Plasma 25-hydroxyvitamin D levels and survival in patients with advanced or metastatic colorectal cancer: Findings from CALGB/SWOG 80405 (Alliance)

Chen Yuan, Kaori Sato, Bruce W. Hollis, Sui Zhang, Donna Niedzwiecki, Fang Shu Ou, I. Wen Chang, Bert H. O'Neil, Federico Innocenti, Heinz Josef Lenz, Charles D. Blanke, Richard M. Goldberg, Alan P. Venook, Robert J. Mayer, Charles S. Fuchs, Jeffrey A. Meyerhardt, Kimmie Ng

Research output: Contribution to journalArticle

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Abstract

Purpose: Previous studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival. However, the influence of vitamin D status on disease progression and patient survival remains largely unknown for patients with advanced or metastatic colorectal cancer. Experimental Design: We prospectively collected blood samples in 1,041 patients with previously untreated advanced or metastatic colorectal cancer participating in a randomized phase III clinical trial of first-line chemotherapy plus biologic therapy. We examined the association of baseline plasma 25(OH)D levels with overall survival (OS) and progression-free survival (PFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs), adjusted for prognostic factors and confounders. Results: At study entry, 63% of patients were vitamin D deficient (<20 ng/mL) and 31% were vitamin D insufficient (20–<30 ng/mL). Higher 25(OH)D levels were associated with an improvement in OS and PFS (Ptrend = 0.0009 and 0.03, respectively). Compared with patients in the bottom quintile of 25(OH)D (≤10.8 ng/mL), those in the top quintile (≥24.1 ng/mL) had a multivariable-adjusted HR of 0.66 (95% CI, 0.53–0.83) for OS and 0.81 (95% CI, 0.66–1.00) for PFS. The improved survival associated with higher 25 (OH)D levels was consistent across patient subgroups of prognostic patient and tumor characteristics. Conclusions: In this large cohort of patients with advanced or metastatic colorectal cancer, higher plasma 25 (OH)D levels were associated with improved OS and PFS. Clinical trials assessing the benefit of vitamin D supplementation in patients with colorectal cancer are warranted.

Original languageEnglish (US)
Pages (from-to)7497-7505
Number of pages9
JournalClinical Cancer Research
Volume25
Issue number24
DOIs
StatePublished - Dec 15 2019

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Colorectal Neoplasms
Survival
Vitamin D
Disease-Free Survival
Confidence Intervals
25-hydroxyvitamin D
Phase III Clinical Trials
Biological Therapy
Proportional Hazards Models
Disease Progression
Research Design
Randomized Controlled Trials
Clinical Trials
Drug Therapy
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Plasma 25-hydroxyvitamin D levels and survival in patients with advanced or metastatic colorectal cancer : Findings from CALGB/SWOG 80405 (Alliance). / Yuan, Chen; Sato, Kaori; Hollis, Bruce W.; Zhang, Sui; Niedzwiecki, Donna; Ou, Fang Shu; Wen Chang, I.; O'Neil, Bert H.; Innocenti, Federico; Lenz, Heinz Josef; Blanke, Charles D.; Goldberg, Richard M.; Venook, Alan P.; Mayer, Robert J.; Fuchs, Charles S.; Meyerhardt, Jeffrey A.; Ng, Kimmie.

In: Clinical Cancer Research, Vol. 25, No. 24, 15.12.2019, p. 7497-7505.

Research output: Contribution to journalArticle

Yuan, C, Sato, K, Hollis, BW, Zhang, S, Niedzwiecki, D, Ou, FS, Wen Chang, I, O'Neil, BH, Innocenti, F, Lenz, HJ, Blanke, CD, Goldberg, RM, Venook, AP, Mayer, RJ, Fuchs, CS, Meyerhardt, JA & Ng, K 2019, 'Plasma 25-hydroxyvitamin D levels and survival in patients with advanced or metastatic colorectal cancer: Findings from CALGB/SWOG 80405 (Alliance)', Clinical Cancer Research, vol. 25, no. 24, pp. 7497-7505. https://doi.org/10.1158/1078-0432.CCR-19-0877
Yuan, Chen ; Sato, Kaori ; Hollis, Bruce W. ; Zhang, Sui ; Niedzwiecki, Donna ; Ou, Fang Shu ; Wen Chang, I. ; O'Neil, Bert H. ; Innocenti, Federico ; Lenz, Heinz Josef ; Blanke, Charles D. ; Goldberg, Richard M. ; Venook, Alan P. ; Mayer, Robert J. ; Fuchs, Charles S. ; Meyerhardt, Jeffrey A. ; Ng, Kimmie. / Plasma 25-hydroxyvitamin D levels and survival in patients with advanced or metastatic colorectal cancer : Findings from CALGB/SWOG 80405 (Alliance). In: Clinical Cancer Research. 2019 ; Vol. 25, No. 24. pp. 7497-7505.
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abstract = "Purpose: Previous studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival. However, the influence of vitamin D status on disease progression and patient survival remains largely unknown for patients with advanced or metastatic colorectal cancer. Experimental Design: We prospectively collected blood samples in 1,041 patients with previously untreated advanced or metastatic colorectal cancer participating in a randomized phase III clinical trial of first-line chemotherapy plus biologic therapy. We examined the association of baseline plasma 25(OH)D levels with overall survival (OS) and progression-free survival (PFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs), adjusted for prognostic factors and confounders. Results: At study entry, 63{\%} of patients were vitamin D deficient (<20 ng/mL) and 31{\%} were vitamin D insufficient (20–<30 ng/mL). Higher 25(OH)D levels were associated with an improvement in OS and PFS (Ptrend = 0.0009 and 0.03, respectively). Compared with patients in the bottom quintile of 25(OH)D (≤10.8 ng/mL), those in the top quintile (≥24.1 ng/mL) had a multivariable-adjusted HR of 0.66 (95{\%} CI, 0.53–0.83) for OS and 0.81 (95{\%} CI, 0.66–1.00) for PFS. The improved survival associated with higher 25 (OH)D levels was consistent across patient subgroups of prognostic patient and tumor characteristics. Conclusions: In this large cohort of patients with advanced or metastatic colorectal cancer, higher plasma 25 (OH)D levels were associated with improved OS and PFS. Clinical trials assessing the benefit of vitamin D supplementation in patients with colorectal cancer are warranted.",
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T1 - Plasma 25-hydroxyvitamin D levels and survival in patients with advanced or metastatic colorectal cancer

