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Vol. 68. Issue 4.
Pages 226-234 (July - August 2017)
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Vol. 68. Issue 4.
Pages 226-234 (July - August 2017)
Review article
DOI: 10.1016/j.otoeng.2017.06.008
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Spanish Consensus for the Management of Sinonasal Tumors
Consenso español para el tratamiento de los tumores nasosinusales
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Fernando Lópeza,b,
Corresponding author
flopez_1981@yahoo.es

Corresponding author.
, Juan José Grauc, José Antonio Medinad, Isam Alobide
a Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Oviedo, Spain
b Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain
c Servicio de Oncología Médica, Hospital Clínic de Barcelona, Universidad de Barcelona, Barcelona, Spain
d Servicio de Oncología Radioterápica, Hospital Universitario Virgen de la Victoria, Málaga, Spain
e Unidad de Rinología y Base de Cráneo, Servicio de Otorrinolaringología, Hospital Clínic de Barcelona, Universidad de Barcelona, Barcelona, Spain
Article information
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Tables (3)
Table 1. Mean Rate of Frequency and Survival of Sinonasal Carcinomas According to Histological Subtype and Location.
Table 2. Primary Treatment of the Main Histopathological Subtypes.
Table 3. Key Aspects.
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Abstract

Sinonasal tumors are rare neoplasms with distinctive clinical, aetiological and pathological features. The diagnosis and treatment of these tumors is challenging because of their low incidence, histological diversity and production of nonspecific symptoms in the early stages. They have a variable prognosis depending on their histology, origin and staging. Their location, close to neurocritical structures, which are of special relevance to surgery and postoperative treatment, makes their treatment difficult and complex, leading to high morbidity and mortality. Surgery followed by radiotherapy is the mainstay of treatment. To provide the best possible care, patients with sinonasal cancer should be treated in clinical referral centres specialising in skull-base pathologies. Such centres should include a multidisciplinary team led by otolaryngologist surgeons. This article outlines a consensus protocol for the management of these tumors devised by the Spanish Society of Otolaryngology in collaboration with the Spanish Society of Medical Oncology and the Spanish Society for Radiation Oncology.

Keywords:
Consensus
Sinonasal tumors
Treatment
Management
Surgery
Resumen

Los tumores nasosinusales son neoplasias poco frecuentes. Su epidemiología, histopatología y características clínicas son diferentes a las del resto de neoplasias malignas de cabeza y cuello. El diagnóstico y tratamiento de estos tumores plantea diversos desafíos debido a su escasa incidencia, su diversidad histológica, la producción de sintomatología inespecífica en los estadios precoces y por tener un pronóstico variable en función de su histología, lugar de origen y estadificación. Su localización centrofacial y la proximidad de estructuras como la órbita y la base del cráneo hacen que su tratamiento sea difícil y complejo, conllevando una elevada morbimortalidad. La cirugía seguida de radioterapia es el tratamiento de elección en la mayor parte de los casos. Para conseguir unos buenos resultados se requiere de equipos multidisciplinares altamente especializados. En este artículo se expone un protocolo de consenso para el tratamiento de los tumores nasosinusales realizado por la Sociedad Española de Otorrinolaringología en colaboración con la Sociedad Española de Oncología Médica y la Sociedad Española de Oncología Radioterápica.

Palabras clave:
Consenso
Tumores nasosinusales
Tratamiento
Manejo
Cirugía
Full Text
Epidemiology

The incidence rate of sinonasal tumors (SNT) is <1 case per 100000 inhabitants per year.1–4 They account for 3%–5% of all malignant tumors of the head and neck.1 SNT are most common in males and are diagnosed around 50 years of age, even though they may present at any age.5

Although the nostrils and sinuses occupy a small anatomical space, they may give rise to a wide histological diversity of tumors.6 Between 50% and 90% of SNT are epithelial in type,1,7 with epidermoid carcinoma being the most frequent (5%–80%), followed by adenocarcinoma (10%–20%).2–4,8Table 1 shows the frequency of the different histological subtypes, which may vary geographically, and also average survival.1,5,6

Table 1.

