Nutrition and Inflammation in Patients with Head and Neck Cancer

December 9, 2024 updated by: Uppsala University

Inflammation and Metabolism After Radiotherapy- Predictors of Survival in Patients with Head and Neck Cancer

An estimated 1500 people in Sweden will annually be diagnosed with head and neck cancer (HNC). Five year survival is approximately 69%. Long-term sequelae are common and in particular nutritional problems and fatigue. Radiotherapy (RT) is the cornerstone of treatment, either as single modality treatment or combined modality treatment. RT can induce immune responses at the site of tumor. It has been demonstrated that RT can lead to a strong systemic immune response . We have previously shown that an increase of conventional measures of systemic immune response to RT varied significantly across individuals. We predict that local immune response plays a major role in the antitumor effect. We also predict that a strong systemic immune response contributes to malnutrition and influence on survival. And malnutrition may lead to a worse response to RT.

The overall aim of this multicenter observational longitudinal study is to prospectively identify immunological and metabolic variables that affect the outcome of HNC patients. We will systematically investigate the local and systemic immune response induced by RT as well as explore alterations in metabolite composition induced by disease and treatment through global metabolite profiling. A platform for studies on immuno-metabolic changes in HNC patients has been established in the Uppsala-Orebro and Northern regions. Approximately 370 patients per year are eligible. Findings in this study can have implications on the development of personalized therapy in patients with HNC. The long-term benefit of the study will be the identification of measures for improved patient surveillance in order to improve the general and nutritional outcomes.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The incidence of head and neck cancer (HNC) has increased in Sweden during the last decades. Radiotherapy (RT) is a cornerstone of treatment either as single or combined modality treatment. There is emerging awareness that RT affects the immune system. For HNC patients treated with RT nutritional problems and fatigue are the most common long-term adverse effects. About 60% have advanced stage of disease at time of diagnosis. Recurrence as well as early death within two years is common.

Our hypothesis: there is a complex association between immune response, metabolic factors and survival.

The aim of this multicenter patient-centered observational longitudinal study is to prospectively identify immunological and nutritional/metabolic variables that affect the outcome of HNC patients. We will systematically investigate the local and systemic immune response induced by RT as well as explore alterations in metabolite composition induced by disease and treatment through global metabolite profiling (metabolomics). This highly biologically relevant data may be used to search for specific biomarkers of malnutrition, markers which would be of prognostic and/or diagnostic value. Moreover, analytically reliable data allows for a more comprehensive mechanistic understanding, as such, a particular focus lies in ensuring a high data quality. We have established a platform for a study on immuno-metabolic changes in HNC patients in the Uppsala-Orebro and Northern regions. Findings in this large-scale observational study can have implications on the development of personalized therapy in patients with HNC.

Survey of the field. There is restricted information on the importance of local and systemic immune response to RT in HNC patients. RT has systemic effects in addition to its local effects on tumors and surrounding tissue. Pro-inflammatory cytokines are activated by RT and have been associated with increased symptom burden in cancer treatment. Interleukin-6 (IL-6) is a potent inflammatory cytokine with diverse functions. In lung cancer mice xenograft studies irradiation has shown to induce an increase in IL-6 levels and migration of macrophages to the tumor tissue. An association between C-reactive protein (CRP) and IL-6 in plasma has been demonstrated in esophageal adenocarcinoma patients. Relapse-free patients are reported to have an increased proportion of Natural killer cells (NK-cells) in peripheral blood long-term after treatment. We have earlier followed a cohort of HNC patients during RT with repeated blood samples. high-sensitivity C-reactive protein (hCRP) increased during RT, and patients with the most pronounced weight loss had the greatest hCRP increase. Metabolic factors are reported to affect HNC patients in many ways. Severe malnutrition before treatment of HNC is reported to lead to increased mortality. In a secondary study in patients with oropharyngeal cancer (n = 357) we found that a high BMI gives significantly better 5-year survival than a low BMI. However, it is difficult to evaluate the results in the majority of nutritional studies in HNC patients because most prospective studies have included relatively few patients and many of the results obtained in retrospective studies have been conflicting. Patient's metabolic profile might work as a nutritional marker and be distinctly linked to nutritional status. The blood metabolome can be examined in detail in cancer patients to better identify different metabolic pathways. The nutritional status is strongly connected to the immune status. It is e.g. reported that L-arginine is crucial for the function of T-cell. As the immune system at the site of the tumor can inhibit cancer growth the local anti-tumorigenic immune status is important. Thus the nutritional status predicts the immune status and malnutrition is connected to a weaker immune response. It is unclear how the nutritional status is connected with the systemic immune status.

Research questions

  1. The correlation between weight change and pro-inflammatory cytokines.
  2. The correlation between weight change and immune response in tumour microenvironment.
  3. Change of blood metabolome.
  4. Change of Bioelectrical impedance analysis (BIA) measurements.
  5. Change of fatty acid profile in blood.
  6. Patient-reported outcome measure (PROM)
  7. Patient-reported stress levels.
  8. Return to work.
  9. PROM and relation to treatment and overall survival.

