Anshu K. Jain • Nicole M. Hsu • Tony J. C. Wang • K. S. Clifford Chao
Paranasal Sinus and Nasal Cavity Cancer Highlights
Key Recent Clinical Studies
Dirix et al. (IJROBP 2010) showed 2-year local control of 76% and 2-year overall survival of 89% for patients treated with postoperative IMRT. Acute and late side effects were also reduced, as compared to conformal RT. (PMID 20338694)
Duprez et al. (IJROBP 2012) showed 5-year local control of 59% and 5-year overall survival of 52% for patients treated with IMRT. (PMID 22027259)
New Target Delineation Contours
FIGURE 5-7. CTV1 and CTV2 delineation in a patient with clinically T4N2bM0 squamous cell carcinoma of the nasal cavity who received definitive IMRT. The patient presented with a nasal mass. CT showed a tumoral lesion originating from the nasal cavity, extending into the orbital cavity and maxillary sinus. Both the primary site and the bilateral neck were treated with definitive IMRT.
1. ANATOMY
1.1. Nasal Cavity
• The nasal cavity begins at the limen nasi and extends posteriorly to the choana. The choanae communicate directly with the nasopharynx. The nasal cavity is located between the base of the cranium superiorly and the hard palate inferiorly. It is divided into right and left halves by a midline septum. The bones and cartilages that compose the roof and sides of the external nose are shown in Figures 5-1 and 5-2.
• The vomer articulates with the body of sphenoid and makes the posteroinferior portion of the septum. The perpendicular plate of the ethmoid makes up the superior aspect of the septum and is contiguous with the cribriform plate, which is paper-thin and offers minimal protection to tumor invasion. The septum is frequently deviated to one side of the nasal cavity.
• There are three turbinates (inferior, middle, and superior), or conchae, which are projections from the lateral wall of the nasal cavity and act to warm, humidify, and filter air. The spaces between the inferior turbinate and floor of the nasal cavity, between the middle and inferior turbinates, and between the superior and middle turbinates are the inferior, middle, and superior meatus, respectively (Fig. 5-3). The nasolacrimal duct enters the nasal cavity through the inferior meatus. The frontal sinus and anterior ethmoid cells communicate with the nasal cavity through the middle meatus. The posterior ethmoid cells and sphenoid sinuses open into the superior meatus.
• The pterygopalatine fossa is situated inferiorly to the inferior orbital fissure, and the infraorbital nerve is located superior to this fossa as it enters the foramen rotundum.
1.2. Ethmoid Sinus
• The ethmoid sinus is composed of numerous air cells, which are located between the medial walls of the orbit and the lateral walls of the nasal cavity (Fig. 5-3). These air cells are divided into two main groups: anterior and posterior ethmoid cells. The partition between these cavities is thin and gives no resistance to tumor spread.
• The ethmoid sinus is bordered laterally by the lacrimal bone and the lamina papyracea. The lamina papyracea is the lateral plate of the ethmoid labyrinth bone, which forms a large part of the medial orbital wall. Due to its thin and extremely porous nature, the lamina papyracea offers little resistance to tumor spread into the orbit from the ethmoid sinus. The roof of the ethmoid sinuses is the skull base. The fovea ethmoidalis is the thin orbital plate of the frontal bone that comprises the roof of the ethmoid cells. The posterior ethmoid cells are closely related to the optic canal and optic nerve.
• The olfactory nerve is a collection of sensory nerve fibers that extend from the nasal cavity up to the olfactory bulbs, which lie on the ventral aspect of the frontal lobes, through the perforations within the cribriform plate of the ethmoid bone. As the fibers of the olfactory nerve penetrate the cribriform plate, it provides a route for tumor invasion into the anterior cranial fossa.
1.3. Sphenoid Sinus
• The sphenoid sinus is the most posterior paranasal sinus and is contained in the body of the sphenoid bone. The hypophysis and optic chiasm are located superiorly, the cavernous sinuses and carotid arteries are located laterally, the nasal cavity and ethmoid sinuses are located anteriorly, and the nasopharynx is located inferiorly. The clivus and brainstem are situated posteriorly. Each sphenoid sinus communicates with the nasal cavity via the sphenoethmoid recess, by means of an aperture in the anterior wall of the sinus.