Mean Rate of Frequency and Survival of Sinonasal Carcinomas According to Histological Subtype and Location.

  Frequency (%)  5-Year Survival Rate (%) 
Histological subtype
Epidermoid carcinoma  50  50 
Adenocarcinoma  13  60 
Melanoma  5–7  35 
Stesioneuroblastoma  70 
Cystic adenoid  70 
Undifferentiated  35 
Neuroendocrines  65 
Others  13  Variable 
Location
Nostrils  45  70 
Maxilar sinus  36  45 
Ethmoid labyrinth  10  40 
Frontal sinus  35 
Sphenoidal sinus  40 
More than one location  Variable 

Sources: Turner and Reh1 and Youlden et al.5

With regard to location, SNT begin in the nasal cavities in approximately 45% of cases, in the maxillary sinus in 35% of cases and in the ethmoids in 10% of cases.1,5 Primary tumors of the frontal sinus and the sphenoid sinus are exceptional (<1%). Despite the above, precise distribution is difficult to define give that, on diagnosis, the great majority involve over more than one location.

Aetiopathogenesis

The aetiopathogenic mechanisms of SNT are as yet unknown precisely. Although it is less obvious than in pharyngolaryngeal carcinomas, there is sufficient evidence to suggest that tobacco smoke produces them.5 Overall, there is a 40% risk attributable to the development of a SNT associated with different occupations. For adenocarcinomas the risk would be 90% and for epidermoid carcinomas 30%.9 The professionals who work with wood are up to 500–900 times at greater risk of developing adenocarcinomas and 20 times greater risk of developing epidermoid carcinomas, compared with the general population.7 Furthermore, the risk of developing an adenocarcinoma is 10 times greater in workers of the fur trade sector than that of the general population.7 Other substances which have been associated with the development of SNT, mainly with epidermoid carcinomas, are formalhydride, chrome, nickel, radium and several substances used in the textile industry.7 The presence of the human papiloma virus (HPV) 16 and 18 has been shown to fall within the biological factors associated with the development of SNT, and primarily in epidermoid carcinomas.10 Genetic-molecular analysis not only helps in the understanding of the pathogenesis of these tumors, but enables the establishment of prognostic markers and the identification of potential therapeutic targets.7

Clinical Features

In their preliminary stages SNT are confined to the sinus cavities and do not usually give rise to symptoms that suggest malignancy. Symptomatology is nonspecific and stimulates an inflammatory process. It is only in advanced stages when the SNT grow to considerable size or affect neighbouring structures that more significant clinical features appear. These may be grouped into 4 syndromes: 1) nasal (nasal obstruction, rhinorrhea, epistaxis); 2) orbital (proptosis, diplopia, ophthalmoplegia, pain); 3) neurological (facial algias, cranial nerve deficits), and 4) facial (facial deformity, masses, ulcers). Sudden unilateral symptomatology should indicate a suspicion of SNT, and the corresponding tests should be performed for diagnosis. However, due to nonspecific and silent preliminary clinical features, SNT are often diagnosed in advanced stages. Lymph node involvement is not common on diagnosis, (2%–20%), and varies depending on tumoral histology and structures involved.7,11 Distant metastasis is generally exceptional (2%–10%).7,11

Diagnosis

Clinical examination should begin with a full otorhinolaryngology examination. Rhinoscopy only provides limited data and an endoscopy is standard. Imaging studies are essential because they determine the spread of the tumor and lead to treatment planning. At present, when there is suspicion of a malignant SNT, either computed tomography (CT) or magnetic resonance imaging (MRI) should be performed.12 MRI is considered the standard imaging tool for postoperative follow-up. The value of (PET)-CT has not been defined but it is of particular importance in patients who are at risk of metastasis or recurrence or where this may be suspected.13 Biopsies must be taken as deeply as possible so as to avoid necrotic regions.

