The present study involved 52 patients with BM, recruited on presentation to NSIA-LUTH and followed-up after receiving WBRT treatment. Presented in Table 1 is the summary of the socio-demographic and clinical data collected from the recruited patients. On average, the patients were ~ 53 years old and predominantly female (82.7%). The majority (90.4%) of the patients were originally from or based in the urban areas, married (80.8%), and had post-secondary education (82.7%). Breast, lung, and head and neck were the most reported primary tumor types, making up 65.4%, 13.5%, and 5.3% of the cases, respectively. Although, 27% of the cohort presented with a Karnofsky performance status (KPS) above 60, a 46.1% largely presented with a KPS below 50. Additionally, more than at least half (59.6%) of the patients presented with co-morbidities, and 92.3% were already on steroids. A 36.5% had received radiotherapy to other sites, meanwhile 63.5% had no prior radiotherapy treatments.
Table 1
Patient socio-demographics and clinical data (n = 52, enrolled patients)
Variable | Total |
Age (mean ± SD) | 53 ± 12.3 |
Sex | |
Male | 9 (17.3%) |
Female | 43 (82.7%) |
Place of residence | |
Urban | 47 (90.4%) |
Rural | 5 (9.6%) |
Level of education | |
Secondary | 9 (17.3%) |
Post-secondary | 43 (82.7%) |
Marital status | |
Single | 5 (9.6%) |
Married | 42 (80.8%) |
Divorced | 1 (1.9%) |
Widow | 4 (7.7%) |
Occupation | |
Employed | 31 (59.6%) |
Unemployed | 15 (28.8%) |
Self-employed | 5 (9.6%) |
Retired | 1 (1.9%) |
Primary tumor | |
Anaplastic thyroid | 1 (1.9%) |
Breast | 34 (65.4) |
Carcinoid tumor | 1 (1.9%) |
Cup | 1 (1.9%) |
GI | 1 (1.9%) |
Head and neck | 3 (5.8%) |
LT thigh | 1 (1.9%) |
Lungs | 7 (13.5%) |
Parotid | 1 (1.9%) |
Prostate | 1 (1.9%) |
Renal | 1(1.9%) |
ECOG performance status | |
KPS 90–100 | 7 (13.5%) |
KPS 70–80 | 7 (13.5%) |
KPS 50–60 | 14 (26.9%) |
KPS 30–40 | 13 (25.0%) |
KPS 10–20 | 11 (21.1%) |
KPS 0 | - |
Prior radiotherapy | |
Yes | 19 (36.5%) |
No | 33 (63.5%) |
Co-morbidities | |
Present | 31 (59.6%) |
Absent | 21 (40.4%) |
Medication used | |
Steroids | 48 (92.3%) |
Analgesic | 2 (3.8%) |
Analgesic/steroids | 2 (3.8%) |
GI = Gastrointestinal; LT thigh = left thigh sarcoma; KPS = Karnofsky performance status |
Insert Table 1here
The descriptive analysis output for both EORTC QLQ-C15-PAL and EORTC QLQ-BN20 subscales are presented in Table 2 and Table 3, respectively. Accordingly, it was revealed that the subscales were not normally distributed (sig. p < 0.05), however, the Shapiro-Wilk statistic (W) closer to 1 suggested a good fit. A goodness-of-fit test ascertained the assumption, yielding non-significant Chi square Pearson (p = 0.325) and Deviance (p = 1.000) residuals, indicating that the model fit the data well.
