Epidemiological factors in patients with larynx cancer treated by surgery, radiotherapy or therapeutic associations

The larynx is an organ that makes up the upper airways and communicates the laryngopharynx to the trachea. Palpable anterior is considered an important reference in surface anatomy [1]. Its cavity is divided into three portions: supraglotte, glottis and infraglottis. Being a vocal organ, it is essential in the formation of sounds and voice production. However, its anatomical proximity to structures of the masticatory apparatus and digestive system, causes serious pathological disorders, such as laryngeal cancer, to affect not only the larynx, but also structures close to it, generating signifi cant functional damage, social and psychological in the patient, certainly changing their quality of life [2].


Introduction
The larynx is an organ that makes up the upper airways and communicates the laryngopharynx to the trachea.
Palpable anterior is considered an important reference in surface anatomy [1]. Its cavity is divided into three portions: supraglotte, glottis and infraglottis. Being a vocal organ, it is essential in the formation of sounds and voice production.
However, its anatomical proximity to structures of the masticatory apparatus and digestive system, causes serious pathological disorders, such as laryngeal cancer, to affect not only the larynx, but also structures close to it, generating signifi cant functional damage, social and psychological in the patient, certainly changing their quality of life [2]. times more likely to develop laryngeal cancer, and people who associate smoking with alcoholic beverages, the incidence rises to 43 times. In order to choose a more adequate and

Abstract
The aim of this research was to analyze the infl uence of epidemiological factors in patients with laryngeal carcinoma treated by surgery, radiotherapy or therapeutic associations. A quantitative retrospective analysis was performed, based on a master's thesis, of 34 individuals with this pathology, taking into consideration: gender, age, life habits and type of treatment. These factors were associated with the projections of the number of new cases, starting in 2018, according to INCA and IARC data. Due to lifestyle, men are more likely to get laryngeal cancer, and the association of alcohol and tobacco increases the chance and degree of manifestation of this carcinoma. In relation to age, the age group between 55 and 69 years is the most affected. The most indicated treatment is radiotherapy due to the low rate of serious complications, with minimal effect on the patient's life, which does not need hospitalization; besides being a non-invasive, extremely precise technique used in tumors that need a great accuracy, which allows the elimination of the tumor, preserving the structure and functionality of the larynx. by surgery, radiotherapy or therapeutic associations. Arch Otolaryngol Rhinol 5(2): 043-049. DOI: http://doi.org/10.17352/2455-1759.000095 effective treatment, there is a need to understand the evolution of laryngeal carcinoma, to classify the staging and the best therapeutic approach [6].
The understanding of the dissemination of laryngeal carcinoma is important for tumor staging purposes and for a better defi nition of the therapeutic approach, which considers factors such as: age, gender, size, extension, patient health status, team experience and availability of services. Treatment includes the following therapies: surgery, radiation therapy, chemotherapy and immunotherapy. These can be used alone or in combination, aiming at regional control and patient survival, with the preservation of the surrounding regions [7,8].
Quality of life assessment is of paramount importance in the treatment of patients with head and neck cancer, as these usually cause signifi cant aesthetic and functional impairment.
The identifi cation and description of disease effects and treatment in individuals' lives may result in changes in the therapeutic and rehabilitation procedures and, consequently, assist the physician and the patient in deciding on the best therapy to be used. Therefore, the objective of this study was to analyze the epidemiological factors that infl uence the development of laryngeal carcinoma, considering the risk factors and the types of treatment performed by the patients.

Methodology
A quantitative and retrospective study, using epidemiological data from a master's study, performed with patients treated

Theoretical reference
Larynx: The larynx is a complex musculocartilaginous organ located in the infra-hyoid region and capable of performing several important functions, the main one being linked to the protection of the lower airways, followed by respiratory and phonatory functions. The larynx allows air to enter the lungs, preventing the inhalation of substances passing through the common regions of the respiratory and digestive tract.
In certain groups of animals acts producing the emission of sounds, such as the modulation of the human voice, which leads to the transmission of signals that determine behaviors.
In order to perform these functions, the linear mucosal tube that composes the larynx is capable of altering its conformation through a complex interaction between cartilages, ligaments and muscles [9].
Larynx cancer: According to INCA [10], (2018), cancer is the name given to a set of more than 100 diseases that have in common the disordered growth of cells that invade other tissues and organs and can spread to various regions of the body.
Carcinoma is the type of cancer that arises when the cell of any epithelial tissue undergoes a malignant alteration. 11 In the case of carcinoma of the larynx, there is a change in the mucosa of the organ, causing a disordered cellular growth.
According to studies by INCA 5 (2018), tumors that affect the head and neck region, laryngeal cancer is the most frequent and represents the second most common type of respiratory cancer in the world, with about 25% of malignant neoplastic tumors and 2% of all malignancies.

