Pretreatment Vitamin Research Articles

The Role of Vitamin D in Patients with Inflammatory Bowel Disease Treated with Vedolizumab.

Many clinical factors can contribute to the efficacy of medical therapy in Inflammatory Bowel Disease (IBD). We assessed their effects on the efficacy of vedolizumab therapy in a cohort of patients with IBD. We conducted a retrospective study on patients between 18 and 80 years of age with ulcerative colitis (UC) or Crohn's disease (CD) who were seen in the IBD program at Houston Methodist in Houston, TX and treated with vedolizumab for at least 6 months from 2018 to 2022. We investigated factors prior to the initiation of therapy that best predicted treatment response, with an emphasis on vitamin D levels and examined several variables including patients' demographics and clinical information on disease location and severity and nutritional status before and after the initiation of vedolizumab. Post-treatment data were gathered after a minimum of 6 months of vedolizumab therapy. The clinical parameters used for the study were the Harvey-Bradshaw Index for CD and the Activity Index for UC. There were 88 patients included in our study of whom 44 had CD and 44 had UC.; median age was 39.5 (31.0, 53.25) years; 34% patients were male; and 80.7% were Caucasian. All patients received an induction dosing of 300 mg vedolizumab at 0, 2, and 6 weeks then maintenance dosing as standard of care every 8 weeks. Among UC patients with vitamin D ≥ 30 ng/mL at the initiation of vedolizumab therapy, UC Endoscopic Index of Severity (UCEIS) scores after 6 months of therapy were significantly lower than in those who had low pre-treatment vitamin D levels (1.5 vs. 3.87, p = 0.037). After treatment, vitamin D levels improved more significantly in the higher pre-treatment vitamin D group, with a median level of 56 ng/mL, than in the lower pre-treatment vitamin D group, with a median level of only 31 ng/mL (p = 0.007). In patients with CD with vitamin D ≥ 30 ng/mL at the initiation of vedolizumab therapy, we found higher iron saturation (12 vs. 25%, p = 0.008) and higher vitamin B12 levels (433.5 vs. 885 pg/mL, p = 0.003) than in those with vitamin D < 30 ng/mL. After treatment, CD patients with high pre-treatment vitamin D levels had significantly higher vedolizumab levels (27.35 vs. 14.35 μg/mL, p = 0.045) than those with low pre-treatment vitamin D. Post-treatment scores and inflammatory markers in CD patients (HBI, CRP, ESR, and SES-CD) were lower in those who had lower baseline vitamin D. Our results show higher pre-treatment vitamin D levels predicted significant endoscopic improvement in patients with ulcerative colitis (UC). Improving vitamin D levels lowered C-reactive protein levels significantly in CD patients. Higher vitamin D levels were seen after treatment in both UC and CD patients. Vitamin D can play a role in clinical and endoscopic outcomes and should be assessed routinely and optimized in patients with IBD.

Pretreatment Vitamin D Concentrations Do Not Predict Therapeutic Outcome to Anti-TNF Therapies in Biologic-Naïve Patients With Active Luminal Crohn's Disease.

Vitamin D has a regulatory role in innate and adaptive immune processes. Previous studies have reported that low pretreatment vitamin D concentrations are associated with primary non-response (PNR) and non-remission to anti-TNF therapy. This study aimed to assess whether pretreatment 25-hydroxyvitamin D concentrations predicted PNR and non-remission to infliximab and adalimumab in patients with active luminal Crohn's disease. 25-Hydroxyvitamin D concentrations were measured in stored baseline samples from 659 infliximab- and 448 adalimumab-treated patients in the Personalised Anti-TNF Therapy in Crohn's disease (PANTS) study. Cut-offs for vitamin D were deficiency <25 nmol/L, insufficiency 25-50 nmol/L, and adequacy/sufficiency >50 nmol/L. About 17.1% (189/1107; 95% CI, 15.0-19.4) and 47.7% (528/1107; 95% CI, 44.8-50.6) of patients had vitamin D deficiency and insufficiency, respectively. 22.2% (246/1107) of patients were receiving vitamin D supplementation. Multivariable analysis confirmed that sampling during non-summer months, South Asian ethnicity, lower serum albumin concentrations, and non-treatment with vitamin D supplementation were independently associated with lower vitamin D concentrations. Pretreatment vitamin D status did not predict response or remission to anti-TNF therapy at week 14 (infliximab Ppnr = .89, adalimumab Ppnr = .18) or non-remission at week 54 (infliximab P = .13, adalimumab P = .58). Vitamin D deficiency was, however, associated with a longer time to immunogenicity in patients treated with infliximab, but not adalimumab. Vitamin D deficiency is common in patients with active Crohn's disease. Unlike previous studies, pretreatment vitamin D concentration did not predict PNR to anti-TNF treatment at week 14 or nonremission at week 54.

Prognostic role of plasma vitamin D and its association with disease characteristics in germ cell tumours.

