C-Reactive Protein and C-Reactive Protein-Based Scores to Predict Survival in Esophageal and Junctional Adenocarcinoma: Systematic Review and Meta-Analysis.

BACKGROUND: Esophageal adenocarcinoma (EAC) has a poor prognosis; predictive markers of prognosis would facilitate advances in personalized therapy. C-reactive protein (CRP) and CRP-based scores are increasingly recommended across oncology; however, their role and value in EAC is unclear. This systematic review and meta-analysis examined CRP cut-point and scores and how they may best be applied in predicting survival in EAC. METHODS: A systematic literature search was conducted in EMBASE, Medline, Web of Science, Cochrane, Scopus and CINAHL databases, from inception to 1st October 2020. Studies reporting data from adults with EAC including adenocarcinoma of the gastro-esophageal junction (AEG), pre-treatment CRP or CRP-based score and Hazard Ratio (HR) for survival were included. QUIPS tool assessed risk of bias. Meta-analysis was undertaken. RESULTS: A total of 819 records were screened. Eight papers were included, with data for 1475 people. CRP cut-points ranged from 2.8 to 10 mg/L. The Glasgow Prognostic Score (GPS) and modified GPS were the most commonly reported scores. On meta-analysis, elevated preoperative GPS/mGPS was significantly associated with worse overall survival (hazards ratio [HR] 1.81, 95% confidence interval [CI] 1.25-2.62, p = 0.002); results were similar in subgroup analyses of multimodal treatment, M0 disease, and R0 resection. CONCLUSIONS: This is the first review to evaluate comprehensively the evidence for CRP and CRP-based scores in EAC. Meta-analysis demonstrated that elevated preoperative GPS or mGPS was significantly associated with reduced overall survival in EAC, including AEG. There is insufficient evidence to support use of CRP alone. Future studies should examine GPS/mGPS in EAC prospectively, alone and combined with other prognostic markers.

Malnutrition risk at solid tumor diagnosis: the malnutrition screening tool in a large US cancer institute.

BACKGROUND: In cancer, malnutrition is common and negatively impacts tolerance and outcomes of anti-tumor therapies. The aim of this study was to evaluate the prevalence of malnutrition risk and compare the clinicodemographic features between those with high malnutrition screening tool (MST) scores (i.e., ≥ 2 of 5 = high risk for malnutrition, H-MST) to low scores (L-MST). METHODS: A cohort of 3585 patients (May 2017 through December 2018), who completed the MST at least once at the time of diagnosis of any stage solid tumor, were analyzed. Logistic regression tested for associations between clinicodemographic factors, symptom scores, and H-MST prevalence. RESULTS: The median age was 64 years (25-75 IQR, 55-72), with 62% females and 81% White. Most common tumor primary sites were breast (28%), gastrointestinal (GI) (21%), and thoracic (13%). Most had non-metastatic disease (80%). H-MST was found in 28%-most commonly in upper (58%) and lower GI (42%), and thoracic (42%) tumors. L-MST was most common in breast (90%). Multivariable regression confirmed that Black race (OR 1.9, 95% CI 1.5-2.4, p = < 0.001), cancer primary site (OR 1.6-5.7, p = < 0.001), stage IV disease (OR 1.8, 95% CI 1.4-2.2, p = < 0.001), low BMI (OR 4.2, 95% CI 2.5-6.9 p = < 0.001), and higher symptom scores were all independently associated with H-MST. CONCLUSIONS: Twenty-eight percent of solid tumor oncology patients at diagnosis were at high risk of malnutrition. Patients with breast cancer rarely had malnutrition risk at diagnosis. Significant variation was found in malnutrition risk by cancer site, stage, race, and presence of depression, distress, fatigue, and trouble eating/swallowing.

Spray Pattern and Plume Geometry Testing and Methodology: An IPAC-RS Working Group Overview.

