Malignant Tumors of the Nasal Cavity Treatment & Management
- Author: Ricardo L Carrau, MD, FACS; Chief Editor: Arlen D Meyers, MD, MBA more...
Surgery is the mainstay of treatment for most sinonasal tumors. Radiation as the sole modality of treatment is recommended for unresectable cases, poor surgical candidates, or for lymphoreticular tumors. Combination therapy of surgery and adjuvant radiotherapy with or without chemotherapy is given in situations with an advanced tumor (T3 and T4), positive surgical margins, perineural spread, perivascular invasion, cervical lymphatic metastasis, and in recurrent tumors. Chemotherapy may also have a palliative role for cytoreduction.
Radiation may be used as a single modality, as an adjunct to surgery, or as palliative therapy. It is the primary treatment for lymphoreticular tumors and in patients who are poor surgical candidates, refuse surgical treatment, or have tumors that are deemed inoperable. As an adjunct to surgery, it can be given preoperatively or postoperatively with similar oncological results. Preoperative radiation is given in cases of bulky tumor to help decrease the tumor volume that would have resulted in severe cosmetic and functional morbidity with resection. We favor giving radiation therapy after surgery, as a smaller volume of tumor cells exist, the margins of the non-radiated tumor can be better defined during surgery, and the postoperative wound healing is more predictable.
Radiological response to radiotherapy is used as a means to assess treatment response, but evidence suggests that early response is not a significant prognostic indicator, albeit there is a tendency for improved outcomes in sinonasal squamous cell carcinoma that shows an early response.
The role of chemotherapy for the treatment of tumors of the sinonasal tract is usually adjunctive to radiotherapy (radiosensitizer) or palliative, using its cytoreductive effect to relieve pain, obstruction, or to debulk a massive external lesion. It is increasingly being given concurrently with radiation and used in patients at high risk of recurrence, such as those with positive margins after resection, perineural spread, or extracapsular spread in regional metastases.
Surgical resection is usually performed with curative intent. Oftentimes, obtaining wide surgical margins may not be possible because of the proximity of critical structures. Postoperative radiation is then recommended to reduce the incidence of local recurrence. In some cases, palliative excision or debulking may be considered to alleviate intractable pain, or to relieve decompression of the optic nerve or orbit, or to drain obstructed paranasal sinuses.
Traditionally, the surgical resection is carried out in an en bloc fashion and usually via an open approach. The types of resection and surgical approaches used will depend on tumor size and its extension.
Tumors confined to the nasal cavity can be assessed via a variety of approaches including transanasal endoscopic, sublabial, lateral rhinotomy approaches or a combination of endoscopic and open techniques. Advanced tumors may require orbital exenteration, partial or total maxillectomy or anterior cranial base resection. Resection of the anterior skull base is considered the criterion standard for malignant tumors that are in contact with or transgress the anterior skull base. Select patients selected patients may be treated using endonasal-endoscopic approaches. Resections may be extended laterally to join a temporal craniotomy to include the pterygoid plates, the pterygopalatine fossa, and the floor of the middle cranial fossa en bloc.
Bony erosion of the orbital walls does not constitute an indication for orbital exenteration. In rare cases, the periorbita has been breached by tumor requiring an orbital exenteration. The prognosis in these cases is usually poor.
Absolute contraindications for surgery include those patients who are not medically fit due to medical or nutritional problems, presence of distant metastases, invasion of the prevertebral fascia, invasion of the cavernous sinus by a high-grade malignancy, involvement of the carotid artery in a high-risk patient (as determined by carotid flow studies), and bilateral invasion of the optic nerves or optic chiasm. Relative contraindications include invasion of the brain and intracranial involvement of neural structures by adenoid cystic carcinoma. These situations usually have a poor prognosis, but in selected patients a surgical resection may offer significant palliation or local control.
