Feasibility of preemptive pharmacogenetic testing in colorectal cancer patients within a community oncology setting

Introduction Pharmacogenetics, in hand with precision medicine in oncology, represents an opportunity to holistically tailor a patient’s treatment regimen using both somatic and germline variants to improve efficacy and decrease toxicity. Colorectal cancer patients represent a population with frequent use of fluoropyrimidine and irinotecan and are an ideal opportunity for implementation of preemptive pharmacogenetics as evidence supports pharmacogenetic testing for DPYD and UGT1A1 to reduce fluoropyrimidine and irinotecan toxicities. Methods This was a single arm proof-of-concept study at a large community-based health system. Participants provided samples for pharmacogenetic testing via an external vendor prior to chemotherapy initiation and an oncology pharmacist was responsible for pharmacogenetic interpretation and pharmacogenetic-guided therapeutic recommendation to the treating provider. Results A total of 24 (60%) participants had a UGT1A1 variant. All participants (100%) were DPYD*1/*1. Results were available and interpreted for 29/40 (72.5%) participants prior to scheduled chemotherapy initiation (p value <0.014). Of the participants whose results were available in 5 weekdays or less (n = 23), 20 (87%) were communicated with the treating provider prior to scheduled chemotherapy administration. A total turnaround time of 5 days or less was significantly associated with PGx feasibility in a community-based oncology clinic (p = 0.03). Conclusions In conclusion, we were able to show that implementation of preemptive pharmacogenetic testing into a community oncology clinic with results interpretation available prior to scheduled initiation of chemotherapy was feasible. As pharmacogenetic testing in oncology expands, pharmacists should be prepared to optimize supportive medication regimens as well as chemotherapy with pharmacogenetic results.

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Patterns of osteoporosis (OP) in survivors of colorectal cancer (CRC) enrolled on SWOG trials.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.10056 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 10056-10056

Author(s):

Afsaneh Barzi ◽

Dawn L. Hershman ◽

Cathee Till ◽

Heinz-Josef Lenz ◽

Howard S. Hochster ◽

...

Keyword(s):

Colorectal Cancer ◽

Fracture Risk ◽

Cancer Patients ◽

Phase Iii ◽

P Value ◽

National Hospital Discharge Survey ◽

Prostate Cancer Prevention ◽

The Difference ◽

Using Data ◽

Colorectal Cancer Patients

10056 Background: There are currently 1.5 million CRC survivors in US and this number will continue to rise with advancements in treatment. The risk of OP in CRC survivors has not been well described. Methods: We used data from 3 SWOG CRC treatment trials, all of which were phase III and had long term follow-up. Enrollees were linked to Medicare claim files for identification of OP and fractures using HCPCS and ICD9 codes. First, we compared patterns of osteoperosis and fracture risk by sex in colorectal cancer patients. To assess whether patterns of fracture risk by sex differed between patients with vs. without colorectal cancer, we compared the difference in fracture risk by sex in colorectal cancer patients to the difference in fracture risk by sex in the general U.S. population, using data from the National Health Interview Survey (NHIS) and the National Hospital Discharge Survey (NHDS). Finally, we assessed whether absolute estimates of osteoperosis and fracture risk differed between men with colorectal cancer and men without colorectal cancer. Comparison data for men without colorectal cancer were obtained from the placebo arm of the Prostate Cancer Prevention trial (PCPT). Results: We linked 1233 CRC cases with Medicare claims. The median age at CRC diagnosis was marginally higher for women (65 vs 64 ys, p = 0.03). 47% of females, 15% of men with CRC, and 19% of men without CRC had a OP diagnosis. The female to male ratio of osteoporotic fracture in general U.S. population was 1.67, while the same ratio in CRC survivors was 2.84, an increase of 70% (p-value < 0.001). Conclusions: Our study indicates that the risk disparity for OP fracture for females is much greater in CRC survivors than in the general U.S. population. This may be due to more OP diagnoses for female CRC survivors, but not for male CRC survivors.