Classification

Clinical classification of epithelial origin SNT is based on location and spread, in accordance with the 7th edition of the tumor-nodes-metastases (TNM) of the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC).14,15 The Kadish–Morita16 classification may be used for the esthesioneuroblastomas, and a specific classification (mmTNM)15 was proposed by UICC for sinonasal mucous melanomas. In melanomas the Hyams histopathological classification is an important element to determine their prognosis.17 In the case of tumors of mesenchymal ancestry or haematolymphoids specific classification systems are used, although in the majority of cases the subtype and histological grade are more important for defining treatment and prognosis.

Treatment

The complexity of SNT treatment together with its low incidence necessitates that this pathology be treated in benchmark centres, which are generally multidisciplinary in order that the best possible outcome may be achieved. The best therapeutic strategy must focus on local control of the disease and in reducing the rate of distant metastasis, with an acceptable rate of morbidity. Complete surgical resection +/− postoperative radiotherapy (RT) is the basis of SNT treatment.7 However, it is important to have an integral, tailor-made treatment (surgery, RT, chemotherapy (CT), biological therapies) in accordance with the tumor stage, histology, age and patient comorbidities and whether previous treatment has been received.

Surgery

Surgery is the treatment of choice in both preliminary stages and with recurrences. The aim of surgery is to obtain the greatest irradicality possible through tumor excision and the obtainment of free cancer margins. To do this, the use of surgical skull-base techniques means that SNT involving nearby structures may be resected. Furthermore, with the available reconstructive methods (e.g. regional or free flaps) extremely extensive resections may be made. However, on occasions, although it is technically viable, because of the location of these tumors, fatal prognosis and the possibility of causing great morbidity (e.g. extensive cerebral infiltration, of the optic chiasm, or the cavernous sinus or aggressive histologies), subtotal resection together with RT and/or CT would be the most suitable therapeutic option. Up until now there has been no evidence that when the tumor infiltrates neurocritical structures, aggressive resections would substantially improve survival rates. Surgery may also be used as palliative care. Surgical approaches used vary according to tumor location, spread and reconstructive possibilities. Choice should not be based on an open or endoscopic approach, but on which one provides the greatest possible radicalness. On occasions, provided that indication is correct, an open (or combined) surgical approach may be justified. In addition to radicalness the approach which leads to lower morbidity in the patient should be chosen, taking into account the surgical team's expertise.

Open surgery has been the standard treatment of choice for SNT. The approaches have evolved with good results, with an acceptable rate of morbidity and mortality.18 The performing of open approaches using small incisions or degloving reduces scars, and avoids major facial scars. It would be complex to make a detailed description of the different possible surgical approaches, but Fig. 1 provides a guide to general action.

Figure 1.

Integral management of sinonasal tumor symptoms.

(0.68MB).

At present, endoscopic surgery has become the central focus of SNT treatment.4,19–23 Endoscopic approaches using any of the surgical procedures described mean that the SNT19 may be dealt with. Compared with standard approaches, they may address profound midfacial lesions, with direct exposure of the mid-line, lower manipulation of the cerebral parenchyma and neurovascular structures and early tumor de-vascularisation. Oncological outcomes are similar to those obtained with open methods, and the fragmented tumoral resection does not appear to compromise oncological findings, provided that resection margins are negative.21 Lower invasiveness of the endoscopic technique does not reduce the necessary radicalness in resection. From the patient's viewpoint, the advantages are reduction in time in surgery and hospitalisation, lower rate of complications, and the absence of facial incisions. The indications for performing an endoscopic resection are similar to those of conventional surgery, since if complete resection of the tumor using endoscopy is not obtained, it will also be difficult to achieve this using conventional approaches without raising morbidity.24 On occasions, an endoscopic approach may be combined with open surgery.

