Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Colorectal Neoplasms

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

This group will be screened with the risk-based model. The input of the model will be gathered with the FIT, a validated questionnaire, and from data of the Dutch general population registry. The threshold of the model will be set at a calculated risk of 0.10. To comply with ethical guidelines, all participants in this group with a FIT result of \>=15 mcg Hb/g faeces and a calculated risk of \<0.10 will also be offered a colonoscopy.

This group will be screened with the FIT. The threshold of the FIT will be set at \>= 15 mcg Hb/g faeces.

The intervention will be a risk-based logistic regression model that takes multiple variables into account to calculate the risk of advanced neoplasia as an outcome.

Risk-based logistic regression model

FIT is a stool-based test that detects human blood in faeces.

Evelien Dekker, PhD MD

Colorectal Carcinoma (CRC) is the third most frequent diagnosed cancer worldwide, with 1.4 million new cases every year. In an attempt to reduce this number many countries have implemented a nationwide screening programme targeted at detecting CRC in an early phase using fecal immunochemical tests (FITs). People with an elevated level of blood in their stool are offered a colonoscopy, an invasive medical procedure where CRCs and premalignant lesions (together also referred to as advanced neoplasia) can be detected accurately.

However, the current screening method using FIT is not optimal. In FIT-based CRC screening studies, 1 in 4 participants with CRC and 2 in 3 participants with advanced neoplasia receive a negative FIT result. In contrast, an estimated 1 in 2 FIT-positives have advanced neoplasia at colonoscopy.

Recent studies have demonstrated that a risk model that takes into account the FIT result and other risk factors for CRC could enhance the effectiveness of a FIT-based CRC screening programme.

The objective of this study is to assess the yield of advanced neoplasia in the colon and rectum of a FIT-based risk model at colonoscopy, compared to that of a FIT-only CRC screening strategy. Our hypothesis is that a risk-based model yields significantly more advanced neoplasia at colonoscopy than the FIT by itself, and that it does not affect participation rate.

To assess this hypothesis, the investigators have designed a clinical trial in which the investigators randomize 23,000 asymptomatic individuals between the age of 55 and 75 years old to either risk-based screening (intervention group) or FIT-only screening (control group). The intervention group will receive a questionnaire on risk factors of CRC (e.g. smoking, family history of CRC), and a FIT. The control group will only receive the FIT. The positivity threshold of the FIT in both groups will be set at 15 micrograms haemoglobin per gram faeces. The positivity threshold of the risk-based model in the intervention group will be set at 0.10 (out of a range of 0 to 1), a threshold that is calculated with a goal to match the positivity rate of the control group.

Participants with a result that is above the thresholds of the FIT and/or the risk-based model will be invited to undergo a colonoscopy according protocol of the Dutch national screening program. After the study has ended, the investigators will compare both groups to assess our hypotheses.

INTRODUCTION AND RATIONALE Colorectal Cancer (CRC) is the third most frequent diagnosed cancer worldwide, with 1.4 million new cases every year. Mortality of CRC is estimated at around 40%. To reduce the incidence of CRC and to abate the negative consequences associated with CRC, methods for early detection of (pre)malignant colorectal lesions have extensively been researched and implemented. Colonoscopy is the reference standard for the detection of advanced neoplasia, but it requires trained endoscopists, carries a high burden, harbours a risk for complications in patients, and increases societal costs.

Most screening programs use methods to select screening participants with a high risk of advanced neoplasia for colonoscopy. One such method is the detection of blood in stool with faecal immunochemical tests (FITs).

Multiple nation-wide screening programs have now been implemented using FIT, including one in the Netherlands. In the Dutch CRC screening program, using a FIT threshold of 47 µg Hb/g faeces, the sensitivity of FIT in detecting CRC is 85.5%. The sensitivity of FIT in detecting advanced neoplasia (AN) is however substantially lower: 38%.

FIT-based screening also generates a high number of false positives, leading to unnecessary colonoscopies and distress for those patients. Approximately 1 in 2 FIT-positives has advanced neoplasia; the first round of the Dutch CRC screening program, using a FIT threshold of 47 µg Hb/g faeces, reached a positive predictive value of 54%.

Previous studies have demonstrated the existence of clinical risk factors for CRC, such as male gender, age, family history of CRC, and smoking. In a ZonMW sponsored project (ZonMW 50-50115-96-521) our group has shown that higher age, male sex, a family history with close relatives in whom CRC was diagnosed, and active smoking were all associated with the presence of advanced neoplasia (Stegeman et al, Gut, 2014).

