|Year : 2020 | Volume
| Issue : 1 | Page : 25-31
Prevalence of Vitamin D deficiency in treatment-naive individual consecutive cancer patients
Avinash Pandey, Anjana Singh, Shivkant Singh
Department of Medical Oncology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
|Date of Submission||09-Dec-2019|
|Date of Decision||10-Jan-2020|
|Date of Acceptance||15-Jan-2020|
|Date of Web Publication||24-Feb-2020|
Department of Medical Oncology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar
Source of Support: None, Conflict of Interest: None
Background: There is a lack of information regarding Vitamin D deficiency in treatment-naive cancer patients.
Aim: The aim of this was to study the prevalence of Vitamin D deficiency in cancer patients.
Objectives: The objective was to measure the extent of Vitamin D insufficiency and deficiency in treatment-naive consecutive individual cancer patients from Eastern India.
Materials and Methods: All consecutive new patients seen between April 2019 and September 2019 were offered a baseline test to measure serum 25-hydroxy Vitamin D [25 (OH) D] levels along with routine investigations. Vitamin D insufficiency was diagnosed when serum 25 (OH) D level was between 20 and 30 ng/mL, whereas patients with a level <20 ng/mL were designated as Vitamin D deficient. Patients with a Vitamin D level <10 ng/mL were termed as having severe Vitamin D deficiency. Descriptive statistics and frequency distribution were used in SPSS software, and Pearson's Chi-squared test was used to compare between the categorical variables.
Results: Of 252 patients, 140 (56%) were female; median age was 51 years (range, 19–84 years) and 204 (81%) were diagnosed with solid organ malignancies. Mean (±standard deviation) Vitamin D level was 18.94 (±10.4). 169/252 (67%) had Vitamin D deficiency, whereas another 52/252 (21%) had Vitamin D insufficiency. Among these, 44/169 (26%) had severe Vitamin D deficiency. Females were more deficient compared to males, 76% versus 55% (P = 0.002). Vitamin D deficiency in younger (<50 years) and older (>50 years) population was 73% and 61% (P = 0.144); while that in solid versus hematolymphoid malignancies was 69% versus 58% (P = 0.173). In the three most common tumors, namely breast (21%), colorectal (8%), and ovary (8%), Vitamin D deficiency was noted in 75% of patients in each group. Vitamin D deficiency was the highest (84%) in esophageal and stomach cancer patients.
Conclusion: More than two-thirds of Indian cancer patients are Vitamin D deficient. Patients with upper gastrointestinal, breast, colorectal, and ovarian cancers and female patients are the most vulnerable groups.
Keywords: Cancer, nutrition, Vitamin D deficiency, Vitamin D supplementation, Vit D
|How to cite this article:|
Pandey A, Singh A, Singh S. Prevalence of Vitamin D deficiency in treatment-naive individual consecutive cancer patients. Cancer Res Stat Treat 2020;3:25-31
|How to cite this URL:|
Pandey A, Singh A, Singh S. Prevalence of Vitamin D deficiency in treatment-naive individual consecutive cancer patients. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Apr 10];3:25-31. Available from: http://www.crstonline.com/text.asp?2020/3/1/25/279071
| Introduction|| |
Lower serum 25-hydroxy Vitamin D [25 (OH) D] level is associated with a higher incidence of colorectal, breast, ovarian, and prostate cancers in several epidemiological studies.,,, Moreover, patients with higher serum Vitamin D levels (>30 ng/mL) have been shown to have a decreased case fatality rate by half to three-fourth in the above malignancies.,,, Supplementation of Vitamin D in human cancer xenograft and animal models with healthy breast and colon tissues induces proliferation arrest and reduces carcinogenesis, respectively.,,, Although the recommendation to supplement Vitamin D in deficient healthy individuals exists, it has not yet been shown to reduce cancer incidence in prospective clinical trials.,,, Similarly, smaller prospective interventional trials have explored the use of high dose Vitamin D (>800–2000 International Units [IU] daily) in early, advanced or metastatic colorectal cancers, but its favorable impact on cancer mortality remains elusive and inconclusive till date., There is no published literature on the prevalence of Vitamin D deficiency in patients diagnosed with cancer from India which is a hot tropical country with abundant sunlight throughout the year. We conducted a prospective study on treatment-naive consecutive cancer patients presenting to our center to determine the prevalence and extent of Vitamin D deficiency.