• The right and left sphenoid sinuses are divided by a septum. Because the septum is often incomplete or, at best, very thin, it is rarely located in the anatomic midline, and the sphenoid sinuses are often asymmetric.
1.4. Maxillary Sinus
• Each maxillary sinus forms a pyramidal structure: it is bordered medially by the nasal cavity, superiorly by the floor of the orbit, anterolaterally by the facial bone, and posteromedially by the infratemporal fossa. The nasal wall forms the base, and the apex extends into the zygomatic process of the maxilla. Behind the posterior wall of the maxillary sinus lies the pterygomaxillary fossa, which contains the internal maxillary artery, sphenopalatine ganglion, vidian canal, greater palatine nerve, and foramen rotundum.
• The roots of the first and second molar teeth, and occasionally of other teeth, project into the floor of the sinus. The level of the floor varies during the course of a lifetime as the maxillary sinus pneumatizes. Typically from birth into adolescence the floor of the sinus is above that of the nasal cavity; the floor gradually sinks during pneumatization so that by mid-adolescence and adulthood, when the maxillary sinus is fully developed, the floor moves below the floor of the nasal cavity.
1.5. Frontal Sinus
• The frontal sinuses are contained between the lamina of the frontal bones and are rarely symmetric as they are separated by a bony septum that frequently deviates from the midline. The posterior wall of frontal sinuses, which separates them from the anterior cranial fossa, is usually thick, whereas the floor of the frontal sinus is separated from the anterior ethmoid cells by thin, bony walls.
2. NATURAL HISTORY
• At the time of diagnosis, most lesions are advanced and commonly involve several adjacent sinuses, the nasal cavity, and often the nasopharynx. See Figure 5-4 for a graphic representation of tumor spread.
• “Ohngren’s line” is an imaginary line originally described in the 1930s, which extends from the medial canthus of the eye to the angle of the mandible. It is a dividing line that can be used to roughly estimate prognosis: tumors inferior or anterior to Ohngren’s line are associated with a better survival rate as they involve fewer critical structures, while lesions superior or posterior to Ohngren’s line tend to have a poorer prognosis because there is a higher likelihood of involving the orbit, optic nerve, ethmoids, pterygopalatine fossa, and carotid artery.
FIGURE 5-1. A-1: Opened sinuses, color coded. A-2: Cast of frontal and maxillary sinuses, color coded. A-3: Lateral radiograph of sinuses. P, pharynx. Dotted outline represents the ptergyopalatine fossa. (From Agur AMR, Dalley AF, eds. Grant’s Atlas of anatomy, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:698, with permission.)
FIGURE 5-2. Inferiormost orbit, and middle and internal ear. Key: 1, Cartilaginous nasal septum; 2, Frontal process of the maxilla; 3, Angular artery; 4, Nasolacrimal duct; 5, Orbicularis oculi muscle; 6, Middle turbinate; 7, Superior turbinate; 8, Perpendicular plate of the ethmoid bone; 9, Maxillary sinus; 10, Sphenoid sinus; 11, Inferior oblique muscle; 12, Frontal process of the zygomatic bone; 13, Zygomatic process of the temporal bone; 14, Sphenoid bone; 15, Internal carotid artery; 16, Cavernous sinus; 17, Cranial nerves VII and VIII; 18, Cochlea of the inner ear; 19, Anterior (superior) semicircular canal; 20, Endolymphatic duct; 21, Ear ossicles (A. stapes; B. malleolarincal joint); 22, Petrous portion of the temporal bone; 23, Mastoid process of the temporal bone; 24, Mastoid air cell; 25, Sigmoid sinus; 26, Falx cerebelli; 27, Occipital bone; 28, Temporalis muscle; 29, Tendon of the temporalis muscle; 30, Superficial temporal vessels; 31, Tragus cartilage of the auricle. (From Dean D, Herbener TE. Cross-Sectional Human Anatomy. Baltimore: Lippincott Williams & Wilkins, 2000.)