Recent advances in preoperative imaging, intraoperative navigation system, endoscopic instrumentation, and hemostatic materials have made endoscopic resection of nasal and paranasal sinus tumors a viable alternative to the traditional techniques. Its role in resecting small lesions confined to the nasal cavity is well established. With increasing experience, endoscopic endonasal approaches have expanded beyond the nasal cavity and paranasal sinuses to areas such as the infratemporal fossa and cranial cavity. Endoscopic techniques can be used alone or in combination with open approaches, according to the different degree of involvement of the anterior skull base.
A retrospective study by Swegal et al indicated that endoscopic resection of sinonasal mucosal melanoma produces similar results to those of open resection and can therefore provide an alternative approach to treatment of the disease. The study, which involved 25 patients, including 12 individuals who underwent the endoscopic procedure and 13 who underwent open resection, reported disease-free survival rates of 1.2 and 1.9 years, respectively, with the number of local, distance, and multiple failures being similar between the two groups.
The primary concern about using an entirely endoscopic approach to resect malignant sinonasal tumors is the adherence of oncological principles. Although the instrumentation may be different, the surgical strategy and goals are similar. En bloc excision of the entire tumor is not necessary; rather, the authors perform a sequential layered resection of the area of invasion. The cribriform plate and its attached dura from the posterior wall of the frontal sinus back to the planumsphenoidale and between the orbits can be resected sequentially with adequate margins. Frozen sections are used to confirm clear margins.
In order to reach the area of invasion, debulking the tumor first is frequently necessary. This does not violate normal tissue planes because the tumor is residing in an air-filled cavity. Currently, no evidence exists that debulking increases the risk of local recurrence. Examples of other neoplasms that are removed in a piecemeal without compromise of results include laser resection of pharyngeal and laryngeal squamous cell carcinomas and microscopically controlled excision of skin cancers in Moh’s technique.
Expansion of the indications to use an endonasal endoscopic approach for the resection of advanced sinonasal tumors that have transgressed the skull base followed the development of more effective means of reconstruction to seal off the intracranial cavity from the nasal cavity. The nasoseptal flap is the biggest advance in the reconstruction of the skull base in endoscopic sinus surgery. It drastically decreases the rate of cerebrospinal fluid leak. Other pedicled flaps that have been described for reconstruction include the tranasionpericranial flap, transpterygoidtemporoparietal fascia flap, inferior turbinate flap, and palatal flap.
Advantages of the endoscopic approach include the avoidance of facial incisions, low morbidity and shorter length of hospital stay. Early oncologic outcomes are at least equivalent to those of open approaches, however, long long-term follow-up and larger cohorts of patients are needed before it gains universal acceptance.[53, 54]
Contraindications to a completely endoscopic endonasal approach include invasion of the orbit, involvement of superficial tissues such as the anterior and lateral portion of the frontal sinus, anterior wall of the maxillary sinus and nasal bones, and invasion of the skin.
Wide resection of tumors of the nasal cavity and paranasal sinuses can result in facial disfigurement and speech and swallowing difficulties. The main goals of postsurgical rehabilitation of these massive multilayered defects are primary wound healing, preservation or reconstruction of the facial contour, and restoration of oronasal separation, thus facilitating speech and swallowing and separation of the nasal cavity from the cranial cavity. Functional considerations take precedence over aesthetics.Reconstruction options range from simple closure to the use of free tissue grafts (fat, cadaveric acellular dermis, fascia) to the use of vascularized flaps such as pedicled regional flaps (eg, pectoralis major, latissimusdorsi, trapezius) or free microvascular flaps (eg, radial forearm, anterolateral thigh), as seen in the images below. Flaps are recommended to replace resected facial skin, to provide support for the orbit or brain, or to isolate the cranial cavity from the nasal cavity. Adental obturator or prosthesis is commonly used for oronasal separation, although in patients undergoing a free flap the fistula is usually corrected as part of the reconstruction.
