Abstract OT2-01-05: A randomized controlled trial comparing post-operative intensive follow-up with standard follow-up in high-risk breast cancer patients (JCOG1204: INSPIRE)
Authors: Hojo T , Masuda N , Shibata T , Mizutani T , Shien T , Kinoshita T , Iwatani T , Kanbayashi C , Kitagawa D , Tsuneizumi M , Iwata H 
Published: May 2019

Abstract
Background: The standard follow-up after surgery for breast cancer includes periodic interviews, clinical examinations, and mammography, but many institutions are conducting intensive follow-up including periodic computed tomography(CT), magnetic resonance imaging(MRI), and bone scintigraphy in the world, despite the lack of evidence to support this approach. While intensive follow-up may contribute to prolonged survival through earlier diagnosis and treatment of relapse, it has the disadvantages of high effort and costs placed on patients(pts) and healthcare workers, radiation exposure for imaging examinations, and overtreatment owing to false-positive results. Although past two randomized trials could not show significant difference in overall survival (OS), as imaging methods have remarkably improved, leading to the earlier detection of relapse, and medical therapies have remarkably improved in recent years, randomized controlled trials are needed to confirm whether intensive follow-up can really prolong survival sufficiently to offset these disadvantages in high-risk breast cancer pts.
Trial design: This study is a multi-institutional two-arm open label randomized controlled phase III trial being conducted with the participation of 42 hospitals belonging to the Breast Cancer Study Group of Japan Clinical Oncology Group. Eligible pts are randomized either to the intensive follow-up group or to the standard follow-up group; the former will undergo physical examination, bone scintigraphy, chest and abdominal CT, brain MRI/CT and frequent tumor markers, whereas the latter will undergo physical examination at the same frequency and tumor markers will be evaluated once a year. Mammography once a year is planned for both groups. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000012429.
Eligibility criteria: High-risk breast cancer pts, who are expected to have recurrence rates of over 30% within 5 years after surgery. The main inclusion criteria are as follows: four or more axillary nodal metastases in the estrogen receptor (ER) positive pts without neoadjuvant chemotherapy(NC)., axillary node metastases in ER-negative pts without NC, axillary nodal metastases in ER-positive pts with NC, histologically proven residual invasive cancer in the breast or axilla in ER-negative with NC.
Specific Aims: The primary endpoint is OS, and secondary endpoints are disease-free survival, relapse-free survival, distant metastasis–free survival, OS in intrinsic subtypes, actual number of implemented examinations, compliance with pre-specified examinations, and adverse events.
Statistical methods: The primary endpoint will require a total of 538 events to be assessed in order to obtain a statistical power of 80% with a one-sided significance level of 0.05. Thus, the planned sample size to compare the two survival curves is set at 1500 pts, assuming an accrual time of 6 years and a follow-up time of 7 years according to the Schoenfeld and Richter's method.
Present accrual and target accrual: The trial was activated in November 2013. 773 pts have been enrolled by the end of June 2018.
Contact: Principal investigator Takashi Hojo MD tahojo@east.ncc.go.jp
Citation Format: Hojo T, Masuda N, Shibata T, Mizutani T, Shien T, Kinoshita T, Iwatani T, Kanbayashi C, Kitagawa D, Tsuneizumi M, Iwata H. A randomized controlled trial comparing post-operative intensive follow-up with standard follow-up in high-risk breast cancer patients (JCOG1204: INSPIRE) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-01-05.