RESULTS

Baseline characteristics
The demographic and clinicopathological characteristics of the 591 GIST patients are listed in Table 1 and Table S1. The study population consisted of 280 (46.8%) male and 311 (53.2%) female patients. The median age was 57 (range: 21 - 86) years. The median follow-up time was 56 (range: 4-138) mo. The mean ± SD findings for the HALP, PNI, NLR, PLR, and LMR values were 45.81 ± 33.73, 49.04 ± 5.43, 2.64 ± 1.74, 152.8 ± 84.6 and 5.13 ± 3.00, respectively. The mean ± SD of tumor size was 6.16 ± 4.87 cm. One hundred ninety-one tumors (32.3%) had a mitotic index of > 5 / 50 high-power field. A total of 34.0% (201/691) of the GIST patients received adjuvant therapy with imatinib or sunitinib. According to NIH risk classification, 72 (12.2%) patients were classified as very low risk, 178 (30.1%) patients as low risk, 114 (19.3%) patients as intermediate risk, and 227 (38.4%) patients as high risk. Recurrence occurred in 62 GIST patients.
 
Association of HALP and clinicopathological factors
The clinicopathological characteristics between the high and low groups of HALP were categorized and analyzed as shown in Table 1 and Table S1. Together, 229 patients were assigned to the low HALP group and 362 patients to the high HALP group. The results demonstrated that tumor site, tumor size, mitotic index, Ki67, NIH risk category, and adjuvant therapy were significantly associated with HALP (all P < 0.05).
PSM analysis was further carried out to avoid confounding variables that might interfere with the association between RFS and HALP level. After 1:1 matching, PSM analysis identified 229 pairs of GIST patients. After PSM, HALP was still associated with sex, Ki67, and recurrence but not with any other clinicopathological characteristics (Table 1 and Table S1).
 
Association of clinicopathological factors and RFS
Before PSM, tumor site, tumor size, mitotic index, Ki67, NIH risk category, NLR, PLR, PNI, and HALP were associated with RFS (all P < 0.05) (Table 2). RFS in GIST patients with low HALP was significantly worse than in those with high HALP (Figure 2). Cox multiple regression analysis showed that HALP was an independent prognostic factor for RFS in GIST patients before PSM (HR: 0.506, 95% confidence interval (CI): 0.291-0.879, P = 0.016).
After PSM, tumor site, tumor size, mitotic index, Ki67, NIH risk category, PNI, NLR, PLR, and HALP were still related to RFS (all P < 0.05) (Table 2). RFS was also significantly worse in GIST patients with low HALP than in those with high HALP (Figure 2). Furthermore, Cox multiple regression analysis showed that HALP was an independent prognostic factor for RFS in GIST patients (HR: 0.558, 95%CI: 0.319-0.976, P = 0.041).
 
Subgroup analysis
The clinicopathological characteristics of high-risk GIST patients between the high and low groups of HALP were categorized in Table S1. Together, 125 patients were assigned to the low HALP group and 102 patients to the high HALP group. The results demonstrated that sex and Ki67 were associated with HALP (both P < 0.05). Not surprisingly, patients in the low HALP group had significantly worse survival than patients in the high HALP group (Figure 2). Furthermore, Cox multiple regression analysis indicated that HALP was an independent prognostic factor for RFS in GIST patients (HR: 0.469, 95%CI: 0.245-0.896, P = 0.022) (Table S2).
 
Sensitivity analysis
Time-dependent ROCs were generated for HALP, PNI, NLR, LMR, and PLR to predict 5-year RFS. According to the results, the 5-year AUC reached 0.661 in the HALP group, while PNI, NLR, LMR, and PLR reached 0.622, 0.591, 0.505, and 0.627, respectively (Figure 3).