Plume characterization for orally inhaled and nasal drug products (OINDP) provides valuable information during OINDP development. Spray pattern and plume geometry techniques, methods, and technology have evolved over the past 20 years since the publication of the original 1998 FDA MDI DPI draft guidance. The International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) discusses the historical context and background to plume geometry and spray pattern characterization studies; provides an analysis of the current regulatory context; addresses results from its industry surveys on application and value of such testing; and presents case studies and best practices-seeking to provide insights to regulatory bodies and other stakeholders. Assessment and consideration of published studies and industry experience note the value of plume geometry and spray pattern in development, and that further data is needed regarding their use in assessing formulation characteristics. Continued dialogue between industry and regulatory bodies is needed to establish the optimum use of these techniques.

Potentially actionable pharmacogenetic variants and symptom control medications in oncology.

PURPOSE: We estimated the prevalence of potentially actionable pharmacogenetic (PGx) variants related to symptom control medications (SCMs) based on institutional prescribing patterns and correlated presenting symptoms with SCM prescribing. METHODS: This was a retrospective study of adult ambulatory cancer patients undergoing electronic distress screening (EDS) within 90 days of intake to the cancer hospital. We estimated the proportion prescribed SCM(s) with PGx evidence within 90 days of intake. Those with potentially actionable variants were estimated using population frequency data from 1000 genomes. The expected number at risk of altered drug response was estimated. The associations between symptom scores and SCM(s) were estimated with logistic regression and threshold analyses performed with receiver operating characteristic (ROC) curves. RESULTS: Of 6985 patients, 3222 (46%) received ≥ one SCM. Of these, 2760 (86%) received SCM(s) with PGx evidence for CYP2B6, CYP2C19, CYP2D6, or SLC6A4; 2719 (84%) received a drug metabolized by CYP2D6, most commonly hydrocodone (40.4%), ondansetron (35.6%), oxycodone (24.2%), and/or tramadol (7.1%). Based on this, about one quarter were expected to have altered metabolism and/or drug response. One third were prescribed two or more SCMs with PGx evidence. About half reported at least one severe symptom, which significantly correlated with SCM prescribing (p < 0.001). Threshold scores were identified that highly correlated with SCM prescribing for anxiety, depression, nausea, neuropathy, pain, and sleep. CONCLUSION: About half presented with significant symptom burden, which highly correlated with SCM prescribing. Most received SCMs with PGx evidence. Preemptive PGx testing for these variants should be evaluated in prospective trials to evaluate the impact on symptom control.

Early-onset pancreatic cancer: an institutional series evaluating end-of-life care.

PURPOSE: Little is known about the use of palliative and hospice care and their impact on healthcare utilization near the end of life (EOL) in early-onset pancreatic cancer (EOPC). METHODS: Patients with EOPC (≤ 50 years) were identified using the institutional tumor registry for years 2011-2018, and demographic, clinical, and rates of referral to palliative and hospice services were obtained retrospectively. Predictors of healthcare utilization, defined as use of ≥ 1 emergency department (ED) visit or hospitalization within 30 days of death, place of death (non-hospital vs. hospital), and time from last chemotherapy administration prior to death, were assessed using descriptive, univariable, and multivariable analyses including chi-square and logistic regression models. RESULTS: A total of 112 patients with EOPC with a median age of 46 years (range, 29-50) were studied. Forty-four percent were female, 28% were Black, and 45% had metastatic disease. Fifty-seven percent received palliative care at a median of 7.8 weeks (range 0-265) following diagnosis. The median time between last chemotherapy and death was 7.9 weeks (range 0-102). Seventy-four percent used hospice services prior to death for a median of 15 days (range 0-241). Rate of healthcare utilization at the EOL was 74% in the overall population. Black race and late use of chemotherapy were independently associated with increase in ED visits/hospitalization and hospital place of death. CONCLUSIONS: Although we observed early referrals to palliative care among patients with newly diagnosed EOPC, short duration of hospice enrollment and rates of healthcare utilization prior to death were substantial.

We report performance status in oncology-but not nutritional status?