Multiple CRC risk models have been developed using these risk factors, but most show only weak discriminatory power. Others have proposed risk models that additionally included molecular markers, increasing performance and discriminatory power, but these markers can be cumbersome to collect and can be costly in respect to the relative cheap FIT test. the investigators propose to combine CRC risk factors with the quantitative FIT result. FIT is a quantitative test with a variable cut-off level, and individuals with higher values of faecal haemoglobin are at higher risk of having advanced neoplasia at the cost of a lower specificity. Therefore, the quantitative result can be used as a weight-factor in a risk model.

Based on information on these risk factors for CRC and the quantitative FIT-result, our FIT-based risk model for CRC screening calculates the personal risk of having advanced neoplasia at colonoscopy. Inviting screening participants with elevated risk for colonoscopy, rather than those whose FIT result exceeds a pre-specified threshold, has the potential to increase the effectiveness and efficiency of FIT-based CRC screening. However, this requires participants to complete the questions about risk.

Our hypothesis is that integration of FIT score with known risk factors (age, gender, smoking, and family history of CRC) improves the number of participants in whom advanced neoplasia is detected, relative to the number of invitees. The investigators will compare a risk-based approach to screening, as described above, to the conventional FIT-only screening in a randomized controlled screening trial.

OBJECTIVES The study hypothesis is that risk-based CRC screening significantly outperforms FIT-only CRC screening in terms of the relative number of invitees in whom advanced neoplasia is detected at colonoscopy.

Primary Research Question: does risk-based CRC screening result in a higher relative number of invitees in whom advanced neoplasia is detected at colonoscopy compared to FIT-only CRC screening?

Secondary Research Questions:

i) Does risk-based CRC screening result in a higher standardized screening yield in whom advanced neoplasia is detected at colonoscopy compared to FIT-only CRC screening? ii) Is the participation rate of risk-based CRC screening non-inferior compared to FIT-only screening? iii) Does risk-based CRC screening result in a higher relative number of invitees in whom advanced neoplasia is detected at colonoscopy compared to FIT-only CRC screening at higher FIT-positivity thresholds (from 15 µg Hb /g faeces)? iv) Does risk-based CRC screening result in a higher relative number of invitees in whom proximally located advanced neoplasia is detected at colonoscopy compared to FIT-only CRC screening?

METHODS The investigators will perform a randomized controlled trial in 23,000 randomly selected men and women (aged 55 to 75 years) eligible for participation in the national CRC screening programme. All eligible participants will be second time invitees, living within a 25 km radius from the colonoscopy centre Bergman Clinics Amsterdam, which is accredited for the national population screening program.

Eligible individuals are randomly allocated on a 1:1 basis to an invitation for either risk-based CRC screening (intervention group) or FIT-only screening (control group). Randomization per household will be done before invitation. Study invitations are sent out by Foundation of Population Screening Mid-West (BoMW) early November 2019 before sending the FIT sample kit of the national screening program to the study cohort from January 2020 to April 2020. The study invitation is combined with a leaflet containing information on study participation. It will also contain an informed consent form, and a one-page questionnaire (if allocated to the intervention arm) with a self-addressed envelope to the research facility. The informed consent form will bear a unique study identification code.

The model that the investigators will use in this study for risk-based screening is derived from a model developed in a primary colonoscopy screening trial (Stegeman et al, Gut, 2014). The investigators have re-evaluated our multivariable risk model for CRC, with the aim to simplify it for daily practice. A number of risk factors (such as elements from diet) added little to the performance of the model, whereas collecting the necessary information proved rather tedious. The quantitative FIT result, age, sex, family history and smoking behaviour were the most decisive factors in the model.

This simplified FIT-based risk model had a performance like that of the extended model in the development dataset. In this study the investigators will calculate the risk of harbouring advanced neoplasia with our simplified FIT-based risk model, based on the quantitative FIT result, age, sex, family history and smoking behaviour (see below). The threshold and expected positivity rate of the risk-based model will be matched to the expected positivity rate of the FIT-only group.

Regression equation of the updated model:

ln(odds AN) = -4.955073942+0.9196052173\*Smoking+0.3364761549\* √FIT+0.370575346\*family history of CRC-0.006934851\*FIT+0.0228752117\*age+0.070972656\*gender

Probability of advanced neoplasia:

P (AN)=e\^((odds AN))/(1+e\^((odds AN))) If invitees that are allocated to the intervention group (i.e. questionnaire and FIT) only return the questionnaire, they do not qualify for a colonoscopy. When consenting invitees in the intervention group prefer not to complete the questionnaire, FIT tests will be analysed at a cut-off of 15 µg Hb/g faeces.

The type of FIT that will be used is the one used in the Dutch national screening programme: FOB-Gold (Sentinel, Italy). FIT-analyses and sending of FIT results will be performed according to the logistics as being used in the national screening. The FIT result and the result of the questionnaire will be entered in a database, to calculate the participant's risk. All FIT positives (≥15 µg Hb/g faeces) will be referred for consultation for colonoscopy at regional endoscopic centres. For the purpose of this study, FIT-negative but risk-positive participants (i.e. the combination of the results of the questionnaire and the quantitative FIT result) will also be invited for consultation for colonoscopy.

