Pretreatment Vitamin D Deficiency Is Associated With Impaired Progression-Free and Overall Survival in Hodgkin Lymphoma.

Abstract

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.

• Authors: Sven Borchmann, Melita Cirillo, Helen Goergen, Lydia Meder, Stephanie Sasse, Stefanie Kreissl, Paul Jan Bröckelmann, Bastian von Tresckow, Michael Fuchs, Roland Tillmann Ullrich, Andreas Engert
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 37 Issue 36 Pg. 3528-3537 (12 20 2019) ISSN: 1527-7755 [Electronic] United States
• PMID: 31622132 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Calcitriol

Topics

• Adolescent
• Adult
• Aged
• Animals
• Antineoplastic Agents (pharmacology)
• Calcitriol (pharmacology)
• Case-Control Studies
• Disease-Free Survival
• Drug Resistance, Neoplasm (drug effects)
• Female
• Heterografts
• Hodgkin Disease (complications, drug therapy, mortality)
• Humans
• Male
• Mice
• Middle Aged
• Neoplasm Recurrence, Local (epidemiology)
• Progression-Free Survival
• Treatment Outcome
• Vitamin D Deficiency (complications)
• Young Adult