FIGURE 5-3. Cross section of nasal cavity: anterior view. (From Bickley LS, Szilagyi, P. Bates’ Guide to Physical Examination and History Taking, 8th ed. Philadelphia: Lippincott Williams & Wilkins, 2003.)
• There is often orbital invasion from maxillary sinus or ethmoid sinus cancers. Orbital invasion from nasal cavity tumors occurs late.
• The anterior cranial fossa is invaded by way of the cribriform plate and roof of the ethmoid sinuses. The middle cranial fossa is invaded by way of the infratemporal fossa, pterygoid plates, or lateral extension from the sphenoid sinus.
• Lesions involving the olfactory region tend to destroy the septum and may invade the nasal bone, producing expansion of the nasal bridge, and progress to skin invasion.
• Lesions of the anterolateral infrastructure of the maxillary sinus commonly extend through the lateral inferior wall and appear in the oral cavity, where they erode through the maxillary gingiva or into the gingivobuccal sulcus (Fig. 5-5). Tumor that extends posteriorly from the maxillary sinus has immediate access to the base of the skull.
• Lymph node metastases generally do not occur until the tumor has extended to areas that contain abundant capillary lymphatics (Table 5-1). The anterior nasal cavity has the same lymphatic drainage as that of the external nose and tends to drain to the submandibular lymph nodes. The middle and posterior nasal cavity, as well as the paranasal sinuses, drain via the nasopharynx to the retropharyngeal and superior jugulodigastric lymph nodes.
3. DIAGNOSIS AND STAGING SYSTEM
3.1. Signs and Symptoms
• History of recurrent nasal obstruction and recently worsened sinusitis are common symptoms. Minor and intermittent epistaxis may be observed. The mass may protrude from the nose.
• Obstruction of the nasolacrimal system may cause epiphora. Frontal headache, dysosmia (aberration of sense of smell) or anosmia (loss of sense of smell), diplopia, and proptosis secondary to invasion of the orbit are other signs and symptoms that can be observed in paranasal sinus and nasal cavity tumors.
3.2. Physical Examination
• The anterior nasal cavity is inspected by a nasal speculum. A fiberoptic nasoendoscopy must be performed to further evaluate the nasal cavity, sinuses, and nasopharynx. The neck is palpated for adenopathy.
• Cranial nerve examination is very important in paranasal and nasal cavity tumors to evaluate the extension of tumor.
FIGURE 5-4. Patterns of spread. (A) Coronal. (B) Sagittal. The primary cancer (paranasal ethmoid sinus) invades in various directions, which are shown as color-coded vectors (arrows) representing stages of progression: Tis, yellow; T1, green; T2, blue; T3, purple; T4a, red; T4b, black. There are three vectors of invasion: into the orbit; into the nasal passage and paranasal sinuses; and intracranial. (From Rubin P, Hansen JT. TNM Staging Atlas with Oncoanatomy, 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2012:21, modified from Agur AMR, Dalley AF, eds. Grant's Atlas of Anatomy, 12th edition. Philadelphia: Lippincott Williams & Wilkins, 2009.)
3.3. Imaging
• High-resolution sinonasal computed tomography (CT) and magnetic resonance imaging (MRI) should be performed in both the axial and the coronal planes. An attempt should be made to match the imaging planes of both modalities for direct comparison. The anterior skull base, floor of orbit, and cavernous sinus are evaluated on coronal sections. The orbital apex, pterygopalatine fossa, infratemporal fossa, and face are studied on axial sections. Sections must be 3 mm or less in thickness.
• The lymph nodes are not routinely studied in sinonasal cancer. If there is soft tissue, nasopharynx mucosa involvement, or in cases of high-grade lesions, the neck is examined.
• The absence of bone on CT is not necessarily an indication of bone invasion as many bony elements in this region are very thin and easily obliterated.
• Because of the conical shape of the orbit, the maxillary antrum projects into the posteromedial floor of the orbit on axial images.
• Normal perineural enhancement should not be confused with pathologic enhancement of the nerve when evaluating perineural spread of the tumor along the infraorbital nerves.
