To our knowledge, our study is the first to examine the contribution of risk factors for long-term disease outcomes among B-NHL survivors using PAF estimates within a large-scale population-based study. Cancer treatment contributed greatly to chronic disease risks such as heart disease, COPD, and chronic kidney disease. Being overweight or obese at baseline contributed more to congestive heart failure and pneumonia than cancer treatment, while smoking at baseline was not a major contributor to the aging-related disease risks in this cohort. Having baseline comorbidities was consistently a large component of attributable risk for these diseases.
Cancer treatment was a contributor to heart disease, COPD, and chronic kidney disease among B-NHL survivors in our study. Specifically, 10.5% of risks relating to heart disease and COPD were attributed to chemotherapy, while 14.9% of chronic kidney disease risk was attributed to chemotherapy. A strong association between chemotherapeutic agents and renal complications may be expected, considering the mechanisms involved in metabolizing and excreting toxic agents from the body. In addition to an established association between chemotherapy and cardiovascular disease risks, the use of chemotherapy can also result in acute or chronic lung complications, depending on dose rate, duration of treatment, preexisting lung disease, and concurrent use of steroids . Few studies evaluated associations between specific NHL treatment regimens and aging-related disease risks. Our current finding supports the association between cancer treatment and chronic disease risks for B-NHL survivors in a population-based cohort.
In terms of lifestyle factors, smoking was not a large contributor to these aging-related disease risks in our cohort, possibly due to the low prevalence of smokers in Utah. Nevertheless, smoking contributed to varying levels of risk for heart disease, COPD, and acute renal failure. Being overweight or obese at baseline contributed more to congestive heart failure (18.4%) and pneumonia (7.9%) than cancer treatment in our cohort. Given that obesity is a risk factor of several aging-related diseases in the general population , the health-related implications are similar for B-NHL survivors, as a population-based study of 1,286 NHL survivors reported that obesity prior to cancer diagnosis was associated with poorer survival . Few studies evaluated associations between lifestyle factors and aging-related disease risks, however, as prior studies focused more on survival outcomes and not on clinical implications after treatment.
Given the correlation between high CCI score and worse survival outcomes in prior studies involving DLBCL patients [38–40], we found that having preexisting comorbidities at cancer diagnosis was a consistent contributor to cardiovascular, pulmonary, and renal disease risks in our B-NHL survivor cohort. This suggests that the management of comorbidities may be integral in reducing the risks of aging-related diseases among individuals once diagnosed with B-NHL. This also warrants further research in investigating the risks pertaining to the potential interplay of concomitant prescriptions for preexisting comorbidities and cancer treatment regimens. Although our results may potentially underestimate the impact of preexisting comorbidities, considering that we excluded prevalence of the outcome of interest to investigate incidence of disease, it allows us to identify the extent to which multiple disease risks are associated with each risk factor and avoids double-counting of comorbidities.
The strengths of this study include the utilization of PAF, which was used to estimate the role of risk factors on disease incidence among B-NHL survivors. Another strength is the large sample size, which provided sufficient power to examine several outcomes for the B-NHL survivors. In addition, our follow-up period was ≥ 5 years after cancer diagnosis allows for a focus on long term health outcomes. This approach also helps to minimize the impact of surveillance bias in our study. The data used in the study incorporate medical records from the state’s two largest healthcare providers as well as statewide ambulatory surgery and inpatient data, which provide comprehensive medical record data for a large number of individuals. In contrast to cancer survivor studies that rely on self-reports of the disease, which are susceptible to survival bias, our study is less susceptible to survival bias because we used long-term health records as the source for disease diagnoses.
This study also has a number of limitations. The attributable risks of lifestyle factors observed in this cohort such as smoking and obesity at baseline may not be generalizable to other populations because of the lower prevalence of exposure in Utah compared to other states. However, other risk factors such as cancer treatment and presence of preexisting comorbidities may be important to other B-NHL cohorts. While this study utilized comprehensive electronic medical record data from the two largest statewide healthcare systems, along with statewide ambulatory surgery and inpatient data, there is the possibility that study participants could have been diagnosed with disease outcomes in hospitals and clinics not covered by data sources. However, our data source also include statewide records; thus, the majority of the population was covered.
Another limitation of this study is that some subjects had missing baseline BMI data, which were addressed by imputation of BMI values. It was required that baseline BMI recorded at least one year prior to the NHL survivor’s cancer diagnosis to minimize temporal issues. We assured that inferences for our results did not change whether we used only those with BMI included or those whose BMI was imputed. Smoking was identified using ICD codes, which may be a limitation because only heavy smokers who used cessation services may be captured. However, the proportion of smokers identified was fairly similar to the expected Utah population smoking prevalence. Treatment data were limited to broad categories and did not include type of drug, dosage, specific chemotherapy cycles, and duration of treatment. However, the treatment data that were available provided evidence that risks for aging-related disease outcomes vary by treatment type and by age at diagnosis.
In conclusion, we observed that cancer treatment contributed greatly to heart disease, COPD, and chronic kidney disease. Being overweight or obese at baseline contributed more to congestive heart failure and pneumonia than cancer treatment, whereas smoking was not a major contributor to these aging-related disease risks in this cohort. Preexisting comorbidities significantly contributed to all these disease risks. This suggests the significant impact of baseline comorbidities on long-term, aging-related disease risks and demonstrates a need for lifestyle interventions aimed at mitigating these risk factors to achieve better outcomes for B-NHL patients and survivors after cancer diagnosis and treatment.