Colonoscopy will be performed by endoscopists accredited for our national screening programme and according to national and international quality guidelines. Quality indicators and endoscopic findings will be systematically recorded in a database, according to the standards of the national screening programme. Lesions will be immediately removed, if possible, and otherwise biopsies will be obtained. Histopathological assessment of these tissue samples will provide a definitive diagnosis. Data on location, size, macroscopic aspect, morphology and polypectomy will be recorded for all colonic lesions, which will be collected and evaluated by an accredited GI-pathologist according to the Vienna criteria. Advanced adenomas are defined as adenomas larger than 10 mm, adenomas with high-grade dysplasia or adenomas with a villous component of at least 25%. Advice regarding surveillance colonoscopy after removal of adenomatous polyps, large (≥10 mm) serrated lesions or cancer will be given to the clients according to the Dutch CBO consensus.

Screening invitees can leave the study at any time for any reason if they wish to do so without any consequences. The investigator can decide to withdraw a screening invitee from the study for urgent medical reasons.

STATISTICAL ANALYSIS

Primary outcome The difference in screening yield will be estimated and expressed as an absolute difference per 1,000 invitees, with 95% confidence intervals. The investigators will test the null hypothesis of no difference in yield between the intervention and control group using the chi-square test.

Secondary outcome The standardized screening yield will be calculated by ranking participants according to their calculated risk (in risk-based screening) and comparing the yield of risk-based screening for the number of positives that matches the number of FIT-positives with FIT-only screening with a chi-square test. Additionally, the investigators will use the McNemar test statistic to test the null hypothesis of no gain in screening yield in the intervention group only, where the investigators can compare referrals based on FIT only with referrals based on FIT and calculated risk.

The participation rate will be calculated through the number of participants relative to the number of invitees in each arm. Differences in participation rate will be assessed using the chi square test. The difference in screening yield of proximally located advanced neoplasia between both arms will be estimated and expressed as an absolute difference per 1,000 invitees (with 95% confidence intervals). The null hypothesis of no difference in yield will be tested using the chi square test.

Statistical significance level P-values of lower than 0.05 will be considered statistically significant. All analysis between both arms are based on the intention-to-screen principle, unless stated otherwise. Statistical analyses will be performed using R.

Additional outcomes Model performance in comparison to the FIT will be assessed with the net reclassification improvement (NRI). In addition, the yield of the FIT-based risk model and the FIT will be assessed at a broad range of FIT thresholds and will be estimated and expressed as the number of detected advanced neoplasia per 1,000 invitees (intention-to-screen) and per 1,000 colonoscopies (per protocol). Differences in the yield will be tested using a chi square test. Any missing data that was intended to be used as input for the risk-model, will be classified as '0'.

ETHICAL CONSIDERATIONS The study will be conducted according to the principles of the Declaration of Helsinki (Version October 2008) and the Population Screening Act (WBO). Permission to conduct this study has been granted by the Dutch Health Council and the Dutch Minister of Healthcare.

The researchers conduct a parallel group randomized controlled trial. Asymptomatic individuals will be randomized to either risk-based screening or FIT-only screening.

Combining Risk Factors and Faecal Immunochemical Testing in Colorectal Cancer Screening: a Randomized Controlled Trial

Conditional on the permission of the Dutch government, anonymized research data may be shared after publication of the results in a peer-reviewed paper.

The primary outcome is the yield of advanced neoplasia, defined as the relative number of invitees in whom advanced neoplasia is detected at colonoscopy.

standardized screening yield: ranking the number of participants according to their calculated risk and comparing the yield of risk-based screening for the number of positives that matches the number of FIT-positives with FIT-only screening.

participation rate, defined as the relative number of invitees participating in screening.

yield of advanced neoplasia, defined as the relative number of invitees with advanced neoplasia detected at colonoscopy, at FIT-positivity thresholds of 15 µg Hb/g faeces and higher.

yield of proximally located advanced neoplasia, defined as the relative number of referred participants in whom proximally located advanced neoplasia is detected at colonoscopy.

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Professor

PVQ and PedsQL will be used to collect research data. The same measurement tools will be used in the collection of pre-test, mid-term and post-test data. After obtaining the necessary written and verbal permissions from the parents in the intervention group included in the research, 12-week individualized nursing care will be applied. It is planned to make three measurements, namely pre-test, interim evaluation and post-test, from the parents in the intervention groups.

