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Treatment Guidelines and Outcome

As anticipated, squamous cell carcinoma and ad-enocarcinoma are the most frequently encountered malignant tumors of the maxillary sinus and of the naso-ethmoid complex, respectively. Therefore, treatment guidelines as herein reviewed specifically apply to such tumors and to other histotypes requiring a similar treatment planning, while alternative treatment schedules for specific tumors will be discussed in the dedicated sections.

Malignant tumors of the maxillary sinus are generally diagnosed at an advanced stage, since the symptoms during the early phase of growth are vague and somewhat nonspecific. This means that most of the lesions we are faced with have already extended beyond the limits of the maxillary sinus, invading the nasal fossa, ethmoid, orbit, palate, pterygopalatine and infratemporal fossa, cheek, and/or skull base.

Since recurrences at the primary site are the main cause of treatment failure, any effort should be done to properly eradicating the primary lesion. The application of this principle is made currently easier by the tremendous improvement of reconstructive techniques, which allow a satisfactory rehabilitation of functional deficits and aesthetic defects.

There is general consensus that early lesions (T1-T2) require surgery, which according to the location and extent of the lesion as delineated by imaging and intraoperative confirmed, can varies from different types of partial maxillectomies (i.e., inferior maxil-lectomy, medial maxillectomy, subtotal maxillec-tomy) to radical maxillectomy (See Chapter 5). Even though there is no definitive proof that postoperative radiotherapy may be beneficial in improving the local control rate of early lesions, its use seems to be indicated whenever at the examination of the surgical specimen poor prognostic findings such as positive margins, high-grade, perineural spread, or vascular invasion are detected.

Locally advanced lesions (T3-T4) of the maxillary sinus are best treated by a combination of surgery and radiotherapy. A radical maxillectomy extended to the adjacent anatomic structures involved by the tumor (premaxillary subcutaneous tissues, skin of the cheek, infratemporal and pterygopalatine fossa, pterygoid plates, ethmoid) is indicated for most T3 lesions.

Along the years the philosophy of management in patients with orbit involvement has evolved from a very aggressive ablative surgery towards a more conservative approach. There is indeed convincing evidence in the literature that sparing orbital content whenever the periorbita is not transgressed by the tumor does not compromise the local control rate of the disease (Carrau et al. 1999). In this setting, partial resection of the periorbita with frozen sections to precisely assess the deep extent of invasion and reconstruction with fascia lata are recommended. Invasion of the orbital fat or muscles through the periorbita requires instead clearance of the orbit (Imola and Schramm 2002), which is associated with a good local control of the disease when the anterior half of the orbit is invaded, whereas involvement of the apex invariably carries a high risk of local recurrence with subsequent intracranial invasion.

The question whether radiotherapy should be administered before or after surgery has not received a definitive answer; however, the general trend is nowadays in favor of postoperative treatment.

An alternative modality of treatment for advanced lesions of the maxillary sinus is the so-called tri-modal therapy, which was introduced back in the 1970s by Sato et al (1970) and has been progressively refined down the years (Icmmura et al. 1998; Nibu et al. 2002). A combination of "conservative surgery", radiation therapy and regional chemotherapy has been used with the intent to minimize the sequelae of aggressive surgery while providing at the same time a satisfactory local control of the disease. Patients treated with this scheme have experienced a 5-year survival rate of up to 76% (Nishino et al. 2000).

In a large series of maxillary sinus cancers, 61.7% of which were squamous cell carcinoma, advanced T stage, presence of nodal metastases, high grade of the tumor, and increasing age of the patient were found to negatively affect the prognosis (Bhattacharyya 2003).

Guidelines for cancer of the naso-ethmoidal complex are quite similar to those for maxillary sinus cancer, surgery with adjuvant postoperative radiotherapy for high-risk patients (extent to critical areas; unfavorable histological findings) being the cornerstone treatment.

During the last decade there has been growing interest in exploring the possibilities of microendo-scopic surgery in the management of selected malignant lesions of the naso-ethmoidal complex (Draf et al. 2000; Stammberger et al. 1999; Goffart et al. 2000; Kuhn et al. 2001, Roh et al. 2004). Even though definitive criteria are far to be established, preliminary results suggest that there are indeed lesions which may be amenable to endonasal removal. In our opinion, indications can not be strictly correlated to T category, but a more detailed analysis of the different situations of tumor extent is required. The size of the tumor is not "per se" a contraindication; for instance, large polypoid lesions simply filling the nasal fossa, with a very limited insertion on any turbinate, the septum, or the lateral wall of the nasal fossa are an excellent indication for microendoscopic surgery. Even involvement of the mucosa lining the lamina papyra-cea does not preclude an endonasal resection, since the entire lamina papyracea and even a portion of the periorbita can be easily removed with the tumor. Lesions growing into the maxillary sinus through the lateral nasal wall but not directly involving the other walls of the sinus can also be managed trans-nasally. Conversely, whenever tumor extends anteriorly and encroaches the lacrimal pathways, lacrimal bone, and/or nasal bones an external approach, preferably through a lateral rhinotomy, is mandatory. In the tumors invading the mucosa covering the ethmoid roof or the cribriform plate our personal preference is for combining a transnasal microendoscopic approach with a subfrontal extradural craniotomy (anterior craniofacial resection), to obtain a safer superior margin of resection. Intuitively, also more advanced lesions involving the anterior skull base and the dura are managed by a similar approach, which requires an intradural resection whenever the dura is in close contact or it is clearly infiltrated by the tumor and therefore needs to be included in the surgical specimen. It is worth mentioning that the introduction of anterior craniofacial resection in the treatment of malignant neoplasms of the naso-ethmoidal complex with a critical superior extension has considerably changed the prognosis of these tumors. In fact, in a recent retrospective multicentric study analyzing 1307 patients who underwent anterior craniofacial resection, Patel et al. (2003) observed a 53% 5-year recurrence-free survival rate. Histology of the tumor, the extent of intracranial extension, and the status of surgical margins were independent significant predictors of both recurrence-free and disease-specific survival (Patel et al. 2003).

Even for malignant tumors of the naso-ethmoidal complex, isolated successful experiences with an alternative treatment schedule have been reported. Knegt et al. (2001) treated a series of 62 patients with adenocarcinoma of the naso-ethmoidal complex with surgical debulking, periodical topical applications of a 5-fluorouracil emulsion, with or without postoperative radiotherapy obtaining an 87% 5-year disease-free survival rate.

When dealing with ethmoid cancer, advanced T stage and histology are considered the most important factors influencing survival, whereas nodal metastasis, due to small incidence, has an unclear effect on survival (Bhattacharyya 2002).

In our opinion, surgery is contraindicated in patients with extensive involvement of the brain, encasement of the internal carotid artery, or extension of the lesion to the cavernous sinus and/or to the optic chiasm, who are better treated by a combination of radiotherapy and chemotherapy.

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