• Although CT can detect intracranial invasion by detecting bony erosion at the sinodural interface, MRI is the better modality for intracranial or leptomeningeal evaluation. The degree of dural involvement and transdural extension is better characterized by MRI. The overlying dura often appears thickened which is enhanced by tumor invasion. Although dural thickening may be a reactive inflammatory change, it should be considered positive until proven otherwise by pathologic analysis.
FIGURE 5-5. Magnetic resonance imaging (MRI) of a patient with T4N0 maxillary adenocystic carcinoma. An extensive soft tissue mass in the left maxillary sinus is extending into the ethmoid and orbit with bone destruction (arrows).
• The earliest sign of orbital invasion is erosion of the cortical bone and displacement of extraconal orbital fat. Tumor spread to the infratemporal fossa can be detected by the presence of erosion of the cortical bone along the posterior wall of the maxillary antrum. This is often seen near the groove of the posterior superior alveolar neurovascular bundle.
3.4. Staging
• In 2010, the American Joint Committee on Cancer issued new TMN staging definitions, including for the nasal and paranasal sinuses.8 The major change from the previous edition is that T4 lesions have been divided into two subgroups as have the corresponding stages. Readers are urged to consult the new seventh edition for details.
4. PROGNOSTIC FACTORS
• Advanced tumors with extension into the base of the skull, nasopharynx, posterior wall, roof of the sphenoid sinus, or cavernous sinus significantly increase surgical morbidity and decrease the likelihood of obtaining clear surgical margins.
• Tumor extension into the periorbital soft tissues typically requires orbital exenteration.
• The prognostic significance of lymph node metastases has been addressed in a number of recent studies. A retrospective review of the Washington University experience identified nodal involvement at diagnosis as a significant predictor of decreased locoregional control and disease-free survival.1
• Similar findings were reported by investigators at Stanford University, who observed a significant decrease in distant relapse among patients who achieved nodal control in the neck as compared with those who experienced a neck relapse (29% vs 81% at 5 years). There was also a trend for decreased survival with nodal relapse.5
• Likewise, in a review of the long-term experience with the treatment of paranasal sinus malignancies at the University of Michigan, Myers et al.6 identified nodal positivity as an adverse prognostic factor for survival. Together, these data indicate a possible role for prophylactic treatment of the ipsilateral cervical lymph nodes in patients presenting with locally advanced, high-grade tumors.
5. GENERAL MANAGEMENT
• Decadewise meta-analysis data showing the cross-tabulation of site, T stage, and treatment modality are summarized in Table 5-2.
• Actuarial locoregional control and disease-specific actuarial survival rates according to treatment modality in patients with nasal cavity and paranasal sinus carcinoma are shown in Table 5-3.
• Blanco et al.1 reported the results of 106 patients with paranasal sinus carcinoma who were treated with curative intent at Washington University. Five-year local tumor control, locoregional tumor control, disease-free survival, and overall survival rates were 61%, 41%, 35%, and 29%, respectively.
• Chen et al.9 reported the clinical outcomes of 127 patients with carcinoma of paranasal sinus and nasal cavity who underwent radiotherapy at the University of California, San Francisco, between 1960 and 2005. The 5-year overall local control, disease-free survival, and overall survival were 62%, 54%, and 52%, respectively.
• Snyers et al.10 reported the long-term outcomes and morbidity of 168 patients with sinonasal cancer who underwent radiotherapy. The 5-year overall survival was 35%, and among the long-term survivors approximately 62% had hormonal deficiency.
• Early-stage malignancies of the nasal cavity and paranasal sinus are typically treated with surgical resection. Advanced-stage malignancies require multimodality treatment with primary surgery followed by postoperative radiation therapy or primary radiation therapy followed by salvage surgery.
• Primary surgery followed by postoperative irradiation to a lesser dose than used for irradiation alone is preferred to reduce the risk of unilateral or bilateral optic nerve injury.11 In most cases, postoperative doses are limited to 60 Gy; 66 to 68 Gy is administered for positive margins.