12 Weeks of Individualized Nursing Care

* 5 individual interviews
* A interview after 2 weeks
* Telephone consultation

Pre-test (PVQ and PedsQL) will be applied after obtaining informed consent from the parents included in the control group after randomization. In the pre-test application, an interim evaluation (PVQ and PedsQL) will be applied to the control group 1 week after and the post-test (PVQ and PedsQL) will be applied 4 weeks later. After the post-test application is completed, a five-day individual interview will be applied to the parents included in the control group.

Individualized nursing care based on the Professional Values Model for parents of pediatric oncology patients

Individualized nursing care

Ayla Kaya, PhD

Emine Efe, Professor

Ayla Kaya, RN, PhD

Objective: This study was planned to evaluate the effectiveness of individualized nursing care based on the Professional Values Model for parents of pediatric oncology patients.

Method: Simple randomization will be used to evaluate the intervention and control groups. The sample of the study will be the parents of children aged 1-18 years (Intervention group: 35 parents, Control group: 35 parents) diagnosed with cancer in the Akdeniz University Hospital Pediatrics, Hematology and Oncology clinic and hospitalized. Portrait Values Questionnaire and PedsQL Health Care Satisfaction Hematology/Oncology Module Parent Form will be used to collect data. A 12-week individualized nursing care based on the Professional Values Model will be applied to 35 parents in the intervention group. The effectiveness of the program will be evaluated after all post-test applications are completed.

Study Design: A single-blind, randomized controlled trial

Participants and Setting: The population of the research will be the parents of the children hospitalized in the Pediatrics, Hematology and Oncology Clinic of Akdeniz University Hospital. Parents who agreed to participate in the research (Intervention group: 35 parents, Control group: 35 parents) will form the sample of the research. Simple randomization will be used to evaluate the intervention and control groups.

Randomization, allocation, and blinding: After obtaining informed consent from the parents, each will be given a unique sequence number in a sealed envelope. In this study, random selection of participants and assignment to groups will be done by a nurse at the clinic where the research was conducted. Thus, the researcher who implements the training will be blinded. The Consolidated Reporting Standards (CONSORT) flowchart (Moher et al., 2012) will be followed to manage the random allocation process. The 12-week individualized nursing care practice will be carried out by a nurse with sufficient communication skills, 11 years of pediatric oncology clinical and responsible nursing experience, and a doctoral degree in pediatric nursing in the study team. Thus, the difference that may arise from the educator will be eliminated. Depending on the nature of the intervention administered, researchers and participants will not be blinded. The data will be analyzed by the statistician who is unaware of the intervention and control groups. Thus, it will be possible to be blind in terms of statistics and reporting.

Instruments: Parent Descriptive Information Form, Portrait Values Questionnaire (PVQ) and Pediatric Quality of Life Inventory (PedsQL) Health Care Satisfaction Hematology/Oncology Module Parents Form will be used to collect data. Parent Descriptive Information Form was created by the researchers in order to determine the socio-demographic characteristics of the sample. Form consists of a total of 15 items. PVQ is a 40-item scale developed by Schwartz et al. (2001) to measure individuals' value orientations more effectively. Participants were asked to mark how similar the items were to themselves with a 6-level rating. The scale consists of 40 items and 10 sub-dimensions. The sub-dimensions are described as follows. Turkish validity and reliability was established (Demirutku \& Sümer, 2010). PedsQL was developed by James Varni et al. in 2000 and adapted into Turkish in 2012 by Kürtüncü Tanır and Kuğuoğlu. PedsQL; 1) general satisfaction (3 items), 2) knowledge (5 items), 3) family involvement (4 items), 4) communication (5 items), 5) technical skills (4 items), 6) emotional needs (4 items) It is a versatile inventory consisting of 25 items. The inventory has only the parent form. In the inventory prepared according to the five-point Likert system, it is expressed as I am not satisfied (1), I am not satisfied (2), I am undecided (3), I am satisfied (4) and I am very satisfied (5).

Data collection: The data will be collected in a time period that will not disrupt the care practices of the sick child, at the place and time deemed appropriate by the clinical nurse and the parent.

İntervention Group The research will be implemented in five stages.

Stage 1: Obtaining the permission of the ethics committee and the institution related to the research

Stage 2: Preliminary Application of the Research. - Preliminary practice will be conducted with the parents of five children hospitalized in the clinic in order to evaluate the intelligibility and applicability of the individualized nursing care content developed on the basis of the Professional Values Model. Parents included in the preliminary application will not be included in the research sample.

Stage 3: Implementation

* Pre-test (PVQ and PedsQL) will be applied after obtaining informed consent from the parents included in the intervention group after randomization.
* Individual interviews will be held for five days, one meeting each day, with the parents included in the initiative group. The contact information of the research team will be shared with the parent.
* During the five-day individual interviews, the knowledge, skills and training needs of the parents and counseling support will be provided by the research team.
* After a five-day individual interview, a break-in interview will be held two weeks later, questions will be answered, and the parent will be counseled over the phone in a 12-week period.