Epidemiology
Data from INCA [10], (2018) show that 80 to 90% of all cancers are associated with environmental factors, and the development of malignant neoplasia is directly related to the time and intensity at which cells are exposed to sources that lead to of the disease.
The highest frequency of laryngeal carcinoma incidence is related to males and over 40 years of age. This is due to lifestyle, especially with regard to smoking and alcoholism. In addition to acting alone, the association of alcohol and tobacco is also an important risk factor for the development of malignant tumors, with continuous cigarette use and alcohol consumption acting synergistically, making this combination the most imminent carcinogenic fator [12]. Patients with laryngeal cancer who maintains smoking and/or drinking have a reduced probability of cure and an increased risk of developing a secondary tumor in the head and neck [6].
Another factor that contributes to the development of cancer is age. Data from the Brazilian Institute of Geography and Statistics (IBGE) [13], show that, by 2060, a quarter of the Brazilian population should be over 65 years of age. Aging results in cellular changes, increasing the chances of occurrence of malignant changes. The fact that the body is constantly and permanently dividing its own cells is a risk factor for the elderly. This is because, during the process of mitosis, it is common to see changes in cellular genetic material that, under normal conditions, are corrected and eliminated by the immune system. However, in elderly people, this may not occur correctly, contributing to the appearance of defective cells and, consequently, to their excessive and disorderly growth, leading to the onset of câncer [14]. In addition, it should be considered that elderly people are exposed, throughout life, to several risk factors that cause cancer, leading to modifi cations in the structure of cellular DNA [6]. infections and genetic syndromes; as well as occupational exposure to certain elements such as: wood dust, chemicals used in metallurgy, petroleum, plastics, textile industries and asbestos, which contribute to an increased risk of occurrence. Stress and misuse of voice are also damaging factors to the larynx. Speaking very loudly and without pauses provoke vocal calluses [15].
Regardless of the stage at which a tumor is detected there is a need to classify each case according to its extent. The method used for tumor classifi cation is called staging, which records the evolution of the disease and whether it is restricted to the organ of origin or extends to other organs and tissues. The need to classify cancers is based on the fact that survival rates are different when the disease is restricted to the organ of origin and when it is spread to other organs. Staging a malignant tumor means evaluating its degree of spreading. To this end, there are internationally established rules, which are constantly improving [16].
Staging of a tumor considers not only the growth rate and extent of the disease, but also the type of tumor and its binding to the host. The classifi cation of malignant neoplasms into groups obeys to some factors, such as tumor location, size or volume, direct and lymphatic invasion, distant metastasis, histopathological diagnosis, systemic manifestations, duration of signs and symptoms, gender, age of the patient, among others. The most commonly used classifi cation system is that proposed by the International Union Against Cancer (UICC) and is called the TNM Malignant Tumor Classifi cation System. This system is based on the anatomical extension of the disease, taking into account the characteristics of the primary tumor (T), lymph node characteristics of the organ in which the tumor is located (N), and the presence or absence of distant metastases (M). These parameters receive graduations, generally from T0 to T4, from N0 to N3 and from M0 to M1, respectively. The treatment of cancer will depend on the staging of the disease. A well-conducted staging will lead to properly applied therapeutic conducts [16].

Treatments
The choice of the best treatment for laryngeal cancer will depend on several factors, such as: age, gender, size and extent of tumor volume and patient health status, taking into account the team's experience and the availability of services in the region of housing. The treatment indicated may be: surgery, radiotherapy, chemotherapy and immunotherapy, and can be used alone or in combination with other therapies, using two or more forms of treatment in the same tumor. 8

Surgery
Surgery is commonly used in the removal of laryngeal carcinoma, but for this technique to be indicated, one must take into account the stage of the cancer, type, location and involvement of surrounding tissues [17].
For each region of the affected larynx and tumor stage, there is a type of surgery indicated, such as: endoscopic surgery, where the endoscope passes through the patient's oropharynx to where the tumor is located, and is applied to biopsy or treat tumors of the larynx at an early stage ; cordectomy, used to treat superfi cial and very small glottic cancers where all or part of the vocal folds are removed; partial laryngectomy, which removes part of the larynx, removing all cancerous tissue and preserving the organ as much as possible; and total laryngectomy, which removes the entire larynx, causing the patient to lose speech but maintains the swallowing system intact [17].