Table 2
Descriptive statistics for the EORTC QLQ-C15-PAL
| Period | No. patients (N) | Mean (SD) | Lower bound | Upper bound | Normality (Shapiro-Wilk, W) |
Physical functioning | Baseline | 52 | 2.5 (1.1) | 2.2 | 2.8 | 0.87 |
| Day 7 | 49 | 2.2 (1.0) | 1.9 | 2.5 | 0.89 |
| Day 30 | 46 | 2.1 (1.0) | 1.8 | 2.4 | 0.88 |
| Day 90 | 28 | 1.8 (0.8) | 1.4 | 2.1 | 0.85 |
| Day 180 | 20 | 1.8 (0.9) | 1.4 | 2.2 | 0.86 |
Emotional functioning | Baseline | 52 | 1.6 (0.8) | 1.4 | 1.9 | 0.74 |
| Day 7 | 49 | 1.4 (0.7) | 1.2 | 1.6 | 0.71 |
| Day 30 | 46 | 1.6 (1.7) | 1.1 | 2.1 | 0.39 |
| Day 90 | 28 | 1.2 (0.4) | 1.1 | 1.4 | 0.56 |
| Day 180 | 20 | 1.2 (0.3) | 1.0 | 1.3 | 0.58 |
Fatigue | Baseline | 52 | 2.1 (0.8) | 1.9 | 2.3 | 0.90 |
| Day 7 | 49 | 1.9 (0.8) | 1.7 | 2.1 | 0.89 |
| Day 30 | 46 | 1.7 (0.7) | 1.5 | 2.0 | 0.82 |
| Day 90 | 28 | 1.9 (0.6) | 1.7 | 2.1 | 0.91 |
| Day 180 | 20 | 1.8 (0.4) | 1.6 | 2.0 | 0.87 |
Pain | Baseline | 52 | 2.2 (0.9) | 2.0 | 2.5 | 0.92 |
| Day 7 | 49 | 2.0 (0.8) | 1.8 | 2.2 | 0.92 |
| Day 30 | 46 | 1.9 (0.7) | 1.6 | 2.1 | 0.88 |
| Day 90 | 28 | 1.8 (0.7) | 1.5 | 2.1 | 0.88 |
| Day 180 | 20 | 1.9 (0.6) | 1.6 | 2.2 | 0.90 |
Dyspnea | Baseline | 52 | 1.3 (0.6) | 1.2 | 1.5 | 0.57 |
| Day 7 | 49 | 1.2 (0.4) | 1.1 | 1.3 | 0.45 |
| Day 30 | 46 | 1.1 (0.4) | 1.0 | 1.3 | 0.41 |
| Day 90 | 28 | 1.2 (0.4) | 1.0 | 1.3 | 0.47 |
| Day 180 | 20 | 1.2 (0.5) | 1.0 | 1.4 | 0.45 |
Insomnia | Baseline | 52 | 2.1 (0.9) | 1.8 | 2.4 | 0.86 |
| Day 7 | 49 | 1.9 (0.8) | 1.6 | 2.1 | 0.82 |
| Day 30 | 46 | 1.8 (0.8) | 1.6 | 2.1 | 0.81 |
| Day 90 | 28 | 1.6 (0.6) | 1.4 | 1.9 | 0.76 |
| Day 180 | 20 | 2.1 (0.5) | 1.8 | 2.3 | 0.69 |
Appetite loss | Baseline | 52 | 1.9 (0.9) | 1.6 | 2.1 | 0.81 |
| Day 7 | 49 | 1.5 (0.6) | 1.3 | 1.7 | 0.72 |
| Day 30 | 46 | 1.5 (0.8) | 1.3 | 1.7 | 0.68 |
| Day 90 | 28 | 1.5 (0.6) | 1.3 | 1.8 | 0.73 |
| Day 180 | 20 | 1.7 (0.7) | 1.4 | 2.0 | 0.78 |
Nausea | Baseline | 52 | 1.4 (0.7) | 1.2 | 1.6 | 0.60 |
| Day 7 | 49 | 1.3 (0.6) | 1.1 | 1.4 | 0.49 |
| Day 30 | 46 | 1.2 (0.5) | 1.1 | 1.4 | 0.59 |
| Day 90 | 28 | 1.1 (0.3) | 1.0 | 1.2 | 0.36 |
| Day 180 | 20 | 1.3 (0.5) | 1.1 | 1.5 | 0.58 |
Constipation | Baseline | 52 | 1.6 (0.8) | 1.3 | 1.8 | 0.67 |
| Day 7 | 49 | 1.5 (0.9) | 1.3 | 1.8 | 0.67 |
| Day 30 | 46 | 1.2 (0.6) | 1.1 | 1.4 | 0.46 |
| Day 90 | 28 | 1.1 (0.5) | 0.9 | 1.3 | 0.29 |
| Day 180 | 20 | 1.1 (0.2) | 1.0 | 1.2 | 0.24 |
W = Shapiro-Wilk test statistic |
Table 3
Descriptive statistics for the EORTC QLQ-BN20
| Period | No. patients (N) | Mean (SD) | Lower bound | Upper bound | Normality (Shapiro-Wilk, W) |
Future uncertainty | Baseline | 52 | 1.8 (0.7) | 1.6 | 2.1 | 0.87 |
| Day 7 | 49 | 1.7 (0.6) | 1.5 | 1.8 | 0.86 |
