Universität zu Köln

Borchmann, Sven, Cirillo, Melita, Goergen, Helen, Meder, Lydia ORCID: 0000-0002-9547-5812, Sasse, Stephanie, Kreissl, Stefanie, Broeckelmann, Paul Jan, von Tresckow, Bastian, Fuchs, Michael, Ullrich, Roland Tillmann and Engert, Andreas (2019). Pretreatment Vitamin D Deficiency Is Associated With Impaired Progression-Free and Overall Survival in Hodgkin Lymphoma. J. Clin. Oncol., 37 (36). S. 3528 - 3539. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Borchmann, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirillo, Melita UNSPECIFIED UNSPECIFIED UNSPECIFIED Goergen, Helen UNSPECIFIED UNSPECIFIED UNSPECIFIED Meder, Lydia UNSPECIFIED orcid.org/0000-0002-9547-5812 UNSPECIFIED Sasse, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreissl, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Broeckelmann, Paul Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED von Tresckow, Bastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuchs, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Ullrich, Roland Tillmann UNSPECIFIED UNSPECIFIED UNSPECIFIED Engert, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-124113
DOI:	10.1200/JCO.19.00985
Journal or Publication Title:	J. Clin. Oncol.
Volume:	37
Number:	36
Page Range:	S. 3528 - 3539
Date:	2019
Publisher:	AMER SOC CLINICAL ONCOLOGY
Place of Publication:	ALEXANDRIA
ISSN:	1527-7755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXTENDED-FIELD RADIOTHERAPY; 25-HYDROXYVITAMIN D LEVELS; D INSUFFICIENCY; CHEMOTHERAPY; PROGNOSIS; SUPPLEMENTATION; DOXORUBICIN; EXPRESSION; REGIMEN; CYCLES Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12411