title: Low Serum Vitamin D Levels Are Associated With Inferior Survival in Follicular Lymphoma: A Prospective Evaluation in SWOG and LYSA Studies.
abstract: OBJECTIVE
  Recent literature reports a potential association between high vitamin D and improved lymphoma prognosis. We evaluated the impact of pretreatment vitamin D on follicular lymphoma (FL) outcome.
  
  
  METHODS
  SWOG participants were previously untreated patients with FL enrolled onto SWOG clinical trials (S9800, S9911, or S0016) involving CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab) between 1998 and 2008. Participants included in our second independent cohort were also previously untreated patients with FL enrolled onto the Lymphoma Study Association (LYSA) PRIMA trial of rituximab plus chemotherapy (randomly assigned to rituximab maintenance v observation) between 2004 and 2007. Using the gold-standard liquid chromatography-tandem mass spectrometry method, 25-hydroxyvitamin D was measured in stored baseline serum samples. The primary end point was progression-free survival (PFS).
  
  
  RESULTS
  After a median follow-up of 5.4 years, the adjusted PFS and overall survival hazard ratios for the SWOG cohort were 1.97 (95% CI, 1.10 to 3.53) and 4.16 (95% CI, 1.66 to 10.44), respectively, for those who were vitamin D deficient (< 20 ng/mL; 15% of cohort). After a median follow-up of 6.6 years, the adjusted PFS and overall survival hazard ratios for the LYSA cohort were 1.50 (95% CI, 0.93 to 2.42) and 1.92 (95% CI, 0.72 to 5.13), respectively, for those who were vitamin D deficient (< 10 ng/mL; 25% of cohort).
  
  
  CONCLUSIONS
  Although statistical significance was not reached in the LYSA cohort, the consistent estimates of association between low vitamin D levels and FL outcomes in two independent cohorts suggests that serum vitamin D might be the first potentially modifiable factor to be associated with FL survival. Further investigation is needed to determine the effects of vitamin D supplementation in this clinical setting.
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kelly
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Bryan
authors.initials: B
authors.lastname: Goldman
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Pauline
authors.initials: P
authors.lastname: Brice
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Oliver
authors.initials: O
authors.lastname: Press
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Olivier
authors.initials: O
authors.lastname: Casasnovas
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Pierre
authors.initials: P
authors.lastname: Soubeyran
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rimsza
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Michael
authors.initials: M
authors.lastname: LeBlanc
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ.
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
authors.affiliation: Jennifer L. Kelly and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gilles Salles, Hospices Civils de Lyon, Université Claude Bernard Lyon-1, Pierre Benite; Pauline Brice, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris; Olivier Casasnovas, Centre Hospitalo-Universitaire de Dijon, Dijon; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux 2, Bordeaux; Corinne Haioun, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil; Luc Xerri, Institut Paoli Calmettes, Marseille; Hervé Tilly, Centre Henri Becquerel, Rouen, France; Bryan Goldman, Oliver Press, and Michael LeBlanc, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Richard I. Fisher, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA; and Lisa Rimsza, University of Arizona, Tucson, AZ. jonathan_friedberg@urmc.rochester.edu.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D000069283:Rituximab / Q000008:administration & dosage; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000175:diagnosis / Q000401:mortality
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D014807:Vitamin D; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C104450:25-hydroxyvitamin D; C119496:tositumomab I-131; D011241:Prednisone
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