Sinonasal neoplasms are rare entities, representing only 3% of malignancies in the head and neck region . Within this subset, a tremendous amount of diversity can be appreciated in tumor biology, histopathology, and treatment paradigms. In addition, these tumors arise adjacent to or involving very delicate structures, including the orbit, skull base, and brain . These factors contribute to a lack of consensus regarding appropriate follow-up after surgery or other treatment for sinonasal malignancy. Rates of local recurrence are generally estimated at 10–30% even when surgical margins are pathologically negative [3–5], demonstrating a clear need for postoperative surveillance .
In the literature, sinonasal tumors are often grouped into the larger category of head and neck tumors, and surveillance recommendations are generally based on data for this category overall. There is a paucity of literature addressing posttreatment surveillance of sinonasal malignancy specifically, and there are potential pitfalls in simply combining its management with that of head and neck cancer as a whole. The paranasal sinuses offer a large potential space for tumors to grow, and they tend to present at a late stage . Nasal obstruction or impeded sinus outflow is often attributed to more benign causes early on, further contributing to delayed detection and treatment. Postoperatively, mucosal inflammation can persist far longer in the tissue of the sinonasal skull base than in tissue of the deeper areas of the head and neck . Reasons for this discrepancy are likely related to the high environmental exposure of the paranasal sinuses, with pathogens, allergens, and irritants all inciting inflammatory response and disrupting mucociliary clearance [8,9]. Persistent mucosal inflammation postsurgery or postradiation can often be confounded with tumor recurrence on endoscopy or imaging [10▪▪]. Further, distorted anatomy from these interventions can make comparative follow-up extremely challenging .
Despite the aforementioned limitations, the sheer scarcity of studies evaluating surveillance strategies for paranasal sinus malignancies necessitates the inclusion and discussion of some general head and neck cancer guidelines throughout this article. Squamous cell carcinomas (SCCs) represent the vast majority of tumors in the paranasal sinuses and head and neck overall [11–13], so there is certainly some validity in generalizing the available information. However, it is also important to note that a wide variety of tumors beyond SCCs occur in the paranasal sinuses, which can range from extremely benign to exceptionally aggressive, such as in the case of mucosal melanoma [14,15]. Dutta et al.[16▪] studied 13 295 patients with sinonasal malignancy using data from the Surveillance, Epidemiology, and End Results database, providing insight for site and tumor-specific data. After SCC, mature B-cell non-Hodgkin's lymphoma and adenocarcinoma were the next most common histologic subtypes [16▪]. With a variety of treatment options often specifically tailored to tumor subtype, surveillance strategies should correspondingly have an unambiguous set of guidelines. Over the past 2 years, several studies have examined surveillance data for sinonasal malignancy, bringing to light some significant new findings that can help practicing otolaryngologists better tailor follow-up regimens for their patients. This new information, in combination with currently accepted surveillance strategies, will be discussed in the following sections.
SURVEILLANCE IN SINONASAL MALIGNANCY
Surgical intervention is the primary treatment for most sinonasal malignancies, and postsurgical surveillance is the main focus of the majority of the literature. De Visscher and Manni  highlighted the impact of routine patient follow-up for head and neck cancer, demonstrating that survival is improved significantly when asymptomatic recurrence was detected at routine visits, prior to patient self-referral. Since then, other studies have attempted to categorize predictors of recurrence, such as orbital and neural invasion, and histologic subtype [16▪,18,19]. Khalili et al.[10▪▪] conducted a retrospective review of 100 patients with sinonasal malignancy at the University of Pennsylvania, finding 30 recurrences over the time period followed. This study reviewed endoscopy and a variety of imaging modalities for predictive value in detecting recurrence, providing information about sensitivity and specificity in surveillance, and making several important recommendations. MRI was the dominant tool for structural imaging, and 77% of patients had at least one evaluation by PET-computed tomography (PET/CT). Overall, imaging demonstrated higher sensitivity than endoscopy for detecting recurrence, whereas endoscopy had similar specificity (Table 1) [10▪▪]. This was the first study of its kind to evaluate each surveillance modality separately.
