Abstract：
OBJECTIVE: Given the substantial lack of knowledge, we aimed to assess clinical/dosimetry predictors of late hematological toxicity on patients undergoing pelvic-nodes irradiation (PNI) for prostate cancer (PCa) within a prospective multi-institute study.
METHODS: Clinical/dosimetry/blood test data were prospectively collected including lymphocytes count (ALC) at baseline, mid/end-PNI, 3/6 months and every 6 months up to 5-year after PNI. DVHs of the Body, ileum (BMILEUM), lumbosacral spine (BMLS), lower pelvis (BMPELVIS), and whole pelvis (BMTOT) were extracted. Current analysis focused on 2-year CTCAEv4.03 Grade ≥ 2 (G2+) lymphopenia (ALC < 800/μL). DVH parameters that better discriminate patients with/without toxicity were first identified. After data pre-processing to limit overfitting, a multi-variable logistic regression model combining DVH and clinical information was identified and internally validated by bootstrap.
RESULTS: Complete data of 499 patients were available: 46 patients (9.2 %) experienced late G2+ lymphopenia. DVH parameters of BMLS/BMPELVIS/BMTOT and Body were associated to increased G2+ lymphopenia. The variables retained in the resulting model were ALC at baseline [HR = 0.997, 95 %CI 0.996-0.998, p < 0.0001], smoke (yes/no) [HR = 2.9, 95 %CI 1.25-6.76, p = 0.013] and BMLS-V ≥ 24 Gy (cc) [HR = 1.006, 95 %CI 1.002-1.011, p = 0.003]. When acute G3+ lymphopenia (yes/no) was considered, it was retained in the model [HR = 4.517, 95 %CI 1.954-10.441, p = 0.0004]. Performances of the models were relatively high (AUC = 0.87/0.88) and confirmed by validation.
CONCLUSIONS: Two-year lymphopenia after PNI for PCa is largely modulated by baseline ALC, with an independent role of acute G3+ lymphopenia. BMLS-V24 was the best dosimetry predictor: constraints for BMTOT (V10Gy < 1520 cc, V20Gy < 1250 cc, V30Gy < 850 cc), and BMLS (V24y < 307 cc) were suggested to potentially reduce the risk.
METHODS: Clinical/dosimetry/blood test data were prospectively collected including lymphocytes count (ALC) at baseline, mid/end-PNI, 3/6 months and every 6 months up to 5-year after PNI. DVHs of the Body, ileum (BMILEUM), lumbosacral spine (BMLS), lower pelvis (BMPELVIS), and whole pelvis (BMTOT) were extracted. Current analysis focused on 2-year CTCAEv4.03 Grade ≥ 2 (G2+) lymphopenia (ALC < 800/μL). DVH parameters that better discriminate patients with/without toxicity were first identified. After data pre-processing to limit overfitting, a multi-variable logistic regression model combining DVH and clinical information was identified and internally validated by bootstrap.
RESULTS: Complete data of 499 patients were available: 46 patients (9.2 %) experienced late G2+ lymphopenia. DVH parameters of BMLS/BMPELVIS/BMTOT and Body were associated to increased G2+ lymphopenia. The variables retained in the resulting model were ALC at baseline [HR = 0.997, 95 %CI 0.996-0.998, p < 0.0001], smoke (yes/no) [HR = 2.9, 95 %CI 1.25-6.76, p = 0.013] and BMLS-V ≥ 24 Gy (cc) [HR = 1.006, 95 %CI 1.002-1.011, p = 0.003]. When acute G3+ lymphopenia (yes/no) was considered, it was retained in the model [HR = 4.517, 95 %CI 1.954-10.441, p = 0.0004]. Performances of the models were relatively high (AUC = 0.87/0.88) and confirmed by validation.
CONCLUSIONS: Two-year lymphopenia after PNI for PCa is largely modulated by baseline ALC, with an independent role of acute G3+ lymphopenia. BMLS-V24 was the best dosimetry predictor: constraints for BMTOT (V10Gy < 1520 cc, V20Gy < 1250 cc, V30Gy < 850 cc), and BMLS (V24y < 307 cc) were suggested to potentially reduce the risk.
