A new standardized incidence ratio metric for second primary cancer among cancer survivors by accounting for competing risks
Principal Investigator
Name
Summer Han
Degrees
PhD
Institution
Stanford University School of Medicine
Position Title
Associate Professor
Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
PLCO-1419
Initial CDAS Request Approval
Dec 18, 2023
Title
A new standardized incidence ratio metric for second primary cancer among cancer survivors by accounting for competing risks
Summary
There were approximately 16.9 million cancer survivors in 2019 in the U.S. This number is projected to reach 22.1 million 2030. Recent improvements in treatment and cancer early-detection programs via cancer screening have also prolonged cancer survival, increasing the number of long-term cancer survivors. These long-term cancer survivors are now at high risk of developing second primary cancers (SPC) compared with the risk of initial primary cancer (IPC) in the general population. Different from recurrent or metastatic diseases evolved from the IPC, the SPC are new malignancies among cancer survivors, comprising 13% of total incident cancers.
To quantify the disease burden of new primary cancer among cancer survivor population, the National Cancer Institute (NCI) provides a method called the multiple primary-standardized incidence ratio (MP-SIR) through MP-SIR session of SEER*Stat software, comparing the incidence of SPC in cancer survivors with the incidence of IPC in the general population (Sung et al., 2020 [JAMA]). Given that the standardized incidence ratio (SIR) is used to determine whether the age-standardized occurrence of cancer in a population of interest is high or low compared to the occurrence in a reference population, it compares the incidence rates of SPC among survivors to the incidence rates of IPC in the general population. However, in the current MP-SIR method, it is not straightforward whether the competing risk of death is adjusted (Sung et al., 2020 [JAMA]), potentially causing over-estimation of MP-SIR, especially when the IPC type is highly affected by competing risk of death. However, addressing this issue has been limited due to its requirement of a long-term followed-up data capturing the incidence of SPC among cancer survivors, and the ambiguity about a test statistic for MP-SIR in the presence of competing risk for estimating confidence intervals.
We aim to propose a new MP-SIR metric based on the ratio of two cause-specific cumulative incidence functions (or Aalen-Johansson estimators) with improved confidence interval using large prospective data covering the development of IPC and SPC, and to apply the new MP-SIR metric across different SPC and IPC types in terms of competing risk of death.
The potential impact of this paper is enormous given that we will provide a novel statistical method to estimate an unbiased corrected MP-SIR metric to update the current NCI SEER*Stat’s MP-SIR session (Sung et al., 2020 [JAMA]). Thus, we would like to comprehensively evaluate our new MP-SIR metric across different SPC and IPC types to validate our method, as well as to accurately quantify SPLC burden among cancer survivors by accounting for different competing risk of death.
To quantify the disease burden of new primary cancer among cancer survivor population, the National Cancer Institute (NCI) provides a method called the multiple primary-standardized incidence ratio (MP-SIR) through MP-SIR session of SEER*Stat software, comparing the incidence of SPC in cancer survivors with the incidence of IPC in the general population (Sung et al., 2020 [JAMA]). Given that the standardized incidence ratio (SIR) is used to determine whether the age-standardized occurrence of cancer in a population of interest is high or low compared to the occurrence in a reference population, it compares the incidence rates of SPC among survivors to the incidence rates of IPC in the general population. However, in the current MP-SIR method, it is not straightforward whether the competing risk of death is adjusted (Sung et al., 2020 [JAMA]), potentially causing over-estimation of MP-SIR, especially when the IPC type is highly affected by competing risk of death. However, addressing this issue has been limited due to its requirement of a long-term followed-up data capturing the incidence of SPC among cancer survivors, and the ambiguity about a test statistic for MP-SIR in the presence of competing risk for estimating confidence intervals.
We aim to propose a new MP-SIR metric based on the ratio of two cause-specific cumulative incidence functions (or Aalen-Johansson estimators) with improved confidence interval using large prospective data covering the development of IPC and SPC, and to apply the new MP-SIR metric across different SPC and IPC types in terms of competing risk of death.
The potential impact of this paper is enormous given that we will provide a novel statistical method to estimate an unbiased corrected MP-SIR metric to update the current NCI SEER*Stat’s MP-SIR session (Sung et al., 2020 [JAMA]). Thus, we would like to comprehensively evaluate our new MP-SIR metric across different SPC and IPC types to validate our method, as well as to accurately quantify SPLC burden among cancer survivors by accounting for different competing risk of death.
Aims
[1] To propose a new MP-SIR-CIF metric based on the ratio of two cause-specific CIFs (or Aalen-Johansson estimators)
[2] To apply the new MP-SIR-CIF across different cancer types in terms of competing risk of death, compared with the naïve MP-SIR method.
[2-1] Any multiple primary cancer among survivors of cancer type of high 5-year survival rates (i.e., low competing risk) including breast, prostate, melanoma, thyroid, and colorectal cancers
[2-2] Any multiple primary cancer among survivors of cancer types of low 5-year survival rates (i.e., high competing risk) or smoking-driven cancer types including pancreatic, glioma, liver, head and neck, lung, bladder, liver, upper GI cancers
Collaborators
• Summer Han
• Eunji Choi