Performance status (PS) scales are used routinely in clinical oncology to evaluate functional status and help direct treatment decisions. PS is also used to determine research protocol eligibility, indicate treatment response, and evaluate toxicity in oncology clinical trials. Malnutrition (like poor PS) is associated with adverse outcomes such as lower tolerance to anti-tumor treatment, poor quality of life, and decreased survival. Nutritional status is therefore arguably as important as PS for cancer outcomes. Despite well-documented adverse consequences for patients, malnutrition also often goes undiagnosed until severe depletion is evident. If the predictive importance of nutritional status is comparable to PS, why is nutritional status not routinely used along with PS to guide treatment decisions? There is compelling evidence to support the predictive abilities of both PS and nutritional status in cancer outcomes and treatment decision-making. Perhaps, PS may be a proxy for nutritional status. Nutritional status might also serve as an effective tool for patient selection and stratification in oncology trials. Together with PS, it might provide important and distinct prognostic information; we propose both should be routinely included in outcome studies. The extent to which impaired PS may be a surrogate for malnutrition warrants investigation. Given its comparable importance to PS, it is inexcusable that nutritional status is not given the prominence it deserves as a key patient-reported outcome.

Self-reported and objective taste and smell evaluation in treatment-naive solid tumour patients.

BACKGROUND: Taste and smell abnormalities (TSA) commonly occur in cancer and are associated with anorexia, early satiety, malnutrition, weight loss and reduced quality of life. A recent study found a high TSA prevalence in newly diagnosed cancer patients before treatment. This suggests that TSA may originate from the tumour itself. No previous study has examined TSA, both subjectively and objectively, in newly diagnosed, treatment-naïve cancer patients. This study aimed to address this gap. METHODS: This prospective observational study recruited consecutive, newly diagnosed, treatment-naïve patients with solid tumours at Radiation Oncology Out-patients. Self-reported taste and smell changes since becoming ill were evaluated using modified Taste and Smell Survey, and objective taste and smell tests were conducted using 'Sniffin' Sticks Olfactory Test® and Burghart Taste Strips®. Nutritional status was assessed with abridged Patient-Generated Subjective Global Assessment. RESULTS: Thirty completed the study. Seventy-four per cent had at least one TSA. Taste changes and/or abnormalities were more prevalent than smell, and subjective taste changes more common than objective abnormalities. Although less common, smell abnormalities impacted quality of life more. TSA characteristics were heterogeneous. Forty-seven per cent were at malnutrition risk. No association was found between TSA and nutritional status. CONCLUSIONS: Over two thirds had at least one TSA and almost half were at malnutrition risk. Self-reported TSA included changes in taste and smell perception, and most commonly persistent bad taste. This study demonstrated the complexity of TSA assessment and the prevalence, severity and impact of these and related symptoms in treatment-naïve cancer patients.

Enteral and parenteral nutrition in cancer patients, a comparison of complication rates: an updated systematic review and (cumulative) meta-analysis.

INTRODUCTION: Weight loss in cancer patients is a worrisome constitutional change predicting disease progression and shortened survival time. A logical approach to counter some of the weight loss is to provide nutritional support, administered through enteral nutrition (EN) or parenteral nutrition (PN). The aim of this paper was to update the original systematic review and meta-analysis previously published by Chow et al., while also assessing publication quality and effect of randomized controlled trials (RCTs) on the meta-conclusion over time. METHODS: A literature search was carried out; screening was conducted for RCTs published in January 2015 up until December 2018. The primary endpoints were the percentage of patients achieving no infection and no nutrition support complications. Secondary endpoints included proportion of patients achieving no major complications and no mortality. Review Manager (RevMan 5.3) by Cochrane IMS and Comprehensive Meta-Analysis (version 3) by Biostat were used for meta-analyses of endpoints and assessment of publication quality. RESULTS: An additional seven studies were identified since our prior publication, leading to 43 papers included in our review. The results echo those previously published; EN and PN are equivalent in all endpoints except for infection. Subgroup analyses of studies only containing adults indicate identical risks across all endpoints. Cumulative meta-analysis suggests that meta-conclusions have remained the same since the beginning of publication time for all endpoints except for the endpoint of infection, which changed from not favoring to favoring EN after studies published in 1997. There was low risk of bias, as determined by assessment tool and visual inspection of funnel plots. CONCLUSIONS: The results support the current European Society of Clinical Nutrition and Metabolism guidelines recommending enteral over parenteral nutrition, when oral nutrition is inadequate, in adult patients. Further studies comparing EN and PN for these critical endpoints appear unnecessary, given the lack of change in meta-conclusion and low publication bias over the past decades.

