Clinical trial NCT05857202: Oxidative Stress and Inflammation Biomarkers in Surgically Treated Patients With Laryngeal Cancer
Official title: Oxidative Stress and Inflammation Biomarkers in Correlation to Postoperative Pain Modulation in Surgically Treated Patients With Laryngeal Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Oxidative Stress Induction
Laryngeal Cancer
Interleukins
Pain Management
Quality of Life
Pain, Postoperative
Keywords: oxidative stress
laryngeal cancer
pain management
interleukins
Lead sponsor: Clinical Centre of Serbia
Sponsor class: OTHER
Collaborators: name: Faculty of Medicine, University of Belgrade
First posted: 2023-05-12
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study would include 100 patients with squamocellular carcinoma of the larynx surgically treated at the tertiary referral center. The diagnosis of laryngeal carcinoma was confirmed by otorhinolaryngological clinical examination, laryngomicroscopic examination with the biopsy and histopathologic examination. Additional diagnostics (chest radiography and computed tomography of the neck and ultrasonography of the abdomen) were performed to determine the TNM stage of the disease.

The modality of surgical treatment was decided on the institutional Oncological Board and involved resection of the tumor (cordectomy, partial or total laryngectomy) with or without some form of the neck dissection in case of cervical lymphadenopathy.

Brief summary: A experimental interventional prospective study will include patients with squamocellular carcinoma of the larynx surgically treated at the tertiary referral center. Clinical and demographic characteristics of the patients would be noted. The visual analog scale (VAS), Brief Pain Inventory questionnaire, Diagnosing Neuropathic Pain 4 (DN4) and Pain Detect Questionnaire were used for pain assessment. Questionnaire Quality of Life in Head and Neck Cancer Patients (QLQ - H\&N35) was used to assess the quality of life in patients with surgically treated laryngeal carcinoma. The type and consumption of analgesics used after surgery was monitored. The analgesics were used according to WHO Ladder. Blood samples ware taken from the patients for the analysis of oxidative stress parameters and inflammation parameters before the operative treatment and after the operative treatment (1-2 postoperative day and 9-10 postoperative day). The concentrations of interleukin 1 (IL-1) and 6 (IL-6), glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1) and malondialdehyde (MDA) in the serum were determined.

The aim of the study will be to assess concentrations of inflammatory biomarkers (IL-1, IL-6) and oxidative stress factors (MDA, SOD, GPKS1) in postoperative course in surgically treated patients with laryngeal carcinoma and in possible complication occurrence. Also, their correlation to type and dosage of used analgesics, to pain assessment questionnaire scores and QOL questionnaire scores in surgically treated patients with laryngeal carcinoma will be assessed.

Detailed description: Patient selection

A experimental interventional prospective study would include 100 patients with squamocellular carcinoma of the larynx surgically treated in the period from October 2022 to February 2023 at the tertiary referral center. This study was approved by the Institutional Ethics Committee (745/5-22), and all patients signed the informed consent form prior to their inclusion in the study. The diagnosis of laryngeal carcinoma was confirmed by otorhinolaryngological clinical examination and laryngomicroscopic examination of the larynx with the biopsy and histopathologic examination of the tissue. Additional diagnostics (chest radiography and computed tomography of the neck and ultrasonography of the abdomen) were performed to determine the TNM stage of the disease. Study included patients with all stages of operable laryngeal carcinoma (T1-T4, N0-N2), without previous treated malignancies. Exclusion criteria were inoperable malignant disease, presence of distant metastases, previously treated malignancies, presence of neurological or other severe comorbidities which prevent surgical treatment, the presence of neurological or other severe physical and metabolic comorbidities, substance abuse, and the inability to provide informed consent.

The modality of treatment for every patient was decided on the institutional Oncological Board (consisting of a radiotherapist, head and neck surgeons, an oncologist, and a histopathologist). Open surgical treatment involved resection of the tumor (cordectomy, partial or total laryngectomy) with or without some form of the neck dissection in case of cervical lymphadenopathy. Demographic, clinical and histopathological characteristics (age and gender, tobacco use, histopathological tumor grade, TNM classification, and therapy modality) were noted.

Quality of life assessment

Questionnaire Quality of Life in Head and Neck Cancer Patients (QLQ - H\&N35) was used to assess the quality of life in patients with surgically treated laryngeal carcinoma.

