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子宫内膜癌患者术前血液学参数异常;反映肿瘤侵袭性还是对放疗反应降低?

Abnormal preoperative haematological parameters in Endometrial cancer; reflecting tumour aggressiveness or reduced response to radiotherapy?

机构信息

Department of Obstetrics and Gynaecology, Radboud University Medical Centre, Nijmegen, the Netherlands.

Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands.

出版信息

J Obstet Gynaecol. 2024 Dec;44(1):2294332. doi: 10.1080/01443615.2023.2294332. Epub 2024 Jan 7.

Abstract

BACKGROUND

In endometrial cancer (EC), preoperative anaemia, thrombocytosis and leucocytosis appear to be associated with worse prognosis. It remains unclear whether these parameters solely reflect tumour aggressiveness, or also impact response to adjuvant treatment. Therefore, our primary aim is to evaluate the prognostic relevance of anaemia, thrombocytosis and leucocytosis on survival in EC. Secondary, to explore their predictive relevance in response to radiotherapy in EC.

METHODS

A retrospective multicentre cohort study was performed within 10 hospitals. Preoperative haematological parameters were defined as: Anaemia - haemoglobin <7.45 mmol/L (<12 g/Dl), thrombocytosis - platelets >400 × 10 platelets/L, leucocytosis - leukocytes >10 × 10/L. The relationship of haematological parameters with clinicopathological characteristics, ESGO/ESTRO/ESP risk groups and survival were evaluated. Furthermore, the predictive value of haematological parameters was determined on the overall response to adjuvant radiotherapy and for the ESGO/ESTRO/ESP intermediate-risk group solely receiving radiotherapy.

RESULTS

A total of 894 patients were included with a median follow-up of 4.5 years. Anaemia was present in 103 (11.5%), thrombocytosis in 79 (8.8%) and leucocytosis in 114 (12.7%) patients. The presence of anaemia or thrombocytosis was significantly associated with ESGO/ESTRO/ESP high-risk (respectively,  = 0.002 and  = 0.041). In the entire cohort, anaemia remained independently associated with decreased disease-specific survival (HR 2.31, 95% CI (1.19-4.50),  = 0.013) after adjusting for age, the abnormal haematological parameters and ESGO/ESTRO/ESP risk groups. In patients that were treated with adjuvant radiotherapy ( = 239), anaemia was associated with significant reduced 5-year disease-specific and recurrence-free survival ( = 0.005 and  = 0.025, respectively). In ESGO/ESTRO/ESP intermediate risk patients that received solely vaginal brachytherapy ( = 74), anaemia was associated with reduced disease-specific survival ( = 0.041).

CONCLUSIONS

Current data demonstrate the importance of preoperative anaemia as independent prognostic factor in patients with EC. Moreover, anaemia seems to be associated with reduced response to radiotherapy. Prospective validation in a larger study cohort is needed to verify anaemia as predictive biomarker for radiotherapy. In endometrial cancer, preoperative abnormal haematological parameters like, anaemia, thrombocytosis and leucocytosis appears to be associated with FIGO advanced-stage and unfavourable outcome. It remains unclear whether anaemia, thrombocytosis or leucocytosis solely reflecting worse prognosis by advanced tumour stage, or also impact response to adjuvant treatment. Current data demonstrate that anaemia is independent associated with decreased disease-specific survival and anaemia seems related with reduced response to radiotherapy and in specific to vaginal brachytherapy in ESGO/ESTRO/ESP intermediate risk patients. Specific applied adjuvant treatment is needed if patients with anaemia have a reduced response to radiotherapy in EC. Prospective validation in a larger study cohort is required to verify anaemia as predictive biomarker for radiotherapy and to further evaluate the prognostic/predictive impact of anaemia in addition to the molecular subgroups.

摘要

背景

在子宫内膜癌(EC)中,术前贫血、血小板增多和白细胞增多似乎与预后更差相关。目前尚不清楚这些参数是否仅反映肿瘤侵袭性,还是也会影响辅助治疗的反应。因此,我们的主要目的是评估术前贫血、血小板增多和白细胞增多对 EC 患者生存的预后相关性。其次,探索这些参数在 EC 患者放疗反应中的预测相关性。

方法

在 10 家医院进行了回顾性多中心队列研究。术前血液学参数定义为:贫血-血红蛋白<7.45mmol/L(<12g/dl),血小板增多-血小板>400×109/L,白细胞增多-白细胞>10×109/L。评估血液学参数与临床病理特征、ESGO/ESTRO/ESP 风险组和生存的关系。此外,还确定了血液学参数对辅助放疗总体反应的预测价值,以及仅接受放疗的 ESGO/ESTRO/ESP 中危组的预测价值。

结果

共纳入 894 例患者,中位随访时间为 4.5 年。103 例(11.5%)患者存在贫血,79 例(8.8%)患者存在血小板增多,114 例(12.7%)患者存在白细胞增多。贫血或血小板增多与 ESGO/ESTRO/ESP 高危组显著相关(分别为=0.002 和=0.041)。在整个队列中,在调整年龄、异常血液学参数和 ESGO/ESTRO/ESP 风险组后,贫血仍然与疾病特异性生存降低独立相关(HR 2.31,95%CI(1.19-4.50),=0.013)。在接受辅助放疗的患者(=239 例)中,贫血与显著降低的 5 年疾病特异性和无复发生存率相关(=0.005 和=0.025,分别)。在仅接受阴道近距离放疗的 ESGO/ESTRO/ESP 中危组患者(=74 例)中,贫血与疾病特异性生存降低相关(=0.041)。

结论

目前的数据表明,术前贫血作为 EC 患者的独立预后因素非常重要。此外,贫血似乎与放疗反应降低有关。需要在更大的研究队列中进行前瞻性验证,以验证贫血作为放疗预测生物标志物的作用。在子宫内膜癌中,术前异常的血液学参数,如贫血、血小板增多和白细胞增多,与 FIGO 晚期和不良结局相关。目前尚不清楚贫血、血小板增多或白细胞增多是否仅反映晚期肿瘤阶段的预后较差,还是也会影响辅助治疗的反应。目前的数据表明,贫血与疾病特异性生存率降低独立相关,贫血似乎与放疗反应相关,特别是在 ESGO/ESTRO/ESP 中危组患者的阴道近距离放疗中。如果 EC 患者贫血对放疗反应降低,则需要应用特定的辅助治疗。需要在更大的研究队列中进行前瞻性验证,以验证贫血作为放疗预测生物标志物的作用,并进一步评估其在除分子亚组之外的预后/预测中的影响。

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