Correction to: Enteral and parenteral nutrition in cancer patients, a comparison of complication rates: an updated systematic review and (cumulative) meta-analysis.

The appendices were incorrectly numbered in the original article. Please see below correcct appendices.

Diet and nutrition information on nine national cancer organisation websites: A critical review.

INTRODUCTION: National Cancer Organisations (NCO) provide web-based diet and nutrition information for patients with all types and stages of cancer. We examined diet and nutrition information provided by nine NCO in English-speaking countries. METHODS: Diet and nutrition information was examined under four headings: disease phases, treatment modalities, nutrition impact symptoms and cancer primary sites. We also examined the degree of concordance between NCO websites and appraised the readability of materials. RESULTS: Nine NCO websites from six English-speaking countries were included: Australia, Canada, Ireland, New Zealand, the United Kingdom and the United States. All provided general healthy eating advice. Information at diagnosis and pre-treatment was inadequate, but well-addressed for survivorship. Specific treatment modalities such as biological and hormone therapy were largely ignored. Symptom management was well-addressed, with some exceptions. Cancer site-specific advice was readily available. All recommended consultation with a dietitian/healthcare professional for personalised guidance. Only one met the universal health literacy standard. CONCLUSIONS: NCO websites provided important general diet and nutrition information for cancer patients. The information was reliable and safe, but more in-depth, evidence-based and health-literate information is required. There is an urgent need for an international consensus for consistent cancer diet and nutrition advice.

EEG Correlates of Central Origin of Cancer-Related Fatigue.

The neurophysiological mechanism of cancer-related fatigue (CRF) remains poorly understood. EEG was examined during a sustained submaximal contraction (SC) task to further understand our prior research findings of greater central contribution to early fatigue during SC in CRF. Advanced cancer patients and matched healthy controls performed an elbow flexor SC until task failure while undergoing neuromuscular testing and EEG recording. EEG power changes over left and right sensorimotor cortices were analyzed and correlated with brief fatigue inventory (BFI) score and evoked muscle force, a measure of central fatigue. Brain electrical activity changes during the SC differed in CRF from healthy subjects mainly in the theta (4-8 Hz) and beta (12-30 Hz) bands in the contralateral (to the fatigued limb) hemisphere; changes were correlated with the evoked force. Also, the gamma band (30-50 Hz) power decrease during the SC did not return to baseline after 2 min of rest in CRF, an effect correlated with BFI score. In conclusion, altered brain electrical activity during a fatigue task in patients is associated with central fatigue during SC or fatigue symptoms, suggesting its potential contribution to CRF during motor performance. This information should guide the development and use of rehabilitative interventions that target the central nervous system to maximize function recovery.

Clinical significance of weight changes at diagnosis in solid tumours.