Radiotherapy
This treatment modality consists in the use of ionizing radiation in the treatment of benign and malignant tumors.
Within radiotherapy there are two modalities that stand out: teletherapy and brachytherapy, both used in the treatment of laryngeal cancer.
The teletherapy or external radiotherapy consists of the use of radiation from an external source that ensures distances of approximately 50 cm to 1 m from the source to the patient.
Within it there are modalities that will be indicated for each stage of laryngeal cancer, such as: 3D conformational radiotherapy, which is strongly used in the treatment of early stage cancer and consists of imaging tests such as magnetic resonance and computed tomography accurately map the location of the tumor, thus performing the radiotherapy planning. The other modality is intensity-modulated radiotherapy, which is indicated for advanced tumors, and uses non-uniform planar fl uence bundles, being specifi c for each patient, in order to guarantee the distribution of the desired dose [8,18].
Brachytherapy is a form of radiotherapy that uses sources of ionizing radiation in direct contact with the tissue to be irradiated. It can be used alone or in association with external radiotherapy and is rarely used to treat laryngeal câncer [18].
Radiotherapy generates adverse effects, ranging from mild to severe, such as: painful wounds in the oral cavity and oropharynx, making swallowing diffi cult; xerostomia due to partial or total loss of salivation; fl ushing and blistering of the skin in the irradiated region; loss of taste; hearing problems; respiratory problems due to edema, and dental caries. Persons treated with radiation in the neck and oropharynx should be aware of their oral health [18].

Chemotherapy
Chemotherapy, other than surgery and radiotherapy, is a form of systemic treatment, that is, it acts throughout the body. Some tumor cells can detach from the primary tumor and migrate to other organs and tissues. Many times chemotherapy becomes the best form of treatment. Several factors, such as total tumor volume, cellular kinetics and intrinsic sensitivity, infl uence the anti-neoplastic agent response. These drugs used to treat cancer affect both normal and neoplastic cells [19,20]. Immunotherapy is still a modality in development, and it is necessary to wait for more conclusive results on its effi cacy and clinical applicability in the different types of tumors. Its improvement and the creation of new therapeutic interventions, with even more effi cient responses and minimal or no toxicity, depend on the persistent continuity of research for treatment [24].
The development and optimization of immunotherapy provide this modality a great notoriety, making it one of the pillars in the fi ght against cancer, by having a more specifi c action, reducing the aggressiveness to healthy cells [24].

Epidemiological data of the sample
The master's thesis [25]  Considering the etiology of laryngeal tumors and the magnitude of the risk due to the interaction between the consumption of alcoholic beverage and the cigarette, whose adverse effects are not simply additives, but multiplicative.
Individuals who consume excessively and simultaneously alcohol and tobacco, attain high risks of developing this pathology [28]. Analyzing the ages of patients with laryngeal carcinoma involved in other studies, several articles were found which, according to the authors, had a mean age of 60 years [31][32][33].
These data corroborate the predisposition found in the analysis of this work.

Relationship between staging and treatment performed
The 34 patients analyzed [24] were classifi ed according to the type of therapy used. These values were entered into a chart for analysis. Of those, 28 (82%) were treated only with radiotherapy, 3 (9%) only used chemotherapy and the remaining 3 (9%) used the association of chemotherapy with radiotherapy (Chart 5).
A predominance of radiotherapy was observed as a form of treatment, relative to the other types of therapies. Thus, the indicated treatment was related to the tumor grade, obtaining the following results: of the 4 grade I patients, 100% were treated with radiotherapy alone (Chart 6A); of the 16 grade II, 3 (19%) were treated with radiotherapy associated with chemotherapy and 13 (81%) only with radiotherapy (Chart 6B); of the 14 grade III patients, 3 (21%) were treated with chemotherapy alone and 11 (79%) with radiotherapy alone (Chart 6C).
It is observed that there is no indication pattern of treatment in relation to tumor staging, but the fact remains that for both stages, radiotherapy treatment was predominant. Among the treatments indicated for the 34 patients the surgery was not indicated.
According to Salvajoli et.al (2013) [8], for grades I and II, the patient should be treated with intent to preserve the larynx, voice and ability to swallow. Radiotherapy is the most appropriate modality for this treatment because it is a noninvasive technique and does not demonstrate the morbidity presented by laryngeal cancer surgery.
A study by Chera et al., [34], aimed to evaluate the results of radiotherapy in patients with squamous cell carcinoma at an early stage in the glottic region. We analyzed the medical records of 585 patients with T1N0 and T2N0 of the larynx between the years of 1964 and 2006 treated with radiotherapy, arriving at the conclusion that radiotherapy has the capacity to cure a high proportion of patients, with a low rate of serious complications.

Conclusion
Male individuals are more likely to develop laryngeal carcinoma due to individuals' lifestyles, such as continued cigarette use and excessive alcohol consumption, which directly infl uence the increase in the risk factor for the development of the disease. The association of these factors, besides contributing directly to the development of the tumor, increases the degree of manifestation of the disease. In addition, people aged 55 to 69 years are among the most affected group of people. It was also observed, according to INCA and IARC estimates, that the number of people affected by laryngeal carcinoma will increase signifi cantly over the years, always maintaining the same proportion for people of the masculine and feminine genres. As a form of treatment, radiotherapy was the most used technique because it is not invasive, presents a low rate of severe complications and does not have the morbidity presented by the surgery, that is, it eliminates the tumor and maintains the functionality of the larynx.