Lead Investigator: Youssef Zeidan, American University of Beirut Medical Center
Title of Proposal Research: Evaluation of Radiotherapy Boost in Women with HER-2 positive Breast Cancer
Vivli Data Request: 5930
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Previous randomized controlled trials have proven similar local recurrence and survival rates in patients with early breast cancer treated with either breast conservative therapy (including Whole Breast IrradiationI) or mastectomy (i.e: the removal of one or both breasts) (Fisher et al., 2002; Litiere et al., 2012). Patients treated with breast conserving surgery often receive a radiation dose boost to the tumor bed in order to prevent tumor recurrence in its original site, since local recurrence mostly happens at the site of the primary tumor harbouring remaining microscopic tumor cells. Previous studies show improvement in local control for patients treated with radiation therapy boost as compared to those with no boost (Bartelink et al., 2007; Bartelink et al., 2015). As such, the National Comprehensive Cancer Network (NCCN) and European guidelines recommend using a radiation therapy boost in patients with high risk of cancer recurrence (Gradishar et al., 2018; Senkus et al., 2015).
However, it remains unclear whether these findings are applicable to HER-2 positive patients in the current era (with advances in chemotherapy, immunotherapy and surgical techniques). HER-2 is the Human Epidermal growth factor, a human protein that can affect the growth of breast cancer cells.
In this context, radiation oncologists need more information about the effect of radiation therapy in this population, to carefully balance the local control benefit of RT boost with its potential side effects.
To date, there are no large studies evaluating the benefit of RT boost in patients with HER-2 positive breast cancer.
We aim at evaluating the effect of RT boost on loco-regional recurrence, any recurrence, overall survival, disease-free survival and distant metastasis-free survival in patients with HER-2 positive breast cancer.
Statistical Analysis Plan:
Statistical Strategy: Performed by Dr. Elie Akl (MD, PhD).
1. Power Calculation
The planned study is a secondary data analysis, which entails a predetermined sample size.
Based on the published numbers in the primary study on this cohort the estimated numbers of participants receiving radiation therapy is 3824. No information regarding radiation doses, sites or boost was published. Therefore, considering a random 1:1 distribution between patients with RT boost or no-boost, we can assume that around 1912 patients received RT boost and 1912 did not. We estimated the LRR proportion in the no-boost group to be of 15%. With an expected 5% reduction in the RT boost group (LRR proportion = 10%) and an alpha of 5%, the power calculation yielded more than 80% power to the study. Larger reductions will yield higher power. For the subgroup analyses (HER-2 positive, breast-conserving surgery, on trastuzumab) with the estimated numbers of 714 participants in the no-boost group and 714 in the RT boost group, an LRR proportion of 15% among the no-boost, a reduction of 5% in the exposed (LRR proportion = 10%) and an alpha of 5%, the power calculation also yielded more than 80% power.
2. Statistical Analysis
Univariate analyses will be conducted to describe the cohort. Categorical variables will be presented as frequencies and percent, and continuous variables as means and standard deviations (SD).
Bivariate analyses will be used to compare characteristics as well as outcomes in frequencies and percent between exposed Boost (+) and unexposed Boost (-) groups, using the independent t-test (continuous variables) or the chi-square test (categorical variables).
Multivariate regression analyses will be used to evaluate the association between radiation therapy boost and LRR while adjusting for potentially confounding variables. Moreover, results will be presented as odds ratios (OR) with their associated 95% confidence intervals (95% CI). Factors considered for inclusion in the multivariate analyses will depend on the statistical significance of the bivariate analyses, as well as the clinical significance of different characteristics.
Moreover, Kaplan Meier curves will be constructed to describe the time to recurrence in both
radiation groups. Furthermore, to adjust for the confounding variables, while considering time to recurrence as an outcome, Cox proportional hazards regression modeling will be used to estimate the Hazard Ratios (HR) with 95% CI.
Statistical significance will be set at an alpha of 5% for a two-sided p-value. Analyses will be conducted using STATA.
Requested Studies:
A Randomized Three-Arm, Multicenter Comparison of 1 Year and 2 Years of Herceptin Versus No Herceptin in Women With HER2-Positive Primary Breast Cancer Who Have Completed Adjuvant Chemotherapy
Sponsor: Roche
Study ID: NCT00045032
Sponsor ID: BO16348
Public Disclosures:
Abi Jaoude J, Kayali M, de Azambuja E, Makki M, Tamim H, Tfayli A, El Saghir N, Geara F, Piccart M, Poortmans P, Zeidan YH. De-intensifying radiation therapy in HER-2 positive breast cancer: to boost or not to boost?. International Journal of Radiation Oncology-Biology-Physics. 2020 Nov 15;108(4):1040-6. doi: 10.1016/j.ijrobp.2020.06.078