Testicular cancer is the most common malignancy among young men. Vitamin D has pluripotent effects on cancer pathogenesis and plays a role in the metastatic cascade. The aim of this study is to analyze plasma vitamin D in association with clinico-pathological findings and prognosis in patients with germ-cell tumors (GCTs). This study included 120 newly diagnosed and/or relapsed GCT patients treated from April 2013 to July 2020, for whom plasma was available in the biobank. Blood samples were drawn the 1st chemotherapy cycle as well as before the 2nd cycle. Plasma vitamin D was measured using ELISA and correlated with disease characteristics and the outcome. For survival analysis, the cohort was dichotomized into "low" and "high" based on median vitamin D. There was no significant difference in vitamin D plasma levels between healthy donors and GCT patients (p = 0.71). Vitamin D level was not associated with disease characteristics except for brain metastases, where patients with brain metastases had a vitamin D level that was 32% lower compared to patients without brain metastases, p = 0.03. Vitamin D was also associated with response to chemotherapy, with an approximately 32% lower value in patients with an unfavorable response compared to a favorable response, p = 0.02. Moreover, low plasma levels of vitamin D were significantly associated with disease recurrence and inferior progression-free survival (PFS), but not with overall survival (OS) (HR = 3.02, 95% CI 1.36-6.71, p = 0.01 for PFS and HR = 2.06, 95% CI 0.84-5.06, p = 0.14 for OS, respectively). Our study suggests the prognostic value of pretreatment vitamin D concentrations in GCT patients. Low plasma vitamin D was associated with an unfavorable response to therapy and disease recurrence. However, it remains to be determined whether the biology of the disease confirms a causative role for low vitamin D and whether its supplementation affects the outcome.

Association of plasma vitamin D with outcomes in patients with germ cell tumour.

429 Background: Testicular cancer is the most common malignancy among young men. Vitamin D has pluripotent effects on cancer pathogenesis and plays a role in the metastatic cascade. The aim of this study is to analyze plasma vitamin D in association with clinico-pathological findings and prognosis in patients with testicular germ-cell tumours (GCTs). Methods: This study included 120 newly diagnosed and/or relapsed GCTs patients treated from April 2013 to July 2020. Blood samples were drawn at the time before 1st chemotherapy cycle as well as before the 2nd cycle. Plasma vitamin D was measured using ELISA and matched with disease characteristics and correlated with the patient outcome. For survival analysis the cohort was dichotomized to “low” and “high” based on median vitamin D. Results: Mean ± standard error of mean plasma vitamin D in GCTs patients was 15.87±0.68 mg/ml. Patients with brain metastases had significantly lower D vitamin compared to patients without brain metastases (10.9 ± 3.05 vs 15.99 ± 0.7, p=0.034). Vitamin D was not associated with other patient characteristics. Low vitamin D was associated with an unfavorable response compared to favorable responses (11.26 ± 1.84 vs 16.47± 0.74, p=0.016), with disease recurrence (16.19 vs 13.71, p=0.011) and with inferior progression-free survival but not with overall survival (HR= 3.02, 95%CI (1.36-6.71), p=0.014 for PFS and HR= 2.06, 95%CI (0.84 – 5.06), p=0.135 for OS, respectively). Conclusions: Our study suggests a prognostic value of pretreatment vitamin D concentrations in GCTs patients. Low plasma vitamin D was associated with unfavorable response to therapy and disease recurrence. However, it remains to elucidated whether the biology of the disease confirms a causative role of low vitamin D and if its supplementation affects the outcome.

P662 Pre-treatment vitamin D concentrations do not predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease

Abstract Background Vitamin D has a regulatory role in innate and adaptive immune processes. Previous small studies have reported that low pre-treatment vitamin D concentrations are associated with primary non-response and shorter drug persistence to anti-TNF therapy. We sought to assess whether pre-treatment 25-hydroxyvitamin D concentrations predicted primary non-response and non-remission to infliximab and adalimumab in patients with Crohn’s disease recruited to the PANTS (Personalised Anti-TNF Therapy in Crohn’s disease) study. Methods We used composite endpoints using the Harvey Bradshaw Index (HBI) in adults and the short paediatric Crohn’s disease activity index (sPCDAI) in children, corticosteroid use, and C-reactive protein (CRP) to define primary non-response (Figure 1). Remission was defined as CRP of ≤3 mg/L and HBI of ≤4 points (short paediatric Crohn’s disease activity index ≤15 in children), without corticosteroid therapy or exit for treatment failure. 25-hydroxyvitamin D concentrations were measured in stored baseline serum samples and cut-offs for vitamin D status were: deficiency &amp;lt; 25nmol/L, insufficiency 25-50nmol/L and adequacy/sufficiency &amp;gt; 50nmol/L. Results Samples from 659/898 infliximab (526 Remicade; 133 biosimilar CT-P13) and 448/605 adalimumab (448 Humira) treated patients included in the effectiveness analysis of the PANTS study were included. Overall, 17.1% (189/1107; 95% confidence interval [CI] 15.0 - 19.4%) and 47.7% (528/1107; 95% CI 44.8 - 50.6%) patients had vitamin D deficiency and insufficiency, respectively. At baseline, 22.2% (246/1107) patients were receiving some form of vitamin D supplementation. Multivariable linear regression analysis confirmed that baseline sampling during non-summer months (Figure 2), South Asian ethnicity, lower serum albumin concentrations, higher HBI and nontreatment with vitamin D supplements were independently associated with lower vitamin D concentrations (Figure 3). Primary non-response at week 14 and non-remission at week 54 occurred in 19.3% (116/600; 95% CI 16.4 - 22.7%) and 58.8% (351/597; 95% CI 54.8- 62.7%) patients treated with infliximab and 25.3% (100/396; 95% CI 21.2- 29.8%) and 65.3% (246/377; 95% CI 60.3- 69.9%) of patients treated with adalimumab, respectively. Pre-treatment vitamin D status did not predict response or remission status to anti-TNF therapy at week 14 (infliximab Ppnr = 0.87, adalimumab Ppnr = 0.18) or non-remission at week 54 (infliximab P = 0.12, adalimumab P = 0.59) (Figure 4). Conclusion Vitamin D deficiency is common in patients with active Crohn’s disease. Unlike previous studies, pre-treatment serum 25-hydroxyvitamin D concentration did not predict primary non-response to anti-TNF treatment at week 14 or non-remission at week 54.

Vitamin D Insufficiency and Clinical Outcomes with Chimeric Antigen Receptor T-Cell Therapy in Large B-cell Lymphoma

Vitamin D insufficiency is a potentially modifiable risk factor for poor outcomes in newly diagnosed large B-cell lymphoma (LBCL). However, the role of circulating vitamin D concentrations in relapsed/refractory LBCL treated with CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) is currently unknown. This was a single-center, observational study that evaluated the association of pre-CAR-T 25-hydroxyvitamin D (25-OHD) status with 100-day complete response, progression-free survival, overall survival, and CAR-T–related toxicity in 111 adult relapsed/refractory LBCL patients. Vitamin D insufficiency was defined as ≤30 ng/mL in accordance with the Endocrine Society guidelines. The median pre-CAR-T 25-hydroxyvitamin D concentration was 24 ng/mL (interquarile range = 18-34). Vitamin D–insufficient patients (≤30 ng/mL; n = 73 [66%]) were significantly younger than their vitamin D–replete (>30 ng/mL; n = 38 [34%]) counterparts (P= .039). The vitamin D–insufficient cohort was enriched for de novo LBCL as the histological subtype (P= .026) and had a higher proportion of tisagenlecleucel as the CAR-T product (P= .049). There were no other significant differences in the baseline characteristics between the two groups. In vitamin D–insufficient compared to –replete patients, 100-day complete response was 55% versus 76% (P= .029), and 2-year overall survival was 41% versus 71% (P= .061), respectively. In multivariate analysis, vitamin D insufficiency remained significantly associated with 100-day complete response (odds ratio 2.58 [1.05-6.83]; P= .045) and overall survival (hazard ratio 2.24 [1.08-4.66], P= .030). In recipients of tisagenlecleucel, vitamin D insufficiency was associated with significantly lower cell viability of the infused CAR-T product (P= .015). Finally, pretreatment vitamin D insufficiency did not predict for subsequent CAR-T–related toxicity. This is the first report to demonstrate that vitamin D insufficiency is associated with inferior clinical outcomes in CAR-T recipients. Further study into the mechanistic insights of this finding, and the potential role of vitamin D supplementation to optimize CAR-T are warranted.

Association Between Vitamin D Supplementation and Statin-Associated Muscle Symptoms: A Systematic Review.

Although low vitamin D levels are associated with statin-associated muscle symptoms (SAMS), it remains unclear if vitamin D supplementation leads to symptom improvement. We performed a systematic review to evaluate the association of vitamin D supplementation with resolution of SAMS. We searched Medline (PubMed), Embase and Cochrane Library till 12 December 2021. Full length articles that reported on the association between vitamin D supplementation in adult patients with SAMS were included. We identified 8 interventional studies comprising 669 participants. Majority of the participants were of Caucasian ethnicity and the mean age of participants ranged from 59.5 to 64.8 years old. The studies recruited patients with initial mean pre-treatment vitamin D levels ranging from 17.8 to 22.0ng/mL. Follow up duration ranged from 2 to 24 months and mean post-treatment vitamin D levels ranged from 34.3 to 56.0ng/mL. We found that vitamin D supplementation was associated with improved statin tolerance in 509 out of 606 (83.9%) patients across the 7 studies whichreported patient numbers after supplementation (95%CI=0.81-0.87, I2=72% n=7). None of the studies were randomized controlled trials (RCTs) and hence placebo effect of vitamin D could not be ruled out. Nocebo effect of statin was also not assessed by any of the studies. Vitamin D supplementation in patients with mild-moderate vitamin D insufficiency was associated with improvement of SAMS. However, quantitative efficacy analysis was not possible and this observed association is likely confounded by nocebo and placebo effects. RCTs are required to conclusively assess the utility of vitamin D supplementation in improving SAMS.