Stage 4: Interim Evaluation

- Interim evaluation (PVQ and PedsQL) will be made 1 week after the pre-test application.

Stage 5: Post-Testing and Evaluation

* The post-test (PVQ and PedsQL) will be applied 4 weeks after the end of the five-day individual interview.
* After the final test data collection phase of the research is completed, the data obtained will be analyzed using the Statistical Package of Social Science (SPSS) 23.0 software package program. The process of evaluating the data will be carried out with the support of a statistician.

Professional Values Model

The Professional Values Model (PDM), which will guide this study, was developed by Kaya and Boz (2019). This model has the feature of being the first theoretical model developed for nurses in Turkey. The framework of the model consists of three basic concepts: "Individual Values", "Professional Values of Nurses" and "Quality of Nursing Care". In the model, the logical relationship between these basic concepts is explained and the importance of individual and professional values, patient satisfaction and increasing the job satisfaction of nurses, as a result, responsibilities in reaching quality nursing care are defined. According to the assumption in the model; the effort to increase the individual values of the individuals receiving care increases the satisfaction of nursing care and the quality of nursing care. Based on this assumption in the model, the nursing care to be applied in this study was developed on the basis of the Professional Values Model.

Individual Interviews Regarding Parents' Care Needs

Interview 1

First meeting, intimate communication with the parent Explanation of the purpose and importance of the study and pre-test application Parents sharing their individual characteristics and experiences, Encouraging the parent to ask questions, determining the need for care in the next meeting

Interview 2

Elimination of the priority maintenance requirement identified in the previous session Determining the parent's perception of health and illness and discussing it on the subject Encourage parents to ask questions and express themselves Determining the maintenance need to be eliminated at the next meeting

Interview 3

Elimination of the priority maintenance requirement identified in the previous session Allowing parents to share their difficulties, experiences, and feelings Enabling the parent to communicate with other patients in the clinic Determining the maintenance need to be eliminated at the next meeting

Interview 4

Elimination of the priority maintenance requirement identified in the previous session Discussion of solutions for the solution of the problems experienced with the parents, the methods used in coping and support systems, and counseling Identifying parental concerns and providing counseling Determining the maintenance need to be eliminated at the next meeting

Interview 5

Elimination of the priority maintenance requirement identified in the previous session Arrangement of the parent's clinic room in accordance with the needs of the curative care environment Post-test application and sharing contact information with the child and parent, informing that they can communicate at any time if needed.

Control Group

* Pre-test (PVQ and PedsQL) will be applied after obtaining informed consent from the parents included in the control group after randomization.
* In the pre-test application, an interim evaluation (PVQ and PedsQL) will be applied to the control group 1 week after and the post-test (PVQ and PedsQL) will be applied 4 weeks later.
* After the post-test application is completed, a five-day individual interview will be applied to the parents included in the control group.

Measurement and Evaluation:

Portrait Values Questionnaire and Pediatric Quality of Life Inventory Health Care Satisfaction Hematology/Oncology Module Parents Form will be used to collect research data. The same measurement tools will be used in the collection of pre-test, mid-term and post-test data. After obtaining the necessary written and verbal permissions from the parents in the intervention group included in the research, 12-week individualized nursing care will be applied. No intervention will be applied to the control group. It is planned to make three measurements, namely pre-test, interim evaluation and post-test, from the parents in the intervention and control groups. After the final test data collection phase of the research is completed, the data obtained will be analyzed using the Statistical Package of Social Science (SPSS) 23.0 software package program. The process of evaluating the data will be carried out with the support of a statistician.

Ethical Considerations

Approval from the Akdeniz University Ethics Committee and the necessary written permissions from the Akdeniz University Hospital, where the research will be conducted, will be obtained in order to conduct the research. During individual interviews, the duration of the meeting will be kept as short as possible and the distance between people will be at least 1.5 meters (preferably 2 meters). Everyone in the room will wear a mask during their stay. The windows will be opened and the room will be ventilated frequently. Before starting the study, when the parents are first met, clear and understandable information about the aims of the research and the steps to be followed will be presented by the researcher. It will be made clear that participation in the study is voluntary and that refusal to participate will not affect the care received in the clinic. Before the application of the research, the parent will be informed verbally or in writing about the research and informed consent will be obtained. After the post-test application is completed, the five-day individual interview will also be applied to the parents included in the control group.

The statistician will be blind in evaluating the results. The intervention and control group will be defined as group 1 and group 2 for statistical analysis. Scales will be evaluated by the researcher who cannot be blinded due to the nature of the study.