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Perbandingan indeks massa tubuh, lingkar pinggang, dan rasio pinggang pinggul sebagai faktor risiko kanker kolorektal

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.8.2.2016.12670 ◽

2016 ◽

Vol 8 (2) ◽

Author(s):

Yuansun Khosama ◽

Heber B. Sapan ◽

Jimmy Panelewen ◽

Laurens T. B. Kalesaran

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Cancer Patients ◽

Body Fat ◽

P Value ◽

Fat Tissue ◽

Anthropometric Parameters ◽

Cross Sectional ◽

Significant Difference ◽

Colorectal Cancer Patients

Abstract: Globally, colorectal cancer is the 4th cause of deaths. Risk factors of colorectal cancer are divided into modified and unmodified; obesity is one of the modified factors. It is accepted that insulin resistance and metabolic dysfunction act as a link between obesity and colorectal cancer. Distribution of fat tissue in Asian including Indonesian differs from that in Western people. Although of the same body mass index (BMI), Asian have higher fat tissue level than the Westerns. Body fat tissue can be measured by using BMI, waist circumference (WC), and waist-hip ratio (WHR). Acurate anthropometric measurements play some important roles in prevention of colorectal cancer. This study aimed to compare the three anthropometric parameters in colorectal cancer patients. This was a descriptive analytical study with a cross sectional design. Subjects were colorectal patients admitted to Surgery Department of Sam Ratulangi University Manado and its collaborationg hospitals from June 2015 to December 2015. There were 33 colorectal cancer patients in this study consisted of 22 males and 11 females. The ages ranged from 27 years to 77 years. The sensitivity result was as follows: BMI 33.3%, WC 51%, and WHR 42%, meanwhile the specifity result was 75.80%; 60.60%; and 60.60% respectively. The X2 test showed a P value of 0.327. Conclusion: Statistically, BMI, WC, and WHR showed no significant difference as the risk factors of colorectal cancer. However, the three parameters have to be used together to detect the accumulation of body fat tissue. It is suggested that the detection has to be applied in primary health care to diminish the colorectal cancer risk.Keywords: colorectal cancer, BMI, WC, WHRAbstrak: Kanker kolorektal (KKR) merupakan penyebab kematian keempat terbanyak di dunia. Secara garis besar faktor risiko KKR terbagi atas yang tidak dapat dimodifikasi dan yang dapat dimodifikasi, salah satunya ialah obesitas. Resistensi insulin dan disfungsi metabolik menjadi penghubung antara obesitas dan karsinoma kolorektal. Distribusi lemak tubuh pada orang Asia, termasuk Indonesia, berbeda dengan distribusi lemak tubuh pada orang Barat. Pada indeks massa tubuh (IMT) yang sama, orang Asia memiliki kadar lemak tubuh yang lebih tinggi dibandingkan orang Barat. Kadar lemak tubuh dapat dinilai melalui pengukuran IMT, lingkar pinggang (LP), dan rasio pinggang-pinggul (RPP). Penelitian ini bertujuan untuk membandingkan ketiga parameter ukuran antropometri tubuh pada pasien KKR. Penentuan patokan antropometri tubuh yang tepat membantu tindakan preventif KKR. Jenis penelitian ialah deskriptif analitik dengan desain potong lintang. Subyek penelitian ialah pasien KKR yang dirawat di Bagian Bedah Fakultas Kedokteran Universitas Sam Ratulangi Manado dan RS jejaringnya sejak bulan Juni 2015-Desember 2015. Hasil penelitian mendapatkan 33 pasien KKR (22 laki-laki dan 11 perempuan). Usia pasien berkisar 27-77 tahun. Sensitivitas IMT ialah 33,3%; LP 51%; dan RPP 42%, sedangkan spesifisitas berturut-turut ialah 75,80%; 60,60%; dan 60,60%. Uji X2 mendapatkan nilai P = 0,327. Simpulan: IMT, LP, dan RPP secara statistik tidak menunjukkan perbedaan bermakna sebagai faktor risiko KKR. Ketiganya harus diukur bersama-sama untuk mendeteksi akumulasi lemak tubuh. Disarankan deteksi harus dimulai di pelayanan primer untuk mengurangi risiko KKR.Kata kunci: KKR, IMT, LP, RPP

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Derajat Toksisitas Hemoglobin Pada Penderita Kanker Kolorektal Yang Mendapat Kemoterapi CapeOX

ARTERI : Jurnal Ilmu Kesehatan ◽

10.37148/arteri.v1i4.86 ◽

2020 ◽

Vol 1 (4) ◽

pp. 299-305

Author(s):

