Results
Baseline patients’ characteristics are shown in Table 1. Among 168 patients, 108 patients (64%) had completed the 6 scheduled administrations, 48 patients (29%) had discontinued 223Ra because of progressive disease or death, while 12 (7%) were still receiving therapy at the time of the analysis. A total of 2264 questionnaires have been collected and analyzed, 1132 of which were EORTC QLQ-C30 and 1132 were QLQ-BM22. The median follow-up time from the first 223Ra-treatment to either death or last contact (last 223Ra administration, last follow-up phone call or last follow-up 99mTc-diphosphonate bone scan), was 11±8 months (range 1-38). Median OS time was 12 months (95%CI 10 - 13 months), as shown in Figure 1. The univariate analysis evaluating the prognostic value of all baseline clinical variables showed that patients’ Hb, PLT, tALP, and PSA values were independently associated with an increased risk of death. As shown in Table 2, almost all items of both baseline EORTC QLQ-C30 and QLQ-BM22 questionnaires were significantly associated with OS on univariate analysis. Only age (p=0.095), dyspnea (p=0.511), diarrhea (p=0.055) and financial difficulties (p=0.218) were not significantly associated with improvement in OS. When adjusting for other measures on multivariate analysis, baseline patients’ Hb, tALP, and two EORTC QLQ-C30 items (PF2-physical functioning and DY-dyspnea) were significantly associated with OS. After data reduction, the first principal component (PC) explained 90% of the total variation, being then a satisfactory summary of the nineteen questionnaire items. The weights of the first PC are presented in Table 3. Each subject QoL score was calculated as the sum of the product of each loading and the corresponding item measurement. The score ranges from -222 to 200. The new QoL score showed good area under the curve (AUC 0.73); ROC curve is shown in Figure 2. The threshold selected by maximizing the sensitivity and specificity was 7. The entire cohort was stratified into two subgroups on the basis of the baseline QoL cut-off so obtained; the estimated overall survival and log-rank test show that patients with a baseline QoL < 7 had a median OS time of 8 months (95%CI 6 - 11 months), while those with a baseline QoL ≥ 7 had a median OS time of 16 months (95%CI 12 - 24 months), showing a significant association between higher levels of baseline QoL and longer survival (log-rank p<0.001) (Figure 3). The baseline value of our QoL score was significantly associated with OS at univariate analysis (HR = 0.993, 95% CI 0.991-0.996) with a p value <0.001 and when adjusting for other measures on multivariate analysis, baseline patients’ Hb (HR = 0.816, 95% CI 0.717 – 0.927), tALP (HR = 1.008, 95% CI 1.003 – 1.013) and our QoL score (HR = 0.995, 95% CI 0.992 – 0.998) were significantly associated with OS (Table 4). The joint model showed a significant deterioration of global-QoL during both 223Ra-therapy, and the follow-up period (p < 0.001), as shown in Figure 4.