Effect of Individualized Nursing Care for Parents of Pediatric Oncology Patients

Evaluation of the Effect of Individualized Nursing Care Based on the Professional Values Model for Parents of Pediatric Oncology Patients: A Randomized Controlled Trial

An increase in parents' awareness of their individual values is a measure of outcome. This increase will be measured by the "Portrait Values Questionnaire". The higher the average score, the higher the awareness of individual values. Statistical significance will be set at p \< 0.05. One week after the "pre-test" for the intervention group, an "intermediate evaluation" will be made with the same measurement tool. In the interim evaluation, it will be evaluated whether there is an increase according to the pre-test score. 12 weeks after the "Portrait Values Questionnaire" and the "pretest", the same group will be given a "posttest" with the same measurement tool. In the post-test, it will be evaluated whether there is an increase in the mid-test and pre-test scores. If there is an increase in both "interim evaluation" and "post-test" scores compared to the "pretest" scores, it can be stated that the training program is effective on individual values.

The increase in the level of awareness of the satisfaction level of the parents is a measure of outcome. This increase will be measured by the "Pediatric Quality of Life Inventory Health Care Satisfaction Hematology/Oncology Module Parents Form". The higher the average score, the higher the parent satisfaction. Statistical significance will be set at p \< 0.05. One week after the "pre-test" for the intervention group, an "intermediate evaluation" will be made with the same measurement tool. In the interim evaluation, it will be evaluated whether there is an increase according to the pre-test score. 12 weeks after the "pretest", the same group will be given a "posttest". In the post-test, it will be evaluated whether there is an increase in the mid-test and pre-test scores. If there is an increase in both "interim evaluation" and "post-test" scores compared to the "pretest" scores, it can be stated that the training program is effective on parent satisfaction.

Akdeniz University

Research Assistant Dr.

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Childhood Acute Lymphoblastic Leukemia

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

All Drugs and Chemicals

Methotrexate

The group of patients which are treated with 3g/m2 MTX, low risk ALL or NHL

3g MTX

The group of patients which are treated with 5g/m2 MTX, they are high or middle risk ALL patients

5g MTX

Weiqun Xu

\* The pharmacokinetics of MTX were assessed with regards to the relevance of several different patient specific factors in 291 pediatric patients, who were administered with high dose of MTX. Population pharmacokinetics of MTX analysis was performed by using nonlinear mixed effects modeling.

* Methotrexate (MTX) is one of the critical components for treating all forms of acute lymphoblastic leukemia (ALL), which is the most common pediatric cancer. Unfortunately, high dose MTX has several undesirable side effects and MTX toxicity vastly differs from patient to patient.
* The pharmacokinetics of MTX were assessed with regards to the relevance of several different patient specific factors in 291 pediatric patients, who were administered with high dose of MTX. Population pharmacokinetics of MTX analysis was performed by using nonlinear mixed effects modeling.
* The final model was validated using nonparametric bootstrap analysis. Body surface area (BSA), pre-hydration, baseline serum creatinine and 24 h creatinine clearance rate were statistically significant covariates for distributional volume (V) and renal clearance (CL). Herein, is the first report of analysis of the importance of a series of patient factors on pharmacokinetics of MTX by one-compartment model. Using these data, we have established an efficient population pharmacokinetic model for MTX, which can be used to predict safe clinical application of MTX especially in children with ALL.

Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Lymphoblastic Malignancies

Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Acute Lymphoblastic Leukemia: Significant Impact Factors and Establishment of a Clinically Relevant Model

The serum MTX is higher than 1umol/L in 48 hours or 0.1umol/L in 96 hours

The Children's Hospital of Zhejiang University School of Medicine

Doctor

Anti-Infective Agents

Central Nervous System Depressants

Ethanol

This group will comprise of 10,000 patients who have been referred for a colonoscopy. We will be collecting information on their past medical history, smoking history, alcohol history, medication history and family history in addition to their colonoscopy findings. In 6000 of these patients, they will have blood tests, Faecal Immunochemical Test (FIT) level, blood or saliva for DNA extraction and stool microbiome taken. In 4000 of these patients, we will record recent blood tests of interest and they will have no new samples taken. All 10000 patients will also either complete a food frequency questionnaire or endoscopy patient experience questionnaire.

This will be 10,000 patients who will consent for future contact for future research studies.

Colonoscopy

Sara Koo

Amy Burns

Colin Rees

Ajay Verma

Roisin Bevan

This is a cross-sectional study aimed at identifying factors which best predicts patients at high risk of colorectal cancer or colorectal adenomas and to develop a risk prediction model.

Bowel cancer is the second commonest cause of cancer death in the UK with 16000 people dying per year. Although the NHS Bowel Cancer Screening Programme (BCSP) detects cancers at an earlier stage only 10% of all cancers are detected through screening.

