Symptoms and General Pathology

All Conditions

Gland and Hormone Related Diseases

Postoperative Complications

Hypothyroidism

Thyroid Diseases

Endocrine System Diseases

Participants administered daily levothyroxine at 1.6mcg/kg to a target normal TSH, measured at 6 weeks after the initiation of therapy

Levothyroxine

Placebo

Patients that require treatment for cancers of the head and neck often require a combination of surgery and/or radiation and chemotherapy. Hypothyroidism is one of the most common complications, and has been associated with post-operative complications such as wound healing problems, fistula formation, and decreased quality of life and survival. Several studies have examined hypothyroidism after radiation to the head and neck, but few have examined this after non-thyroid head and neck surgery. Head and neck resection is theorized to devascularize the thyroid, thus resulting in post-operative hypothyroidism.

Synthroid is a synthetic thyroid hormone often used in cases of patients with proven hypothyroidism and after surgical thyroid removal. It's use has been in effect and studied for over fifty years.

Treatment algorithms for hypothyroidism are well published. However, treatment of subclinical hypothyroidism (elevated TSH with normal or near-normal T3/T4) is controversial. The rate of subclinical hypothyroidism after non-thyroid head and neck surgery is high (up to 20%), and is associated with post-operative complications as noted above.

Therefore the investigators propose a double blinded randomized controlled trial comparing outcomes of patients that develop subclinical hypothyroidism after head and neck surgery, who are given a standardized dose of synthroid treatment versus those treated with placebo. The main outcomes to be examined are post-operative complications (wound healing issues, fistula formation), survival, and quality of life measures.

Background and Scope:

Hypothyroidism is one of the most common complications following multimodality treatment for head and neck cancer, with an incidence of 7-58% depending on the subsite. The causes for this high rate of hypothyroidism following treatment for head and neck cancer are multifactorial. Patients treated for head and neck cancer often require radiation therapy (RT). The negative effects of RT on the thyroid are well published, and the resultant hypothyroidism can have widespread implications on a patient's physical and mental health. Head and neck surgery has also been hypothesized to devascularize and disturb the overall anatomical structure of the thyroid, thus contributing to the high incidence of hypothyroidism after surgery.

Despite the literature demonstrating the connection between head and neck cancer treatment and hypothyroidism, complications from this illness after major head and neck surgery remain common. Decreased survival as well as increased rates of fistulas, infections, and wound breakdown are some of the physical consequences. Other possible issues include decreased functional outcomes and increased mental illness, as these are known consequences of untreated hypothyroidism. While several studies have examined the rate and timing of hypothyroidism after radiation to the head and neck, there is a paucity of literature on the effect of surgery on thyroid function. Specifically, in patients treated with single modality surgery, and in patients treated with primary surgery before the start of RT, when the risk of wound complications is high.

Synthroid is a synthetic thyroid hormone, and is the mainstay of treatment of patients with proven hypothyroidism and after surgical thyroid removal. Its use has been in effect and studied for over fifty years. Side effects of the drug most commonly occur with overdosing and will mimic those of hyperthyroidism, which may include: heart palpitations, abdominal pain, nausea, anxiety, confusion, agitation, insomnia, weight loss, and increased appetite. There is a low chance (\< 1%) of allergic reaction to the drug, which may include shortness of breath, swelling of the face and tongue.

Whereas treatment algorithms for clinical hypothyroidism are well established, treatment of subclinical hypothyroidism remains controversial. Subclinical hypothyroidism refers to a state of elevated thyroid stimulating hormone (TSH), with normal or near-normal thyroid hormone levels (T3 and T4), or a lack of symptoms of hypothyroidism. Endocrinologists disagree on whether this disease should be treated, since it is almost always asymptomatic, and the treatment is mainly for relief of symptoms. Head and neck cancer patients, however, represent a special population, in which the effects of subclinical hypothyroidism can result in consequences besides symptoms, such as wound healing issues and fistula development as described above. Studies have shown that the rate of subclinical hypothyroidism during head and neck cancer treatment is high.

Therefore the investigators propose a single blinded randomized controlled trial comparing outcomes of patients with subclinical hypothyroidism, who are given a standardized dose of synthroid treatment after head and neck surgery versus those treated with conventional therapy. A secondary goal of this study is to determine the rate of clinical and subclinical hypothyroidism after surgical treatment for head and neck cancer, without RT or before the start of RT.

Objectives:

Primary Objectives:

* To assess the effect synthroid treatment in patients with subclinical hypothyroidism following head and neck surgery and it's effects on survival, gastrostomy tube (G-tube) rates, fistula formation, wound breakdown, and infection.