Routine, long-term follow-up is necessary for proper oncological surveillance. Examination of the treated site can help to identify recurrence or even a new primary tumor. Rigid or flexible endoscopy can help to facilitate this evaluation in a postoperative patient. Abnormal findings or new symptoms that are suspicious for recurrence warrant further radiological evaluation (CT scan, MRI, or both).
The extensive nature of surgical resection can cause a variety of complications including bleeding, cerebrospinal fluid leak, infection (including intracranial abscess and meningitis), and blindness.
The proximity of the eye can also lead to potentially severe ophthalmic complications. Sacrifice of the nasolacrimal duct during a maxillectomy and subsequent stenosis of the lacrimal sac opening may lead to epiphora. Performing a dacryocystorhinostomy during resection can prevent this complication. Limitation of extraocular eye movement may occur after trauma to the muscle, its motor innervation, or upon entrapment in craniofacial osteotomies. This latter complication should be managed by urgent surgical release. Limitation of extraocular muscle movement due to edema or neuromuscular contusion is managed expectantly. Alternating eye patching may alleviate diplopia.The optic nerve may be compressed during the mobilization of the specimen or during craniofacial resection. High-dose steroids and emergent surgical decompression are recommended. Enophthalmos or hypophthalmos may develop because of the loss of the inferior orbital and/or medial support and can be prevented with appropriatereconstructive techniques.
Traditionally, external beam radiation fields include the anterior (eyelids, conjunctiva, lacrimal gland and apparatus, cornea, lens, and the rest of the anterior chamber) and posterior orbital segments. This can result in orbital complications in close to 100% of patients. Anterior segment irradiation may lead to dry eye, severe keratitis, panophthalmitis, and blindness within a year. Enucleation may be necessary for uncontrolled panophthalmitis or a painful eye. If the anterior segment is spared, a delayed loss of vision may still develop in 3-5 years due to postradiation retinopathy or optic neuropathy.The incidence of these complications is related to total dose and fractionation and increase with the use of concomitant chemoradiation. They are rare below 3500 cGy, 50-65% with 6000-7000 cGy, and above 85% with 8000 cGy. Other common side effects from radiation therapy include xerostomia, mucositis, trismus, and osteonecrosis.
Over the past 2 decades, 3D conformal radiation therapy and, more recently, intensity modulated radiation therapy (IMRT) have replaced conventional external beam. These techniques minimize the dose delivered to vitals structures close to the tumor. As a result, side effects from high-dose radiation have decreased, and the patients’ quality of life has improved. This is achieved without compromising the clinical outcome for the patients.
With IMRT, the incidence of optic nerve and other ocular complications have greatly decreased.[19, 56, 57, 58] Claus et al compared the complication rates of external beam radiation with 3D-conformation and IMRT in 47 patients who underwent postoperative radiation following resection of adenocarcinoma of the ethmoid sinuses. Radiation-induced severe dry eye syndrome, characterized by chronic conjunctivitis and keratitis, and accompanied by a significant decrease of the vision was observed in 7 cases, all of whom were treated with conventional radiation techniques. Enucleation of the eye was necessary in one patient to control the symptoms. Another 2 patients had optic neuropathy. No neuropathy was found in the group treated with IMRT. Chen et al reported a longitudinal study of 127 patients treated with RT from 1960-2005 at UCSF. The incidence of grade 3 and 4 late ocular toxicity among patients treated with conventional RT, 3D CRT, and IMRT was 20%, 9%, and 0%,respectively. In another series by Hoppe et al, none of the patients who underwent IMRT developed Grade 3–4 late ocular complications. As the experience with IMRT increases, the late complication rates are anticipated to also continue to decrease.
The North American Skull Base Society is currently investigating the role of high-dose IMRT and concomitant cisplatin chemotherapy with or without surgery for advanced paranasal cancers. The protocol is under development with the goal to determine the feasibility of nonsurgical therapy for these tumors in a multi-institution setting.