• For unresectable lesions, high-dose irradiation remains the only alternative with either once-per-day fractionation of 1.8 to 2.0 Gy to a total dose of 70 Gy or twice-daily treatment (1.1 to 1.2 Gy per fraction with a 6-hour interfraction interval) to total doses of 74 to 79 Gy.11
• No clear role for chemotherapy as either an induction or a concomitant agent has been defined. Concurrent cisplatin with radiotherapy has been reported with varying results.12 Investigators in Japan have attempted superselective intra-arterial infusions of cisplatin as a radiosensitizer.13 Investigators at the University of Chicago have evaluated the use of a neoadjuvant chemotherapy regimen in the treatment of advanced sinonasal tumors14 with encouraging results.
5.1. Nasal Cavity
• Tumors of the nasal cavity may be accessed via various approaches, including transnasal endoscopic, sublabial, or lateral rhinotomy approaches, or a combination of endoscopic and open techniques, depending on the size and extent of the lesion.
• Small tumors confined to the nasal cavity can be managed endoscopically, while advanced tumors that extend into the perimeter of the sinonasal region (such as the orbit, the sinuses, or the cranium) may require orbital exenteration, partial or total maxillectomy, or anterior cranial base resection.
• In 45 patients with nasal cavity cancers (18 treated with definitive irradiation and 27 treated with surgery and irradiation), the 5-year disease-specific and overall survival rates were 83% and 75%, respectively.15
5.2. Ethmoid Sinus
• If the tumor is resectable, surgery is usually performed first. Postoperative irradiation is advised, even if resection margins are negative.
• Resection requires a medial maxillectomy and an en bloc ethmoidectomy. If the tumor extends superiorly to involve the fovea ethmoidalis or cribriform plate, a combined craniofacial approach is required.
5.3. Maxillary Sinus
• Most malignancies are typically advanced and require radical maxillectomy including the entire maxilla, nasal bone, ethmoid sinus, and, in some instances, the pterygoid plates through a traditional or modified Weber–Ferguson incision. The globe and orbital floor are preserved for inferiorly located tumors.
• Orbital exenteration is indicated when the tumor has spread through the periorbital soft tissues including the lids, lacrimal apparatus, fat, muscles, or globe.
• If the ethmoid roof is involved, craniofacial resection is required.
• Early infrastructure lesions are often managed by surgery alone, but in most cases of maxillary sinus cancer, irradiation is given postoperatively, even if the margins are clear.
• Surgical management may be contraindicated if there is tumor extension into the skull base, nasopharynx, cavernous sinus, or carotid artery, or if distant metastases are present.
• Borderline resectable lesions are occasionally treated with definitive-dose external-beam irradiation, followed by salvage surgery if technically feasible.
• It is reasonable to expect 5-year survival rates of approximately 60% to 70% for T1 and T2 lesions and 30% to 40% for T3 and T4 lesions after resection and postoperative irradiation.11 For advanced, unresectable disease, average 5-year survival rates of 10% to 15% are achieved with high-dose irradiation alone.11
5.4. Sphenoid Sinus
• Irradiation with salvage surgery is usually the treatment of choice as primary surgical resection would result in significant cosmetic and functional morbidity. (See “General Management” for a description of radiation dose guidelines.)
5.5. Neck
• Elective neck dissection is indicated only for clinical nodal disease as there is <10% risk of occult cervical metastasis.
• Patients with recurrent or poorly differentiated cancers and tumors that extend to an area with dense capillary lymphatics (nasopharynx, oropharynx, and oral cavity) have a higher risk of metastasis and are often given elective neck irradiation of 50 to 54 Gy over 5 to 6 weeks, administered in 1.8- to 2-Gy daily fractions.
• Reports have identified a higher risk for nodal failure in patients with maxillary sinus carcinomas, with some investigators arguing for elective neck irradiation for T3 or T4 squamous cell lesions,5 while others have advocated ipsilateral elective neck irradiation for all stages of maxillary sinus carcinoma.7
6. INTENSITY-MODULATED RADIATION THERAPY IN NASAL CAVITY AND PARANASAL SINUS CARCINOMAS
6.1. Target Volume Determination
• If chemotherapy has been delivered before radiation, the targets should be outlined on the planning CT according to their prechemotherapy extent.