Postoperative endoscopic examination is a current standard of care during the surveillance period and allows for complete evaluation of the surface of the posterior nasal cavity and nasopharynx. Complex reconstructions and radiation effects can make endoscopy more difficult, and certain areas are more amenable to evaluation by structural imaging. Khalili et al.[10▪▪] demonstrated that endoscopy has a sensitivity of 25% and specificity of 89%. Positive predictive value (PPV) of endoscopy depends on patient symptomatology: 13% PPV in the asymptomatic patient to 83% in the context of suspicious symptoms on history or physical exam. Interestingly, recurrences identified by endoscopy were exquisitely amenable to additional surgical intervention; all patients diagnosed with recurrence on endoscopy and treated with salvage surgery were alive at the end of the study period, whereas patients diagnosed by other modalities had a greater than 50% mortality rate during the same timeframe [10▪▪].
Suspicious endoscopic findings most often lead to correlation with imaging or biopsy. The low PPV of endoscopy leads to a number of unnecessary biopsies, which are often difficult to perform due to concerns of cerebrospinal fluid leaks, osteoradionecrosis, or tissue inflammation [20▪▪]. It is important to note that routine biopsy, in the setting of normal endoscopic findings, has shown no survival benefit in nasopharyngeal malignancy surveillance . Overall, endoscopy is most useful to the clinician in conjunction with patient-driven symptomatic follow-up, and it can identify superficial recurrences that are more amenable to surgical salvage.
Posttreatment imaging plays a critical role in surveillance, assessing structures that are unreachable by endoscopy or submucosal in location. CT, MRI, and 18F-fluorodeoxyglucose (18FDG) PET/CT are often used in concert, with specific modalities having unique benefits. Maroldi et al.[22▪▪] published a 2015 analysis regarding the use of imaging in sinonasal tumor recurrence and outlined important principles to consider. First, surgery and radiation cause confounding but expected imaging changes. Edema of the surgically scarred mucosa or enhancement surrounding a tissue flap can persist for months following treatment [22▪▪]. Imaging modalities and interpretation should be based on characteristic patterns of recurrence for specific tumor subtypes. For example, adenoid cystic carcinoma tends to have perineural recurrence, so histologic tumor data can provide robust information to guide imaging interpretation [22▪▪]. Although local recurrence is a more frequent pattern of progression than distant spread, it is important to note that choice of imaging should adequately cover all areas of interest, including potential areas of metastases. In studies of routine follow-up, imaging tends to diagnose more recurrences than endoscopy, and imaging-driven biopsies have improved sensitivity, accuracy, and PPV than biopsies due to suspicious endoscopic exams (PPV 72 vs. 43%) [10▪▪]. An additional advantage of imaging is a very high aggregate negative predictive value (NPV) (91%) in assessing sinonasal tumor recurrence [10▪▪,23]. This high NPV makes a negative imaging report reassuring for the practicing otolaryngologist, especially in the asymptomatic patient. Table 1 details statistical measures of performance for imaging in follow-up, utilizing aggregate CT, MRI, and 18FDG-PET data.
MRI is the most widely used structural imaging choice for sinonasal tumor surveillance. It is strictly superior to CT in spatial resolution, identifying surgical or postradiation complications and in detecting recurrence. T2-weighted MRI is frequently used for signal discrimination, whereas T1-weighted images are more appropriate for postcontrast comparison [22▪▪]. A baseline MRI examination, currently recommended at 3–4 months posttreatment for head and neck cancer , provides a comparison for all future exams. This allows for continued assessment of size stability or enhancement changes of the treatment site [25,26]. In the recent literature, MRI has demonstrated higher or comparable PPV (46–84%) to other imaging modalities in assessing sinonasal recurrence [10▪▪,27▪]. Because MRI is so interpretation-dependent, this level of variation in performance parameters is to be expected; individual institutions or providers may have different levels of suspicion even when reading the same imaging study. Radiation-induced soft tissue swelling can cause similar contrast enhancement in both recurrent tumor and postradiation fibrosis , but new techniques such as dynamic contrast-enhanced MRI may prove useful to help distinguish between these changes . Diffusion-weighted MRI (DWI) also has utility in distinguishing tumor from inflammation in head and neck cancer, with several caveats in sinonasal cancer specifically. DWI has high-susceptibility artifact in this space due to the complex bone–fat–air interface, and the diverse histologies, such as intestinal-type adenocarcinoma, can appear with variations of enhancement in this modality [22▪▪]. Despite these limitations, MRI and specialized magnetic resonance sequences serve as the gold-standard structural imaging techniques for screening for sinonasal tumor recurrence.