Impact of Etanercept on Vitamin D Status and Vitamin D-binding Protein in Bio-naïve Patients with Psoriasis.

High levels of serum vitamin D-binding protein have been shown previously in patients with psoriasis compared with healthy controls; a possible role in inflammation is implied. The primary objective of this study was to investigate the impact of 24-week etanercept treatment on vitamin D status and vitamin D-binding protein in patients with psoriasis. The secondary aim was to explore whether pre-treatment vitamin D levels could predict the treatment effect. A prospective observational study was performed, including 20 patients with psoriasis and 15 controls. Serum samples were analyzed for, among others, vitamin D metabolites, vitamin D-binding protein and highly sensitive Creactive protein. Baseline levels of vitamin D-binding protein were higher in patients with self-reported arthropathy than in those without. After 24 weeks’ treatment, an improvement in psoriasis was noted, as was a decrease in highly sensitive C-reactive protein. Vitamin D-binding protein decreased in those with self-reported arthropathy. Higher baseline levels of vitamin D were associated with faster and greater improvement in psoriasis. Vitamin D-binding protein may have an inflammatory biomarker role.

Vitamin D Is Associated with α4β7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease.

Vitamin D downregulates the in vitro expression of the gut-tropic integrin α4β7 on immune cells. The clinical relevance of this finding in patients with inflammatory bowel disease [IBD] is unclear. We tested the hypothesis that vitamin D is associated with α4β7 immunophenotypes and risk of vedolizumab [anti-α4β7] failure in IBD. We performed single-cell immunophenotyping of peripheral and intestinal immune cells using mass cytometry [CyTOF] in vedolizumab-naïve patients with IBD [N = 48]. We analysed whole-genome mucosal gene expression [GSE73661] from GEMINI I and GEMINI long-term safety [LTS] to determine the association between vitamin D receptor [VDR] and integrin alpha-4 [ITGA4] and beta-7 [ITGB7] genes. We estimated the odds of vedolizumab failure with low pre-treatment vitamin D in a combined retrospective and prospective IBD cohort [N = 252] with logistic regression. Immunophenotyping revealed that higher 25[OH]D was associated with decreased α4β7+ peripheral blood mononuclear cells [R = -0.400, p <0.01] and α4β7+ intestinal leukocytes [R = -0.538, p = 0.03]. Serum 25[OH]D was inversely associated with α4β7+ peripheral B cells and natural killer [NK] cells and α4β7+ intestinal B cells, NK cells, monocytes, and macrophages. Mucosal expression of VDR was inversely associated with ITGA4 and ITGB7 expression. In multivariate analysis, 25[OH]D <25 ng/mL was associated with increased vedolizumab primary non-response during induction (odds ratio [OR] 26.10, 95% confidence interval [CI] 14.30-48.90, p <0.001) and failure at 1-year follow-up [OR 6.10, 95% CI 3.06-12.17, p <0.001]. Low serum 25[OH]D is associated with α4β7+ immunophenotypes and predicts future vedolizumab failure in patients with IBD. This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Comparison of Oral Isotretinoin vs Azithromycin in the Treatment of Acne Vulgaris

Background: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous follicles, common inadolescents, characterized by comedones, papules, pustules, cysts, nodules, and occasionally scars. Thisstudy was designed to compare multi B vitamins, folic acid and homocysteine levels in patients withmoderate to severe acne vulgaris with those of the apparently healthy control group and to investigate theeffect of isotretinoin and azithromycin treatments on these biochemical parameters and comparison betweentwo drugs.Methods: This study was conducted on sixty women patients with acne and thirty as a control group. Thepatients were allocated into two groups, A and B, group A was given 500 mg of azithromycin taken onalternative days for 3 months and group B was given 40mg/day isotretinoin for 3 months.Results: The study showed significant differences (p&lt;0.05) in serum levels of vitamins B6, B7, B12 andfolic acid, while no significant difference in serum homocysteine in patient group when compared to controlgroup. The results showed significant positive correlation between serum vitamins and clinical score andsignificant difference were detected in both group when compared between pre and post treatment.Conclusions: The results indicate higher pre-treatment vitamin B12 levels, versus the control group andpositive correlation between clinical score and vitamin B12, support the assertion that vitamin B12 playsa role in the etiopathogenesis of acne vulgaris. Both azithromycin and isotretinoin were effective in acnetreatment but azithromycin has less side effects.

Time out: should vitamin D dosing be based on patient's body mass index (BMI): a prospective controlled study.

