Vitamin D levels and its relationship with successful completion of adjuvant chemotherapy and improved survival in early stage colorectal cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 549-549
Author(s):  
Khurram Bilal Tariq ◽  
Aaron Gopal ◽  
Asha Nayak-Kapoor

549 Background: Vitamin D deficiency is associated with increased colorectal cancer (CRC) risk and decreased colorectal cancer survival. The purpose of this study was to determine the effect of colorectal cancer adjuvant treatment on the vitamin D status in CRC. Methods: 102 patients at the GCC with Stage I-III CRC were selected between 2009 -2011. A retrospective analyses of baseline vitamin D in these patients was made to determine if vitamin D level predicts survival. Those patients who have received neoadjuvant treatment were excluded. Only patients who had a baseline vitamin D level drawn at baseline were included. Vitamin D sufficiency was defined as serum level of 30ng/ml or greater, insufficiency as 20 to 29ng/ml and deficiency as less than 20ng/ml. Results: Mean age of the patients was 76.4 years. 45 % were Stage I , 35% comprised Stage II and 25% were Stage III. 25OHD Level was insufficient in 85% and deficient in 10% and sufficient in only 5% of the patients. In the patients who received chemotherapy (45% ), those with sufficient vitamin D levels had a statistically longer survival than those with deficient levels (p<0.002). Also the patients with sufficient levels, they were more likely to complete the 6 months of chemotherapy than those with deficient levels (p<0.006). The median Vitamin D level for all 102 patients was 22.8ng/ml. Patients with sufficient vitamin D levels were more likely to have lower body mass index (p<0.01). There was no correlation between race and level of vitamin D. Patients with a sufficient vitamin D Level (25 patients), had a survival which was significantly more than those with deficient levels (p<0.001). Patients with sufficient vitamin D levels were more likely to have stage I and II disease than stage III ( p <0.04). For each stage of CRC, patients with sufficient vitaminD levels had a better overall survival than those with deficient vitamin D level(p<0.01). Conclusions: Patients with sufficient levels of vitamin D are associated with better overall survival in early stage CRC. Whether aggressive vitamin D repletion would improve the outcome in vitamin D deficient CRC patients remains unknown.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3606-3606
Author(s):  
James M. Kinross ◽  
Pol Canal-Noguer ◽  
Marko Chersicola ◽  
Primož Knap ◽  
Marko Bitenc ◽  
...  

3606 Background: Colorectal cancer (CRC) screening programs suffer from poor uptake and biomarkers have limited diagnostic accuracy. The measurement of the methylation status of tumor-derived cell-free DNA in plasma may address these challenges. We used a targeted methylation panel, tumor-derived signal deduction and machine learning algorithm to refine a blood test for the detection of early-stage CRC. Methods: This was a prospective, international multicenter observational cohort study. Plasma samples were collected either prior to a scheduled colonoscopy as part of standard colorectal cancer screening or prior to colonic surgery for primary CRC. Differentially methylated regions (DMRs) were initially selected by analyzing CRC and control tissue samples with whole genome bisulfite sequencing. A targeted sequencing assay was designed to capture these DMRs in plasma ctDNA. Individual sequencing reads were evaluated for cancer-specific methylation signal and scores calculated for each DMR in a sample. A panel of methylation scores originating from 203 DMRs was used in a prediction model building and validated in a test cohort of patients. Results: Calculated scores were used to train a machine learning model on 68 ctDNA samples from 18 early stage (I-II) and 16 late-stage (III-IV) CRC patients and 34 age, BMI, gender and country of origin matched neoplasia-free controls (median age 63 [50-74], mean BMI 27 [19.5-37], female 50%, Spanish and Ukrainian population, distal cancers 50%). This model was then applied to an independent set of subjects from Spanish, Ukraine and Germany, including 36 stage I-IV cancer patients (median age 61.5 [55-82], BMI 28 [16-39], female 47%, 42% of the tumors were distal) and 159 age and sex matched controls. 87 of the control patients had a negative colonoscopy finding (cNEG), 19 had hyperplastic polyps (HP), 37 had small non-advanced adenomas (NAA) and 16 were diagnosed with other benign gastrointestinal diseases (GID). The model correctly classified 92% (33/36) of CRC patients. Sensitivity per cancer stage ranged from 83% (5/6) for stage I, 92% (11/12) for stage II, 92% (12/13) for stage III to 100% (5/5) for stage IV. Specificity of the model was 97% (154/159), with 100% (37/37) NAA, 94% (15/16) GID, 95% (18/19) HP and 97% cNEG patients correctly identified. Lesion location, gender, BMI, age and country of origin were not significantly correlated to prediction outcome. Conclusions: Methylation sequencing data analyzed using read-wise scoring approach combined with a machine-learning algorithm is highly diagnostic for early-stage (I-II) CRCs (89% sensitivity at 97% specificity). This method could serve as the basis for a highly accurate and minimally invasive blood-based CRC screening test with significant implications for the clinical utility of ctDNA in early-stage cancer detection.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Inge van den Berg ◽  
Robert R. J. Coebergh van den Braak ◽  
Jeroen L. A. van Vugt ◽  
Jan N. M. Ijzermans ◽  
Stefan Buettner