Yusmaidi ◽

Jordy Oktobiannobel ◽

Muhammad Nur ◽

Bella Sabila Dananda

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

The United States ◽

Hematological Toxicity ◽

P Value ◽

Chemotherapy Drugs ◽

Number Of Patients ◽

Significant Difference ◽

The Difference ◽

Colorectal Cancer Patients

Advances in the treatment and use of chemotherapy have been shown to improve the life expectancy rate for colorectal cancer patients. Studies conducted in China and Hongkong have shown that CapeOX combination chemotherapy regimens are more commonly used than in Europe and the United States. However, the use of chemotherapy drugs containing oxaliplatin and capecitabine can cause side effects such as hematological toxicity, which is one of them is anemia. This study aims to determine the difference in the form of a decrease in the average levels of hemoglobin and the degree of hemoglobin toxicity in colorectal cancer patients undergoing CapeOX chemotherapy. The Design in this study is a historical (retrospective) cohort. This study sample was 70 colorectal cancer patients who received CapeOX chemotherapy for 6 cycles at RSUD Dr. H. Abdul Moeloek in 2018-2019. Consecutive sampling is used in the sampling method. The statistical analysis is using Paired T-Test. There is a significant difference in the average hemoglobin level of colorectal cancer patients (p-value = <0.005), which receive CapeOX chemotherapy for 6 cycles. Besides, there is an increase in the number of patients who get hemoglobin toxicity and the chemotherapy cycle. In the first cycle, 59 patients (84.3%) got hemoglobin toxicity after chemotherapy, and the number continued to increase to 69 patients (98.6%) in the sixth cycle. There was a decrease in hemoglobin levels in colorectal cancer patients who received CapeOX chemotherapy with p-value = <0.05 and increased patients who got hemoglobin toxicity.

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Comparison Between Wells’ Criteria and Khorana Score in Detecting Asymptomatic Deep Vein Thrombosis in Colorectal Cancer Patients in Dr. Hasan Sadikin Hospital

Journal of Indonesian Society for Vascular and Endovascular Surgery ◽

10.36864/jinasvs.2021.1.006 ◽

2021 ◽

Vol 2 (1) ◽

pp. 17-19

Author(s):

Teguh Marfen Djajakusumah ◽

Putie Hapsari ◽

Daniel Marthin Situmorang ◽

Muhammad Faiz Ulurrosyad

Keyword(s):

Colorectal Cancer ◽

Deep Vein Thrombosis ◽

Cancer Patients ◽

P Value ◽

Risk Category ◽

Vein Thrombosis ◽

High Risk Category ◽

Asymptomatic Patients ◽

Colorectal Cancer Patients ◽

Deep Vein

Background: Deep vein thrombosis is a blood clot that occurs in the deep veins. Fifty percent of patients with deep vein thrombosis do not show clinical symptoms. The incidence of deep vein thrombosis in colorectal cancer patients is higher than in other cancer patients. Several scoring system models, such as Wells’ criteria and Khorana score, were developed to help diagnose deep vein thrombosis . Methods: This study was a prospective observational analytic with cross sectional design that compared the Khorana score with Wells’ criteria in predicting the occurrrence of asymptomatic deep vein thrombosis in colorectal cancer patients. Comparisons were made using Chi Square analytical test and diagnostic tests. Results: A total of 63 patients were obtained. Using Wells’ criteria, 55 patients (87.3%) fell into the mild risk category, 8 patients (12.7%) in the moderate risk category and no patients in the high risk category. Using Khorana score, 35 patients (55.6%) fell into the mild risk category, 28 (44.4%) patients in the moderate risk category, and no high risk category patients were found. There were 14 patients (22.2%) with asymptomatic deep vein thrombosis and 49 patients (77.8%) without deep vein thrombosis. Comparison of the proportion of Wells’ criteria with asymptomatic patients has a p-value of 0.48, while Khorana score with asymptomatic patients has a p-value of 0.001. Conclusion: Khorana score is better than Wells’ criteria in detecting asymptomatic deep vein thrombosis in colorectal cancer patients.

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Disparities in the Use of Chemotherapy and Monoclonal Antibody Therapy for Elderly Advanced Colorectal Cancer Patients in the Community Oncology Setting

The Oncologist ◽

10.1634/theoncologist.2008-0061 ◽

2008 ◽

Vol 13 (8) ◽

pp. 876-885 ◽

Cited By ~ 46

Author(s):

Trevor McKibbin ◽

Christopher R. Frei ◽

Rebecca E. Greene ◽

Peter Kwan ◽

Jody Simon ◽

...