MRI has largely replaced CT as the primary imaging modality for surveillance, and there are few situations in which CT would be preferred for evaluation. In general, CT can be more useful in assessing acute intracranial complications in the immediate postoperative period and can have utility in specific tumor subtypes [22▪▪]. CT also has an advantage in immediate cost, but not necessarily in long-term cost of surveillance due to lower performance parameters. In younger individuals with sinonasal malignancy, clinicians must consider the risks associated with continued exposure to CT radiation and the risk for second malignancies [29,30]. Overall, CT proves to be most useful when combined with 18FDG-PET in surveillance.
18FDG-PET/CT has proven to be useful in detecting recurrence in head and neck cancer as a broad category. Although its role in surveillance is still being defined , the National Comprehensive Cancer Network (NCCN) clinical practice guidelines include PET/CT as a recommended imaging modality following treatment completion . Alone, PET/CT can identify 95% of asymptomatic recurrences in head and neck tumor patients in the first 24 months after completion of treatment, making it more sensitive than MRI and CT scans together [23,32,33]. Beyond this, PET/CT is incredibly useful in detecting distant metastases, as it allows detection of unexpected areas of hypermetabolism . PET/CT highlights hypermetabolic activity typically seen in neoplastic tissue , but is notably nonspecific for tumor cells. Young granulation tissue, macrophages, and fibroblasts all avidly take up FDG markers, especially following radiotherapy [36,37]. This gives PET/CT a high NPV [22▪▪], but often a poor specificity and PPV, most strikingly observed in sinonasal recurrence specifically (Table 1). A comparison of performance parameters between FDG-PET/CT in sinonasal malignancy and head and neck malignancy overall demonstrates that the high performance in head and neck tumors does not apply to neoplasms in the sinonasal cavity , with specificity falling from ∼80% in head and neck cancer overall to 40% in sinonasal cancer, and PPV falling from ∼75% in head and neck cancer overall to ∼50% in sinonasal cancer. Much of this decrement in precision is due to the inflammatory environment that is augmented in the posttreatment sinonasal cavity, which causes nonspecific FDG uptake [34,38,39].
Stemming directly from the poor PPV of PET/CT is the additional time, cost, and reduction in patient quality of life caused by diagnostic evaluation for false positives . Many centers will do FDG-PET follow-up one to four times per year, incurring tremendous additional treatment costs despite lack of concrete evidence for surveillance effectiveness. Therefore, determining effective timing and interval of PET/CT evaluation is of high importance, and recent advancements in the literature provide some clarity in this regard. For head and neck cancer overall, the 3-month posttreatment PET/CT has been validated and is generally accepted as a useful timeframe [23,38,40,41]. This allows for confounding inflammation and fibrosis to be attenuated [23,42], while not unnecessarily prolonging the initial follow-up and missing early recurrence. However, a retrospective analysis of PET/CT in posttreatment sinonasal malignancy from 2000 to 2015 at the University of Pennsylvania [20▪▪] demonstrated a prolonged hypermetabolic period, even without tumor recurrence. This period endures long beyond the period described for other head and neck tumors. Statistical difference in standardized uptake value (a measure of FDG avidity) showed possible extension of hypermetabolism up to 1 year [20▪▪], again suggesting that sinonasal malignancy is an entity more distinct than previously thought. These findings are corroborated by earlier data from Gil et al., which show improved specificity and PPV (85 and 67%, respectively) of PET/CT when it is performed at least 6 months posttreatment. Overall, the prolonged state of inflammation in the sinonasal cavity predicates the need for a new guideline for posttreatment PET/CT. Despite false positives, it should be performed at least once, due to its ability to rule out recurrence, but should not be performed on a frequent basis unless tumor subtype or histology requires closer intervals [10▪▪]. Local recurrence or metastasis occurs at a much higher rate in individuals with advanced or high-grade disease, and these patients may also warrant earlier and more frequent PET/CT evaluation [10▪▪,20▪▪,44▪].