The recommended daily dose of vitamin D is 2000 IU was found to be insufficient in many patients. The objective of the present study is to find whether the daily dose of vitamin D should be based on BMI. Two hundred and thirty patients with an established vitamin D deficiency (serum level of 25 Hydroxy vitamin D3 (25OHD3) of ≤20 ng/ml) and patients with BMI ≥30 kg/m2 were included in the study. Demographic data, comorbidities and BMI were recorded. Pre-treatment and post-treatment serum 25OHD3, calcium, phosphorus and parathyroid hormone (PTH) were tested at 0-, 3- and 6-month periods. Patients were treated with a standard dose of 50 000 IU of vitamin D weekly and 600/1200 mg of calcium a day. Once their level of 25OHD3 reached ≥30 ng/ml, patients were randomised into two groups. Group A received a standard recommended maintenance dose of 2000 IU daily and Group B patients received 125 IU/kg/m2 of vitamin D3. The data were entered in the database and analysed. The mean age of Group A was 50⋅74 ± 7⋅64 years compared to 52⋅32 ± 7⋅21 years in Group B. In both groups, pre-treatment vitamin D level was ≤15 ng/ml and increased to 34⋅6 ± 2⋅6 and 33⋅7 ± 2⋅4 ng/ml at the end of 3 months treatment with a dose 50 000 IU of vitamin D3 and calcium 600/1200 mg once a day for group A and group B, respectively. At 6 months, patients in Group A 25OHD3 level was 22⋅8 ± 3⋅80 and in Group B was 34⋅0 ± 1⋅85 ng/ml (P < 0⋅001). This preliminary study suggests that obese patients need higher dosage of vitamin D than the recommended dose. It is prudent that the dosage should be based on the BMI to maintain normal levels for a healthy musculoskeletal system.

Association of Vitamin D Deficiency with Inferior Treatment Outcomes in Patients with Newly Diagnosed Classic Hodgkin Lymphoma: MD Anderson Cancer Center Experience

Introduction Vitamin D deficiency is a modifiable risk factor for multiple malignancies. There is growing evidence that associates vitamin D deficiency with progression-free survival (PFS) and overall survival (OS) in patients with classic Hodgkin lymphoma (cHL). Supplemental ergocalciferol/cholecalciferol may improve chemosensitivity of malignant cells to chemotherapy as evidenced by reduction in the rate of tumor growth in a cHL- xenograft animal model. The goal of our study is to explore the association of pretreatment vitamin D levels on survival outcomes of patients with cHL. Methods We retrospectively reviewed the records of patients who were first seen at The University of Texas MD Anderson Cancer Center between January, 2016 and May, 2020 for newly diagnosed cHL. Patient charts were reviewed to assess demographic information, clinical staging at the time of vitamin D assessment, pretreatment 25-hydroxyvitamin D (25(OH) D) level and vitamin D supplementation. Vitamin D deficiency was defined as a 25(OH)D level &amp;lt; 30 nmol/L. PFS and OS outcomes were evaluated for these patients. Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age, and 25(OH) D level, and frequency counts and percentages for categorical variables such as race, gender, vitamin D supplementation and response were analyzed. The Kaplan-Meier method was used for time-to-event analysis including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results 644 patients met the inclusion criteria of which 483 patients had their vitamin D levels assessed at the time of initial visit to this center. The median patient age at diagnosis was 33 years with 52% males. Advanced stage (stages III and IV) occurred in 45% of patients of which the International Prognostic Score was ≥4 in 13% of patients. Patients received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) based therapy (77%), brentuximab vedotin (BV) based therapy (13%) and other agentss (6%). Patient demographics are outlined in Table.1. Pretreatment 25(OH)D level was assessed in 75% of the patients. The median 25(OH)D level was 25 nmol/L (range: 2-78 nmol/L). Vitamin D deficiency was present in 320 of 483 (66%) patients. Ergocalciferol/cholecalciferol supplementation was used in 29% of patients. There was no statistically significant association of vitamin D deficiency with advanced stage (p-value: 0.64). PFS rate at 10 years was significantly longer in patients with normal 25(OH)D level (40% vs 27%, p-value: 0.0481). Ergocalciferol/cholecalciferol supplementation was associated with a 6% improvement of PFS, however this difference was not statistically significant. No OS difference was noted between vitamin D deficient and non-deficient patients, an observation that persisted in patients on vitamin D supplementation versus not on supplementation. Conclusions Vitamin D deficiency was associated with inferior PFS with a 13% difference in vitamin D deficient versus non-deficient patients. There was a numerical PFS benefit associated with ergocalciferol/cholecalciferol supplementation. An OS benefit was not observed as the duration of follow up may not have been sufficient to observe the differential impact of vitamin D levels. Vitamin D screening and replacement is done in patients with newly diagnosed cHL and should be encouraged given the potential benefit from such approach. Prospective studies are warranted to establish the relationship between vitamin D level, supplementation and outcomes in cHL patients. Figure Disclosures Parmar: Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents &amp; Royalties, Research Funding.Nieto:Affimed:Consultancy, Other: Grant Support;Novartis:Other: Grant Support;Astra Zeneca:Other: Grant Support;Secura Bio:Other: Grant Support.Chuang:Sage-Evidence=Based Medicine &amp; Practice:Consultancy.Wang:Lu Daopei Medical Group:Honoraria;Beijing Medical Award Foundation:Honoraria;OncLive:Honoraria;Molecular Templates:Research Funding;Verastem:Research Funding;Dava Oncology:Honoraria;Guidepoint Global:Consultancy;Nobel Insights:Consultancy;Oncternal:Consultancy, Research Funding;InnoCare:Consultancy;Acerta Pharma:Research Funding;VelosBio:Research Funding;BioInvent:Research Funding;Juno:Consultancy, Research Funding;Kite Pharma:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Pulse Biosciences:Consultancy;Loxo Oncology:Consultancy, Research Funding;Targeted Oncology:Honoraria;OMI:Honoraria, Other: Travel, accommodation, expenses;Celgene:Consultancy, Other: Travel, accommodation, expenses, Research Funding;AstraZeneca:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Janssen:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;MoreHealth:Consultancy;Pharmacyclics:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding.Lee:Takeda:Research Funding;Seattle Genetics:Research Funding;Oncternal Therapeutics:Research Funding;Guidepoint Blogal:Consultancy;Celgene:Research Funding;Bristol-Myers Squibb:Consultancy, Research Funding;Aptitude Health:Speakers Bureau.