| Day 30 | 46 | 1.5 (0.6) | 1.4 | 1.7 | 0.81 |
| Day 90 | 28 | 1.5 (0.7) | 1.3 | 1.8 | 0.79 |
| Day 180 | 20 | 1.7 (0.6) | 1.4 | 2.0 | 0.90 |
Visual disorder | Baseline | 52 | 1.6 (0.7) | 1.4 | 1.8 | 0.79 |
| Day 7 | 49 | 1.5 (0.5) | 1.3 | 1.6 | 0.82 |
| Day 30 | 46 | 1.5 (0.6) | 1.3 | 1.7 | 0.79 |
| Day 90 | 28 | 1.3 (0.4) | 1.1 | 1.5 | 0.72 |
| Day 180 | 20 | 1.4 (0.5) | 1.1 | 1.6 | 0.76 |
Motor dysfunction | Baseline | 52 | 1.9 (0.8) | 1.7 | 2.2 | 0.89 |
| Day 7 | 49 | 1.8 (0.7) | 1.6 | 2.1 | 0.92 |
| Day 30 | 46 | 1.8 (0.7) | 1.6 | 2.0 | 0.91 |
| Day 90 | 28 | 1.5 (0.4) | 1.4 | 1.7 | 0.80 |
| Day 180 | 20 | 1.6 (0.5) | 1.3 | 1.8 | 0.90 |
Communication deficit | Baseline | 52 | 1.5 (0.8) | 1.3 | 1.7 | 0.68 |
| Day 7 | 49 | 1.3 (0.5) | 1.1 | 1.5 | 0.63 |
| Day 30 | 46 | 1.3 (0.6) | 1.1 | 1.4 | 0.52 |
| Day 90 | 28 | 1.2 (0.4) | 1.0 | 1.3 | 0.51 |
| Day 180 | 20 | 1.1 (0.2) | 1.0 | 1.1 | 0.45 |
Headache | Baseline | 52 | 2.4 (1.1) | 2.5 | 2.8 | 0.85 |
| Day 7 | 49 | 1.7 (0.8) | 1.4 | 1.9 | 0.77 |
| Day 30 | 46 | 1.4 (0.6) | 1.2 | 1.5 | 0.64 |
| Day 90 | 28 | 1.2 (0.4) | 1.0 | 1.3 | 0.47 |
| Day 180 | 20 | 1.4 (0.6) | 1.1 | 1.6 | 0.63 |
Seizures | Baseline | 52 | 1.4 (0.7) | 1.2 | 1.6 | 0.58 |
| Day 7 | 49 | 1.2 (0.5) | 1.1 | 1.4 | 0.52 |
| Day 30 | 46 | 1.3 (0.7) | 1.5 | 1.5 | 0.53 |
| Day 90 | 28 | 1.1 (0.3) | 1.0 | 1.2 | 0.29 |
| Day 180 | 20 | 1.1 (0.3) | 1.0 | 1.2 | 0.35 |
Drowsiness | Baseline | 52 | 1.6 (0.8) | 1.3 | 1.8 | 0.70 |
| Day 7 | 49 | 1.5 (0.6) | 1.3 | 1.6 | 0.69 |
| Day 30 | 46 | 1.4 (0.7) | 1.1 | 1.6 | 0.58 |
| Day 90 | 28 | 1.2 (0.5) | 1.0 | 1.4 | 0.54 |
| Day 180 | 20 | 1.2 (0.4) | 1.0 | 1.3 | 0.43 |
Hair loss | Baseline | 52 | 1.1 (0.4) | 1.0 | 1.2 | 0.34 |
| Day 7 | 49 | 1.2 (0.6) | 1.0 | 1.3 | 0.34 |
| Day 30 | 46 | 1.2 (0.5) | 1.0 | 1.3 | 0.36 |
| Day 90 | 28 | 1.1 (0.3) | 1.0 | 1.2 | 0.29 |
| Day 180 | 20 | 1.0 (0.0) | 1.0 | 1.0 | - |
Itchy skin | Baseline | 52 | 1.1 (0.3) | 1.0 | 1.2 | 0.40 |
| Day 7 | 49 | 1.1 (0.4) | 1.0 | 1.3 | 0.31 |
| Day 30 | 46 | 1.1 (0.4) | 1.0 | 1.2 | 0.32 |
| Day 90 | 28 | 1.0 (0.2) | 1.0 | 1.1 | 0.19 |
| Day 180 | 20 | 1.1 (0.2) | 1.0 | 1.2 | 0.24 |
Weakness of both legs | Baseline | 52 | 1.9 (0.9) | 1.6 | 2.1 | 0.78 |
| Day 7 | 49 | 1.8 (1.0) | 1.6 | 2.1 | 0.78 |
| Day 30 | 46 | 1.7 (0.9) | 1.5 | 2.0 | 0.76 |
| Day 90 | 28 | 1.3 (0.5) | 1.1 | 1.5 | 0.59 |
| Day 180 | 20 | 1.3 (0.4) | 1.0 | 1.5 | 0.54 |
Bladder control | Baseline | 52 | 1.8 (0.9) | 1.6 | 2.1 | 0.78 |
| Day 7 | 49 | 0.6 (0.8) | 1.4 | 1.8 | 0.71 |
| Day 30 | 46 | 1.4 (0.8) | 1.2 | 1.7 | 0.63 |
| Day 90 | 28 | 1.3 (0.5) | 1.1 | 1.5 | 0.58 |
| Day 180 | 20 | 1.3 (0.6) | 1.0 | 1.5 | 0.52 |
W = Shapiro-Wilk test statistic |
Insert Table 2here
Insert Table 3here