Wound complications include bleeding, infection (skin, meningitis, or intracranial abscess), and loss of reconstructive flaps or skin grafts. Crusting in the nasal cavity after surgery or irradiation is a common problem and may lead to infection. Frequent irrigation with normal saline solution can soften the crust and maintain nasal hygiene. Meningitis or intracranial abscess is more likely in the presence of a CSF fistula, which can occur after destruction of the skull base and disruption of the dura mater. Treatment involves intravenous antibiotics, drainage of intracranial abscess, and repair of the fistula with dural graft or vascularized flap, if available. Osteoradionecrosis of the maxilla or mandible can occur in up to 10% of patients with poor dentition and recently extracted dentition. Antibiotics and local debridement of the necrotic bone will be needed.
Outcome and Prognosis
The prognosis of treatment outcome depends on several important factors as follow:
Tumor histopathology is an important independent prognostic factor. Low-grade esthesioneuroblastoma, adenocarcinomas, and chondrosarcomas have the best prognosis, while malignant melanoma has the worst outcome. Other high-grade tumors such as squamous cell carcinoma and adenocarcinoma have an intermediate survival rate.
Extent of disease. Invasion into dura and brain has a poor prognosis associated with a high incidence of local recurrence and a worse survival rate.
Surgical margins. Obtaining clear surgical margins intraoperatively has a prognostic value that is independent of tumor type and extent of the disease.
Overall survival at 5 years, according to a large study by Patel et al, was best for low-grade neoplasms such as esthesioneuroblastoma (78%) and low-grade sarcomas (69%), intermediate for high-grade sarcomas (57%), adenocarcinoma (52%), salivary malignancies (46%), and squamous cell carcinoma (44%), and worst for undifferentiated/ anaplastic carcinoma (37%) and mucosal melanoma (18%).
The aforementioned study by Gerth et al found the overall 5-year survival rate in patients below age 20 years to be 62.5%, with the lowest survival rates occurring among patients aged 1-4 years and 15-19 years (median survival 205 and 104 mo, respectively).
Future and Controversies
Treatment of the orbit
Before the 1970s, the classic surgical treatment for sinonasal cancers in close proximity to the orbit involved radical excision with orbital exenteration. The introduction of orbital preservation surgery has decreased the indications and need for removal of orbital structures. The main concerns are the oncological safety of orbital preservation and the function of the preserved eye.
Controversy remains regarding which is the limit of the degree of orbital invasion that allows the safe sparing of the orbital contents. Most studies do not show any statistically significant difference in local recurrence or actuarial survival between those patients who undergo orbital preservation and those who do not. Some propose that the eye can be safely preserved in most patients with ethmoid or maxillary sinus cancer invading the orbital wall, including malignancies that invade the orbital soft tissues with penetration through the periorbita, provided that they can be completely dissected away from the orbital fat. Indications for orbital exenteration include involvement of the orbital apex, unresectable full thickness invasion through periorbita into the retrobulbar fat, extension into the extraocular eye muscles, and invasion of the bulbar conjunctiva or sclera.
Malposition of the globe and nonfunctional eyes often result when patients have not had an adequate and rigid reconstruction of the orbital floor. Rigid reconstruction of the bony orbit using titanium mesh with or without calvarial bone grafts is recommended; these are then covered with local, regional, or microvascular free flaps.
The role of endoscopic sinus surgery for the resection of malignant tumors of the nasal cavity and paranasal sinuses will continue to evolve and the results closely scrutinized. More long-term results, comparing its results with traditional surgery such as craniofacial resection are needed. Surgeons embracing this approach need to understand the limits of this approach and continue to adhere to oncological principles.
The use of IMRT will continue to gain acceptance and probably will be the standard mode of radiation treatment given for all head and neck patients in the future. Reductions in short-term acute toxicities are well established, but late complications need to be continuously evaluated. The emergence of proton therapy may further reduce the complications due to radiation therapy.
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