PURPOSE: Weight changes occur throughout the cancer trajectory. Most research has focused on changes during or after treatment, so clinical significance of change at diagnosis remains unclear. This study aimed to determine prevalence, predictors and prognostic significance of weight changes at diagnosis in outpatients with solid tumours presenting to a tertiary academic medical centre. METHODS: A retrospective study of the electronic medical record was conducted (n = 6477). Those with weight recorded within 6 months of cancer diagnosis (pre-diagnosis, T0) and 2 subsequent weights (diagnosis, T1; final visit, T2) were identified (n = 4258). Percentage weight change was categorised into four bands (0.1-2.4%; 2.5-5%; 5.01-9.9%; ≥ 10%) for gain and loss. A stable category was also included. RESULTS: Mean age is 61 ± 12.5 years. Common tumour sites: breast (17%; n = 725), prostate (16%; n = 664), lung (14%; n = 599). 15% (n = 652) had metastatic disease at T1. 98% (n = 4159) had weight change at T1. Head & neck and upper gastrointestinal cancers were significantly associated with weight loss (p < 0.001). Worst survival occurred with ≥ 10% weight gain or ≥ 10% weight loss. Overweight or obese body mass index with any percentage weight change band was associated with better overall survival. CONCLUSIONS: Most had evidence of clinically significant weight changes at diagnosis. Weight loss at diagnosis was associated with a higher risk of further weight loss. A detailed weight history at cancer diagnosis is essential to identify and intervene for those most at risk of weight change-related early mortality.

Device mechanics and evaluation of inspiratory flow rate required of the beclomethasone dipropionate breath-actuated inhaler.

Background: Approximately 80% of patients with asthma and chronic obstructive pulmonary disease incorrectly use a metered-dose inhaler and, therefore, fail to obtain full benefit from their inhaler medication. Beclomethasone dipropionate (BDP) hydrofluoroalkane, an inhalation aerosol administered via a breath-actuated inhaler (BAI) has been designed to improve ease of use over press-and-breathe metered-dose inhalers by eliminating the need for hand-breath coordination. Objective: To present the mechanics of the BAI device, assess the minimum reliable inspiratory flow rate required to trigger an actuation, and evaluate if intended users can safely and effectively use the BDP BAI according to the instructions for use (IFU). Methods: Six random batches (three batches each of 40 µg and 80 µg) of 10 inhalers were evaluated for the minimum inspiratory flow rate required for actuation trigger. Each inhaler was tested for actuation at five flow rates: 12, 14, 16, 18, and 20 L/min. Simulated-use testing was conducted with 91 participants from six representative user groups in the United States to assess the use of a placebo-filled production-equivalent BDP BAI according to the IFU. Results: Across the 40-µg batches, 83% of the devices actuated at 16 L/min and 100% actuated at 18 and 20 L/min. For the 80-µg batches, 67% and 100% actuated at 18 L/min and 20 L/min, respectively. All the participants demonstrated successful use of the BDP BAI during the study session. Isolated safety-critical errors with the potential for no-dose delivery were recorded for 15 participants but were considered unrelated to the design of the IFU. Conclusion: The BDP BAI consistently triggered actuation at an airflow rate of 20 L/min and was successfully used based on guidance from the IFU only. This device provides an alternative for patients who find it difficult to use metered-dose inhaler devices correctly.

The pathophysiology of cancer-related fatigue: current controversies.

Fatigue is one of the most common and debilitating cancer symptoms, and is associated with impaired quality of life. The exact pathophysiology of cancer-related fatigue (CRF) is poorly understood, but in any individual, it is likely multifactorial and involves inter-related cytokine, muscular, neurotransmitter, and neuroendocrine changes. Underlying CRF mechanisms proposed include central and peripheral hypotheses. Central mechanisms include hypotheses about cytokine dysregulation, hypothalamic-pituitary-adrenal-axis disruption, circadian rhythm disruption, serotonin, and vagal afferent nerve function while peripheral mechanisms include hypotheses about adenosine triphosphate and muscle contractile properties. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is characteristic. The purpose of this article is to provide a narrative review of the literature and present the current controversies in the pathophysiology of CRF, particularly in relation to central and peripheral hypotheses for CRF. An understanding of pathophysiology may facilitate direct and simple therapeutic interventions for those with cancer.

Oropharyngeal Dysphagia Evaluation Tools in Adults with Solid Malignancies Outside the Head and Neck and Upper GI Tract: A Systematic Review.