Pain assessment

The visual analog scale (VAS) was used for pain assessment. Scores were based on self-reported measures of pain severety that are recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 cm on the left end of the scale marks ''no pain'' and 10 cm on the right end of the scale marks ''the worst pain'').

Brief Pain Inventory questionnaire, Diagnosing Neuropathic Pain 4 (DN4) and Pain Detect Questionnaire were used for quality assessment of postoperative pain

Postoperative analgesia

The type and consumption of analgesics used after surgery was monitored. The analgesics were used according to WHO Ladder: (1) for mild to moderate pain, a non-opioid (acetaminophen or non-steroid anti-inflammatory drug , NSAID) with or without an adjuvant; (2) for moderate or severe pain, a non-opioid with an opioid for moderate pain and (3) an opioid for moderate to severe pain not combined with another agent.

Measurement of the Oxidative Stress and Inflammatory Parameters

Blood was taken from the patients for the analysis of oxidative stress parameters and inflammation parameters before the operative treatment and after the operative treatment (1-2 postoperative day and 9-10 postoperative day). The concentrations of interleukin 1 (IL-1) and 6 (IL-6), glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1) and malondialdehyde (MDA) in the serum were determined by coated enzyme-linked immunosorbent assay (ELISA) kits, according to the manufacturer's instructions (Elabscience, Wuhan, China). The ELISA kits for determination of concentrations of IL-1 and IL-6 were based on the Sandwich ELISA principle, with plates pre-coated with an antibody specific to human cytokines. The optical density (OD) was measured spectrophotometrically at 450 nm, using a Multiskan EX plate reader (Thermo Fisher Scientific, Vantaa, Finland). The concentration of analytesin of the tested samples was calculated by comparing the OD of the samples to the standard curve created with GraphPad Prism 9.0 software (GraphPad Software Inc., San Diego, CA, USA).

Statistical analysis

Categorical data was described by absolute and relative numbers (in percentages), while numerical data was reported as arithmetic mean and standard deviation or median and interquartile range (IQR), depending on the data distribution. The normality was evaluated using mathematical (Shapiro-Willk, skewness and kurtosis, and coefficient of variation) and graphical (histogram, box plot) methods. For the evaluation of changing of pain intensity, parameters of oxidative stress, and biomarkers of inflammation Friedman test was applied with Wilcoxon signed rank test as post-hoc testing method. For analyzing the association between pain intensity (VAS), parameters of oxidative stress, and biomarkers of inflammation Spearman's rank correlation coefficient was used, because variables didn't have normal distribution. In order to evaluate all possible factors that influence the level of oxidative stress expressed as SOD and MDA levels, linear regression analysis (enter method) was performed reporting regression coefficient B, 95% confidence level (CI) of B, and p value. Univariate analysis was done first, and all significant factors were combined in multivariate models. All statistical methods were considered significant if p value was less or equal 0.05. The analysis was performed in IBM SPSS ver. 26.

Eligibility criteria: Inclusion Criteria:

* patients with all stages of diagnosed and operable laryngeal squamocellular carcinoma (T1-T4, N0-N2)

Exclusion Criteria:

* inoperable malignant disease
* presence of distant metastases
* previously treated malignancies
* presence of neurological or other severe comorbidities which prevent surgical treatment
* the presence of neurological or other severe physical and metabolic comorbidities
* substance abuse
* the inability to provide informed consent.

Primary outcomes:
measure: Correlation between inflammatory marker IL-1 and pain intensity
timeFrame: 7 days
measure: Correlation between inflammatory marker IL-6 and pain intensity
timeFrame: 7 days
measure: Correlation between inflammatory marker CRP and pain intensity
timeFrame: 7 days
measure: Correlation between oxidative stress marker MDA and pain intensity
timeFrame: 7 days
measure: Correlation between anti- oxidative stress marker SOD and pain intensity
timeFrame: 7 days
measure: Correlation between anti- oxidative stress marker GPX1 and pain intensity
timeFrame: 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: Belgrade
country: Serbia
facility: Clinic for otorhinolaryngology and maxillofacial surgery, Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade
Study officials:
affiliation: Clinic for otorhinolaryngology and maxillofacial surgery, Clinical center of Serbia
name: Ana D Jotic, MD, PhD
role: STUDY_DIRECTOR
affiliation: Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade
name: Katarina R Savic Vujovic, MD, PhD
role: STUDY_DIRECTOR
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