T2 - Findings from CALGB/SWOG 80405 (Alliance)

AU - Yuan, Chen

AU - Sato, Kaori

AU - Hollis, Bruce W.

AU - Zhang, Sui

AU - Niedzwiecki, Donna

AU - Ou, Fang Shu

AU - Wen Chang, I.

AU - O'Neil, Bert H.

AU - Innocenti, Federico

AU - Lenz, Heinz Josef

AU - Blanke, Charles D.

AU - Goldberg, Richard M.

AU - Venook, Alan P.

AU - Mayer, Robert J.

AU - Fuchs, Charles S.

AU - Meyerhardt, Jeffrey A.

AU - Ng, Kimmie

PY - 2019/12/15

Y1 - 2019/12/15

N2 - Purpose: Previous studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival. However, the influence of vitamin D status on disease progression and patient survival remains largely unknown for patients with advanced or metastatic colorectal cancer. Experimental Design: We prospectively collected blood samples in 1,041 patients with previously untreated advanced or metastatic colorectal cancer participating in a randomized phase III clinical trial of first-line chemotherapy plus biologic therapy. We examined the association of baseline plasma 25(OH)D levels with overall survival (OS) and progression-free survival (PFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs), adjusted for prognostic factors and confounders. Results: At study entry, 63% of patients were vitamin D deficient (<20 ng/mL) and 31% were vitamin D insufficient (20–<30 ng/mL). Higher 25(OH)D levels were associated with an improvement in OS and PFS (Ptrend = 0.0009 and 0.03, respectively). Compared with patients in the bottom quintile of 25(OH)D (≤10.8 ng/mL), those in the top quintile (≥24.1 ng/mL) had a multivariable-adjusted HR of 0.66 (95% CI, 0.53–0.83) for OS and 0.81 (95% CI, 0.66–1.00) for PFS. The improved survival associated with higher 25 (OH)D levels was consistent across patient subgroups of prognostic patient and tumor characteristics. Conclusions: In this large cohort of patients with advanced or metastatic colorectal cancer, higher plasma 25 (OH)D levels were associated with improved OS and PFS. Clinical trials assessing the benefit of vitamin D supplementation in patients with colorectal cancer are warranted.

AB - Purpose: Previous studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival. However, the influence of vitamin D status on disease progression and patient survival remains largely unknown for patients with advanced or metastatic colorectal cancer. Experimental Design: We prospectively collected blood samples in 1,041 patients with previously untreated advanced or metastatic colorectal cancer participating in a randomized phase III clinical trial of first-line chemotherapy plus biologic therapy. We examined the association of baseline plasma 25(OH)D levels with overall survival (OS) and progression-free survival (PFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs), adjusted for prognostic factors and confounders. Results: At study entry, 63% of patients were vitamin D deficient (<20 ng/mL) and 31% were vitamin D insufficient (20–<30 ng/mL). Higher 25(OH)D levels were associated with an improvement in OS and PFS (Ptrend = 0.0009 and 0.03, respectively). Compared with patients in the bottom quintile of 25(OH)D (≤10.8 ng/mL), those in the top quintile (≥24.1 ng/mL) had a multivariable-adjusted HR of 0.66 (95% CI, 0.53–0.83) for OS and 0.81 (95% CI, 0.66–1.00) for PFS. The improved survival associated with higher 25 (OH)D levels was consistent across patient subgroups of prognostic patient and tumor characteristics. Conclusions: In this large cohort of patients with advanced or metastatic colorectal cancer, higher plasma 25 (OH)D levels were associated with improved OS and PFS. Clinical trials assessing the benefit of vitamin D supplementation in patients with colorectal cancer are warranted.

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