Risk Factors for Development of Hypocalcemia in Patients With Cancer Treated With Bone-Modifying Agents.

This retrospective analysis describes the prevalence of and risk factors associated with the development of hypocalcemia in patients with cancer receiving bone-modifying agents (BMAs) as supportive care. Patients with cancer treated with an intravenous or subcutaneous BMA, including pamidronate, zoledronic acid, or denosumab, at a tertiary care/safety net hospital in 2005 through 2015 were included in this retrospective review. We reviewed the medical records for predictive clinical and laboratory parameters and for patient outcomes. A total of 835 patients with cancer received at least one dose of a BMA during the specified time frame; 205 patients (25%) developed hypocalcemia of CTCAE grade ≥1 within 8 weeks of BMA initiation, 18 of whom (8.8%) had grade ≥3, and 3 patients died as a result. Multivariate analysis showed that patients with hematologic malignancy (odds ratio [OR], 1.956; P=.025), bone metastases (OR, 2.443; P=.017), inpatient status (OR, 2.592; P<.001), and deficient baseline vitamin D levels (OR, 2.546; P<.023) were more likely to develop hypocalcemia. Hypercalcemia before BMA administration (OR, 0.474; P=.032) was protective. Certain patient populations, including those with hematologic malignancies and/or bone metastases, warrant closer monitoring of calcium levels while receiving BMAs because of the high rate of hypocalcemia. Low pretreatment vitamin D levels are associated with the development of hypocalcemia. These data support close monitoring of calcium levels in patients with cancer receiving BMAs, in addition to adequate repletion of vitamin D before initiation of BMAs when possible.

Vitamin D deficiency increases severity of paclitaxel-induced peripheral neuropathy.

Approximately 25% of patients receiving weekly paclitaxel for breast cancer require treatment disruptions to avoid severe, irreversible peripheral neuropathy (PN). Vitamin insufficiencies are PN risk factors in many diseases, but their relevance to chemotherapy-induced PN is unknown. We investigated whether baseline insufficiency of vitamin D, vitamin B12, folate, or homocysteine increased PN in patients with breast cancer receiving weekly paclitaxel in a retrospective analysis of a prospective observational study. Patient-reported PN was collected at baseline and during treatment on the Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (CIPN20). The primary analysis tested associations between vitamin deficiency and the maximum increase from baseline in the CIPN20 sensory subscale (ΔCIPN8). Secondary analyses tested for association with PN-induced treatment disruptions and adjusted associations for treatment and clinical variables. 25-hydroxy-vitamin D was the only nutrient with sufficient deficiency (< 20ng/mL) for analysis (15/37 = 41%). Vitamin D-deficient patients had a greater mean PN increase than non-deficient patients (ΔCIPN8 ± SD, 36 ± 23 vs. 16 ± 16, p = 0.003) and a non-significant, approximately threefold increase in risk of treatment disruption (OR 2.98, 95% CI [0.72, 12.34], p = 0.16). In multivariable models adjusted for clinical and treatment variables, baseline vitamin D level was inversely associated with PN (β = -0.04, p = 0.02). Pre-treatment vitamin D deficiency was associated with PN in women receiving weekly paclitaxel for breast cancer. Vitamin D deficiency may be an easily detected PN risk factor that could be resolved prior to treatment to prevent PN, avoid treatment disruptions, and improve treatment outcomes.

