When requesting the SEER Research Plus data, you must acknowledge the data limitations for the radiation therapy and chemotherapy information fields included in the data. You may review the language of the agreement below (this cannot be used to request access to the data).
The population-based Surveillance, Epidemiology, and End Results (SEER) registries collect information on radiation therapy (RT) and chemotherapy given as part of the first course of treatment. RT data are classified by the type of RT received or “no/unknown – no evidence of radiation was found in the medical records examined”. Chemotherapy data are categorized as either “yes – patient had chemotherapy” or “no/unknown – no evidence of chemotherapy was found in the medical records examined”. These data are available upon request after acknowledging the limitations associated with analyses of the data. Three main limitations affect recommended analyses using the SEER radiation therapy and data: 1) the completeness of the variables; and 2) the biases associated with unmeasured reasons for receiving or not receiving RT/chemotherapy; 3) the interpretation of sequence data variables. Below we further describe the issues and analyses that could be problematic.
Completeness of the Variables
One recent publication comparing SEER data with SEER-Medicare data reported that overall sensitivity was 80% for SEER RT data and 68% for SEER chemotherapy data. Sensitivity varied by cancer site, stage, and patient characteristics. The overall positive predictive value was high (>85%) for all treatments and cancer sites except chemotherapy for prostate cancer. This analysis used a fairly broad definition for chemotherapy use based on Medicare claims, and further sensitivity analysis is ongoing.1
Although sensitivity was moderate, specificity was high, meaning that if RT or chemotherapy was captured in SEER, it was most likely received by the patient. But if it was not captured in SEER, then we do not know whether it was not received by the patient or whether it was missed by the registry. As treatment is increasingly received outside of the hospital setting, there is a diminishing likelihood that it is captured completely. Because we cannot accurately distinguish between “no treatment” and “unknown if patients received treatment,” the variables that are released upon request are classified as “yes” or “no/unknown”.
Examples of analyses that would NOT be supported by the RT/chemotherapy data, due to the incompleteness of the variable, include:
- Estimates of population prevalence of treatment or patterns of care in the population without appropriate comment on the limitations of the data (e.g., clearly labeling both treatment categories as "yes" and "no/unknown" wherever they appear)
- Estimates of compliance with guidelines
- Comparison of treatment levels in different groups, e.g., investigating health disparities, without adequately stated limitations
- Comparison of outcomes by treatment received
Since we have high confidence that an individual received RT/chemotherapy if the variable is listed as "yes", analyses such as identifying a cohort of patients who received treatment in order to identify risk of adverse events, including risk of second cancers, would be supported by the data.
Biases Associated with Who Receives Treatment
Unlike clinical trials, many factors involved in determining the course of treatment will not be captured in the registry data. Such factors include: patient preferences, physician recommendations, comorbidities, and proximity to treatment providers. Because the data collected do not include these and other factors that are related to why a patient did or did not receive RT/chemotherapy, we do not recommend comparing outcomes conditioned on treatment or comparative effectiveness research using the SEER data without careful consideration of possible biases and appropriate adjustments, potentially using data beyond standard SEER data (e.g. SEER-Medicare linked data). For example, survival differences observed for patients who did vs. did not receive chemotherapy cannot be attributed to the efficacy or effectiveness of treatment without controlling for the factors that determined treatment receipt. Similarly, observed differences cannot be generalized to describe the benefit an individual would expect to receive from chemotherapy treatment.
Sequence Treatment Variables
Starting with the November 2019 submission of data, the Research Plus databases include two variables indicating the sequence of systemic therapy and radiation therapy with respect to surgery, “RX SUMM--SYSTEMIC/SUR SEQ” and “RX SUMM--SURG/RAD SEQ”. We recommend caution when using these variables to identify patients that could have received neoadjuvant treatment because:
- Surgery in the context of this data item may refer to any surgical procedure recorded in any surgery-related data items, such as an excisional biopsy of the primary tumor, a removal of a distant metastatic lymph node, etc.
- Although the variables report the sequence of surgery and other treatment modalities, it does not consider the timing of events. Thus, it is possible that radiation may have been given more than 6 months, or just 6 days prior to surgery and not constitute neoadjuvant.
- The systemic treatment administered before surgery might not have had neo-adjuvant intent or would not have been administered long enough to expect a relevant tumor response (i.e., endocrine therapy administered days before mastectomy).
- There may be missing information about radiation and/or systemic treatment, which may underestimate the frequency of neoadjuvant treatment.
- Surgery does not refer to most definitive surgery. For example, it might refer to the removal of regional or distant lymph nodes.
Because of the limitations listed above, we strongly caution investigators to consider the potential for misclassification bias when using the sequence treatment variables to select cases that might have received radiation therapy or systemic treatment with neoadjuvant intent.
Definitions
Neoadjuvant: Systemic therapy provided prior to a curative surgery with an intention of producing an outcome of reduction in tumor size prior to surgery.
Intraoperative radiation therapy (IORT): An intensive radiation treatment that is administered during surgery. IORT allows direct radiation to the target area while sparing normal surrounding tissue. IORT is used to treat cancers that are difficult to remove during surgery and when there is a concern that microscopic amounts of cancer may remain. IORT is often combined with conventional radiation therapy, which is usually administered before surgery. IORT allows higher effective doses of radiation to be used compared with conventional radiation therapy, as it allows doctors to temporarily move nearby organs or shield them from radiation exposure.
Reference:
- Noone AM, Lund JL, Mariotto A, Cronin K, McNeel T, Deapen D, Warren JL. Comparison of SEER Treatment Data with Medicare Claims. Med Care 2014 Mar 15. [Epub ahead of print]
I have read and understand the limitations of the SEER RT and chemotherapy data described above and will include a description of relevant limitations in any analyses published using the SEER data. I acknowledge that the SEER Program has advised me that there are substantive concerns about using these data to address certain research questions as described above. I understand that any findings from such analyses may be inaccurate or misleading.