• The target volume specification for definitive and postoperative intensity-modulated radiation therapy (IMRT) in paranasal sinus and nasal cavity cancers is discussed in Chapter 4.
• Suggested target volume determination for paranasal sinus and nasal cavity cancers is summarized in Table 5-4.
6.2. Target Volume Delineation
• In patients receiving postoperative IMRT, clinical target volume 1 (CTV1) encompasses the residual tumor and the region adjacent to it but not directly involved by the tumor and the surgical bed with soft tissue invasion by the tumor or extracapsular extension by metastatic neck nodes. CTV2 includes primarily the prophylactically treated neck.
• In patients receiving definitive IMRT, CTV1 encompasses the gross tumor (primary and enlarged nodes) and the region adjacent to it but not directly involved by the tumor. CTV2 includes primarily the prophylactically treated neck.
• CTV1 and CTV2 delineation in a patient with clinically T2N0M0 squamous cell carcinoma of ethmoid sinus who received definitive IMRT is shown in Figure 5-6. The patient presented with a headache, which was initially thought to be sinusitis pain. But further studies revealed a mass in the ethmoid sinus extending into the nasal cavity. Biopsy of this mass showed a squamous cell carcinoma. There was no palpable adenopathy in the neck. Only the primary site was treated with definitive IMRT.
• CTV1 and CTV2 delineation in a patient with clinically T4N2bM0 squamous cell carcinoma of nasal cavity who received definitive IMRT is shown in Figure 5-7. The patient presented with a nasal mass. CT showed a tumoral lesion originating from the nasal cavity, extending into the orbital cavity and maxillary sinus. On physical examination, there was evidence of skin involvement on the nose and a palpable lymph node at the junction of levels II and I on the right side of the neck. Both the primary site and the bilateral neck were treated with definitive IMRT.
• CTV1 and CTV2 delineation in a patient with clinically T4aN0M0 poorly differentiated carcinoma of sinonasal region receiving definitive IMRT is shown in Figure 5-8. The patient presented with a history of left facial numbness, left eye proptosis, and left-sided tooth pain. CT showed a destructive mass in the left nasal ethmoid region with destruction of the left maxillary sinus and involvement of the medial orbital wall, extending into the orbit. The patient received two cycles of neoadjuvant chemotherapy consisting of VP-16 and carboplatin. After chemotherapy, proptosis completely resolved, and MRI showed striking improvement in the patient’s lesion in the nasal cavity and the ethmoid region. However, he still had persistent disease. The primary site was treated with definitive IMRT to spare orbital functions and the lacrimal gland. Bilateral upper jugular nodes were prophylactically treated because of the advanced stage. The gross disease received 70 Gy, whereas prechemotherapy tumor volume was treated with 60 Gy. Reduced radiation dose to precheotherapy tumor volume can be considered to optimize the critical normal tissue (optic nerve, optic chiasm, or brain stem) sparing. However, physicians may elect to carry prechemotherapy tumor volume to full dose.
6.3. Normal Tissue Delineation
• Normal tissue delineation is shown in Figure 5-9.
6.4. Suggested Target and Normal Tissue Doses
• See Chapter 4 for suggested target and normal tissue doses.
• To avoid excessive risk of damage to vision, fraction dose to CTV1 may be reduced to 1.8 or 1.9 Gy if CTV1 is in close proximity of the optic nerve or optic chiasm.
6.5. Intensity-Modulated Radiation Therapy Results
• Reports on early experience of IMRT for paranasal and nasal cavity carcinoma are discussed here. A total of 9 patients with paranasal and nasal cavity carcinoma were treated with IMRT between February 1997 and December 2000 at Washington University16: three patients were treated postoperatively, and six patients were treated with definitive IMRT. The T stages were T1 (1 patient), T3 (1 patient), and T4 (7 patients). The N stages were N0 (6 patients), N1 (1 patient), and N2 (2 patients) (American Joint Committee on Cancer staging: stage I [1 patient], stage II [1 patient], and stage IV [7 patients]). The median follow-up time was 36 months (range 13 to 42 months). No locoregional recurrence or distant metastasis was observed. All patients were alive, except 1, who died of intercurrent disease. Gastrostomy tube placement was required in two patients during the course of IMRT. Grade 3 late xerostomia developed in one patient. Altered vision (2 patients) and otitis requiring tympanostomy tube (1 patient) were the other serious late complications of IMRT.