Variables and measures All patients will be treated in accordance with local and national guidelines. Nutrient based local guidelines ensure that the patients receive nutritional support when needed. Baseline measurements will be taken before treatment starts, and follow-ups will take place at 4 and 7 weeks after start of treatment and at 3, 6, 12, and 24 months post treatment.

A Web-Based Patient Case Report Form (CRF) has been developed for a reliable, secure and easier data collection including the following variables:

Cancer-free survival, cancer-related death as well as death not related to cancer disease, interval between treatment and recurrence.

Explanatory variables:

  1. Body Composition measured by BIA and validated against body composition measured by Dual-energy X-ray absorptiometry (DXA).
  2. Characterization of immune profile in tumor tissue. Surgical biopsy of the tumor at the endoscopy for histopathological diagnosis and after RT when possible. Two methods will be applied to analyse the biopsies: 1) Multiplex tissue staining using the PerkinElmar Opal system which provides a quantitative and spatial composition of the immune cell infiltrates. 2) The RNA based Immunobiology Panel, which allows the measurement of the gene expression of hundreds of immune markers.
  3. Immune profile in serum: analyzed with a multiplex assay using the Science for Life Laboratory (SciLife) platform.
  4. Fatty acid profiling in serum with gas chromatography techniques.
  5. Metabolomic parameters assessed with a multi-platform approach based on nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) connected to the ultra-performance liquid chromatography (UPLC).
  6. Body weight (kg) estimated 6 months before start of treatment, body weight registered at start of treatment and at all the follow-ups.

Questionnaires:

Nutritional follow-up with Patient Reported Outcome Measure Head and Neck Symptom Checklist (PROM - HNSC) (14). Quality of life (QoL) HNC specific questionnaire European Organization for Research and Treatment Quality of Life instrument (EORTC QLQ-H & N 35) (15). Hospital Anxiety and Depression Scale (HADS). Stress with questionnaire Perceived Stress Questionnaire (PSQ) (16).

Study design A prospective observational longitudinal study to elucidate all the research questions.

Estimated sample size About 1500 HNC patients are diagnosed annually in Sweden. The number of patients in this study before the exclusion criteria is approximately 370 patients/year.

Material: Patient selection - population, sample This multicenter study is a collaboration between the Uppsala-Orebro region and the Northern region. The patients are recruited at three university hospitals: Some of the patients are after treatment followed-up at their County Hospital. Inclusion criteria: curative treatment of patients with newly diagnosed HNC, and a World Health Organization (WHO) performance status of 0-2.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
522

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Sweden
      • Uppsala, Sweden, SE-75185
        • Department of Otolaryngology, Head & Neck Surgery, Uppsala University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients diagnosed with head and neck cancer at the following three university hospitals:

Uppsala University Hospital, Orebro University Hospital, Umea University Hospital

Description

Inclusion Criteria:

Patients with newly diagnosed head and neck cancer

Exclusion Criteria:

Previous treatment for malignant disease except for skin cancer, severe alcohol abuse, psychiatric disorder, inability to understand Swedish

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Patients with head and neck cancer
All patients with newly diagnosed and untreated head and neck cancer. Exclusion criteria: previous treatment for malignant disorder except for skin cancer, severe alcohol abuse, psychiatric disorder, inability to understand Swedish
Radiation: Radiotherapy
All patients will undergo radiotherapy or surgery, or combined modality treatment
Other Names:
  • Surgery

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pro-inflammatory cytokines in serum
Time Frame: Change from baseline of pro-inflammatory cytokines in serum at 7 weeks
IL-6
Change from baseline of pro-inflammatory cytokines in serum at 7 weeks
Pro-inflammatory cytokines in serum
Time Frame: Change from baseline of pro-inflammatory cytokines at 3 months
IL-6
Change from baseline of pro-inflammatory cytokines at 3 months
Pro-inflammatory cytokines in serum
Time Frame: Change from baseline of pro-inflammatory cytokines at 12 months
IL-6
Change from baseline of pro-inflammatory cytokines at 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Fatty acids in serum
Time Frame: Change from baseline of fatty acids at 7 weeks
FA 14:0
Change from baseline of fatty acids at 7 weeks
Fatty acids in serum
Time Frame: Change from baseline of fatty acids at 3 months
FA 14:0, FA 16:0, FA 18:0, FA 20:0
Change from baseline of fatty acids at 3 months
Fatty acids in serum
Time Frame: Change from baseline of fatty acids at 12 months
FA 14:0
Change from baseline of fatty acids at 12 months
Weight
Time Frame: Change from baseline of weight to 7 weeks
kilogram
Change from baseline of weight to 7 weeks
Weight
Time Frame: Change from baseline of weight to 3 months
kilogram
Change from baseline of weight to 3 months
Weight
Time Frame: Change from baseline of weight at 12 months
kilogram
Change from baseline of weight at 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Uppsala University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
AFA Insurance
Swedish Cancer Society
The Kamprad Family Foundation for Entrepreneurship, Research & Charity

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Goran FE Laurell, Professor, Department of Otolaryngology, Head & Neck Surgery, Uppsala University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2015

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 10, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 10, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 17, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 13, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 160451

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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