Pre-treatment vitamin B12, folate, ferritin, and vitamin D serum levels in patients with warts: a retrospective study

AimTo compare the serum levels of 25-hydroxyvitamin D, ferritin, folate, vitamin B12, zinc, and thyroid stimulating hormone between patients with warts and healthy individuals.MethodsThis retrospective study enrolled 40 patients with warts and 40 healthy individuals treated at the Ufuk University Hospital, Ankara, between July and December 2017. Serum levels of 25-hydroxyvitamin D, ferritin, folate, vitamin B12, zinc, and thyroid stimulating hormone status were evaluated retrospectively.ResultsParticipants with and without warts had similar mean serum 25-hydroxyvitamin D, ferritin, folate, zinc, and thyroid stimulating hormone levels. However, patients with warts had significantly lower mean serum vitamin B12 level (P = 0.010). Patients with warts non-significantly more frequently had decreased serum levels of 25-hydroxyvitamin D, ferritin, and folate (P = 0.330, P = 0.200, P = 0.070, respectively).ConclusionPatients with warts may require evaluation of serum levels of vitamin B12, folate, ferritin, and vitamin D.

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

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. 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. 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. 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.

Low pretreatment serum concentration of vitamin D at breast cancer diagnosis in postmenopausal women.

The aim of the study was to evaluate the rate of and risk factors for low pretreatment vitamin D (VitD) levels in postmenopausal breast cancer (BC) women, compared with postmenopausal women without BC. A cross-sectional clinical study was conducted to compare 209 women with BC (case group) to 418 women without BC (control group), age range: 45 to 75 years. The case group consisted of women diagnosed with BC, amenorrhea ≥12 months, aged ≥45 years, without use of medication or clinical conditions that might interfere with VitD levels. The control group consisted of women with amenorrhea ≥12 months, aged ≥45 years, without BC. The groups were matched for age and time since menopause, at a case: control ratio of 1:2. Serum 25-hydroxyvitamin-D [25(OH)D] concentration was measured in all women 10 to 20 days after BC diagnosis and before the proposed treatment. Serum levels ≥30 ng/mL were defined as sufficient. The Student's t test or gamma distribution, χ test, and logistic regression (odds ratio, OR) were used for statistical analysis. The BC group had a higher body mass index (BMI) and higher percentage of obesity than the control group (57.4% vs 40.2%, P < 0.0001). In addition, rates of insufficient (20-29 ng/mL) and deficient (<20 ng/mL) 25(OH)D levels were higher in BC patients than in controls (55.6% vs 49.3%, P = 0.039 and 26.2% vs 20.3%, P = 0.018), respectively. In risk analysis (adjusted for age, time since menopause, and BMI), BC patients had a 1.5-fold higher risk of developing low VitD levels (OR = 1.52, 95% CI, 1.04-2.22, P = 0.029) than women without BC. Postmenopausal women had an increased risk of VitD deficiency at the time of BC diagnosis, associated with a higher rate of obesity, than women of the same age group without cancer.

Association Between Vitamin D Levels and Treatment Response to Direct-Acting Antivirals in Chronic Hepatitis C: A Real-World Study.

BackgroundLow serum vitamin D levels in chronic hepatitis C (CHC) is associated with advanced liver fibrosis; and there remains an imprecise relationship with the treatment response based on the vitamin D levels. Previous studies have shown conflicting results on the vitamin D levels, and association with treatment response in CHC treated with interferon-based regimens.MethodsPatients with CHC treated with direct-acting antivirals (DAAs) between January 2016 and December 2017 in the community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with the sustained virologic response at 12 weeks post-treatment (SVR 12) were assessed in CHC patients with deficient, insufficient, and normal levels of vitamin D measured before the initiation of DAA therapy.ResultsTwo hundred and ninety-one patients were included in the study. Direct-acting antivirals included in the study were ledipasvir/sofosbuvir ± ribavirin, ombitasvir + paritaprevir + ritonavir + dasabuvir ± ribavirin, and sofosbuvir/velpatasvir. An overall sustained virologic response was achieved in 95% (n = 276) of patients. SVR 12 rates among patients with vitamin D deficiency, vitamin D insufficiency and normal vitamin D levels were 92%, 96.2%, and 97.2% respectively and was not statically significant (P = 0.214). A total of 71 patients were cirrhotic. The prevalence of vitamin D insufficiency (20 - 29.9 ng/mL) and deficiency (< 20 ng/mL) was significantly higher in cirrhotic patients (P = 0.01). Despite this, pretreatment vitamin D levels did not show any impact on the virologic response. The most common adverse effect observed was fatigue. None of the patients had to discontinue the treatment due to adverse events.ConclusionsDAAs are safe and effective with a high overall SVR 12 in CHC and treatment response does not depend on the pretreatment vitamin D levels. The prevalence of both vitamin D insufficiency and deficiency was observed to be higher in cirrhotic cohorts compared to non-cirrhotic counterparts.

