Pretreatment Vitamin D Deficiency Is Associated With Impaired Progression-Free and Overall Survival in Hodgkin Lymphoma
Pretreatment Vitamin D Deficiency Is Associated With Impaired Progression-Free and Overall Survival in Hodgkin Lymphoma
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DOI：
10.1200/jco.19.00985
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发表时间：
2019-12-20
影响因子：
45.3
通讯作者：
Engert, Andreas
中科院分区：
文献类型：
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作者：
Borchmann, Sven;Cirillo, Melita;Engert, Andreas
目的维生素D缺乏症被描述为一个可改变的危险因素的发病率和死亡率在许多常见的癌症，然而，在霍奇金淋巴瘤（HL）的数据是lacking.PATIENTS和METHODS因此，我们进行了一项研究，测量治疗前的维生素D水平在前瞻性治疗的HL患者和相关的临床结果。共有351例来自德国霍奇金研究组临床试验（HD 7，HD 8和HD 9）的患者被纳入。结果50%的患者在计划化疗前维生素D缺乏（< 30 nmol/L）。治疗前维生素D缺乏症在复发/难治性患者中比匹配的无复发对照组更常见（中位基线维生素D，21.4 nmol/L vs 35.5 nmol/L;维生素D缺乏症比例，68% vs 41%; P <0.001）。维生素D缺乏患者的无进展生存期受损（10年差异，17.6%; 95%CI，6.9%至28.4%;风险比，2.13; 95%CI，1.84至2.48; P < .001）和总生存率（10年差异，11.1%; 95% CI，2.1%至20.2%;风险比，1.82; 95% CI，1.53至2.15; P <0.001），在试验和治疗组之间一致。我们证明维生素D状态是一个独立的预测结果，并假设维生素D状态可能是重要的HL的化疗敏感性。随后，我们进行了实验，补充生理剂量的维生素D（骨化三醇）培养的HL细胞系，并证明增加抗增殖作用与化疗相结合。在HL异种移植动物模型中，我们发现补充维生素D（膳食补充剂，胆钙化醇）通过降低肿瘤生长速率来改善肿瘤的化学敏感性，与单独的维生素D或化学疗法相比。我们鼓励将维生素D筛查和替代纳入未来的随机临床试验，以正确阐明维生素D替代的作用HL的治疗。
PURPOSE Vitamin D deficiency is described as a modifiable risk factor for the incidence of and mortality in many common cancers; however, data in Hodgkin lymphoma (HL) are lacking.PATIENTS AND METHODS We thus performed a study measuring pretreatment vitamin D levels in prospectively treated patients with HL and correlated this with clinical outcomes. A total of 351 patients from the German Hodgkin Study Group clinical trials (HD7, HD8, and HD9) were included.RESULTS Fifty percent of patients were vitamin D deficient (< 30 nmol/L) before planned chemotherapy. Pretreatment vitamin D deficiency was more common in relapsed/refractory patients than matched relapse-free controls (median baseline vitamin D, 21.4 nmol/L v 35.5 nmol/L; proportion with vitamin D deficiency, 68% v 41%; P < .001). Vitamin D-deficient patients had impaired progression-free survival (10-year difference, 17.6%; 95% CI, 6.9% to 28.4%; hazard ratio, 2.13; 95% CI, 1.84 to 2.48; P < .001) and overall survival (10-year difference, 11.1%; 95% CI, 2.1% to 20.2%; hazard ratio, 1.82; 95% CI, 1.53 to 2.15; P < .001), consistent across trials and treatment groups. We demonstrated that vitamin D status is an independent predictor of outcome and hypothesized that vitamin D status might be important for the chemosensitivity of HL. We subsequently performed experiments supplementing physiologic doses of vitamin D (calcitriol) to cultured HL cell lines and demonstrated increased antiproliferative effects in combination with chemotherapy. In an HL-xenograft animal model, we showed that supplemental vitamin D (dietary supplement, cholecalciferol) improves the chemosensitivity of tumors by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone.CONCLUSION On the basis of our clinical and preclinical findings, we encourage that vitamin D screening and replacement be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement therapy in HL.