Secondary Objectives

* To determine the rate of clinical and subclinical hypothyroidism after surgery for head and neck cancer
* To determine the factors that are predictive of the development of clinical and subclinical hypothyroidism after surgery for head and neck cancer

Methods:

This is a single-center double blinded randomized placebo-controlled trial of the effects of synthroid treatment immediately after surgery for head and neck cancer. Patient meeting eligibility criteria will be identified at the time of booking for surgery and approached by a member of the research team.

Data will be collected from the medical records on the variables under study in study-specific data sheets. Data sheets will then be de-identified and input into a secure database that will be password protected hard drive in a room that is locked. Data will then be exported for statistical analysis when collection is complete.

The population will be comprised of patients who underwent surgery with or without a combination of RT and/or chemotherapy for the treatment of non-thyroid head and neck cancer. Surgery is defined as surgical resection with primary closure or reconstruction with loco-regional flaps or autogenous free tissue transfer. RT is defined as curative dose therapy. Chemotherapy is defined as any single agent therapy or combination of cisplatin or carboplatin. Patients will be prospectively enrolled starting from March 1, 2015 until March 1, 2016. The expected accrual of this patient group will be 200 patients. The demographics of head and neck mucosal cancers indicate that the male : female ratio will be 3 : 1 and the mean age will be approximately 60 years with a range of 18 - 85 years.

In order to assess pre- and post-operative thyroid function, each patient will undergo blood testing including TSH, free T3, and free T4 levels one week prior to surgery, and weekly following surgery, up to 8 weeks post-operatively (if not receiving radiation), or until 8 weeks after the start of radiation (if receiving radiation therapy).

Patients will be classified into "normal" (normal TSH and normal free T3 and free T4 levels), "hypothyroid" (elevated TSH, decreased free T3 and free T4), or "subclinical hypothyroid" (elevated TSH (4-10mIU/L), normal free T3 and free T4).

Patients with "normal" thyroid function will not be randomized to any treatment arm, but their post-operative outcomes will be recorded, according to section 8.0. Patients who are "hypothyroid" will be treated for their hypothyroidism according to the standard of care, in keeping with American Thyroid Association (ATA) / American Association of Clinical Endocrinologists (AACE) guidelines.

Patients with "subclinical hypothyroidism" will be randomized to either the treatment arm or placebo arm, at the time of discovery of subclinical hypothyroidism (lab value abnormalities as noted above). Patients who are randomized to the treatment arm will be treated with a standard dose of 1.6mcg/kg/day of synthroid, and the target of treatment will be a normalized TSH (0.2-4.0mIU/L), measured at 6 weeks after treatment, according to ATA/AACE guidelines.

Levothyroxine Treatment for Subclinical Hypothyroidism After Head and Neck Surgery

Levothyroxine Treatment of Subclinical Hypothyroidism After Non-thyroid Head and Neck Surgery: A Randomized Controlled Trial

* Rate of fistula formation
* Rate of wound breakdown
* Rate of post-operative infection
* Rate of flap failure (dehiscence and/or necrosis requiring salvage)

Disease-free, disease-specific, and overall survival

University of Alberta

Neoplasms

Head and Neck Neoplasms

The contouring of the different target volumes will be first performed by the radiotherapists. During the Head and Neck Tumor Board, the volumes initially determined by the radiotherapists will be analyzed jointly by the radiotherapists and the patient's ENT surgeon to carry out, if necessary, modifications, taking into account clinical observations, intraoperative findings (if any) and endoscopy findings. Concordance parameters will be calculated in a second time with the determined volumes (in particular, index of concordance, coefficient of similarity).

Systematic consideration of the advice of the ENT surgeon in the determination of the radiotherapy target volumes in head and neck cancers.

Philippe Clément, MD

Radiotherapy (RT), surgery and chemotherapy (CT) are treatments for head and neck cancers, used alone or in combination. Conformal RT with Intensity Modulation (IMRT) is currently the reference technique. IMRT requires a precise definition of the target volumes to be treated and the anatomical structures to be protected from irradiation. Most studies of head and neck cancers published in the literature demonstrate the variability in the contouring of the target volumes between radiotherapists. This may have an impact on dosimetry. To date, no studies have evaluated the impact of the ENT surgeon's evaluation in volumes contouring. The aim of this study is to compare the volumes determined by the radiotherapists alone and those determined jointly by the radiotherapists and the ENT surgeon.