摘要：
目标：鉴于知识的严重缺乏，我们旨在通过一项前瞻性多机构研究,评估前列腺癌(PCa)盆腔淋巴结照射(PNI)患者晚期血液学毒性的临床/剂量学预测因子.
方法：前瞻性收集临床/剂量测定/血液检测数据，包括基线时的淋巴细胞计数（ALC），中/端PNI,PNI后3/6个月和每6个月至5年。身体的DVH,回肠（BMILEUM），腰骶椎(BMLS),下骨盆（BMPELVIS），提取整个骨盆(BMTOT)。当前分析集中于2年CTCAEv4.03级≥2（G2）淋巴细胞减少（ALC<800/μL）。首先确定了更好区分有/无毒性患者的DVH参数。在数据预处理以限制过拟合之后，结合DVH和临床信息的多变量逻辑回归模型被确定,并通过bootstrap进行内部验证.
结果：可获得499例患者的完整数据：46例患者（9.2％）出现G2+晚期淋巴细胞减少。BMLS/BMPELVIS/BMTOT和Body的DVH参数与增加的G2淋巴细胞减少有关。结果模型中保留的变量为基线时的ALC[HR=0.997,95CI0.996-0.998,p<0.0001],烟雾（是/否）[HR=2.9，95CI1.25-6.76，p=0.013]和BMLS-V≥24Gy（cc）[HR=1.006，95CI1.002-1.011，p=0.003]。当考虑急性G3+淋巴细胞减少（是/否）时，它保留在模型中[HR=4.517,95CI1.954-10.441,p=0.0004].模型的性能相对较高（AUC=0.87/0.88），并通过验证得到证实。
结论：PNI后PCa的两年淋巴细胞减少在很大程度上受到基线ALC的调节，具有急性G3+淋巴细胞减少症的独立作用。BMLS-V24是最佳剂量学预测因子：BMTOT的约束（V10Gy<1520cc，V20Gy<1250cc,V30Gy<850cc),和BMLS（V24y<307cc）被建议潜在地降低风险。
方法：前瞻性收集临床/剂量测定/血液检测数据，包括基线时的淋巴细胞计数（ALC），中/端PNI,PNI后3/6个月和每6个月至5年。身体的DVH,回肠（BMILEUM），腰骶椎(BMLS),下骨盆（BMPELVIS），提取整个骨盆(BMTOT)。当前分析集中于2年CTCAEv4.03级≥2（G2）淋巴细胞减少（ALC<800/μL）。首先确定了更好区分有/无毒性患者的DVH参数。在数据预处理以限制过拟合之后，结合DVH和临床信息的多变量逻辑回归模型被确定,并通过bootstrap进行内部验证.
结果：可获得499例患者的完整数据：46例患者（9.2％）出现G2+晚期淋巴细胞减少。BMLS/BMPELVIS/BMTOT和Body的DVH参数与增加的G2淋巴细胞减少有关。结果模型中保留的变量为基线时的ALC[HR=0.997,95CI0.996-0.998,p<0.0001],烟雾（是/否）[HR=2.9，95CI1.25-6.76，p=0.013]和BMLS-V≥24Gy（cc）[HR=1.006，95CI1.002-1.011，p=0.003]。当考虑急性G3+淋巴细胞减少（是/否）时，它保留在模型中[HR=4.517,95CI1.954-10.441,p=0.0004].模型的性能相对较高（AUC=0.87/0.88），并通过验证得到证实。
结论：PNI后PCa的两年淋巴细胞减少在很大程度上受到基线ALC的调节，具有急性G3+淋巴细胞减少症的独立作用。BMLS-V24是最佳剂量学预测因子：BMTOT的约束（V10Gy<1520cc，V20Gy<1250cc,V30Gy<850cc),和BMLS（V24y<307cc）被建议潜在地降低风险。