| Materials and Methods|| |
General study details
Our institute is an apex tertiary referral cancer center in Eastern India. For this study, we offered individual consecutive patients registered between April 1, 2019, and September 30, 2019, in the Department of Medical Oncology testing for baseline serum Vitamin D level, 25-(OH)-D. This test was prescribed, after obtaining informed consent only, in addition to the routine hematological, serological, and biochemical tests to assess baseline organ function in the routine workup of patients with malignancy. Adults over the age of 18 years were eligible. Patients who had received any prior cancer-directed therapies such as radiotherapy, chemotherapy, hormonal therapy, or cancer-directed surgeries (except diagnostic biopsies and cytology) were excluded from the study. Patients with a history of rickets, active pregnancy, renal osteodystrophy, or documented osteoporosis were not eligible to participate. Patients who had a history of any documented or prescribed use of Vitamin D tablets or injectable Vitamin D preparations in the preceding 6 months were excluded from the study [Figure 1]. The study was conducted in accordance with the Declaration of Helsinki and the Indian Council of Medical Research guidelines for ethical conduct. No funding was used for the conduct of the study.
|Figure 1: Flow diagram showing the number of patients who were evaluated for and were enrolled in this prospective observational study, with the results of the Vitamin D level|
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Sample collection and processing
Three milliliters blood sample was drawn from an accessible peripheral vein in a red-top serum separator vacutainer irrespective of fasting or special dietary requirements. From this sample, serum or plasma was removed from the red blood cell clot and stored at 2°C–8°C refrigeration, if the sample could be processed on the same day or was frozen and stored at −20°C if processing was delayed. Care was taken to exclude any sample with gross hemolysis, fibrin, or particulate matter. Samples once thawed were mixed thoroughly by low-speed vortexing or by inverting ten times. Specimens were centrifuged for 3000 g/min in centrifugation tubes to maintain consistency in results. Only clear samples without bubbles were transferred after centrifugation for further processing. For sample processing, The ARCHITECT 25 (OH) D assay was used which is a chemiluminescent microparticle immunoassay for the quantitative determination of 25 (OH) D in human serum and plasma. The ARCHITECT 25 (OH) D assay is standardized against National Institute of Standards and Technology Standard Reference Material 2972. The average turnaround time for reports was 48 to 72 hours.
Patient categorization and management details
The demographic details including age, sex, type of cancer, solid or hematological malignancy, and stage were recorded. Vitamin D insufficiency was defined as serum 25 (OH) D level between 20 and 30 ng/mL, whereas patients with a level <20 ng/mL were designated as Vitamin D deficient. Patients with Vitamin D level <10 ng/mL were categorized as having severe Vitamin D deficiency. As the majority of patients even with moderate Vitamin D deficiency, are clinically asymptomatic with normal calcium, phosphorous and alkaline phosphatase levels, we did not pursue and record the above parameters for each individual Vitamin D deficiency patient. Neither serum parathyroid hormone levels (PTH) nor bone mineral density (BMD) were checked in the patients found to be Vitamin D deficient as these tests were not available in our institute.
Patients were informed during their subsequent visit about their Vitamin D level status, and options for replenishing deficient stores were offered. As this was a noninterventional, observational study to measure the prevalence of Vitamin D deficiency in treatment-naive consecutive individual cancer patients, the decision to get Vitamin D supplements administered was left to the individual patient's discretion after informing them about the possible benefits and risks. Patients were also informed that irrespective of their decision to get Vitamin D supplementation, the tumor directed therapy would not be altered and that there were no conclusive data yet that suggested that administering Vitamin D to deficient cancer patients would improve their outcome or reduce treatment-related toxicities. Patients were offered either oral weekly cholecalciferol (Vitamin D3) 50,000 IU for 8 weeks or a single intramuscular injection of 600,000 IU of cholecalciferol in an Arachis oil depot formulation. This was followed by maintenance dose of 800 IU of Vitamin D3 and 500 mg of elemental calcium daily supplement for 6 months.
All data were recorded in real time in the Outpatient Department of Medical Oncology by a trained data entry operator under the supervision of the physician. Descriptive statistics, including tables, pie charts, and frequency distribution, were derived from SPSS software version 17.0 (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, version 25.0. Armonk, NY, USA). Pearson's Chi-squared test was used to compare between categorical variables.
