clinical Oncology Group Study (JCOG1309, J-FERON). Jpn J Clin Oncol, 47:664-667, 2017

 3. Iwasaki M, Tanaka-Mizuno S, Kuchiba A, Yamaji T, Sawada N, Goto A, Shimazu T, Sasazuki S, Wang H, Marchand LL, Tsugane S. Inclusion of a Genetic Risk Score into a Validated Risk Prediction Model for Colorectal Cancer in Japanese Men Improves Performance. Cancer Prev Res (Phila), 10:535-541, 2017

 4. Kataoka K, Nakamura K, Mizusawa J, Kato K, Eba J, Katayama H, Shibata T, Fukuda H. Surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal cancer trials with preoperative therapy: Literature-based meta-analysis. Eur J Surg Oncol, 43:1956-1961, 2017

 5. Onimaru R, Onishi H, Shibata T, Hiraoka M, Ishikura S, Karasawa K, Matsuo Y, Kokubo M, Shioyama Y, Matsushita H, Ito Y, Shirato H. Phase I study of stereotactic body radiation therapy for peripheral T2N0M0 non-small cell lung cancer (JCOG0702): Results for the group with PTV100cc. Radiother Oncol, 122:281-285, 2017

 6. Kimura T, Nagata Y, Eba J, Ozawa S, Ishikura S, Shibata T, Ito Y, Hiraoka M, Nishimura Y. A randomized Phase III trial of comparing two dose-fractionations stereotactic body radiotherapy (SBRT) for medically inoperable Stage IA non-small cell lung cancer or small lung lesions clinically diagnosed as primary lung cancer: Japan Clinical Oncology Group Study JCOG1408 (J-SBRT trial). Jpn J Clin Oncol, 2017

 7. Drew DA, Nishihara R, Lochhead P, Kuchiba A, Qian ZR, Mima K, Nosho K, Wu K, Wang M, Giovannucci E, Fuchs CS, Chan AT, Ogino S. A Prospective Study of Smoking and Risk of Synchronous Colorectal Cancers. Am J Gastroenterol, 112:493-501, 2017

 8. Yamada M, Oda I, Tanaka H, Abe S, Nonaka S, Suzuki H, Yoshinaga S, Kuchiba A, Koyanagi K, Igaki H, Taniguchi H, Sekine S, Saito Y, Tachimori Y. Tumor location is a risk factor for lymph node metastasis in superficial Barrett's adenocarcinoma. Endoscopy international open, 5:E868-E874, 2017

 9. Watari H, Katayama H, Shibata T, Ushijima K, Satoh T, Onda T, Aoki D, Fukuda H, Yaegashi N, Sakuragi N. Phase III trial to confirm the superiority of pelvic and para-aortic lymphadenectomy to pelvic lymphadenectomy alone for endometrial cancer: Japan Clinical Oncology Group Study 1412 (SEPAL-P3). Jpn J Clin Oncol, 47:986-990, 2017

10. Budhathoki S, Hidaka A, Yamaji T, Sawada N, Tanaka-Mizuno S, Kuchiba A, Charvat H, Goto A, Kojima S, Sudo N, Shimazu T, Sasazuki S, Inoue M, Tsugane S, Iwasaki M. Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort. BMJ, 360:k671, 2018

11. Kodaira T, Kagami Y, Shibata T, Shikama N, Nishimura Y, Ishikura S, Nakamura K, Saito Y, Matsumoto Y, Teshima T, Ito Y, Akimoto T, Nakata K, Toshiyasu T, Nakagawa K, Nagata Y, Nishimura T, Uno T, Kataoka M, Yorozu A, Hiraoka M. Results of a multi-institutional, randomized, non-inferiority, phase III trial of accelerated fractionation versus standard fractionation in radiation therapy for T1-2N0M0 glottic cancer: Japan Clinical Oncology Group Study (JCOG0701). Ann Oncol, 29:992-997, 2018

12. Taguri M, Kuchiba A. Decomposition of the population attributable fraction for two exposures. Ann Epidemiol, 28:331-334, 2018

13. Hishida T, Saji H, Watanabe SI, Asamura H, Aokage K, Mizutani T, Wakabayashi M, Shibata T, Okada M. A randomized Phase III trial of lobe-specific vs. systematic nodal dissection for clinical Stage I-II non-small cell lung cancer (JCOG1413). Jpn J Clin Oncol, 48:190-194, 2018