Results
Seventy-five children had Chichewa Pediatric PROMIS-25 surveys administered at diagnosis prior to initiation of chemotherapy, 35 (47%) during active treatment, and 24 (32%) at follow-up (Figure 1, Table 2). Median age was 10 years (Interquartile range (IQR) 8-12) and 51 (68%) were male. Sixty-one (81%) patients were diagnosed with Burkitt lymphoma and 14 (19%) with Hodgkin lymphoma. Most patients presented with stage III/IV disease (n=48, 66%), poor LPS of ≤ 70 (n=50, 70%), and moderate-to-severe acute malnutrition (n=54, 72%). Median lactate dehydrogenase (LDH) was 555 IU/L (IQR 378-895), with 30 (40%) > 2x LDH upper limit of normal for their age (Table 1).
Of the 75 surveys at diagnosis (Figure 1), patients reported poor HRQoL, with low Mobility and high Anxiety, Depressive Symptoms, Fatigue, and Pain Interference mean domain scores (Table 1, Table 2, Figure 3). Patients also presented with high pain intensity, with 32 (43%) reporting the maximum Pain Intensity of 10 on a scale of 0 to 10 at diagnosis (Table 1, Table 2). Peer Relationships were strong at diagnosis (Table 1, Table 2).
Of the 35 surveys during active treatment (Figure 1), the median time of survey administration was 113 days (IQR 61-210) after diagnosis (Table 2). Mean HRQoL domain scores significantly improved in all domains (p<0.001) (Table 2), and differences between diagnosis and active treatment domain scores exceeded accepted MID thresholds (Table 2, Figure 3). Pain Intensity decreased from a median of 9 (IQR 4-10) at diagnosis to a median of 1 (IQR 1-1) during active treatment (Table 2).
Of the 24 follow-up surveys (Figure 1), two patients (14%) had relapsed lymphoma and were receiving palliative care during follow-up. Median follow-up time was 720 days (IQR 486-1014) since diagnosis (Table 2). All mean HRQoL domains showed continued improvement from diagnosis to active treatment to follow-up timepoints that surpassed the MID (Table 2, Figure 3). Notably, median Pain Intensity score was 0 (IQR 0-0) at follow-up (Table 2).
Of 134 total Pediatric PROMIS-25 surveys administered across the 3 time points, 100/134 (75%) were to patients and 34/134 (25%) were to parents. Of the 34 surveys completed by parent proxy, 14/34 (41%) were for children younger than 8 years, 20/34 (59%) for older children who were too ill to complete the survey on their own. Improvements in HRQoL remained when proxy reports were removed from the analysis (Supplemental Table 1). Almost all surveys (125/134, 93%) were conducted in person, aside from 9/134 (7%) follow-up surveys administered over the phone.
Of the 75 patients enrolled at diagnosis, 37 (49%) of patients died—34/37 (92%) Burkitt, 3/37 (8%) Hodgkin—and 8 (11%) were LTFU (Figure 1). Kaplan-Meier overall survival was 47% (95% CI [37-59%]) at 1-year and 38% (95% CI [28-51%]) at 2-years. Some patient characteristics at diagnosis significantly differed when stratified based on survival outcome (alive vs. LTFU/died) including: diagnosis (Burkitt lymphoma versus Hodgkin lymphoma), Lansky performance score ≤ 70, median LDH, and mean Mobility domain scores (Table 1). Median Pain Intensity scores at diagnosis were also poorer among patients who died/LTFU compared to those who survived (10.0, IQR 6.0-10.0 vs. 8.5, IQR 3.3-10.0; p=0.073) (Table 1).
On exploratory analysis, patients with poor LPS ≤ 70 at diagnosis had an increased mortality risk (Hazard ratio (HR) = 5.20, 95% CI [1.35-6.91], p= 0.007) and worse overall survival compared to those with LPS > 70 (35%, 95% CI [24-51%] vs. 76%, 95% CI [60-97%], p=0.0049) (Figure 2A). Likewise, patients with the highest Pain Intensity score of 10 at diagnosis also had increased mortality risk (HR=1.75, 95% CI [0.97-3.15], p=0.06) and worse survival compared to those with a Pain Intensity score < 10 (36%, 95% CI [23-58%] vs. 56%, 95% CI [43-73%], p=0.058) (Figure 2B). A poor Mobility domain score < 40 at diagnosis was associated with increased mortality risk (HR=2.05, 95% CI [0.73-5.73], p=0.17) and worse survival compared to those with Mobility scores ≥ 40 (44%, 95% CI [33-58%] vs. 60%, 95% CI [36-100%], p=0.16) (Supplemental Figure 1). Although clinically meaningful, this was not statistically significant.
Domain score trajectories were plotted for the 17 patients who completed PROMIS surveys at all three time points (diagnosis, active treatment, and follow-up) to visualize individual changes in HRQoL throughout care (Figure 4). This sub-analysis allows interpretation of longitudinal HRQoL trends in our cohort without potential effects of survivor bias. Overall, HRQoL improvements were observed for most patients (n=15, 88%), with the exception of two patients (12%) who had relapsed disease and worse HRQoL at follow-up.