Presented in Table 4 and Table 5 are the results of the multi-trait scaling analyses for EORTC QLQ-C15-PAL and EORTC QLQ-BN20, respectively. A Spearman’s correlation test showed that there was a significant correlation (p < 0.01) between all items in the EORTC QLQ-C15-PAL, meanwhile in the EORTC QLQ-BN20, there was a significant correlation (p < 0.01) between future uncertainty, motor dysfunction, and communication deficit, as well as between visual disorder and communication deficit (p < 0.05).
Table 4
EORTC QLQ-C15-PAL multi-trait scaling correlation
| | PF | EF | FA | PA |
Physical functioning (PF) | ρ | 1.000 | 0.367** | 0.628** | 0.581** |
| Sig. | - | 0.008 | < 0.001 | < 0.001 |
Emotional functioning (EF) | ρ | 0.367** | 1.000 | 0.606** | 0.468** |
| Sig. | 0.008 | - | < 0.001 | < 0.001 |
Fatigue (FA) | ρ | 0.628** | 0.606** | 1.000 | 0.554** |
| Sig. | < 0.001 | < 0.001 | - | < 0.001 |
Pain (PA) | ρ | 0.581** | 0.468** | 0.554** | 1.000 |
| Sig. | < 0.001 | < 0.001 | < 0.001 | - |
ρ = Spearman’s rank correlation coefficient; sig. = statistical significance (**correlation is significant at the 0.01 level, two-tailed) |
Table 5
EORTC QLQ-BN20 multi-trait scaling correlation
| | FU | VD | MD | CD |
Future uncertainty (FU) | ρ | 1.000 | 0.241 | 0.406** | 0.422** |
| Sig. | - | 0.089 | 0.003 | 0.002 |
Visual disorder (VD) | ρ | 0.241 | 1.000 | 0.190 | 0.310* |
| Sig. | 0.086 | - | 0.17 | 0.026 |
Motor dysfunction (MD) | ρ | 0.406** | 0.190 | 1.000 | 0.327* |
| Sig. | 0.003 | 0.178 | - | 0.018 |
Communication deficit (CD) | ρ | 0.422** | 0.310* | 0.327* | 1.000 |
| Sig. | 0.002 | 0.026 | 0.018 | - |
ρ = Spearman’s rank correlation coefficient; sig. = statistical significance (**correlation is significant at the 0.01 level, *correlation is significant at the 0.05 level, two-tailed) |
Insert Table 4here
Insert Table 5here
The transformed functional and symptom scores from the EORTC QLQ-C15-PAL are depicted in Fig. 1. An increase in functional (i.e., physical and emotional functioning) scores was recorded over time, from baseline till day 180 (end of study), indicating improvement in functioning following WBRT (Fig. 1a). However, physical functioning started to decline after 90 days. Nonetheless, the recorded scores for both physical functioning and emotional functioning at the end of the study were significantly higher (p < 0.001; p < 0.05) than the recorded scores at baseline. A decline in scores was recorded for symptoms, which indicated alleviation overtime (Fig. 1b). However, after 90 days, the scores started to increase (as seen on day 180), indicating the worsening of the symptoms. The raw and transformed scores from EORTC QLQ-C15-PAL and EORTC QLQ-BN20, are provided in Additional file 3.