Contribution of the ENT (Ear, Nose, and Throat) Surgeon's Clinical Evaluation to the Contouring of Target Volumes and Organs Eligible for Radiotherapy in Head and Neck Cancers

Contribution of the ENT Surgeon's Clinical Evaluation to the Contouring of Target Volumes and Organs Eligible for Radiotherapy in Head and Neck Cancers

Fondation Ophtalmologique Adolphe de Rothschild

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

The patient rinses his oral cavity for 2 minutes. Then he screws lid back onto a beaker. The investigator holds the beaker straight so that the end of the aspiration mouth is dipped into the liquid. Then, the investigators takes 2 tubes and pushes them one after the other down on the opening of the beaker. The tubes should fill by themselves. The tubes can't be kept more than eleven days and are send to the Clinident Institute for the analysis.

Oncoral® test

Sophie DUSSART, MD

Justine SEMAL

Erwan DE MONES DEL PUJOL, MD

Alban PASQUIES, MD

Emmanuel BABIN, MD Ph.D

Hervé BENATEAU, MD Ph.D

Vincent PATRON, MD

Martin HITIER, MD

David BLANCHARD, MD

Abdellali ZAKHAR, MD

Marie-Yolande LOUIS, MD

Yann MALLET, MD

Jean-Louis LEFEBVRE, MD Ph.D

Marian DEGARDIN, MD

Sophie EL BEDOUI, MD

Eric LARTIGAU, MD Ph.D

Bernard COCHE-DEQUEANT, MD

Jean TON VAN, MD

Luis SCHIAPPACASSE, MD

Gauthier LEFEBVRE, MD

Louis GRAS, MD

Philippe ZROUNBA, MD

Didier GIRODET, MD

Lofti BEN SLAMA, MD

Angélique GIROD, MD

Gilles DOLIVET, MD

Sophie CORTESE, MD

Ramina MASTRONICOLA, MD

This is a multicentric feasibility study aimed to evaluate the Oncoral® test. The study includes 2 steps. The first one aims to validate the algorithm defined at the time when the test was developed in patients with different tumour stages. Patients will be enrolled before any treatment. They will immediately undergo the test. No follow-up will be realized. In total, 100 patients will be included in this first step. The estimated period of inclusion is 6 months.

If the algorithm is validated, the second step of the study will start. The purpose is to determine the characteristics of the test. Enrollment will concern smokers and alcohol drinkers at high risk of developing an epidermoid carcinoma of the upper aerodigestive tract. Patient follow-up will vary with both the result of the test and the biopsy, up to a maximum of one year. In total, 385 patients will be enrolled in this step during an estimated period of 18 months.

Evaluation of the Oncoral® Test in Epidermoid Carcinomas of the Upper Aerodigestive Tract

The algorithm was first defined when the test was developed in patients on different tumour stages .

Sensitivity, specificity, positive predictive value, negative predictive value.

Sensitivity will be assessed by the calculation : true positives / (true positives + false negatives)

Feasibility will be assessed by :

* the rate of patients who were not able to realise the test (difficulty to rinse the oral cavity)
* the rate of tests that cannot be analysed (inadequate tests, problems of stability, difficulties with the extraction of volatile molecules, DNA or mRNA...) If the rate of unusable tests is greater than 10%, corrective actions will be necessary in order to use this test in the future. These actions will be considered according to the type of problems (adjustments of the test, transport...)

Clinident Institute

Centre Leon Berard

Bonfils fiberscope intubation

Jean-Edgard Mazères, MD

The Bonfils intubation fiberscope (BF), a rigid medical device with a curved tip, is exclusively used in anesthesiology for orotracheal intubation (OTI). The objective of the study was to evaluate the feasibility and the tolerance of an intubation procedure realized by means of the BF (BFI) in awake adult patients with predicted difficult intubation (PDI), in the context of ENT cancer surgery.

The intubation is performed under local anesthesia (either nasal, oral, or intercricothyroidal) and sedation using Remifentanyl (AIVOC) with spontaneous ventilation. The primary endpoint is the rate of BFI meeting quality requirements: the procedure must be both successful (≤ 2 attempts and duration \< 180 sec) and well tolerated (Fahey score \< 2). The secondary endpoints include the difficulties met by the operator during the BFI and patient's perception of the intubation procedure, evaluated in the recovery room and 7 days after the intervention. Sample size is calculated using a one-stage Fleming design with p0=80%, p1=95%, alpha=5% and 80% power, for a total of 32 evaluable patients.

Evaluation of the Bonfils Fiberscope for Predicted Difficult Intubation in Awake Patients With Ear, Nose, and Throat (ENT) Cancer (INVIBO)

INVIBO: Evaluation of the Feasibility and Tolerance of an Intubation Procedure Performed by Means of the Bonfils Fiberscope in Awake Patients With Predicted Difficult Intubation in the Context of ENT Cancer Surgery

Jean-Edgard MAZERES

Squamous Cell Carcinoma of Head and Neck

All Drugs and Chemicals

Imidazole

Enzyme Inhibitors

A radiolabeled imaging agent that has been used for investigating tumor hypoxia with positron emission tomography (PET).