Radiotherapy

Due to the fact that the majority of SNT are diagnosed in advanced stages and that there is a high rate of local recurrence, in the majority of cases postoperative RT is indicated, which should not be administrated more than 6 weeks after surgery.25 Furthermore, the obtainment of optimum oncological margins is complex, which leads to an increase in the adjuvant treatment indications with RT, even in early tumors. Apart from adjuvant use of RT, it may be administered in isolation or in combination with CT, as a radical treatment in some histological subtypes or in highly advanced or inoperable tumors. Preoperative chemoradiotherapy (CRT) is indicated if response may lead to organ preservation. In some cases it may be used as treatment.

Intensity modulated radiation (IMRT) and image guided radiotherapy (IGRT), tomotherapy, volumetric modulated arc therapy (VMAT) and therapy with particles are the techniques of choice in the treatment of SNT. These techniques make it possible for a high radiation dose treatment, minimising toxicity on the nearby neurocritical structures. It is important to know dissemination patterns and tumor recurrence since they facilitate not just surgical planning, but also the outlining of treatment volumes with RT, aimed at preventing the infra-treatment of the areas of microscopic tumor invasion risk (since the majority of the recurrences occur within the irradiated region) and reduce to a minimum the dose of radiation applied to unaffected tissues and vital organs.25

Chemotherapy

Standard indication for the use of CT is palliative treatment in the case of locally advanced tumors or metastases, when surgery and/or RT are contraindicated or are no longer effective. After surgery, the adjuvant CRT reduces the frequency of distant metastasis and improves local control in certain risk situations and aggressive histologies. CRT alone may also be used in certain situations with a curative intent. Finally, neoadjuvant CT (+/− RT) before surgery in the case of locally advanced or unresectable tumors may be helpful for posterior surgery and reduce associated morbidity.26 After CT, if possible, surgery must always form part of the therapeutic plan.27 On occasions, CT would be continued with concomitant CRT, when surgery is not indicated.

Characteristics According to Tumoral Histology

Primary treatment is surgical resection and postoperative RT.21,28 Endoscopic surgery may be safely used in treatment for both preliminary tumors and locally advanced tumors, and has no affect on prognosis.21–23 Even when resection is considered complete, the administration of postoperative RT is necessary to reduce local recurrence. Only in selected cases of local T1–T2 tumors in the removed ethmoids and nostrils with free margins, may adjuvant RT be avoided. In all T3–T4 tumors it is essencial.29

Radical RT could be considered only in selected cases of T1–T2 ethmoid tumors. CT may be administered in combination with RT in 2 main situations: as radical treatment in unresectable tumors, but with a curative intention (although CRT may be suggested in resectable tumors as an alternative to surgery, this treatment should not be first choice), and as adjuvant treatment to surgery in the case of tumors with positive margins, or metastases or with an aggressive histology. Several authors suggest the administration of neoadjuvant CT to reduce tumor size (in T3–T4 tumors), followed by surgery and postoperative CRT.26 Isolated CT or CT in combination with RT could be used in recurrences, provided that this is possible after surgery.

There is no dispute regarding prophylactic treatment (dissection of the neck or RT) of the neck.30 In T3–T4 tumors and in tumors which affect structures with a high lymphatic tropism such as the cheek, the palate or the rhinopharyngeal region, prophylactic treatment either with surgery or preferably with RT would be reasonable. In N+ cases lymph node dissection and RT are elective forms of treatment.

Adenocarcinomas

Surgical resection of the tumor followed by postoperative RT is sometimes is the essential baseline treatment.31 The gold standard surgical treatment is open anterior craniofacial resection or endoscopic resection.22 Endoscopic approaches do not compromise oncological outcome.32–36 The majority of authors recommend postoperative RT since, on occasions, it is difficult to obtain optimum oncological margins and this leads to its administration.33,36 Current CT is unable to help these tumors. Prophylactic cervical treatment benefits have not been proven.31

Cystic Adenoid Carcinomas

Treatment of the primary tumor is surgery followed by RT.37,38 Difficulty in obtaining negative margins and submucosa and perineural spread mean that RT is obligatory.39 Irradiation of the potential pathways of perineural dissemination is essential. At present endoscopic approaches are elective.4 Elective neck treatment does not appear to be justified.37 Although they are radiosensitive tumors, radical RT as a single treatment does not appear to be useful and local relapse is common. However, it could be used in cases which are considered unresectable or where surgery would generate high morbidity. In recent years it appears that the use of techniques such as protontherapy has improved local control, both as adjuvant treatment to surgery and with radical intent.40 The use of CT and biological therapies may have obtained responses, but do not appear to be used for these tumors and would be used for palliative care.41