Optimal timing of surveillance in sinonasal malignancy is ill defined [45,46], and clinicians generally follow NCCN guidelines for head and neck cancer overall. For head and neck SCC, 80–90% of recurrences will occur in the first 2–4 years, with an accepted approach to examine patients four to 12 times in the first year, three to six times in the second year, two to three times in the third through fifth years, and then continued annual follow-up or cessation of follow-up [1,47–49]. The Society for Head and Neck Surgery published data showing that 70% of clinicians follow the same follow-up strategy regardless of TNM (Tumor, Nodes, Metastasis) stage , and an additional study showed that as many as one-third of all follow-up visits could be omitted with no reduction in recurrences detected .
The data regarding head and neck cancer evaluations prompt important considerations when evaluating optimal surveillance timing in sinonasal malignancy. Disease-free interval is significantly affected by tumor site, histology, and carotid, perineural, or clival involvement [52▪▪]. Across studies, average time to recurrence in sinonasal neoplasms is 12–29 months [20▪▪,52▪▪], with less than 25% of recurrences occurring before a 5-month follow-up visit [20▪▪]. However, these data are skewed by certain tumors that are more prone to develop late recurrence, such as chondrosarcoma, adenoid cystic carcinoma, or esthesioneuroblastoma [10▪▪,53▪]. In these late-recurring tumors, it is prudent to extend imaging surveillance beyond the frequency of typical follow-up. Subtypes of sinonasal tumors can also vary greatly based on geographical area, further supporting the need for subtype-specific follow-up protocols [54–57].
From a practical standpoint of recurrence evaluation, patient follow-up should be offered only as frequently as necessary to maximize patient survival. However, more frequent follow-up also provides the clinician an opportunity for counseling on signs of recurrent disease, education about symptomatology, or elimination of risk factors such as smoking and alcohol. Therapy-related complications, such as xerostomia or osteoradionecrosis, can also be addressed at routine follow-up, which patients may need on a more frequent basis than that determined by surveillance protocols.
Once recurrence is proven, a clinician needs to decide if additional surgery would be effective. Kaplan et al.[52▪▪] identified that histology, grade, and orbital invasion are the three most important predictors as to whether a second surgery will be successful, with histology having the strongest effect on survival and disease-free interval. This corroborates previous work showing that posttreatment surveillance is most effective in individuals with originally limited disease .
Sinonasal neoplasms are unique entities and require a more tailored surveillance approach than that dictated by the overall head and neck cancer guidelines. Notably, posttreatment inflammation and other changes persist significantly longer in the sinonasal cavity than in the deeper spaces of the head and neck. Thus, 18FDG-PET/CT has a much higher rate of false positives in sinonasal malignancy surveillance than in surveillance for other types of head and neck cancer. Despite this, the high sensitivity of PET/CT still makes it a necessary and useful tool for clinicians when used more sparingly in the posttreatment period. Endoscopy is most useful in conjunction with symptom-driven follow-up and can also identify treatable recurrences. MRI is the structural imaging modality of choice, with greater predictive performance than CT. The diversity of tumors in the sinonasal cavity makes broad assertions regarding optimal frequency and duration difficult, and a tumor subtype-stratified prospective patient cohort study with standardized surveillance protocols at a variety of time points would be the ideal method to assess appropriate timing. Histology and tumor grade should guide frequency and length of follow-up on a case-by-case basis, until more literature is available on sinonasal tumors specifically. Overall, clinicians should be aware of the ways that sinonasal neoplasms differ from other head and neck neoplasms and tailor their surveillance strategies as necessary.
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Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
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