An observational study in Head and Neck Neoplasms, Radiotherapy Side Effect and Inflammation, sponsored by Uppsala University. Active, not recruiting at 1 site in Sweden. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-13.
Sponsored by Uppsala University · Observational
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.
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
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:
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.
2,710 studies on the registry are indexed under Head and Neck Neoplasms; 594 are open to participants now.
This study's enrollment of 522 is above the median of 100 across 502 observational studies indexed under Head and Neck Neoplasms.
Browse Head and Neck Neoplasms studies →Uppsala University is the lead sponsor of 390 studies on the registry; 86 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients diagnosed with head and neck cancer at the following three university hospitals:
Uppsala University Hospital, Orebro University Hospital, Umea University Hospital
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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
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
Also known as: Surgery
Pro-inflammatory cytokines in serum
IL-6
Time frame: Change from baseline of pro-inflammatory cytokines in serum at 7 weeks
Pro-inflammatory cytokines in serum
IL-6
Time frame: Change from baseline of pro-inflammatory cytokines at 3 months
Pro-inflammatory cytokines in serum
IL-6
Time frame: Change from baseline of pro-inflammatory cytokines at 12 months
Fatty acids in serum
FA 14:0
Time frame: Change from baseline of fatty acids at 7 weeks
Fatty acids in serum
FA 14:0, FA 16:0, FA 18:0, FA 20:0
Time frame: Change from baseline of fatty acids at 3 months
Fatty acids in serum
FA 14:0
Time frame: Change from baseline of fatty acids at 12 months
Weight
kilogram
Time frame: Change from baseline of weight to 7 weeks
Weight
kilogram
Time frame: Change from baseline of weight to 3 months
Weight
kilogram
Time frame: Change from baseline of weight at 12 months
Plan to share: No
Started Nov 2015 (actual). Primary completion is estimated for Dec 2025, 121 months after the start.
Of 215 non-industry observational studies under Head and Neck Neoplasms, half reached primary completion within 71 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 144. This study's planned 121 months is above that.
Counting every sponsor, half of 237 studies reached it within 71 months; a quarter within 29 and three quarters within 142.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in Dec 2024. You cannot join it, but the record below documents what was studied.
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