Abstract Background Colorectal cancer is the third most common type of cancer in the world. We characterize a cohort of patients who survived up to 5 years without recurrence and identify factors predicting the probability of cure. Methods We analyzed data of patients who underwent curative intent surgery for stage I–III CRC between 2007 and 2012 and who had had been included in a large multicenter study in the Netherlands. Cure was defined as 5-year survival without recurrence. Survival data were retrieved from a national registry. Results Analysis of data of 754 patients revealed a cure rate of 65% (n = 490). Patients with stage I disease and T1- and N0-tumor had the highest probability of cure (94%, 95% and 90%, respectively). Those with a T4-tumor or N2-tumor had the lowest probability of cure (62% and 50%, respectively). A peak in the mortality rate for older patients early in follow-up suggests early excess mortality as an explanation. A similar trend was observed for stage III disease, poor tumor grade, postoperative complications, sarcopenia, and R1 resections. Patients with stage III disease, poor tumor grade, postoperative complications, sarcopenia, and R1 resections show a similar trend for decrease in CSS deaths over time. Conclusion In the studied cohort, the probability of cure for patients with stage I–III CRC ranged from 50 to 95%. Even though most patients will be cured from CRC with standard therapy, standard therapy is insufficient for those with poor prognostic factors, such as high T- and N-stage and poor differentiation grade.


2018 ◽  
Vol 29 ◽  
pp. ix41
Author(s):  
D. Ng ◽  
R. Tan ◽  
R. Sultana ◽  
M. Ang ◽  
W. Lim ◽  
...  

BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Hidetoshi Mezawa ◽  
Tsutomu Sugiura ◽  
Michiaki Watanabe ◽  
Chihiro Norizoe ◽  
Daisuke Takahashi ◽  
...  

2021 ◽  
Vol 11 ◽  
pp. 123-133
Author(s):  
Fauzan Herdian ◽  
Fahmi Radityamurti ◽  
Tiara Bunga Mayang Permata ◽  
Handoko Handoko ◽  
Henry Kodrat ◽  
...  

Introduction: Colorectal carcinoma is one of the cancers with a high disease burden globally. Previous observational studies have found a connection between colorectal cancer incidence with sunlight exposure and vitamin D levels. Subsequent studies investigated this relationship further and found various anti-tumoral pathways regulated by vitamin D in colorectal tissue. This paper aims to elucidate the actions of those pathways in preventing the malignant transformation of the colorectal cell by reviewing relevant literature. Methods: A search was conducted on several medical literature electronic databases for original research studying the effects of vitamin D treatment on colorectal adenoma and colorectal cancer and its underlying anti-tumoral mechanism. A total of 122 studies were included for evaluation. Results: Twenty-seven studies passed for analysis. These in vitro and in vivo study reveals that vitamin D treatment can suppress cell proliferation, induce apoptosis, maintain cellular differentiation, reduce the pro-inflammatory response, inhibit angiogenesis, and hinder metastatic progression in colorectal cancer and colorectal adenoma cells by regulating associated gene transcription or directly prevents activation of selected signalling pathways. Five studies have also shown that adding calcium to vitamin D treatment increases the anti-tumoral activity of vitamin D through cross-talk between both of their pathways. Conclusion: Vitamin D could potentially impede colorectal cancer transformation and growth through interaction with various signalling pathways and regulating gene transcription. Further clinical studies are needed to confirm whether vitamin D can be used as the basis of targeted colorectal cancer therapy using its inherent anti-tumoral properties.