Vitamin D deficiency is associated with poor breast cancer prognostic features in postmenopausal women

This study aimed to evaluate the association between pretreatment vitamin D (VD) deficiency with breast cancer prognostic features in Brazilian postmenopausal women. An analytical cross sectional study was conducted with 192 women, aged 45–75 years, attended at University Hospital. Women with recent diagnosis of breast cancer, in amenorrhea >12months and age ≥45 years, without medication use or clinical conditions that interfere with VD values were included. Clinical and anthropometric data were collected. Serum level of 25 hydroxyvitamin D [25(OH)D] was measured in all patients until 20days after breast cancer diagnosis, and was classified as normal (≥30ng/mL), insufficiency (20–29ng/mL) and deficiency (<20ng/mL). Data on breast cancer (histopathological type, grade, tumor stage, lymph node status), hormone status (estrogen receptor, ER, progesterone receptor, PR), human epidermal growth factor receptor type 2 (HER2) and epithelial proliferative activity (Ki-67) were collected. For statistical analysis, the t-student test, the Gamma Distribution (asymmetric variables), the chi-square test and the logistic regression (OR-odds ratio) were used. The median 25(OH)D level was 25.8ng/mL (range 12.0–59.2ng/mL). Sufficient vitamin D levels were detected in 65 patients (33.9%), whereas insufficient levels in 92 patients (47.9%), and deficient levels in 35 patients (18.2%). Participants with insufficient and deficient 25(OH)D levels had a higher proportion of tumors with a high grade and locally advanced and metastatic disease, more positive lymph node, a lower proportion of ER, PR positives tumors and higher Ki-67(p<0.05). Patients with normal vitamin D had a higher frequency of luminal A (47.7%) and luminal B (32.2%) tumors when compared to patients with vitamin D insufficiency or deficiency. Furthermore, all cases of triple negative were detected in women with low VD levels. Multivariate analysis, after adjusting for age, time since menopause and BMI, showed that insufficient and deficient level of vitamin D were significantly associated with negative estrogen receptor (OR 3.77 CI 95% 1.76–8.09 and OR 3.99 CI 95% 1.83–8.68), high Ki-67 (OR 2.50, CI 95% 1.35–4.63, and OR 2.62, CI 95% 1.40–4.98), and positive axillary lymph node status (OR 1.59, CI 95% 1.03–2.33, and OR 1.58, CI 95% 1.02–2.92) respectively. In Brazilian postmenopausal women with breast cancer, there was an association between vitamin D insufficiency or deficiency and tumors with worse prognostic features. Low vitamin D levels were shown to be a risk factor for ER negative tumors, with positive axilla and a higher rate of cell proliferation.

Vitamin D receptor polymorphisms as predictors of response to interferon/ribavirin-based therapy in Egyptians with chronic hepatitis C infection

Objective The aim of the present study was to assess the influence of polymorphisms in vitamin D receptors (VDRs) Fok1 and Apa1 and interleukin 28B rs12979860 C/T on the response to interferon/ribavirin-based therapy in Egyptians with chronic hepatitis C. Background Vitamin D exerts immunomodulatory effects on the host response against infection with hepatitis C virus. Genetic polymorphisms affecting the VDR gene have been implicated in several immune disorders. Patients and methods This retrospective study was conducted on 80 patients who were divided into two groups: group I – the nonresponders group – comprised 40 patients and group II – the sustained virological response (SVR) group – also comprised 40 patients. The present study also included 20 healthy volunteers as controls. Two single nucleotide polymorphisms in VDRs Fok1 and Apa1 and in IL28B rs12979860 C/T) were determined by real-time PCR and restriction fragment length polymorphisms. Results Genotypes of IL28B rs12979860 (CC/CT/TT) were found in 23 (57.5%), 15 (37.5%), and two (5%) patients and of Apa1 (CA/AA/CC) in 24 (60%), 14 (35%), and two (5%) patients. Genotypes of Fok1 (TT/CC/TC) were found in 23 (57.5%), nine (22.5%), and eight (20%) patients, respectively, in the SVR group. Regarding IL28B rs12979860 polymorphisms, patients with a T-allele carrier had higher frequency among nonresponders (87.5%) in comparison with SVR (42.5%). Regarding VDR (Fok1) polymorphisms, patients with a C-allele carrier had higher frequency among nonresponders (92.5%) in comparison with SVR (42.5%). Regarding VDR Apa1 polymorphisms, patients with a C-allele carrier had higher frequency among nonresponders (92.5%) in comparison with SVR (65%). Conclusion Pretreatment vitamin D level was significantly higher in responders, and this can be used as a predictor of response to combination therapy for hepatitis C virus. VDR gene polymorphisms (Fok1 and Apa1) and IL28B rs12979860 polymorphism are independently related to response to interferon/ribavirin-based therapy in chronic hepatitis C.