• A subsequent study from UCSF17 showed that 36 patients treated with IMRT had 2-year and 5-year local control rates of 62% and 58%, respectively. While the results did not appear to demonstrate improvement in disease control as compared with conventional methods, the reported complications were less.
• Dirix et al.18 reported IMRT outcomes for a total of 40 patients treated between 2003 and 2008 with a median follow-up of 30 months. Two-year local control and overall survival were 76% and 89%, respectively. There were no grade 3 or 4 toxicities observed in the IMRT group, either acute or chronic.
• Madani et al.19 reported on 84 patients treated with IMRT. With a median follow-up of 40 months, the 5-year local control and overall survival rates were 59% and 67%, respectively. Encouragingly, toxicity rates were low: radiation-induced blindness was not observed but there was one grade 3 radiation-induced retinopathy.
FIGURE 5-6. Clinical target volume (CTV) delineation in a patient with T2N0M0 ethmoid sinus carcinoma who received definitive intensity-modulated radiation therapy. CTV1 (red line); gross tumor volume (GTV) (yellow line).
FIGURE 5-7. CTV delineation in a patient with T4N2bM0 nasal cavity carcinoma who received definitive IMRT. Bolus was used because of skin involvement by tumor. CTV1 (red line); CTV2 (dark blue line); gross tumor volume (GTV) and lymph node (N) (yellow line).
FIGURE 5-8. CTV delineation in a patient with T4aN0M0 sinonasal carcinoma receiving definitive IMRT after two courses of neoadjuvant chemotherapy. Prechemotherapy gross tumor volume extent was determined by the prechemotherapy MRI fusion study (left). CTV-70Gy (red line) is the persistent disease after chemotherapy to which 70 Gy is administered; CTV-60Gy (dark blue line) is the region to which 60 Gy is administered, encompassing the prechemotherapy gross tumor volume (light blue line). Persistent tumor (yellow line).
FIGURE 5-9. Normal tissue delineation. RL, right lens; LL, left lens; RE, right eye; LE, left eye; RON, right optic nerve; LON, left optic nerve; OC, optic chiasm; M, mandible; PG, parotid gland; SC, spinal cord; BS, brainstem.
• Similarly, Hoppe et al.20 reviewed 37 patients with paranasal sinus, nasal cavity, or lacrimal gland cancer treated postoperatively with IMRT (median dose 60 Gy). After 2 years, local progression-free and overall survival rates were 75% and 80%, respectively, with no incidence of grade 3–4 ophthalmologic toxicity.
• A recent study from Holland21 compared outcomes in 82 patients treated with surgery and radiotherapy or definitive chemoradiation. With 51-month follow-up, 5-year actuarial local control and overall survival rates were 74% and 54%, respectively. Importantly, they compared 3DCRT with IMRT and found LC and OS were not significantly different with RT treatment method, but that late toxicities (17% vs 52%) and visual impairment (12% vs 35%) were lower in IMRT as compared to 3DCRT. The authors noted that this may allow dose escalation with IMRT to improve LC and survival.
• A team in Ghent, Belgium,22 found similar results in a study of 130 patients with sinonasal cancer treated with IMRT: local control and overall survival (5-year actuarial) were 59% and 52%, respectively. No radiation-induced blindness was seen in the 86 patients available for review after 6 months or more.
• Wiegner et al.23 reported results on 52 patients treated with IMRT between 2000 and 2009. With a median follow-up of 26.6 months, 2-year local control and overall survival rates were 64% and 66%, respectively.
• IMRT with carbon ion boost (73 GyE) was used by Jensen et al.24 to treat 29 patients with T4 sinonasal malignancies. At median 5.1-month follow-up, overall radiological response was 50% (CR and PR); longer follow-up is needed to assess survival. Notably, no visual impairment was observed and the early toxicities (seven grade 3 and six grade 2) all resolved at 8 weeks after treatment.
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