Insert Fig. 1 here
Figure 1. A representation of (a) physical and emotional functioning scores with corresponding (b) symptom scores, as reported by the patients in an EORTC QLQ-C15-PAL overtime. The self-assessed scores indicated improved functionality (higher scores) and symptom alleviation (lower scores) following WBRT treatment. (***depicts p < 0.001, # depicts p < 0.05, compared to baseline).
Shown in Fig. 2 are the transformed self-assessed functional (i.e., future uncertainty, visual disorders, motor dysfunction, and communication deficit) scores (Fig. 2a), and the symptom scores (Fig. 2b) for EORTC QLQ-BN20. As observed in the EORTC QLQ-C15-PAL responses, a similar trend in functionality was observed in EORTC QLQ-BN20, with increasing functionality scores over time (until day 90). Meanwhile a continuous decline in symptom scores (corresponding to alleviation) over time until end of study (day 180) was reported, with the exception of headache, for which the score increased on day 180.
Insert Fig. 2 here
Figure 2. Self-assessed (a) functionality scores and (b) symptom scores, as reported by the patients in an EORTC QLQ-BN20 overtime. Improved functionality (higher scores) and symptom alleviation (lower scores) was reported by the patients following WBRT treatment. (* depicts p < 0.05; **depicts p < 0.01, compared to baseline).
Depicted in Fig. 3 is the QoL status following WBRT treatment. Patients reported a gradual improvement in the QoL, with the highest positive responses recorded on day 90 post WBRT. Similarly to the responses recorded in EORTC QLQ-C15-PAL, patients also reported a decline in the QoL after 90 days, which corresponds to the reported decline in physical and emotional functioning, as well as symptom aggravation after 90 days.
Insert Fig. 3 here
Figure 3. QoL measurement in patients presenting with BM, following treatment with WBRT. QoL gradually increased until day 90, and started declining at day 180 (end of study).
The Kaplan-Meier curves of the prognostic factors known to influence patient survival in palliative setting, and possibly affect the clinical benefits of WBRT treatment (1, 5, 13), are presented in Fig. 4a, b, c, d. Also presented in Fig. 4e is the overall survival curve. The KPS score was found to be the only factor that significantly affected patient survival, with patients presenting with a KPS < 50 demonstrating a significantly lower (p = 0.0112) survival percentage than patients with a KPS > 50. Although patients that presented with co-morbidities exhibited a comparatively lower survival percentage than patients without co-morbidities, the difference was not statistically significant. Likewise, the comparison based on the type of primary tumor as well as the history of prior RT did not show any statistical significance in patient survival. Out of 52 patients recruited for the study, 20 survived till end of study (180 days), and the % survival overtime was; day 7 = 94.2%, day 30 = 88.5%, day 90 = 53.8%, and day 180 = 38.5%. The median overall survival was found to be 180 days (~ 6 months).
Insert Fig. 4 here
Figure 4. Kaplan-Meier survival curves for predicted prognostic factors; (a) ECOG performance status, (b) co-morbidities, (c) prior RT, and (d) type of primary tumor, as well as (e) overall survival. Patients with a KPS < 50 exhibited significantly lower survival opportunities compared to their counterparts with a KPS > 50. A 38.5% of the cohort survived till end of study, and the median overall survival was 180 days.