| Results|| |
Of 304 patients screened for the study and offered testing with peripheral blood samples for Vitamin D level estimation, 252 were enrolled [Figure 1]. The median age at diagnosis was 51 years with a range from 19 to 84 years. One hundred and forty patients (56%) were female. A Majority of patients 204 (81%) were diagnosed with solid malignancies. Among them, Stage IV was the most common in 101 patients (50%), followed by Stage III in 77 patients (38%). Breast cancer was the most common malignancy noted in 54/204 (26.5%) followed by gall bladder in 33/204 (16%) and colorectal cancers in 22/204 (11%). Among the hematological malignancies, 21/48 (44%) were nonclassifiable according to stages including acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia; hence, these were grouped together. The majority (22/48 [46%]) of Stage III/IV other hematological cancers were non-Hodgkin lymphoma. Hodgkin lymphoma, multiple myeloma, and chronic lymphocytic leukemia were clubbed together for description and analysis as individual numbers were too small. None of the patients at presentation received any anti-epileptics or steroids, which could have confounded the baseline Vitamin D levels [Table 1].
|Table 1: Demographic and clinical profile of patients for whom baseline pretreatment serum 25 (OH) D levels were obtained|
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The mean (±standard deviation) Vitamin D level was 18.94 ng/mL (±10.4). 169/252 (67%) had Vitamin D deficiency, whereas another 52/252 (21%) had Vitamin D insufficiency. Among these, 44/169 (26%) had severe Vitamin D deficiency. Females were more deficient compared to males, 76% versus 55% (P = 0.002) [Figure 2]. Vitamin D deficiency in younger (<51 years) and older (>51 years) population was 73% and 61% (P = 0.144); while that in solid versus hematolymphoid malignancies was 69% versus 58% (P = 0.173). The three most common tumors among the 252 patients were the breast (21%), colorectal (8%), and ovary (8%); in each of these tumor types, Vitamin D deficiency was noted in 75% of patients. Vitamin D deficiency was the highest (84%) in esophageal and stomach cancer patients [Figure 3]. 47/77 (60%) of Stage III and 45/101 (45%) of Stage IV solid cancer patients had Vitamin D deficiency, whereas 11/77 (14%) and 20/101 (20%) had severe Vitamin D deficiency in the above stages, respectively. No significant difference in Vitamin D deficiency was seen in early or advanced stage cancers on Chi-square test [Table 2].
|Figure 2: Pie chart depicting Vitamin D status across entire study population cohort (n = 252). Normal Vitamin D level > 30 ng/mL, insufficient Vitamin D level 20–30 ng/mL, deficient Vitamin D level 10–20 ng/mL, Severely Deficient Vitamin D level <10 ng/mL)|
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|Figure 3: (a-e) Pie chart showing Vitamin D status across (a) breast (n=54), (b) ovarian (n=21), (c) colorectal (n=22), (d) upper gastrointestinal tract (n=14), and (e) gall bladder cancers (n=33), respectively. (Normal Vitamin D level >30 ng/mL, insufficient Vitamin D level 20–30 ng/mL, deficient Vitamin D level 10–20 ng/mL, severely deficient Vitamin D level <10 ng/mL)|
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|Table 2: Extent and severity of Vitamin D deficiency across major demographic and clinical variables|
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199/221 (90%) of Vitamin D deficient and insufficient patients received Vitamin D supplementation voluntarily after they were informed of the result. Of these, 133/199 (67%) took depot one-time intramuscular preparation, whereas remaining 66/199 (33%) chose to receive weekly oral Vitamin D supplementation for 8 weeks as described in the above dose strength, schedule, and formulations. Compliance to complete all 8 weeks of oral weekly supplementation was 37/66 (57%); compliance for 6 weeks was 47/66 (71%) after only one-time/ first time oral instruction given by the physician without subsequent reinforcement.
| Discussion|| |
The prevalence of Vitamin D deficiency and Vitamin D insufficiency in treatment-naive individual consecutive adult cancer patients was 67% and 21% respectively in our prospective observational study conducted in an apex tertiary regional cancer center in Eastern India. The study confirms that the prevalence of Vitamin D deficiency in cancer patients is high but similar to that seen in otherwise apparently healthy adult individuals residing in regular communities in India.,, More than 75% of patients with breast, colorectal and ovarian cancers had baseline Vitamin D deficiency even before initiating any cancer-directed therapies. Of all the malignancies, the highest occurrence of Vitamin D deficiency was noted in patients with esophageal and stomach cancers at 84%, possibly due to poor oral intake and early cancer cachexia due to compromised nutrition, secondary to diseased, and dysfunctional food-pipe.