Dysphagia is often associated with head and neck and upper gastrointestinal (GI) tract cancers. Evidence suggests that those with solid malignancies in other primary sites may also have swallowing difficulties. Timely and accurate identification of dysphagia is important given the impact it has on hydration, medical treatment, nutrition, prognosis, and quality of life. A systematic review was conducted to identify swallow screening, evaluation, and quality of life tools for those with solid malignancies outside the head and neck and upper GI tract. Ten electronic databases, one journal and two published conference proceedings were searched. Following deduplication, 7435 studies were examined for relevance. No tools were validated solely in this cancer population, though some included this group in larger cohorts. Comments are provided on the diagnostic properties and applicability of these tools. In the absence of appropriate diagnostic instruments, the exact prevalence of dysphagia and its impact on clinical and psychosocial well-being remain unknown. Accurate and adequate measurement of therapeutic intervention is also compromised. This review establishes the need for validated dysphagia evaluation tools for this clinical population.

The Effect of the Pain Symptom Cluster on Performance in Women Diagnosed with Advanced Breast Cancer: The Mediating Role of the Psychoneurological Symptom Cluster.

BACKGROUND: Pain, depression, anxiety, sleep disturbances, and constipation were reported in different symptom clusters at different stages of breast cancer. Managing symptom clusters rather than individual symptoms can improve performance status. AIM: The study examined the effect of pain symptom cluster (pain and constipation) on performance when mediated by the psychoneurological symptom cluster (depression, anxiety, and sleep disturbances) using age as a moderator. DESIGN: A secondary analysis. SETTINGS: Palliative care center at a tertiary medical center in northeast Ohio. PARTICIPANTS: Eighty-six women diagnosed with advanced breast cancer. METHOD: A quantitative cross-sectional approach. RESULTS: Ordinal logistic regression showed that pain symptom cluster did not have a significant mediation effect on performance. Odds ratio indicated that subjects with pain symptom cluster were 63% more likely to be bedridden (odds ratio = 1.63, confidence interval = .69-3.84). Women who reported pain symptom cluster were 5% more likely to have psychoneurological symptom cluster (odds ratio = 1.05, confidence interval = .400-2.774). Stratified analysis of age showed no differences in performance. Post-hoc analysis showed that the components of pain symptom cluster had a significant effect on psychoneurological symptom cluster (odds ratio: 3 [1.18-7.62]). CONCLUSIONS: Pain, constipation, depression, anxiety, and sleep disturbances were highly prevalent in women with advanced breast cancer. However, they tended to cluster in different symptom clusters. Although some findings were not significant, they all supported the direction of the tested hypotheses. Variations in symptom clusters research, including methodology, instruments, statistical tests, and chosen symptom cluster correlation coefficient, should be addressed.

2016 Updated MASCC/ESMO consensus recommendations: Management of nausea and vomiting in advanced cancer.

PURPOSE: The aim of this paper is to review the existing literature related to the management of nausea and vomiting (N & V) in advanced cancer and derive clinical evidence-based recommendations for its management. METHODS: Available systematic reviews on antiemetic drug effectiveness were used. One generic systematic review of antiemetics in advanced cancer (to 2009) was updated to February 2016. Agreement on recommendations was reached between panel members, and these were voted in favor unanimously by the larger antiemetic committee membership (n = 37). RESULTS: The evidence base in this field is minimal with largely poor quality trials or uncontrolled trials and case studies. The level of evidence in most studies is low. The drug of choice for managing N & V in advanced cancer is metoclopramide titrated to effect. Alternative options include haloperidol, levomepromazine, or olanzapine. For bowel obstruction, the recommendation is to use octreotide given alongside an antiemetic (haloperidol) and where octreotide is not an option to use an anticholinergic antisecretory agent. For opioid-induced N & V, no recommendation could be made. CONCLUSION: These new guidelines, based on the existing (but poor) evidence, could help clinicians manage more effectively the complex and challenging symptoms of N & V in advanced cancer.

The psychometric properties of cancer multisymptom assessment instruments: a clinical review.