Stesioneuroblastomas

The treatment of choice is surgery followed by RT.42–44 Surgery or RT alone, and CRT lead to a less favourable outcome. Open or endoscopic craneofacial resection is the treatment approach of choice.45 Endoscopìc approaches should be used whenever possible since these have higher complete resection rates to open surgery approaches.45 Elective neck treatment is not indicated, although in advanced states or in high grade tumors prophylactic cervical irradiation may be considered.46 Postoperative RT is administered due to the difficulty in obtaining negative surgical margins.43 Although stesioneuroblastomas are sensitive to chemotherapy, its use alone is only justified within palliative care. In high grade tumors or with seriously advanced disease, CT neoadjuvant to surgery and to RT may be considered.47

Neuroendocrine and Undifferentiated Carcinomas

Treatment of neuroendocrine and undifferentiated carcinomas consists of intensive multimodal therapy which includes radical surgical resection (using endoscopy, whenever possible) and adjuvant CRT.48–50 This protocol with the 3 therapeutic modalities whenever possible, is the one with the best outcome. Patients with locally inoperable advanced disease or those for whom surgery would lead to major sequelae may be singularly treated with CRT. On occasions, the administration of neoadjuvant CT followed by surgery and CRT would achieve better local control with lower morbidity and lower distant metastasis. In those cases with distant metastasis, palliative CT would be the treatment of choice.

Mucous Melanomas

The treatment of choice is surgery with free margins, whenever possible, both in primary and recurrent tumors.51,52 The approach used may be open or preferably endoscopic. On occasions complete resection is difficult to achieve since, on the one hand, the tumor often spreads beyond the macroscopic lesion and on the other, vital structures which should be preserved are affected. Elective neck treatment is not indicated.51 Although melanomas are considered radio-resistant, it has been observed that radiosensitive areas exist and RT is indicated after surgery in cases of involved or nearby margins52 or as treatment alone in unresectable tumors. Bio CT does not improve survival rates and would only be indicated in a palliative care context or combined with RT.53

Sarcomas

The treatment of choice is surgery. However, due to the difficulty in obtaining free margins, RT and CT play a highly major role.54 Adjuvant RT (on occasion combined with CT) must be administered in the case of involved or nearby margins, high grade tumors or large tumors.54 In the case of rhabdomyosarcomas, mesenchymal chondrosarcomas, osteogenic sarcomas, Ewing sarcomas and highly undifferentiated sarcomas, CT combined with RT may be used as the treatment of choice, although whenever surgery is possible and would not lead to excessive morbidity, it should be used as first line treatment.55

Haematolymphoid Tumors

The most common haematolymphois tumors in the sinonasal are non-Hodgkin lymphomas and plasmocytoma lymphomas.

The haematologist will be in charge of the treatment of lymphomas with CT and RT.56 Standard treatment for plasmocytomas would consist of administrating RT on the tumor. However, in the case of localised tumors surgery should be considered in addition to postoperative RT. Local control and survival outcomes are higher with this treatment.57

Mestastasic Tumors

The role of surgery should be exclusively limited to diagnosis (biopsy) and relief from symptoms (mass reduction). Whenever possible an endoscopic approach should be used so as not to generate morbidity.58 It is only in the case of single metastasis and controlled primary tumor that radical surgery may be considered. In the remaining cases palliative RT and/or CT would be indicated.

Conclusions

In Tables 2 and 3 and Figs. 1–3 we may observe the proposed diagnosis, treatment and follow-up patterns for SNT.

Table 2.

Primary Treatment of the Main Histopathological Subtypes.