Currently, the only criteria for screening is age and no account is taken of other known risk factors such as smoking, alcohol, family history or obesity. Stool FIT (a new stool test which detects blood that can't be seen with the naked eye) will be introduced into the English BCSP, but there is poor evidence for its use in patients presenting with symptoms. There is also emerging data that there may be differences in the gut bacteria of people with and without cancer or pre cancerous bowel polyps (adenomas).

This will be a national multi-centre study over 5-years. 10000 Patients undergoing colonoscopy as part of BCSP or due to symptoms will be recruited. Patients will be asked to fill in a health questionnaire, have their height, weight, waist circumference measured. Patients will also receive blood tests, stool tests or saliva tests depending on the indication for their colonoscopy. The results of the colonoscopy and any samples taken will be collated. Patients will receive a patient experience questionnaire or food frequency questionnaire. A further 10,000 patients from the North of England will be consented to be contacted for future studies with some of the information above collected.

The aim of this study is to develop a risk prediction model to help determine which patients are at highest risk of having adenomas or bowel cancer. The investigators will also explore the significance of the gut bacteria composition in patients with adenomas or cancer to help inform this risk model. Additionally the investigators will develop a large platform of patients who consent to be contacted for future research.

DNA extraction from blood, saliva and stool

COLO-COHORT (Colorectal Cancer Cohort) Study

Incidence of colorectal neoplasia (colorectal cancer and advanced adenomas)

Assessing trends in variation of stool microbiome in patients with normal colon, adenomas, bowel cancer)

A registry of patients who consent to be contacted in the future for future research studies

Newcastle University

South Tyneside and Sunderland NHS Foundation Trust

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Subjects with lung cancer detected by a computed tomography (CT)-scan and referred to a positron emission tomography (PET)/CT-scan are included. The diagnosis of lung cancer is confirmed by means of an pathological biopsy or by a medical doctor specialized in oncology with respect to radiological or clinical data.

Intervention: a fasted venous blood sample is taken before PET-scan

The control group consists of subjects who were referred to the department Nuclear Medicine for an examination of the heart. This control group represents the average population, consists of healthy subjects and patients with non-cancer diseases and who did not undergo a PET/CT-scan.

Intervention: fasted venous blood sample

Collection of a venous blood sample to investigate metabolic changes in blood

Venous blood sample

Michiel J Thomeer, MD, PhD

Lung cancer is the most common cancer in men and the fourth most common cancer in women worldwide. Until today no effective method permits the early detection of lung cancer. Consequently, lung cancer is often diagnosed owing to symptoms of advanced disease. To address this problem, detection methods with an improved sensitivity and specificity are urgently needed.

Over the past decade, accumulating evidence shows that the metabolism of cancer cells differs from that of normal cells. More specifically, the entire metabolism of cancer cells is reorganized or reprogrammed to increase anabolic reactions that induce cell growth and survival. Metabolic reprogramming during the development of cancer is driven by aberrant signaling pathways due to the activation of oncogenes and the loss of tumor suppressor genes. Furthermore, the microenvironment of the tumor plays a role in metabolic reprogramming. The altered cancer metabolism is characterized by an increased glycolysis, the production of lactate and the biosynthesis of macromolecules, such as proteins, lipids and nucleotides. Cancer cells have a high glycolytic rate and eliminate most of the glucose-derived carbon as lactate rather than oxidizing it completely via oxidative phosphorylation, a phenomenon known as the Warburg effect. The breakdown of glucose and other nutrients leads to a high energy production and provides the Krebs cycle with intermediates, which consequently are allocated to metabolic pathways that support biosynthesis. Metabolites are the end products of cellular metabolism and are therefore closely related to the observed phenotype. Disturbances in biochemical pathways which occur during the development of cancer consequently provoke changes in the metabolic phenotype. As a result, low-molecular weight metabolites are very attractive biomarkers for different cancer types. Nuclear magnetic resonance (NMR) spectroscopy enables the identification and quantitative analysis of complex mixtures of metabolites, as in plasma and serum, without an extended sample preparation.

The present study aims to determine the metabolic phenotype of lung cancer by means of proton (1H)-NMR spectroscopy. Once the phenotype determined (training cohort), this has to be validated by an independent cohort.

Subjects Subjects with lung cancer detected by a computed tomography (CT)-scan and referred to a positron emission tomography (PET)/CT-scan are included. The diagnosis of lung cancer is confirmed by means of an pathological biopsy or by a medical doctor specialized in oncology with respect to radiological or clinical data. The control group consists of subjects who were referred to the department Nuclear Medicine for an examination of the heart. This control group represents the average population, consists of healthy subjects and patients with non-cancer diseases and did not undergo a PET/CT-scan. Exclusion criteria are as follows: (1) not fasted for at least 6 hours, (2) poorly controlled diabetes (fasting plasma glucose concentration ≥ 200 mg/dl) in cancer patients, (3) medication intake at the day of blood sampling and (4) treatment or history of cancer in the preceding 5 years.