PURPOSE: Various instruments are used to assess both individual and multiple cancer symptoms. We evaluated the psychometric properties of cancer multisymptom assessment instruments. METHODS: An Ovid MEDLINE search was done. All searches were limited to adults and in English. All instruments published from 2005 to 2014 (and with at least one validity test) were included. We excluded those who only reported content validity. Instruments were categorized by the three major types of symptom measurement scales employed as follows: visual analogue (VAS), verbal rating (VRS), and numerical rating (NRS) scales. They were then examined in two areas: (1) psychometric thoroughness (number of tests) and (2) psychometric strength of evidence (validity, reliability, generalizability). We also assigned an empirical global psychometric quality score (which combined the concepts of thoroughness and strength of evidence) to rank the instruments. RESULTS: We analyzed 57 instruments (17 original, 40 modifications). They varied in types of scales used, symptom dimensions measured, and time frames evaluated. Of the 57, 10 used VAS, 28 VRS, and 19 NRS. The Edmonton Symptom Assessment System (ESAS), ESAS-Spanish, Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), Symptom Distress Scale (SDS), M.D. Anderson Symptom Inventory (MDASI)-Russian, and MDASI-Taiwanese were the most comprehensively tested for validity and reliability. The ESAS, ESAS-Spanish, ASDS-2, Memorial Symptom Assessment Scale (MSAS)-SF, POMS, SDS, MDASI (and some translations), and MDASI-Heart Failure all showed good validity and reliability. CONCLUSIONS: The MDASI appeared to be the best overall from a psychometric perspective. This was followed by the ESAS, ESAS-Spanish, POMS, SDS, and some MDASI translations. VRS-based instruments were most common. There was a wide range of psychometric rigor in validation. Consequently, meta-analysis was not possible. Most cancer multisymptom assessment instruments need further extensive validation to establish the excellent reliability and validity required for clinical utility and meaningful research.

Low 25-hydroxyvitamin D levels in people with a solid tumor cancer diagnosis: the tip of the iceberg?

PURPOSE: Low serum 25-hydroxyvitamin D [25(OH)D] levels have been linked to both cancer incidence and poor prognosis. The frequency of 25(OH)D tests and clinical factors associated with low levels in cancer patients are unknown. PATIENTS AND METHODS: Electronic medical records from 2006 to 2007 of 39,252 adult solid tumor patients were reviewed. Data included demographics, cancer sites (primary and metastatic), and first serum 25(OH)D level during the study period. Laboratory data, comorbidities, selected medications, and anticancer treatment within the prior 2 months were recorded. Data were compared between (1) those tested and not tested and (2) 25(OH)D levels≤10 ng/ml (deficient), 11-30 ng/ml (insufficient), and ≥31 ng/ml (sufficient). Stepwise logistic regression identified independent predictors of low serum 25(OH)D levels. RESULTS: The cohort was 86% Caucasian and 48% female with a mean age of 63±14 years (mean±SD). The most prevalent cancer was breast (19%). In total, 2,098 (5%) had a 25(OH)D test. Of those tested, 133 (6%) had levels≤10 ng/ml and 1,311 (62%) 11-30 ng/ml. Tests were more frequent in females and in those with breast, skin, and thyroid cancers (P<0.001). Low 25(OH)D levels were associated (in univariable analyses) with male gender, non-Caucasian race, gastrointestinal tumor primary sites, metastatic disease, benign liver disease, low serum albumin, and elevated liver enzymes. Significant factors in multivariable models for 25(OH)D levels≤10 and ≤30 ng/ml included non-Caucasian race, primary cancer site, and test calendar month. Vitamin D supplements and recent antineoplastic medication were associated with sufficient levels. CONCLUSIONS: Low (deficient or insufficient) 25(OH)D serum levels were highly prevalent in people with solid tumors. Vitamin D tests were infrequent and paradoxically less often done in high-risk groups. Tests were more frequent in females and in those with breast, skin, and thyroid cancers. Further research should examine role of routine 25(OH)D tests, the clinical consequences of low levels, and therapeutic supplementation in people with cancer.