Abstract
Background:
In the US, there are approximately 8,260 newly diagnosed HL cases and 21,210 death due to HL annually (Siegel et al, Cancer Statistics, 2017). Over the past few decades, a significant survival improvement has been observed due to the advancement in treatment for HL including radiation therapy (RT), multi-agent chemotherapy (CT) regimens and combination of both. However, concerns have been raised due to the risk of late complications from CT and RT, such as pulmonary disease, heart disease and secondary malignancies (Master et al. Anticancer Res. 2017). We aim to investigate whether the use of different treatment modalities are associated with outcome.
Methods:
Data were extracted from the US National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) 18 program. Patients diagnosed with HL from 1985-2014 were included in this analysis. Demographic information including age, sex, race/ethnicity, annual household income, education and insurance status were also collected. HL is categorized by using International Classification of Disease for Oncology (ICD-O-3) into classical HL NOS (CHL NOS), nodular lymphocyte predominant HL (NLP), lymphocyte rich (LR), mixed cellularity (MC), lymphocyte depleted (LD), and nodular sclerosis (NS). Treatment was categorized into RT alone, CT alone, combination of RT and CT, and no RT or CT. Survival time is calculated by using the date of diagnosis and one of the following dates: date of death, date last known to be alive or date of the study cutoff (December 31, 2014). Chi-square test and Cox regression model was adopted by using SAS 9.4.
Exclusion criteria:
1) Exclude those with unknown or unspecified race.
2) Exclude those patients whose survival was <6 months because time of radiotherapy/chemotherapy was not known to the time of diagnosis.
3) Exclude patients with any other type of cancer prior to the diagnosis of HL.
4) Exclude patients with second or later primaries, and who were not actively followed.
Results:
A total 39, 160 patients were included in this analysis. Table 1 shows the Cox regression analysis including adjusted and unadjusted hazard ratios (HRs). Receiving combination modality (both RT and CT) was associated with 45% decreased HR, 95% CI (0.42, 0.70) compared to those who had neither RT or CT. Black race and male patients had a worse survival outcome compared to white race and females, respectively (HR=1.40, HR=1.17). Age was a statistically significant factor associated with increased mortality. Compared to CLH NOS, histology of NS, LC, and NLP were associated with decreased overall mortality (HR=0.84, HR=0.62, HR=0.69, p=0.02) respectively. Stage IV and Stage III were 1.92 and 1.69 times likely to die compared to stage I patients, p<0.01. Those with B symptoms had 48% increased mortality compared to those without, p<0.01. Insured patient had 29% decreased risk of mortality compared to those without insurance, 95% CI (0.54, 0.91). However any Medicaid patients were associated with 36% increased risk of death, 95% CI (1.04, 1.79). Annual household income and education level did not appear to be related to death from HL.
Figure 1 illustrates the change of treatment regimen from 1985-2014. An obvious rising was observed in CT from 34.76% to 58.30% from 1985-2014. The percentage among patients who received neither CT nor RT has been stable over the past 30 years. From 1985-2004, we observed that combination modality had been increasing from 16.20% to 37.48%; and after year of 2004, it started to slowly decrease.
Table 2 presents the HR of death of patient with HL receiving different treatment modality by year of diagnosis. The HRs were not statistically significant associated with the use of combination modality nor single modality (CT or RT only) from 1985-1999. Among year of diagnosis group 2000-2004, 2005-2009, and 2010-2014, patients with combination modality were associated with 22%, 43% and 44% decreased mortality compared to those who did not have any therapy, respectively (p<0.01).
Conclusion:
Our results showed that among all HL patients diagnosed between 1985 and 2014, combination modality was associated with decreased mortality. Similar mortality benefit was not observed among patients receiving single modality. Though the use of combination modality has been decreasing over the past 2 decades, a significant lasting survival benefit compared to single modality was still observed.
No relevant conflicts of interest to declare.