Surgerya  Radiotherapy  Chemotherapy 
Epidermoid carcinoma  Plasmocytomad  Rhabdomyosarcomae 
Mucoepidermoid carcinoma    Lymphoma 
Cystic adenoid carcinoma     
Melanoma     
Nonintestinal adenocarcinoma     
Intestinal type adenocarcinoma     
Osteosarcoma     
Chondrosarcoma     
Angiosarcoma     
Ewing type sarcoma     
Malignant fibrous histiocytoma     
Hemangiopericytoma     
Neurostesioblastoma     
Localised metastasis     
Neuroendocrine carcinoma     
Undifferentiated carcinomab
neuroendocrine carcinoma of small round cellsc
a

In the majority of cases postoperative radiotherapy is indicated.

b

In preliminary studies surgery is indicated followed by chemoradiotherapy. In advanced stages, with serious intracranial, orbital or cavernous sinus involvement, induction chemotherapy followed by surgery and chemoradiotherapy would be administered.

c

Due to raised aggressivity, in the majority of cases preliminary treatment would be chemoradiotherapy. However, in initial stages, surgery followed by chemoradiotherapy should be considered whenever possible.

d

Baseline treatment of plasmocytoma is radiotherapy, but currently when total resection is possible, endoscopic resection is a valid option.

e

If surgical resection is possible, without generating high morbidity, surgery may initially be considered, followed by chemoradiotherapy.

Table 3.

Key Aspects.

Sinonasal carcinomas are rare tumors with poor prognosis, despite advances in surgical techniques and radiotherapy.
Suspected diagnosis of a sinonasal tumor is vital, due to the nonspecificity of its clinical features. After this, an appropriate histopathological diagnosis is required so that the most suitable treatment may be administered. To do this the application of immunohistochemical analysis studies is essential, as is molecular diagnosis.
Surgery is the treatment of choice both in management of the primary tumor and in relaspses. At present, whenever possible, endoscopic approaches should be used, although in certain situations open approaches would be indicated.
Postoperative radiotherapy would be indicated in the majority of cases. The use of precision radiotherapy techniques is key to the improvement of local control over these tumors.
In order to provide the best possible treatment and achieve the best cancer control rates, patients with sinonasal tumors must be treated in benchmark centres which specialise in skull base pathology. A multidisciplinary team comprising ENT surgeons, neurosurgeons, radiotherapists, oncologists, doctors and pathologists should be available in these centres. 
Figure 2.

Summary of treatment of sinonasal tumors.

(0.81MB).
Figure 3.

Follow-up of sinonasal tumors.

(0.13MB).
Conflict of Interests

The authors have no conflict of interests to declare.

Acknowledgements

Our thanks, in alphabetical order to: Drs. Llúcia Alós, Carlos Almodóvar, Miguel Armengot, Manuel Bernal-Sprekelsen, Rubén Cabanillas, Joaquín Cabrera, Enric Cisa, María Costales, María Fueyo, Alfredo García, Esther García, Irene García, Xavier González, Juan Ramón Gras, Ignacio Jiménez, Katarzyna Kolanczjak, Cristóbal Langdon, José Luis Llorente, Irene López, Edgar Mauricio López-Chacón, Carlos Martín-Oviedo, Manuel Mañós, Gabriel Martínez-Capoccioni, Lucía Méndez, Joan Ramón Montserrat, Julia Muñoz and Fernando Rivas, for their participation in preparing this agreement.

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Please cite this article as: López F, Grau JJ, Medina JA, Alobid I. Consenso español para el tratamiento de los tumores nasosinusales. Acta Otorrinolaringol Esp. 2017;68:226–234.

This article summarises the National Consensus of Sinonasal Tumors promoted by the Spanish Society of Otolaryngology and Head and Neck Surgery (SEORL-CCC from the Spanish), the full version of which will be published. Several members of the SEORL-CCC participated, as did members of the Spanish Society of Medical Oncology (SEOM from the Spanish) and the Spanish Radiation Oncology Society (SEOR from the Spanish).

Copyright © 2016. Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello
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