2019 ◽  
Author(s):  
Lin Zhang ◽  
Huachun Zou ◽  
Yang Zhao ◽  
Chunlei Hu ◽  
Adejare (Jay) Atanda ◽  
...  

ABSTRACTObjectivesTo assess the association between blood circulating Vitamin D levels and colorectal cancer risk in the Asian population.DesignThis is a systematic review and dose-response meta-analysis of observational studies that investigated the relationship between blood circulating Vitamin D levels and colorectal cancer risk in the Asian population.Data SourcesRelevant studies were identified through a literature search in MEDLINE, EMBASE, and Web of Science from January 1980 to 31 January 2019. Eligibility criteria: original studies published in peer-reviewed journals investigating the association between blood circulating Vitamin D levels and the risk of colorectal cancer and/or adenoma in Asian countries.Data extraction and synthesisTwo authors independently extracted data and assessed the quality of included studies. Study-specific ORs were pooled using a random-effects model. A dose-response meta-analysis was performed with generalized least squares regression. We applied the Newcastle-Ottawa Scale quality assessment to evaluate the quality of the selected studies.ResultsThe eight included studies encompassed a total of 2,916 cases and 6,678 controls. The pooled ORs of colorectal cancer for the highest versus lowest categories of blood circulating Vitamin D levels was 0.75 [95% CI, 0.58-0.97] up to 36.5 ng/mL in the Asian population. There was heterogeneity among the studies (I2=53.9%, Pheterogeneity=0.034). The dose-response meta-analysis indicated a significant linear relationship (Pnon-linearity=0.11). An increment of 16 ng/mL in blood circulating Vitamin D level corresponded to an OR of 0.79 [95% CI, 0.64-0.97].ConclusionsThe results of this meta□analysis indicate that blood circulating Vitamin D level is associated with decreased risk of colorectal cancer in Asian countries. The dose-response meta-analysis shows that the strength of this association among the Asian population is similar to that among the Western population. Our study suggests that the Asian population should improve nutritional status and maintain a higher level of blood circulating Vitamin D.Strengths and limitations of this studyOur study seeks to extend previous work by including a number of new studies and by distinguishing the Asian population explicitly.The number of included studies is not sufficient to provide a robust estimate, so the results should be interpreted in the context of the limitations of the available data.Heterogeneous definitions of blood circulating Vitamin D categories were used across studies. The variability in definitions could limit comparability between studies.Our study included seven case-control studies; the study design implies that the measurement of blood circulating Vitamin D is measured in individuals already diagnosed with colorectal cancer. Results from case-control studies need to be interpreted cautiously because of the potential for reverse causation.Time of blood sampling in relation to outcome ascertainment also varied among studies. Such cross-sectional measurements may not accurately reflect an individual’s Vitamin D status across time.


2006 ◽  
Vol 24 (30) ◽  
pp. 4833-4839 ◽  
Author(s):  
Robert Timmerman ◽  
Ronald McGarry ◽  
Constantin Yiannoutsos ◽  
Lech Papiez ◽  
Kathy Tudor ◽  
...  

PurposeSurgical resection is standard therapy in stage I non–small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population.Patients and MethodsEligible patients included clinically staged T1 or T2 (≤ 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks.ResultsAll 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months. The 3-month major response rate was 60%. Kaplan-Meier local control at 2 years was 95%. Altogether, 28 patients have died as a result of cancer (n = 5), treatment (n = 6), or comorbid illnesses (n = 17). Median overall survival was 32.6 months and 2-year overall survival was 54.7%. Grade 3 to 5 toxicity occurred in a total of 14 patients. Among patients experiencing toxicity, the median time to observation was 10.5 months. Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83% compared with only 54% for patients with central tumors.ConclusionHigh rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC. Both local recurrence and toxicity occur late after this treatment. This regimen should not be used for patients with tumors near the central airways due to excessive toxicity.