The training cohort consists of 80 subject with lung cancer and 80 controls. The validation cohort consist of 250 subject with lung cancer and 250 controls.

Blood sampling and processing Fasting venous blood samples (BD Vacutainer® LH 17 I.U. 10 ml tube) are collected and stored at 4°C within 5 to 10 minutes. Around 8 hours after blood collection, blood samples are transported on crushed ice to the central laboratory and centrifuged at room temperature (swinging bucket centrifuge, 1600 g, 15 minutes). Subsequently, 4 plasma aliquots of 500 µl are transferred into sterile cryovials and stored at -80°C until examination within 6 months. When subjects give permission to store their biological material, 3 aliquots are stored at the University Biobank Limburg (UBiLim) for biomedical research purposes.

Prior to NMR analysis, plasma aliquots are thawed and homogenized using a vortex mixer. After centrifugation at 13000 g for 4 minutes at 4°C (fixed rotor Eppendorf centrifuge 5415 R, Hamburg, Germany), plasma aliquots are diluted in deuterium oxide (D2O, 99.9%, Cambridge Isotope Laboratories Inc, Andover, USA) containing 180 µg/µl trimethylsilyl-2,2,3,3-tetradeuteropropionic acid (TSP, 98%, Cambridge Isotope Laboratories Inc, Andover, USA) as a chemical shift reference. Finally, the prepared plasma samples are transferred into a 5 mm NMR tube and analyzed.

1H-NMR analyses and assignment of present resonances The 1H-NMR spectra are recorded on a 400 Megahertz (MHz) NMR spectrometer (Varian/Agilent, Nuclear Magnetic Resonance Instruments, Palo Alto, California, USA) with a magnetic field strength of 9.4 Tesla at 294 K. Slightly T2- weighted spectra are acquired using a Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence to attenuate signals of macromolecules, such as proteins and polysaccharides. Additionally, water suppression is performed in order to allow optimal detection and quantification of low-molecular weight metabolites. The 1H-NMR spectra are phased manually, baseline corrected and referenced to the TSP resonance at 0.015 parts per million (ppm). The assignment of the present 1H-NMR resonances occurs by means of spiking experiments. A reference plasma sample is alternately spiked with 34 known metabolites with a concentration of 1 mg compound per 100 µl plasma. The obtained chemical shifts are double checked with Chenomx NMR suite software (Version 7.5, Chenomx Inc., Edmonton, Alberta, Canada). Finally, 1H-NMR spectra are divided in 112 spectral regions, which are integrated and normalized relative to the total integrated area of all spectral regions, irrespective of the remaining water, TSP, fructose and glucose resonances. The end result corresponds to 110 normalized integration regions (all integration regions except those of water and TSP).

Statistical analysis At first, the integration values of all 110 spectral regions are analyzed by means of a student t-test with correction for multiple testing by Benjamini-Hochberg to identify those which differ significantly between lung cancer patients and controls (IBM SPSS Version 20.0, Chicago, Illinois, USA). Secondly, multivariate statistical analyses are performed using SIMCA-P+ (Version 12.0, Umetrics, Umea, Sweden) to investigate whether the metabolic composition of blood plasma allows to discriminate between lung cancer patients and controls. An unsupervised principal component analysis (PCA) was performed to identify intrinsic clusters and outliers within the dataset. After the removal of outliers (detected by a Hotelling's T2 range plot), an orthogonal partial least squares discriminant analysis (OPLS-DA), an extension of partial least squares discriminant analysis (PLS-DA) with an integrated orthogonal signal correction filter, is performed to remove variability not relevant to class separation. The predicted classification is expressed as specificity (the percentage of controls that are actually classified as controls) and sensitivity (the percentage of lung cancer patients that are actually classified as lung cancer patients). The outcome of using the integration values of the significantly different spectral regions, obtained by the student t-test with correction for multiple testing by Benjamini-Hochberg, is compared to the outcome in which the integration values of all 110 spectral regions were used.

Plasma is used to determine the metabolic profile by NMR spectroscopy

LC-NMR Study Biomarkers to Detect Lung Cancer

Search for Biomarkers to Detect Lung Cancer by Means of a NMR Spectroscopic Analysis of Blood Plasma

Plasma: metabolic phenotype by NMR spectroscopy

Time between date of diagnosis and date of death

Time between date of diagnosis and date of disease progression

Subtype of histology, eg adenocarcinoma vs squamous, vs large cell,...

Stage of the lung tumor, defined by the TNM classification

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Spots Global Cancer Trial Database for model

Every month we try and update this database with for model cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for model cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.