Vitamin D deficiency in our study was not significantly different between the younger and older population, between different stages or in solid versus hematological malignancies. However, females had significantly lower Vitamin D levels with >76% having Vitamin D deficiency compared to 55% in males. This could be due to the fact that women, especially after attaining menopause, constitute a 'high risk' group to suffer from chronic Vitamin D deficiency in apparently healthy cohorts too, unless supplemented., The higher number of breast, gall bladder, and ovarian cancers in our study with more women than men overall diagnosed with cancer also made low Vitamin D prevalence more apparent among the women. In Eastern India, gall bladder malignancy is the most common cancer. There are several proposed hypotheses for this high incidence such as high soil arsenic content, proximity to the River Ganga, high prevalence of gall stones, and chronic cholecystitis, but none have been conclusively proven to be the primary inciting factor and have been mere associations with high prevalence in this region., Cancer of the gall bladder was the second-most common malignancy in our study with Vitamin D deficiency of 58% and insufficiency of 27% in this cohort.
India is a tropical country with abundant sun exposure; in spite of this, studies have found a high prevalence of Vitamin D deficiency in the healthy population., Studies from India have shown a significant association between low serum 25 (OH) D levels and a higher risk of breast cancer., Moreover, certain Vitamin D receptor (VDR) gene polymorphisms prevalent in the Indian population such as TaqI and FokI VDR polymorphism are associated with higher risks of developing breast, colorectal, and ovarian malignancies.,,, No study from India has yet reported the prevalence of Vitamin D deficiency in consecutive cancer patients across several malignancies. Our study illustrates the high prevalence of low Vitamin D levels in treatment-naive cancer patients. Whether replenishing depleted Vitamin D stores by pretreatment supplementation alters the tolerance favorably or improves any other cancer-related endpoints have to be further explored.
Vitamin D deficiency is prevalent among cancer patients which is accentuated with cancer-directed therapies, including chemotherapy., However, no evidence exists yet to suggest that the routine supplementation of Vitamin D in deficient cancer patients leads to an improved survival. In hormone-refractory prostate cancer, Vitamin D supplementation failed to improve response rates in a Phase II trial. Similarly, a randomized controlled trial of high dose Vitamin D with docetaxel produced similar response rates with modest improvement in survival for which the study was not powered. Further, a systematic review exploring the role of Vitamin D in prostate cancers confirmed the lack of its benefit in improving outcomes. In breast cancer, high dose Vitamin D failed to reduce the pain score in patients with bone metastasis. Similar interventions in colorectal cancers have also failed to produce any favorable outcomes.,
Although Vitamin D supplementation has yet to prove its value for improving responses or survival, there is some literature to support that supplementation may reduce the toxicity of cancer-directed therapies. When given as a supplement along with aromatase inhibitors in adjuvant hormone-positive breast cancer, Vitamin D significantly decreased treatment-induced musculoskeletal pain, thus improving compliance, reducing drug interruptions, and discontinuations. Similarly, when used along with radical chemoradiotherapy in head-and-neck cancers, Vitamin D decreased oral mucositis, improved swallowing performance status score and quality of life in the 3rd month significantly. However, though these data appear promising, it is still premature to recommend routine high dose Vitamin D supplementation in any malignancy, treated either with curative or palliative intent to reduce toxicity.
Being an observational cross-sectional study, it was beyond the scope of our study to evaluate any difference in toxicities or response rates/outcomes in patients based on the Vitamin D levels. We neither recorded the serum calcium or phosphorous levels of individual patients nor measured serum PTH levels and alkaline phosphatase to identify the subclinical impact of low Vitamin D status. We also did not perform BMD test, even in postmenopausal women with Vitamin D deficiency, to decipher the extent of underlying osteoporosis. The study was done exclusively in adult cancer patients, and hence, our results cannot be extrapolated to the pediatric population, in whom the prevalence of Vitamin D deficiency may be different. We neither performed baseline comprehensive nutritional assessment nor correlated the patients' baseline performance status or serum albumin level with the Vitamin D levels at presentation; hence, the influence of malnutrition on the Vitamin D levels could not be explored. Supplementation of Vitamin D in deficient patients was voluntary and was left to the discretion of individual patients after informing them of the presence of deficiency. We also did not reinforce or pursue regularly, apart from one-time counseling, the need for weekly oral supplementation of Vitamin D for 8 weeks in patients who chose to receive the above method to replenish depleted stores as our primary objective was noninterventional.
| Conclusion|| |
More than two-thirds of adult cancer patients have Vitamin D deficiency even before receiving any cancer-directed therapy. Women and patients with cancer of the upper gastrointestinal tract belong to the high-risk group. Whether pretreatment or concurrent Vitamin D supplementation along with standard therapy can improve cancer-related outcomes or improve compliance with reduced toxicity needs to be evaluated further in prospective randomized clinical trials.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]