Keyword(s):

Colorectal Cancer ◽

Monoclonal Antibody ◽

Cancer Patients ◽

Advanced Colorectal Cancer ◽

Antibody Therapy ◽

Monoclonal Antibody Therapy ◽

Community Oncology ◽

Colorectal Cancer Patients

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HLA-cw polypmorphism and killer cell immunoglobulin-like receptor (KIR) gene analysis in Korean patients with colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.525 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 525-525

Author(s):

Hyung Jin Kim ◽

In Kyu Lee ◽

Won-Kyung Kang ◽

Jung Hyun Kwon ◽

Seong-Taek Oh

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Nk Cells ◽

Cancer Patients ◽

Ethnic Differences ◽

Killer Cell ◽

P Value ◽

Kir Genes ◽

Cancer Group ◽

Colorectal Cancer Patients

525 Background: Many kinds of genetic and environment factors are involved in colorectal cancer development. Natural killer cells (NK cells) play important roles to protect from viral infections and the early development of cancers, and it is activated or inhibited by killer cell immunoglobulin-like receptors (KIR) which bind to HLA class I. KIR genes are encoded on chromosome 19q13.4. And there are 7 kinds of activating KIRs, and another 7 kinds of inhibiting KIRs. The genetic polymorphisms of KIR genes effect the expression of KIR on NK cells, and there are ethnic differences. In this study, we were trying to investigate the KIR genotype of Korean colorectal cancer patients. Methods: DNAs were extracted from the peripheral bloods from normal populations and Korean colorectal cancer patients. KIR genes were amplified using PCR-SSP methods, and HLA-Cw genes were characterized using PCR methods. The results were analyzed between cancer patients and normal control group. Results: KIR2DL2 and KIR2DS2 were found at low rate and KIR2DL3 were found at high rate compare to the Eastern studies, but the rates were similar with Japan study. In this study, KIR2DS5 (33.2% vs. 20.8%, p-value<0.007) was increased in colorectal cancer group, and in rectal cancer subgroup, KIR3DL1 (93.2%, vs. 98.1%, p-value<0.05), KIR2DS2 (7.8% vs. 19.5%, p-value<0.01), KIR2DS4 (93.2% vs. 98.1%, p-value<0.05) were decreased significantly. HLA-Cw6 (9.1% vs. 15.7%, p-value<0.05) and HLA-Cw7 (17.4% vs. 27.7%, p-value<0.02) were decreased in colorectal cancer group, but no difference was found when they were classified to HLA-C1 and HLA-C2 group. Among the patients with HLA-C1 homozygote, KIR2DS2 was decreased significantly (5.8% vs. 14.5%, p-value<0.004). Conclusions: There are ethnic differences of KIR genotypes. KIR2DS5 is increased in Korean colorectal cancer patients, and in rectal cancer subgroup, KIR3DL1, KIR2DS2 and KIR2DS4 are decreased, so there are immunologic differences between colon and rectal cancers. And among the patients with HLA-C1 homozygote, KIR2DS2 is decreased. Therefore KIR2DS2 in presence of their ligand (HLA-C1 group) may have protective effect against colorectal cancer.

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Prediction of risk scores for colorectal cancer patients from the concentration of proteins involved in mitochondrial apoptotic pathway

10.1101/639740 ◽

2019 ◽

Author(s):

Anjali Lathwal ◽

Chakit Arora ◽

Gajendra P. S. Raghava

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Optimization Technique ◽

Risk Scores ◽

Survival Outcomes ◽

P Value ◽

Apoptotic Pathway ◽

Mitochondrial Apoptotic Pathway ◽

Prognostic Tool ◽

Colorectal Cancer Patients

AbstractOne of the major challenges in managing the treatment of colorectal cancer (CRC) patients is to predict risk scores or level of risk for CRC patients. In past, several biomarkers, based on concentration of proteins involved in type-2/intrinsic/mitochondrial apoptotic pathway, have been identified for prognosis of colorectal cancer patients. Recently, a prognostic tool DR MOMP has been developed that can discriminate high and low risk CRC patients with reasonably high accuracy (Hazard Ratio, HR = 5.24 and p-value = 0.0031). This prognostic tool showed an accuracy of 59.7% when used to predict favorable/unfavorable survival outcomes. In this study, we developed knowledge based models for predicting risk scores of CRC patients. Models were trained and evaluated on 134 stage III CRC patients. Firstly, we developed multiple linear regression based models using different techniques and achieved a maximum HR value of 6.34 with p-value = 0.0032 for a model developed using LassoLars technique. Secondly, models were developed using a parameter optimization technique and achieved a maximum HR value of 38.13 with p-value 0.0006. We also predicted favorable/unfavorable survival outcomes and achieved maximum prediction accuracy value of 71.64%. The performance of our models were evaluated using five-fold cross-validation technique. For providing service to the community we also developed a web server ‘CRCRpred’, to predict risk scores of CRC patients, which is freely available at https://webs.iiitd.edu.in/raghava/crcrpred.

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