18F-MISO

Robert J Griffin, PhD

To estimate the mean and standard deviation (SD) of the post-treatment decreases in the interstitial fluid pressure and hypoxia-specific PET-scan signal from GRID-treated tumors in patients with locally advanced squamous-cell carcinoma of the head and neck.

The possible effects of GRID radiotherapy on tumor oxygenation levels and interstitial fluid pressure within the tumors will be measured by assessing the trend and statistical significance of the difference in values for each condition obtained prior to and just after GRID exposure in each subject enrolled in the study. We expect that there may be a trend for increases in tumor oxygenation and decreases in interstitial fluid pressure which would indicate that more accurately timed additional chemotherapy and radiation therapy would improve overall patient outcomes.

Understanding GRID Radiation Therapy Effects on Human Tumor Oxygenation and Interstitial Pressure to Increase Translation of Solid Tumor Therapy

University of Arkansas

Ear, Nose, and Throat Diseases

Otorhinolaryngologic Neoplasms

Otorhinolaryngologic Diseases

Functional respiratory rehabilitation exercise plan. Motor exercise plan. Cardiorespiratory optimization. Early diagnosis of potential problems associated.

Functional respiratory rehabilitation and motor exercise plan.

rehabilitation nursing

José JM Moreira, MSc

The European Commission's current political guidelines demonstrate into a joint plan aimed at improving and controlling cancer disease. Head and neck cancer (HNC) are the sixth most common cancer worldwide. The surgery is one of the most effective treatments, however it significantly compromises the self-care and functional capacity of the patients, so the intervention the Rehabilitation Nurse (RN) is essential.

Objective: Compare the degree of dependence in discharge from patients undergoing HNC surgery with RN intervention versus general nursing care (not RN intervention). The specific objective is to analyze the role of confounders in the effect of the RN intervention on the patient dependence.

Seventy-nine patients with RN intervention who undergoing a different type of surgery (1-Neck dissection, 2-Total laryngectomy with neck dissection, 3-Pelviglossomandibulectomy with neck dissection and tracheotomy, 4-Pelviglossomandibulectomy with neck dissection, pectorals major flap and tracheotomy) and all patients who undergoing the same type of surgery without RN intervention (n=72).

Seventy-nine patients with RN intervention who undergoing a different type of surgery (1-Neck dissection, 2-Total laryngectomy with neck dissection, 3-Pelviglossomandibulectomy with neck dissection and tracheotomy, 4-Pelviglossomandibulectomy with neck dissection, pectorals major flap and tracheotomy) and all patients who undergoing the same type of surgery without RN intervention (n=72). Differences between groups were calculated using non-parametric tests Chi-square for categorical variables and Mann-Whitney U for numeric variable. After correlation tests between variables, statistical analysis was carried out through Poisson regression to a significance level of 5%.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Levothyroxine Treatment for Subclinical Hypothyroidism After Head and Neck Surgery	NCT02548715	Hypothyroidism Neoplasms Postoperative C...	Levothyroxine Placebo	18 Years - 80 Years	University of Alberta
Contribution of the ENT (Ear, Nose, and Throat) Surgeon's Clinical Evaluation to the Contouring of Target Volumes and Organs Eligible for Radiotherapy in Head and Neck Cancers	NCT03265873	Radiotherapy, C... Head and Neck C... Otolaryngology Surgeons Radiation Oncol...	Systematic cons...	18 Years -	Fondation Ophtalmologique Adolphe de Rothschild
Evaluation of the Oncoral® Test in Epidermoid Carcinomas of the Upper Aerodigestive Tract	NCT01361100	Carcinoma	Oncoral® test	40 Years -	Centre Leon Berard
Evaluation of the Bonfils Fiberscope for Predicted Difficult Intubation in Awake Patients With Ear, Nose, and Throat (ENT) Cancer (INVIBO)	NCT01070537	Carcinoma	Bonfils fibersc...	18 Years -	Centre Leon Berard
Understanding GRID Radiation Therapy Effects on Human Tumor Oxygenation and Interstitial Pressure to Increase Translation of Solid Tumor Therapy	NCT01967927	Squamous Cell C...	18F-MISO	18 Years - 80 Years	University of Arkansas
Rehabilitation Nursing Program in Otolaryngology	NCT05246891	Rehabilitation Neck Cancer Otorhinolaryngo...	rehabilitation ...	18 Years - 100 Years	University of Évora

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