2017 ◽  
Vol 17 (2) ◽  
pp. 217-225 ◽  
Author(s):  
Kejia Hu ◽  
David Frederick Callen ◽  
Jiayuan Li ◽  
Hong Zheng

Studies have shown that vitamin D could have a role in breast cancer survival; however, the evidence of the relationship between patients’ vitamin D levels and their survival has been inconsistent. This meta-analysis explores possible dose-response relationships between vitamin D levels and overall survival by allowing for differences in vitamin D levels among populations of the various studies. Studies relating vitamin D (25-OH-D [25-hydroxyvitamin D]) levels in breast cancer patients with their survival were identified by searching PubMed and Embase. A pooled HR (hazard ratio) comparing the highest with the lowest category of circulating 25-OH-D levels were synthesized using the Mantel-Haenszel method under a fixed-effects model. A two-stage fixed-effects dose-response model including both linear (a log-linear dose-response regression) and nonlinear (a restricted cubic spline regression) models were used to further explore possible dose-response relationships. Six studies with a total number of 5984 patients were identified. A pooled HR comparing the highest with the lowest category of circulating 25-OH-D levels under a fixed-effects model was 0.67 (95% confidence interval = 0.56-0.79, P < .001). Utilizing a dose-response meta-analysis, the pooled HR for overall survival in breast cancer patients was 0.994 (per 1 nmol/L), Pfor linear trend < .001. At or above a 23.3 nmol/L threshold, for a 10 nmol/L, 20 nmol/L, or 25 nmol/L increment in circulating 25-OH-D levels, the risk of breast cancer overall mortality decreased by 6%, 12%, and 14%, respectively. There was no significant nonlinearity in the relationship between overall survival and circulating 25-OH-D levels. Our findings suggest that there is a highly significant linear dose-response relationship between circulating 25-OH-D levels and overall survival in patients with breast cancer. However, better designed prospective cohort studies and clinical trials are needed to further confirm these findings.


2018 ◽  
Vol 28 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Jennifer J. Mueller ◽  
Henrik Lajer ◽  
Berit Jul Mosgaard ◽  
Slim Bach Hamba ◽  
Philippe Morice ◽  
...  

ObjectiveWe sought to describe a large, international cohort of patients diagnosed with primary mucinous ovarian carcinoma (PMOC) across 3 tertiary medical centers to evaluate differences in patient characteristics, surgical/adjuvant treatment strategies, and oncologic outcomes.MethodsThis was a retrospective review spanning 1976–2014. All tumors were centrally reviewed by an expert gynecologic pathologist. Each center used a combination of clinical and histologic criteria to confirm a PMOC diagnosis. Data were abstracted from medical records, and a deidentified dataset was compiled and processed at a single institution. Appropriate statistical tests were performed.ResultsTwo hundred twenty-two patients with PMOC were identified; all had undergone primary surgery. Disease stage distribution was as follows: stage I, 163 patients (74%); stage II, 8 (4%); stage III, 40 (18%); and stage IV, 10 (5%). Ninety-nine (45%) of 219 patients underwent lymphadenectomy; 41 (19%) of 215 underwent fertility-preserving surgery. Of the 145 patients (65%) with available treatment data, 68 (47%) had received chemotherapy—55 (81%) a gynecologic regimen and 13 (19%) a gastrointestinal regimen. The 5-year progression-free survival (PFS) rates were 80% (95% confidence interval [CI], 73%–85%) for patients with stage I to II disease and 17% (95% CI, 8%–29%) for those with stage III to IV disease. The 5-year PFS rate was 73% (95% CI, 50%–86%) for patients who underwent fertility-preserving surgery.ConclusionsMost patients (74%) presented with stage I disease. Nearly 50% were treated with adjuvant chemotherapy using various regimens across institutions. The PFS outcomes were favorable for those with early-stage disease and lower but acceptable for those who underwent fertility preservation.


Sign in / Sign up

Export Citation Format

Share Document