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Pretreatment Vitamin D Deficiency Is Associated With Impaired Progression-Free and Overall Survival in Hodgkin
Sven Borchmann1,2,3, Melita Cirillo1, Helen Goergen1
1University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German Hodgkin Study Group, Cologne, Germany.
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.
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